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  • 1995-1999  (215)
  • 1999  (215)
  • Human  (119)
  • Life and Medical Sciences  (96)
  • Nuclear reactions
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Years
  • 1995-1999  (215)
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Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Surgical and radiologic anatomy 21 (1999), S. 139-141 
    ISSN: 1279-8517
    Keywords: Anatomy ; Human ; Cross-section ; Computer-assisted instruction ; Education ; Medical
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The NPAC visible human viewer (NPAC VHV), graphical interface written in JAVA, freely accessible by the Web, allows the display of anatomic cross-sections of the Visible Human Project developed by the National Library of Medicine. In April 1997, the Medical Media Library of Lyons undertook the construction of a French-language mirror site of the NPAC VHV. The aim of this work is to evaluate first year utilisation of this site. From May 1st, 1997 to April 30th, 1998, the mirror site was consulted 34,752 times. In 45.14% of cases, the request came from France, in 4.42% of cases from Belgium, in 3.98% from Canada and in 2.12% from Switzerland. Other connections came either from a country responsible for fewer than 1% of connections or from unidentified computers. Data analysis showed a peak of connections between 15:00 and 17:00, and an increased number of connections from September to March 1998. The NPAC VHV is housed in 5 sites in the world. It is a software very simple to use. As the figures have no legends, it is more appropriate for group teaching than for self-teaching.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 199 (1999), S. 45-56 
    ISSN: 1432-0568
    Keywords: Key words Skin ; Proteoglycan ; Development ; Human ; Fetal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The extracellular matrix of human fetal skin differs substantially from that of adult skin. Fetal skin contains sparse amounts of fibrillar collagen enmeshed in a highly hydrated amorphous matrix composed of hyaluronan and sulfated proteoglycans. Both fetal and adult skin contain two major interstitial proteoglycans that are extracted by chaotrophic agents and detergents. These are the large chondroitin sulfate proteoglycan versican and the small dermatan sulfate proteoglycan decorin. For this study, proteoglycans extracted from fetal and adult skin were compared on Western blots to determine the relative amounts of versican. Decorin present in the same samples provided an internal standard for these studies. Fetal skin differed from adult skin in that it contained a significantly higher proportion of versican than did adult skin. Immunohistochemical studies compared early-fetal with mid-fetal skin and found that versican was a significant component of the interstitial extracellular matrix at both of these stages of skin development. However, by the mid-fetal period, interstitial versican became restricted to the upper half of the dermis, although versican also continued to be highly expressed around hair follicles, glands, and vasculature in the lower half of the dermis. Fetal skin extracts differed from an adult skin extract by the presence of a 66-kDa protein immunologically related to versican and by the absence of a 17-kDa core protein of a proteoglycan related to decorin. Both of these molecular species may represent degradation products of their respective proteoglycans. Monoclonal antibodies which detect epitopes in native chondroitin sulfate glycosaminoglycan chains recognized versican extracted from fetal skin. However, the tissue distribution of these antigens did not entirely conform to that for versican core protein, suggesting that versican in different regions of the skin may be substituted with glycosaminoglycan chains with different microchemistries. The results of these studies indicate that human fetal skin is structurally different from adult skin in terms of both the distribution and the composition of the large, aggregating chondroitin sulfate proteoglycan versican.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1211
    Keywords: Key words NK cells ; Human ; Surface molecule ; Lectin superfamily ; NK gene complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Natural killer (NK) cells constitute the third major population of lymphocytes. They possess the inherent capacity to kill various tumor and virally infected cells and mediate the rejection of bone-marrow grafts in lethally irradiated animals. A large family of NK cell receptors belong to the C-type lectin superfamily and are localized to the NK gene complex on Chromosome (Chr) 6 in the mouse and Chr 12 in the human. Genes in the NK gene complex encode type II receptors and examples include the families of NKR-P1, Ly-49, and NKG2 receptors. Examples of other C-type lectin-like NK cell receptors that occur as individual genes are CD94, CD69, and AICL. Here we report the molecular characterization and chromosomal mapping of a human lectin-like transcript (LLT1) expressed on NK, T, and B cells and localized to the NK gene complex within 100 kilobases of CD69. The cDNA encodes a predicted protein of 191 amino acid residues with a transmembrane domain near the N-terminus and an extracellular domain of 132 amino acid residues with similarity to the carbohydrate recognition domain of C-type lectins. The predicted protein of LLT1 shows 59 and 56% similarity to AICL and CD69, respectively. The predicted protein does not contain any intracellular ITIM motifs, suggesting that LLT1 may be involved in mediating activation signals.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 49 (1999), S. 438-445 
    ISSN: 1432-1211
    Keywords: Key words PA28 ; Proteasome ; Gene structure ; Evolution ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Two proteasome activators PA28α and β, which have been implicated in antigen processing for loading class I MHC molecules, are synthesized in response to Ifn-γ. The human genes encoding these activators (PSME1 and PSME2, respectively) were analyzed by sequencing. Each gene comprised 11 exons, consistent with gene duplication during vertebrate evolution. The intron/exon organization of both genes was highly conserved, the major difference being the absence of the exon encoding the lysine and glutamic acid-rich 'KEKE' motif in PA28β. Two other genes of relevance to the immune system were located close to those for PA28 at 14q11.2 including ISGF3G, a protein involved in transcription after IFNα signalling. These sequences were also characterized.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 73 (1999), S. 7-14 
    ISSN: 1432-0738
    Keywords: Key words Organophosphates ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t 1/2 3.7 h) and spontaneous reactivation (t 1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10−6 M (paraoxon-methyl) and 10−4 M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 μM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t 1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Multijoint movement ; Movement synergy ; Stroke ; Laterality ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies have shown that in neurologically normal subjects the addition of trunk motion during a reaching task does not affect the trajectory of the arm endpoint. Typically, the trunk begins to move before the onset and continues to move after the offset of the arm endpoint displacement. This observation shows that the potential contribution of the trunk to the motion of the arm endpoint toward a target is neutralized by appropriate compensatory movements of the shoulder and elbow. We tested the hypothesis that cortical and subcortical brain lesions may disrupt the timing of trunk and arm endpoint motion in hemiparetic subjects. Eight hemiparetic and six age-matched healthy subjects were seated on a stool with the right (dominant) arm in front of them on a table. The tip of the index finger (the arm endpoint) was initially at a distance of 20 cm from the midline of the chest. Wrist, elbow, and upper body positions as well as the coordinates of the arm endpoint were recorded with a three-dimensional motion analysis system (Optotrak) by infrared light-emitting diodes placed on the tip of the finger, the styloid process of the ulna, the lateral epicondyle of the humerus, the acromion processes bilaterally, and the sternal notch. In response to a preparatory signal, subjects lifted their arm 1–2 cm above the table and in response to a ”go” signal moved their endpoint as fast as possible from a near to a far target located at a distance of 35 cm and at a 45° angle to the right or left of the sagittal midline of the trunk. After a pause (200– 500 ms) they moved the endpoint back to the near target. Pointing movements were made without trunk motion (control trials) or with a sagittal motion of the trunk produced by means of a hip flexion or extension (test trials). In one set of test trials, subjects were required to move the trunk forward while moving the arm to the target (”in-phase movements”). In the other set, subjects were required to move the trunk backward when the arm moved to the far target (”out-of-phase movements”). Compared with healthy subjects, movements in hemiparetic subjects were segmented, slower, and characterized by a greater variability and by deflection of the trajectory from a straight line. In addition, there was a moderate increase in the errors in movement direction and extent. These deficits were similar in magnitude whether or not the trunk was involved. Although hemiparetic subjects were able to compensate the influence of the trunk motion on the movement of the arm endpoint, they accomplished this by making more segmented movements than healthy subjects. In addition, they were unable to stabilize the sequence of trunk and arm endpoint movements in a set of trials. It is concluded that recruitment and sequencing of different degrees of freedom may be impaired in this population of patients. This inability may partly be responsible for other deficits observed in hemiparetic subjects, including an increase in movement segmentation and duration. The lack of stereotypic movement sequencing may imply that these subjects had deficits in learning associated with short-term memory.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 126 (1999), S. 134-138 
    ISSN: 1432-1106
    Keywords: Key words Upper limb ; Posture ; Geometric constraints ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Significant debate exists regarding the neural strategies underlying the positioning and orienting of the hand during voluntary reaching movements of the human upper extremity. Some authors have suggested that positioning and orienting are controlled independently, while others have argued that a strong interdependence exists. In an effort to address this uncertainty, our study employed computer simulations to examine the impact of physiological limitations of joint rotation on the proposed independence of hand position and orientation. Specifically, we analyzed the effects of geometric constraints on final arm postures using a 7 degree-of-freedom model of the human arm. For 20 different hand configurations within the attainable workspace, we computed sets of achievable joint angles by applying inverse kinematics. From each set, we then calculated the locus of possible elbow positions for the particular final hand posture. When the joints were allowed 360° of rotation, the loci formed complete circles; however, when joint ranges were limited to physiological values, the extent of the loci decreased to an average arc angle of 54.6° (±27.9°). Imposition of joint limits also led to practically linear relationships between joint angles within a solution set. These theoretical results suggest a requirement for coordinated interaction between control of the joints associated with hand position and those involved with hand orientation in order to ensure attainable joint trajectories. Furthermore, it is conceivable that some of the correlations observed between joint angles in the course of natural reaching movements result from geometric constraints.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1106
    Keywords: Key words Optokinetic nystagmus ; Positron emission tomography ; Visual motion ; Area V5 ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Positron emission tomography (PET) was used to address the issue of physiological changes in the cerebral cortex associated to optokinetic nystagmus (OKN) in humans. We studied regional cerebral blood flow in eight volunteers during reflexive induction of OKN by a pattern of dots moving unidirectionally (toward the left side). We used two control conditions, with subjects passively viewing either stationary or incoherently moving dots. This paradigm was designed in order to differentiate the OKN-related activations from blood flow changes related to visual motion. When compared with the stationary condition, OKN activated a set of occipital areas known to be sensitive to visual motion. Bilateral activation was found in the striate cortex (V1) and the parieto-occipital fissure, while area V5, the intraparietal sulcus, and the pulvinar were activated only in the left hemisphere. When compared with incoherent motion, OKN activated the V1 and the parieto-occipital fissure bilaterally and the right lingual gyrus, while a signal decrease was observed in the V5 region in both hemispheres. No significant signal changes were found in areas implicated in saccades or in processing vestibular information. These results indicate that processing of OKN-related information is associated with neural activity in a specific set of visual motion areas and suggest that this network can be asymmetrically activated by a strictly unidirectional stimulation. Results are also discussed in terms of the specific kinds of OKN-related information processing subserved by each area in this network.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 126 (1999), S. 175-186 
    ISSN: 1432-1106
    Keywords: Key words Listing’s plane ; Vergence ; Binocular ; Eye movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Earlier studies have reported temporal rotation of Listing’s plane with convergence of the eyes causing torsion, which is dependent on eye elevation. The amount by which the planes rotate differs from study to study. To gain insight into the functional significance of the temporal tilt of Listing’s plane for vision, we examined whether the rotation of the plane depends on the visual conditions, namely on the stimuli driving vergence. In different conditions, accommodative vergence, disparity-vergence, combinations of disparity with accommodation or depth perception were used and the resulting rotation of Listing’s plane was measured. Our findings show, for the first time, that the relationship between convergence and Listing’s-plane temporal rotation depends on the stimuli driving vergence. When the stimulus contains only disparity cues, vergence and Listing’s plane rotate immediately and consistently among subjects. Accommodative vergence, the mutual couplings between vergence and accommodation, can influence the orientation of Listing’s plane, but they do so in a idiosyncratic way. The largest rotation was elicited by stereograms combining disparity-vergence with depth perception. These findings support the idea of a functional role of Listing’s plane rotation for binocular vision, perhaps for depth perception.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 126 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
    Type of Medium: Electronic Resource
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  • 11
    ISSN: 1432-1106
    Keywords: Key words Grip force ; Force control ; Parabolic flight ; Microgravity ; Hypergravity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object’s weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object’s weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Reaching ; Anticipatory postural control ; EMG ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study focused on the developmental changes of postural adjustments accompanying reaching movements in healthy infants. We made a longitudinal study of ten infants between 6 and 18 months of age. During each session multiple surface electromyograms of arm, neck, trunk and leg muscles at the right side of the body were recorded during right-handed reaching movements in two positions (”upright sitting” in an infant chair and ”long-leg” sitting without support). Simultaneously the whole session was recorded on video. Comparable data were present from the same infants at 3–5 months. Additionally, 18 infants (8–15 months) were assessed once during similar reaching tasks, but in these infants electromyographic activity of the trunk and neck muscles at both sides of the body were recorded. Our data revealed two transitions in the development of postural adjustments. The first transition was present around 6 months of age. At this age the postural muscles were infrequently activated during reaching movements. At 8 months ample postural activity reappeared and the infants developed the ability to adapt the postural adjustments to task-specific constraints such as arm movement velocity or the sitting position at the onset of the reaching movement. The second transition occurred between 12 and 15 months. Before 15 months the infants did not show consistent anticipatory postural activity, but from 15 months onwards they did, particularly in the neck muscles.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 127 (1999), S. 355-370 
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Motion ; Functional imaging ; Human ; Flicker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional magnetic resonance imaging was used to map motion responsive regions of the human brain by contrasting passive viewing of moving and stationary randomly textured patterns. Regions were retained as motion responsive if they reached significance either in the group analysis or in the majority of hemispheres in single-subject analysis. They include well-known regions, such as V1, hMT/V5+, and hV3A, but also several occipito-temporal, occipito-parietal, parietal, and frontal regions. The time course of the activation was similar in most of these regions. Motion responses were nearly identical for binocular and monocular presentations. Flicker-induced-activation introduced a dichotomy amongst these motion responsive regions. Early occipital and occipito-temporal regions responded well to flicker, while flicker responses gradually vanished as one moved to occipito-parietal and then parietal regions. Finally, over a more than four-fold range, stimulus diameter had little effect on the motion activations, except in V1.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 124 (1999), S. 351-362 
    ISSN: 1432-1106
    Keywords: Key words Saccadic adaptation ; Gaze ; Short term adaptation ; Transfer to hand movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated whether and how adaptive changes in saccadic amplitudes (short-term saccadic adaptation) modify hand movements when subjects are involved in a pointing task to visual targets without vision of the hand. An experiment consisted of the pre-adaptation test of hand pointing (placing the finger tip on a LED position), a period of adaptation, and a post-adaptation test of hand pointing. In a basic task (transfer paradigm A), the pre- and post-adaptation trials were performed without accompanying eye and head movements: in the double-step gaze adaptation task, subjects had to fixate a single, suddenly displaced visual target by moving eyes and head in a natural way. Two experimental sessions were run with the visual target jumping during the saccades, either backwards (from 30 to 20°, gaze saccade shortening) or onwards (30 to 40°, gaze saccade lengthening). Following gaze-shortening adaptation (level of adaptation 79±10%, mean and s.d.), we found a statistically significant shift (t-test, error level P〈0.05) in the final hand-movement points, possibly due to adaptation transfer, representing 15.2% of the respective gaze adaptation. After gaze-lengthening adaptation (level of adaptation 92±17%), a non-significant shift occurred in the opposite direction to that expected from adaptation transfer. The applied computations were also performed on some data of an earlier transfer paradigm (B, three target displacements at a time) with gain shortening. They revealed a significant transfer relative to the amount of adaptation of 18.5±17.5% (P〈0.05). In the coupling paradigm (C), we studied the influence of gaze saccade adaptation of hand-pointing movements with concomitant orienting gaze shifts. The adaptation levels achieved were 59±20% (shortening) and 61±27% (lengthening). Shifts in the final fingertip positions were congruent with internal coupling between gaze and hand, representing 53% of the respective gaze-amplitude changes in the shortening session and 6% in the lengthening session. With an adaptation transfer of less than 20% (paradigm A and B), we concluded that saccadic adaptation does not ”automatically” produce a functionally meaningful change in the skeleto-motor system controlling hand-pointing movements. In tasks with concomitant gaze saccades (coupling paradigm C), the modification of hand pointing by the adapted gaze comes out more clearly, but only in the shortening session.
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  • 15
    ISSN: 1432-1106
    Keywords: Key words Vibration-induced kinesthetic illusions ; Antagonist vibratory response ; Motor units ; Wrist extensor muscles ; Human ; Microelectromyography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.
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  • 16
    ISSN: 1432-1106
    Keywords: Key words Locomotion ; Load ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Prior work from mammals suggests that load experienced by extensor muscles of the hindlimbs (i.e. Duysens and Pearson 1980; Pearson and Collins 1993; Fouad and Pearson 1997) or cutaneous afferents from the plantar surface of the foot (Duysens and Pearson 1976; Guertin et al. 1995) enhances activity in extensor muscles during the stance phase, and delays the onset of flexor activity associated with the swing phase. The presumed functional significance of this phenomenon is that extensor activity of the supporting limb during walking can: (a) reinforce the supporting function in proportion to the load experienced, and (b) prolong the stance phase until unloading of the limb has occurred. Whether a similar functional role exists for load-sensitive afferents during walking in the human is unknown. In this study, the effect of adding or removing a substantial load (30% of body weight) at the centre of mass was studied in healthy adult human subjects. Loads were applied near the centre of mass to avoid the need for postural adjustments which might confound the interpretation of the results. Subjects walked on a treadmill with either: (a) a sustained increase or decrease in load, or (b) a sudden unexpected increase or decrease in load. In general, subjects responded to the changes in load by changing the amplitude of the extensor electromyographic (EMG) bursts. For example, with sudden unexpected additions in load, the average increase in amplitude was 40% for the soleus across the stance phase, and 134% for the quadriceps during the early part of the stance phase. Extensor EMGs increased with both sustained and sudden increases in load. Extensor EMG durations also increased (average increase in duration of 4% for soleus with sudden loading, and 7% for sustained loading). Cycle duration hardly changed (average increase of 0.5% with both sudden and sustained loading). These results differ from those of infants subjected to a similar perturbation during supported walking. A large change in timing (i.e. an increase in the duration of the stance phase by 30% and the step cycle by 28%) was seen in the infants, with no change in the amplitude of the EMG burst (Yang et al. 1998). These results suggest that the central nervous system can control the timing and amplitude of extensor EMG activity in response to loading independently. Maturation of the two components most likely occurs independently. In the adult, independent control of the two components may provide greater flexibility of the response.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 129 (1999), S. 241-246 
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Visual attention ; Putamen ; Orienting ; Positron emission tomography ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used positron emission tomography (PET) in ten subjects to study the brain regions involved in voluntary shifts of attention. For six scans, subjects performed a visual target detection task in which the location of the target was indicated in advance on some proportion of trials by the appearance of an arrow cue at fixation. The informative cues were successful in speeding reaction time to the target. Blood flow in the left putamen was correlated with the proportion of informative cues provided within a scan. We discuss this finding in terms of three possible interpretations: attentional shifts, response inhibition, and motor preparation related to the use of the right hand to respond. Blood flow in cortical regions commonly associated with attention was not related to cue ratio, a finding that may reflect automatization of the processes involved in interpreting and using the cues.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1432-1106
    Keywords: Key words Coordination ; Posture ; Movement ; Anticipatory postural adjustments ; Axial synergy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The whole-body center of mass (CoM) has been classically regarded as the stabilized reference value for human voluntary movements executed upon a fixed base of support. Axial synergies (opposing displacements of head and trunk with hip segments) are believed to minimize antero-posterior (A/P) CoM displacements during forward trunk movements. It is also widely accepted that anticipatory postural adjustments (APAs) create forces of inertia that counteract disturbances arising from the moving segment(s). In the present study, we investigated CoM stabilization by axial synergies and APAs during a whole-body reaching task. Subjects reached towards an object placed on the ground in front of them in their sagittal plane using a strategy of coordinated trunk, knee, and hip flexion. The reaching task imposed constraints on arm-trajectory formation and equilibrium maintenance. To manipulate equilibrium constraints, differing conditions of distance and speed were imposed. The comparison of distance conditions suggested that axial synergies were not entirely devoted to CoM stabilization: backward A/P hip displacements reduced as head and trunk forward A/P displacements increased. Analysis of upper- and lower-body centers of mass in relation to the CoM also showed no strict minimization of A/P CoM displacements. Mechanical analysis of the effects of APAs revealed that, rather than acting to stabilize the CoM, APAs created necessary conditions for forward CoM displacement within the base of support in each condition. The results have implications for the CoM as the primary stabilized reference for posture and movement coordination during whole-body reaching and for the central control of posture and voluntary movement.
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  • 19
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    Experimental brain research 128 (1999), S. 550-556 
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Kinematics ; Human ; Visual pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In solving the selection-for-action problem, it is believed that attentional mechanisms enable dominance of target over non-target objects. However, under some conditions, information from non-target objects ”interferes” with the action to a relevant target. We investigated the possibility that this interference may result when the irrelevant object activates a specific subset of visuomotor pathways. Participants reached to grasp three-dimensional stimuli while actively attending to a nearby flanker object. The means by which the flanker was presented was manipulated. This relevant object was illuminated either abruptly or gradually. The parvocellular pathway in early visual processing is equally activated in both conditions. The magnocellular pathway is strongly activated by abrupt presentation and weakly activated with gradual presentation of the flanker object. Kinematics of the reach-to-grasp action to the target showed signs of interference only in the sudden illumination condition. This suggests a dissociation between dorsal and ventral cortical streams in terms of relevance for action. Our data suggests that this effect is not due to early visual-pathway differences, but instead reveals a property of a transient object-based visual attention mechanism.
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  • 20
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    Experimental brain research 125 (1999), S. 43-49 
    ISSN: 1432-1106
    Keywords: Key words Proprioception ; Visual localization ; Visual context ; Multisensory integration ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a previous study we investigated how the CNS combines simultaneous visual and proprioceptive information about the position of the finger. We found that localization of the index finger of a seen hand was more precise (a smaller variance) than could reasonably be expected from the precision of localization on the basis of vision only and proprioception only. This suggests that, in localizing the tip of the index finger of a seen hand, the CNS may make use of more information than proprioceptive information and visual information about the fingertip. In the present study we investigate whether this additional information stems from additional sources of sensory information. In experiment 1 we tested whether seeing an entire arm instead of only the fingertip gives rise to a more precise proprioceptive and/or visual localization of that fingertip. In experiment 2 we checked whether the presence of a structured visual environment leads to a more precise proprioceptive localization of the index finger of an unseen hand. In experiment 3 we investigated whether looking in the direction of the index finger of an unseen hand improves proprioceptive localization of that finger. We found no significant effect in any of the experiments. The results refute the hypothesis that the investigated effects can explain the previously reported very precise localization of a seen hand. This suggests that localization of a seen finger is based exclusively on proprioception and on vision of the finger. The results suggest that these sensory signals may contain more information than is described by the magnitude of their variances.
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  • 21
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    Experimental brain research 125 (1999), S. 50-60 
    ISSN: 1432-1106
    Keywords: Key words Pointing errors ; Remembered target Navigation ; Active self-movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied pointing movements to remembered visual targets in a completely darkened room with and without self-made step movements in order to investigate in which coordinate system and to what extent target representations relative to the body are updated for self-induced egomotion. A small red-light-emitting diode on the fingertip provided visual feedback about fingertip position at all times. We asked subjects to make pointing movements that started 2 s after disappearance of a visual target. In this interval of 2 s the subject did or did not make a step. The pointing errors without a step showed that subjects undershot faraway targets in a systematic way, whereas they sometimes overshot nearby targets. We found that the step causes larger pointing errors both in amplitude and direction with a bias in the direction of the step. We explored three different versions of a descriptive model in which polar coordinates were used to describe the pointing movement, and in which either Cartesian or polar coordinates were used to update target position relative to the shoulder for the step. The results suggest that incorporation of the step displacement in the new target position relative to the subject is done in a Cartesian frame of reference. Moreover, the amplitude of the step displacement tends to be underestimated by subjects.
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  • 22
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    Experimental brain research 125 (1999), S. 139-152 
    ISSN: 1432-1106
    Keywords: Key words Reaching movements ; Direction ; Amplitude ; Initial kinematics ; Spatial variability ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The accuracy of reaching movements to memorized visual target locations is presumed to be determined largely by central planning processes before movement onset. If so, then the initial kinematics of a pointing movement should predict its endpoint. Our study examined this hypothesis by testing the correlation between peak acceleration, peak velocity, and movement amplitude and the correspondence between the respective spatial positions of these kinematic landmarks. Subjects made planar horizontal reaching movements to targets located at five different distances and along five radially arrayed directions without visual feedback during the movements.The spatial dispersion of the positions of peak acceleration, peak velocity, and endpoint all tended to form ellipses oriented along the movement trajectory. However, whereas the peaks of acceleration and velocity scaled strongly with movement amplitude for all of the movements made at the five target distances in any one direction, the correlations with movement amplitude were more modest for trajectories aimed at each target separately. Furthermore, the spatial variability in direction and extent of the distribution of positions of peak acceleration and peak velocity did not scale differently with target distance, whereas they did for endpoint distributions. Therefore, certain features of the final kinematics are evident in the early kinematics of the movements as predicted by the hypothesis that they reflect planning processes. However, endpoint distributions were not completely predetermined by the Initial kinematics. In contrast, multivariate analysis suggests that adjustments to movement duration help compensate for the variability of the initial kinematics to achieve desired movement amplitude. These compensatory adjustments do not contradict the general conclusion that the systematic patterns in the spatial variability observed in this study reflect planning processes. On the contrary, and consistent with that conclusion, our results provide further evidence that direction and extent of reaching movements are planned and determined in parallel over time.
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  • 23
    ISSN: 1432-1106
    Keywords: Key words Three-dimensional pointing ; Human ; Remembered targets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The accuracy of visually guided pointing movements decreases with speed. We have shown that for movements to a visually defined remembered target, the variability of the final arm endpoint position does not depend on movement speed. We put forward a hypothesis that this observation can be explained by suggesting that movements directed at remembered targets are produced without ongoing corrections. In the present study, this hypothesis was tested for pointing movements in 3D space to kinesthetically defined remembered targets. Passive versus active acquisition of kinesthetic information was contrasted. Pointing errors, movement kinematics, and joint-angle coordination were analyzed. The movements were performed at a slow speed (average peak tangential velocity of about 1.2 m/s) and at a fast speed (2.7 m/s). No visual feedback was allowed during the target presentation or the movement. Variability in the final position of the arm endpoint did not increase with speed in either the active or the passive condition. Variability in the final values of the arm-orientation angles determining the position of the forearm and of the upper arm in space was also speed invariant. This invariance occurred despite the fact that angular velocities increased by a factor of two for all the angles involved. The speed-invariant variability supports the hypothesis that there is an absence of ongoing corrections for movements to remembered targets: in the case of a slower movement, where there is more time for movement correction, the final arm endpoint variability did not decrease. In contrast to variability in the final endpoint position, the variability in the peak tangential acceleration increased significantly with movement speed. This may imply that the nervous system adopts one of two strategies: either the final endpoint position is not encoded in terms of muscle torques or there is a special on-line mechanism that adjusts movement deceleration according to the muscle-torque variability at the initial stage of the movement. The final endpoint position was on average farther from the shoulder than the target. Constant radial-distance errors were speed dependent in both the active and the passive conditions. In the fast speed conditions, the radial distance overshoots of the targets increased. This increase in radial-distance overshoot with movement speed can be explained by the hypothesis that the final arm position is not predetermined in these experimental conditions, but is defined during the movement by a feedforward or feedback mechanism with an internal delay.
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  • 24
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    Keywords: Key words Hyperventilation ; Magnetoencephalography ; Somatosensory cortex ; Auditory cortex ; Somatosensory evoked response ; Auditory evoked response ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is well established that voluntary hyperventilation (HV) slows down electroencephalographic (EEG) rhythms. Little information is available, however, on the effects of HV on cortical responses elicited by sensory stimulation. In the present study, we recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs), and somatosensory evoked magnetic fields (SEFs) from healthy subjects before, during, and after a 3- to 5-min period of voluntary HV. The effectiveness of HV was verified by measuring the end-tidal CO2 levels. Long-latency (100–200 ms) AEPs and long-latency AEFs originating at the supratemporal auditory cortex, as well as long-latency SEFs from the primary somatosensory cortex (SI) and from the opercular somatosensory cortex (OC), were all reduced during HV. The short-latency SEFs from SI were clearly less modified, there being, however, a slight reduction of the earliest cortical excitatory response, the N20m deflection. A middle-latency SEF deflection from SI at about 60 ms (P60 m) was slightly increased. For AEFs and SEFs, the center-of-gravity locations of the activated neuronal populations were not changed during HV. All amplitude changes returned to baseline levels within 10 min after the end of HV. The AEPs were not altered when the subjects breathed 5% CO2 in air in a hyperventilation-like manner, which prevented the development of hypocapnia. We conclude that moderate HV suppresses long-latency evoked responses from the primary projection cortices, while the early responses are less reduced. The reduction of long-latency responses is probably mediated by hypocapnia rather than by other nonspecific effects of HV. It is suggested that increased neuronal excitability caused by HV-induced hypocapnia leads to spontaneous and/or asynchronous firing of cortical neurones, which in turn reduces stimulus-locked synaptic events.
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  • 25
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    Experimental brain research 125 (1999), S. 265-270 
    ISSN: 1432-1106
    Keywords: Key words Tendon reflexes ; Biceps femoris ; Gait ; Ia afferents ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  During gait it is generally accepted that there is a reduction in amplitude of H-reflexes as compared to standing. For short-latency stretch reflexes, however, it is less clear whether a similar reduction in reflex gain is present during locomotion. Stretches of constant amplitude are hard to produce under these circumstances and for this reason some previous studies on the biceps femoris (BF) have used ”reduced gait” in which the stimulated leg is stepping on the spot while the contralateral leg is walking on a treadmill. With this method it was possible to show that BF tendon jerk reflexes are larger at end swing and therefore are likely to contribute to the EMG burst normally occurring in that part of the step cycle when the BF is rapidly stretched. In the present study two questions were addressed: first, whether the reflex is different in size during gait compared to standing and, second, whether it is modulated in size during the gait cycle not only during reduced but also during normal gait. It was found that during both types of gait there was a general reflex depression with regard to the respective control values obtained during standing at similar EMG activity levels. In previous studies on soleus and quadriceps, discrepancies between EMG activity and reflex amplitude have been ascribed to changes in presynaptic inhibition of Ia terminals mediating the afferent volley of the reflex. Based on the data presented, this may also be true for the BF. In both normal and reduced gait the reflex was similarly modulated in size, showing a maximum at the end of swing. This similarity implies that reduced gait may be useful as an acceptable alternative for normal gait in studies on phase-dependent reflex modulation during locomotion.
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  • 26
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    Experimental brain research 125 (1999), S. 435-439 
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Plasticity ; Synchronization ; Motor system ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used focal transcranial magnetic stimulation to examine the effects of 120 synchronized thumb and foot movements on the motor output map of the right abductor pollicis brevis muscle (APB) (experiment 1). To evaluate the performance, the latencies between the onset of the electromyographic activity (EMG) of the two muscles were measured. As control, 120 asynchronous thumb and foot movements were performed (experiment 2). Exclusively in experiment 1, the center of gravity (CoG) of the output map moved medially in the direction of the foot representation area (mean 7 mm, P〈0.05) and returned into its original location within 1 h. In experiment 2, the CoG remained unchanged (mean displacement, 0.68 mm into a lateral direction; not significant). The effect in experiment 1 was independent of an improvement in performance. We conclude that a short-lasting training of synchronous movements induces modulations of motor output maps which probably occur due to interactions between hand and foot representation areas in the motor cortex.
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  • 27
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    Experimental brain research 124 (1999), S. 422-428 
    ISSN: 1432-1106
    Keywords: Key words Lifting forces ; Size-weight illusion ; Microgravity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Individuals usually report for two objects of equal mass but different volume that the larger object feels lighter. This so-called size-weight illusion has been investigated for more than a century. The illusion is accompanied by increased forces, used to lift the larger object, resulting in a higher initial lifting speed and acceleration. The illusion holds when subjects know that the mass of the two objects is equal and it is likely that this also counts for the enlarged initial effort in lifting a larger box. Why should this happen? Under microgravity, subjects might be able to eliminate largely the weight-related component of the lifting force. Then, if persistent upward scaling of the weight-related force component had been the main cause of the elevated initial lifting force under normal gravity, this elevated force might disappear under microgravity. On the other hand, the elevated initial lifting effort in the large box would be preserved if it had been caused mainly by a persistent upward scaling of the force component, necessary to accelerate the object. To test whether the elevated initial lifting effort either persists or disappears under microgravity, a lifting experiment was carried out during brief periods of microgravity in parabolic flights. Subjects performed whole-body lifting movements with their feet strapped to the floor of the aircraft, using two 8-kg boxes of different volume. The subjects were aware of the equality of the box masses. The peak lifting forces declined almost instantaneously with approx. a factor 9 in the first lifting movements under microgravity compared with normal gravity, suggesting a rapid adaptation to the loss of weight. Though the overall speed of the lifting movement decreased under microgravity, the mean initial acceleration of the box over the first 200 ms of the lifting movement remained higher (P=0.030) in the large box (1.87±0.127 m/s2) compared with the small box (1.47±0.122 m/s2). Under normal gravity these accelerations were 3.30±0.159 m/s2 and 2.67±0.159 m/s2, respectively (P=0.008). A comparable trend was found in the initial lifting forces, being significant in the pooled gravity conditions (P=0.036) but not in separate tests on the normal gravity (P=0.109) and microgravity (P=0.169) condition. It is concluded that the elevated initial lifting effort with larger objects holds during short-term exposure to microgravity. This suggests that upward scaling of the force component, required to accelerate the larger box, is an important factor in the elevated initial lifting effort (and the associated size-weight illusion) under normal gravity.
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  • 28
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    Keywords: Key words Transcranial magnetic stimulation ; Silent period ; Voluntary motor drive ; Motor threshold ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.
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  • 29
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    Experimental brain research 124 (1999), S. 469-473 
    ISSN: 1432-1106
    Keywords: Key words Form from motion ; Visual development ; Visual acuity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The development of dynamic vision was investigated in 400 healthy subjects (200 females and 200 males) aged between 4 and 24 years. The test consisted of a computer-generated random-dot kinematogram in which a Landolt ring was briefly presented as a form-from-motion stimulus. Motion contrast between the ring and background was varied in terms of the percentage of dots moving coherently within the ring in four levels (100%, 50%, 30%, and 20%). The subject’s task was to indicate the position of a gap in the ring (left, right, top, bottom). Results show a clear increase in performance with age for all motion contrast levels, with the greatest changes for the lowest levels. Adult performance was reached at the age of 15 years. Luminance-based static acuity measured with the Landolt test was poorly correlated with acuity for its form-from-motion analogue.
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  • 30
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    Experimental brain research 124 (1999), S. 503-512 
    ISSN: 1432-1106
    Keywords: Key words Reaching movements ; Memory for positions ; Laterality ; Posture copying ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Many recent studies indicate that memory for final position is superior to memory for movement. There is ambiguity about what is meant by the term final position, however. Is it final spatial location or final posture? According to a recently proposed theory by Rosenbaum et al., which maintains that stored postures form the basis for movement planning, when people try to return to recently reached positions, they should try to adopt the postures they just occupied. An alternative view, which holds that movements are primarily planned with respect to spatial locations, predicts that subjects should tend to return to places in external space. We describe an experiment that tested these opposing predictions. The experiment relied on the notion that if people store and use postures, they should ”copy” the posture adopted with one arm to the other arm when possible. The results support this hypothesis.
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  • 31
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    Experimental brain research 126 (1999), S. 235-251 
    ISSN: 1432-1106
    Keywords: Key words Motor learning and memory ; Perseveration ; Prefrontal cortex ; Reversal learning ; Basal ganglia ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ability to inhibit previously learned visuomotor associations is essential for efficient learning of novel behaviors. While the neural basis of the system that might control interactions between competing motor memories is not known, it has been demonstrated that animals with ventral and orbital prefrontal cortex (PFC) deficits have particular difficulties in learning to withhold responses to previously conditioned sensory stimuli. Here we measured regional cerebral blood flow (rCBF), using positron emission tomography, during learning of a novel motor task that required inhibition of a previously learned motor memory. Subjects (n=24) learned reaching movements in a force field (field A). After a variable time interval, some subjects (n=15) learned to reach in a field with a reversed pattern of forces (field B). When the time interval was short (10 min), learning in field B was coincident with a reactivation of regions that had become initially activated during learning in field A: the left putamen and bilaterally in the dorsolateral PFC. Behaviorally, this was accompanied with perseveration that lasted for hundreds of movements, suggesting an instantiation of the internal model for field A during learning in field B. Neither the reactivation nor the perseveration were observed in a different group of subjects that learned field B at 5.5 h. We found that the regions which significantly differentiated the two groups during learning of B were in the ventrolateral PFC (bilaterally): there were sharp decreases in rCBF here in the 5.5 group but not in the 10-min group. At 5.5 h motor learning again involved the striatum, but this time in the left caudate. Neither the caudate nor the ventral PFC had exhibited learning-related activity in field A. Instead, they showed changes in rCBF during the reversal of the learning problem when the previously acquired motor memory was successfully gated. The results demonstrate that: (1) perseveration of a competing motor memory may be linked to reactivation of the neural circuit that participated in acquiring that memory, and (2) the ventral PFC may play an important role in the inhibitory control of the competing motor memory.
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  • 32
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    Keywords: Key words Suprathreshold heat pain ; Adapting temperature ; Temporal parameters ; Spinal dorsal horn neuron ; Descending control ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of stimulus temperature rise rate (2.5ºC/s, 5.0ºC/s, and 10.0ºC/s), adapting (baseline) temperature (25ºC, 30ºC, and 35ºC), and duration of peak stimulus temperature (1.0 s, 2.5 s, 5.0 s, and 10.0 s) on responses evoked by noxious heat stimuli of suprathreshold intensity was studied in wide dynamic range (WDR) neurons of the rat spinal dorsal horn. The spinal neuronal responses were compared with human psychophysical data obtained using the same stimuli. Noxious heat stimuli with a peak temperature of 54ºC were applied with a contact thermostimulator to the glabrous skin of the hindfoot in rats or to the palmar skin in humans. With the highest ramp rate and the highest adapting temperature, the sensory and spinal neuronal response latencies were decreased more than expected on the basis of the change in physical parameters of the stimulus. The magnitudes of sensory and spinal neuronal response were independent of the stimulus ramp rate, whereas pain magnitude estimates and spinal neuronal impulse counts evoked by the same peak stimulus temperature were increased with an increase in the adapting stimulus temperature. The onset latencies of pain reactions and spinal neuronal responses were independent of the peak stimulus duration, whereas the latency of the maximum discharge in spinal neurons increased with prolongation of the peak stimulus. The sensory magnitude estimate of pain and the neuronal impulse count were increased with increase in stimulus duration. Following spinalization, the spinal neuronal responses were stronger and the stimulus duration-dependent increase in the impulse count developed faster. Moreover, the peak frequency of spinal neuronal response increased significantly with prolongation of the heat stimuli after spinalization, but not in animals with an intact spinal cord. The results indicate that stimulus rise rate, stimulus duration, and the adapting temperature are important factors in determining the sensory and spinal neuronal responses to high-intensity heat stimuli. The changes in the total impulse counts evoked by varying supraliminal heat stimuli in spinal dorsal horn WDR neurons corresponded well with the changes in pain magnitude estimates in humans. Also, the changes in spinal neuronal response onset latencies were accompanied by corresponding changes in onset latencies of human pain reactions but not with pain magnitude estimates. The effect of spinalization indicated that descending pathways control not only the response magnitude in the spinal dorsal horn WDR neurons but also the temporal characteristics of the spinal neuronal response.
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  • 33
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    Experimental brain research 127 (1999), S. 83-94 
    ISSN: 1432-1106
    Keywords: Key words Target interception ; Reaching ; Grasping ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The goal of the present study was to understand which characteristics (movement time or velocity) of target motion are important in the control and coordination of the transport and grasp-preshape components of prehensile movements during an interception task. Subjects were required to reach toward, grasp and lift an object as it entered a target area. Targets approached along a track at four velocities (500, 750, 1000 and 1250 mm/s) which were presented in two conditions. In the distance-controlled condition, targets moving at all velocities traveled the same distance. In the viewing-time-controlled condition, combinations of velocity and starting distances were performed such that the moving target was visible for 1000 ms for all trials. Analyses of kinematic data revealed that when, target distance was controlled, velocity affected all transport-dependent measures; however, when viewing time was controlled, these dependent measures were no longer affected by target velocity. Thus, the use of velocity information was limited in the viewing-time-controlled condition, and subjects used other information, such as target movement time, when generating the transport component of the prehensile movement. For the grasp-preshape component, both peak aperture and peak-aperture velocity increased as target velocity increased, regardless of condition, indicating that target velocity was used to control the spatial aspects of aperture formation. However, the timing of peak aperture was affected by target velocity in the distance-controlled condition, but not in the viewing-time-controlled condition. These results provide evidence for the autonomous generation of the spatial and temporal aspects of grasp preshape. Thus, an independence between the transport and grasp-preshape phases was found, whereby the use of target velocity as a source of information for generating the transport component was limited; however, target velocity was an important source of information in the grasp-preshape phase.
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    Experimental brain research 127 (1999), S. 207-212 
    ISSN: 1432-1106
    Keywords: Key words Attention ; Distractor interference ; Path deviation ; Horse race model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been suggested that, when movements are planned within cluttered environments, competing responses programmed to distracting stimuli are inhibited based on their relation to the action being performed. Further, as a result of this inhibition, the path of the movement made to the target object deviates away from the distractor. In contrast to the object avoidance hypothesis, the results of the present study show that, for aiming movements made in environments in which distractors are present, the path of the movement veers toward the distractor. Moreover, the effects of the distractors on the movement trajectory were independent of the direction of limb movement. These findings suggest that, when a distractor is not a potential physical barrier, a response to the distractor may be activated along with the target response and, owing to temporal advantages, cause a deviation of the movement trajectory toward the distractor.
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  • 35
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    Experimental brain research 124 (1999), S. 1-7 
    ISSN: 1432-1106
    Keywords: Key words Temporal cortex ; Connectivity ; Human ; Interhemispheric transfer ; Talairach coordinates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The human anterior commissure is believed, by extrapolation from data obtained in macaque monkeys, to convey axons from the temporal and orbitofrontal cortex. Reports of interhemispheric transfer and sexual dimorphism related to the anterior commissure, however, make more precise data on the human anterior commissure desirable. We investigated the connectivity of the human anterior commissure in six adults (male and female) that had circumscribed hemispheric lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal white matter using the Nauta for anterogradely degenerating axons. Axons originating in the inferior part of temporal or occipital lobes, occipital convexity and possibly central fissure and prefrontal convexity were found to cross the midsagittal plane in the anterior commissure. The largest contigent of commissural axons originated in the inferior part of the temporal lobe; it displayed a roughly topographic organization, preferentially running through the inferior part of the commissure. The inferior temporal contigent seemed to reach homotopic and heterotopic targets in the opposite hemisphere. Among the latter were the amygdala and possibly the orbitofrontal cortex. The present data suggest that the human anterior commissure conveys axons from much larger territories than expected from work on non-human primates. Similarly to the human and non-human primate corpus callosum, the anterior commissure is roughly topographically organized and participates in heterotopic connectivity.
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  • 36
    ISSN: 1432-1106
    Keywords: Key words Aiming movements ; Target size ; Inertial load ; Strategies ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments are reported that investigated the effects of target size and inertial load on the control of rapid aiming movements. Based on kinematic profiles, movements were partitioned into their preprogrammed initial impulse- and feedback-based error correction phases. Electromyographic (EMG) rise rates were examined to investigate whether participants used a speed-sensitive or speed-insensitive control strategy. The results from both experiments showed that initial impulse velocity and EMG rise rates varied as a function of target size, i.e., a speed-sensitive strategy. This was the case whether participants were allowed to make error corrections to their movements (experiment 1) or were instructed to produce initial impulses that hit the target (experiment 2). Both experiments also showed that initial impulse velocity and endpoint variability were inversely related to inertial load. The results from experiment 2 indicated that, while the manipulation of inertial load had no effect on EMG rise rates for movements to a large target, EMG slopes were modulated between inertial load conditions when the target was small.
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  • 37
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    Experimental brain research 128 (1999), S. 578-582 
    ISSN: 1432-1106
    Keywords: Key words Prehension ; Binocular ; Vergence ; Distance perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Human prehension requires accurate information on the properties of an object and on the position of the object relative to the body. In principle, prehension might be more accurate with binocular rather than monocular vision. Previous studies have shown that the kinematics of prehension are altered when one eye is covered. Unfortunately, the source of the useful binocular information cannot be established using this approach. In the current study, we used a perturbation technique to explore whether the human nervous system uses a signal from vergence in prehension. Perturbing vergence caused predictable changes in the kinematics of prehension. Our results thus provide clear evidence that the nervous system uses vergence information in the programming of prehensile movement.
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  • 38
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    Experimental brain research 129 (1999), S. 156-160 
    ISSN: 1432-1106
    Keywords: Key words Optokinetic nystagmus ; Depth-from-motion ; Transparent motion ; Ambiguous ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  When two visual patterns moving in opposite directions are superimposed, they appear to be at different depths and to slide over each other. Because the stimulus does not specify the depth-order between the surfaces, this transparent motion perception is essentially ambiguous. With prolonged observation, the perceived depth-order of the two moving surfaces reverses spontaneously. In the present study, the correlation between the perceived direction of transparent motion and optokinetic nystagmus (OKN) was examined. While viewing superimposed random-dot patterns moving in opposite horizontal or vertical directions, subjects attempted to fixate the center of the stimulus, while paying attention to either the near or far depth plane, and reported any changes of the direction of surface-motion at the attended depth. Even with attention focused on a particular depth, the spontaneous reversal of transparent motion perception still occurred. This indicates that the perceptual reversal may reflect a preattentive mechanism for depth-from-motion. Furthermore, the OKN slow-phase tended to be in the same direction as the perceived motion of the surface at the attended depth. These results support the idea that the mechanisms for OKN maintenance are sensitive to perception of depth-from-motion and, therefore, cortically mediated.
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  • 39
    ISSN: 1432-1106
    Keywords: Key words Elbow movement ; Motor learning ; Reaction time ; Kinematics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Learning of a motor task, such as making accurate goal-directed movements, is associated with a number of changes in limb kinematics and in the EMG activity that produces the movement. Some of these changes include increases in movement velocity, improvements in end-point accuracy, and the development of a biphasic/triphasic EMG pattern for fast movements. One question that has remained unanswered is whether the time course of the learning-related changes in movement parameters is similar for all parameters. The present paper focuses on this question and presents evidence that different parameters evolve with a specific temporal order. Neurologically normal subjects were trained to make horizontal, planar movements of the elbow that were both fast and accurate. The performance of the subjects was monitored over the course of 400 movements made during experiments lasting approximately 1.5 h. We measured time-related parameters (duration of acceleration, duration of deceleration, and movement duration) and amplitude-related parameters (peak acceleration, peak deceleration, peak velocity), as well as movement distance. In addition, each subject’s reaction time and EMG activity was monitored. We found that reaction time was the parameter that changed the fastest and that reached a steady baseline earliest. Time-related parameters decreased at a somewhat slower rate and plateaued next. Amplitude-related parameters were slowest in reaching steady-state values. In subjects making the fastest movements, a triphasic EMG patterns was observed to develop. Our findings reveal that movement parameters change with different time courses during the process of motor learning. The results are discussed in terms of the neural substrates that may be responsible for the differences in this aspect of motor learning and skill acquisition.
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  • 40
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    Experimental brain research 125 (1999), S. 302-312 
    ISSN: 1432-1106
    Keywords: Key words Overarm throwing ; Finger opening ; Proprioceptive feedback ; Perturbations ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory.
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  • 41
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    Keywords: Key words Corticospinal tract ; Handedness ; Spinal premotoneurones ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles . Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.
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  • 42
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    Experimental brain research 125 (1999), S. 389-396 
    ISSN: 1432-1106
    Keywords: Key words Neck muscles ; Vibration ; Proprioception ; Sound localization ; Space perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of transcutaneous vibration of the posterior neck muscles on the lateralization of dichotic sound was investigated in human subjects. Two-alternative forced-choice (left/right) judgements were made on acoustic stimuli presented with different interaural level differences via headphones during neck-muscle vibration. A shift of the subjective auditory median plane toward the side contralateral of vibration was found, indicating that the sound was perceived as shifted toward the side of vibration. The mean magnitude of the vibration-induced intracranial shift was 1.5 dB. The results demonstrate a neck-proprioceptive influence on sound lateralization and suggest that this proprioceptive input is used for a central-nervous transformation of auditory spatial coordinates onto a body-centered frame of reference.
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  • 43
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    Keywords: Key words Reach to grasp ; Human ; Perturbation ; Kinematics ; Motor control ; Parkinson’s disease ; Elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed the adaptive response of the reach-to-grasp movement of 12 Parkinson’s disease (PD) and 12 control subjects to a simultaneous perturbation of target object location and size. The main aim was to test further the reported dysfunction of PD subjects in the simultaneous activation of movement components. Participants were required to reach 30 cm to grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm) diameter. For a small percentage of trials (20/100) a visual perturbation was introduced unexpectedly at the onset of the reaching action. This consisted of a shift of illumination from the central cylinder to a cylinder of differing diameter, which was positioned 20° to the left (n=10) or to the right (n=10). The subject was required to grasp the newly illuminated cylinder. For the Parkinson’s disease subject group, the earliest response to this ’double’ perturbation was in the parameter of peak reaching acceleration, which was on average 50 ms earlier for ’double’ perturbed than for non-perturbed trials. The grasp component response followed more than 500 ms after the earliest transport response. For the control subjects initial signs of a response to the ’double’ perturbation were seen almost simultaneously in the transport parameter of peak arm deceleration, and in the manipulation parameter of maximum grip aperture, but these changes were not evident until more than 400 ms after movement onset. These results indicate that the basal ganglia can be identified as part of a circuit which is involved in the integration of parallel neutral pathways, and which exercise flexibility in the degree to which these components are ’coupled’ functionally. With basal ganglia dysfunction the activation of integration centres that at first gate the flow of information to the parallel channels of reach and grasp seems inefficient.
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  • 44
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    Experimental brain research 125 (1999), S. 521-524 
    ISSN: 1432-1106
    Keywords: Key words Light touch ; Sway ; Centre of pressure ; Hand force ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has previously been shown that light contact with the finger tip on a fixed surface reduces centre of pressure (CoP) fluctuations in the frontal plane when standing in an unstable posture with the feet in line (tandem Romberg stance). Positive cross-correlations between horizontal finger forces and CoP fluctuations with finger forces exhibiting a phase lead suggest the hand provides sensory input for postural stability. The present study investigates whether this is the case for normal posture. We report reduced CoP fluctuations in the sagittal plane when light touch is permitted during normal bipedal stance. Moreover, we find positive crosscorrelations between finger tip forces and CoP fluctuations which are of similar magnitude and phase lag to those observed in tandem Romberg stance. This shows the utility of hand touch input for regulation of normal upright posture as well as inherently unstable postures such as tandem Romberg.
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  • 45
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    Keywords: Key words Microneurography ; Peripheral nerve ; Pacinian afferent ; Cutaneous mechanoreceptor ; Vibrotactile stimuli ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 µm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.
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  • 46
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    Keywords: Key words Corpus callosum ; Interhemispheric transfer ; Positron emission tomography ; Split brain ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied with PET the intra- and interhemispheric pathways subserving a simple, speeded-up visuomotor task. Six normal subjects and one patient with a complete section of the corpus callosum (M.E.) underwent regional cerebral blood flow (rCBF) measurements under conditions of lateralized tachistoscopic visual presentations in a simple manual reaction time paradigm. Confirming previous behavioural findings, we found that on average crossed hand and/or hemifield conditions, i.e. those requiring an interhemispheric transfer of information, yielded a longer RT than uncrossed conditions. This difference (0.7 ms) was dramatically larger (45.6 ms) in the callosum-sectioned patient M.E. In normal subjects the cortical areas selectively activated in uncrossed and crossed conditions were different. In the former condition, most activation foci were anterior to the ventral anterior commissure (VAC) plane, whereas in the latter there was a prevalent parietal and occipital activation. This shows that a simple model in which the cortical visuo-motor pathways are similar in the intra- and the interhemispheric condition, with an extra callosal route for the latter, is too simplistic. Furthermore, these results suggest that the bulk of visuomotor interhemispheric transfer takes place through the widespread callosal fibres interconnecting the parietal cortices of the two hemispheres. The pattern of activation in the two crossing conditions was markedly different in M.E., in whom interhemispheric transfer might take place via his intact anterior commissure or subcortical commissures.
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  • 47
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    Experimental brain research 126 (1999), S. 556-562 
    ISSN: 1432-1106
    Keywords: Key words Acceleration ; Ocular microtremor ; Eye movements ; Partial coherence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel technique for the study of human eye movements was used to investigate the frequency components of ocular drift and microtremor in both eyes simultaneously. The tangential components of horizontal eye accelerations were recorded in seven healthy subjects using light-weight accelerometers mounted on scleral contact lenses during smooth pursuit movements, vestibulo-ocular reflexes and eccentric gaze with and without fixation. Spectral peaks were observed at low (up to 25 Hz) and high (60–90 Hz) frequencies. A multivariate analysis based on partial coherence analysis was used to correct for head movement. After correction, the signals were found to be coherent between the eyes over both low- and high-frequency ranges, irrespective of task, convergence or fixation. It is concluded that the frequency content of ocular drift and microtremor reflects the patterning of low-level drives to the extra-ocular muscle motor units.
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  • 48
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    Experimental brain research 124 (1999), S. 273-280 
    ISSN: 1432-1106
    Keywords: Key words Vestibular system ; Posture control ; Balance ; Cross-spectral analysis ; Coherency ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0–1 Hz, 1–2 Hz, and 0–2 Hz), were used. The stimulation level (range 0.4–1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject – 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject’s feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as ”responders” to galvanic vestibular stimulation.
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  • 49
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    Keywords: Key words Frontal eye field ; Saccade ; Efference copy ; Spatial short-term memory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Physiological studies in monkeys have shown that the frontal eye field (FEF) is involved in the preparation and triggering of purposive saccades. However, several questions of FEF function remain unclear: the role of the FEF in visual short-term memory, its ability to update its spatial map and its role in reflexive saccade inhibition. We have addressed these issues in a patient with a small acute ischemic lesion whose location corresponded very accurately to the region of the left FEF according to the most recent cerebral blood flow studies. An initial study was conducted on days 7 and 8 after the stroke, i.e., before substantial recovery. A first group of paradigms (smooth pursuit, simple saccade tasks) was performed to assess FEF dysfunction. In a second group of paradigms, (1) visual short-term memory was tested by means of memory-guided saccade paradigms with short and long delays (1 and 7 s), (2) spatial updating abilities were tested by a double-step saccade task and two memory-guided saccade tasks in which the central fixation point was displaced during the memorization delay, and (3) reflexive saccade inhibition was tested by the antisaccade task. Results show that the FEF is involved in short-term memorization of the parameters of the forthcoming memory-guided saccade encoded in oculocentric coordinates. Normal results in the antisaccade task suggest that the FEF is not involved in reflexive saccade inhibition.
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  • 50
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    Keywords: Key words Paired-pulse transcranial magnetic stimulation ; Threshold hunting ; Intracortical inhibition ; Intracortical I-wave facilitation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Short-interval, paired-pulse transcranial magnetic stimulation (TMS) is usually used to demonstrate intracortical inhibition. It was shown recently that with short-interval, paired-pulse TMS a facilitation – called intracortical I-wave facilitation – can also be demonstrated. It was the aim of this study to investigate which stimulus conditions lead to intracortical inhibition and what conditions yield an intracortical I-wave facilitation in a hand muscle of normal subjects. Paired-pulse TMS responses with an interstimulus interval of 1.2 ms were obtained from the abductor digiti minimi muscle of four normal subjects. A threshold-hunting paradigm with hunting through first or second stimulus variation was used to obtain a curve of threshold-pair strengths. All subjects showed two branches of stimulus interaction on this diagram. If the first stimulus of a threshold pair was below approximately 65% of resting motor threshold it modified the response primarily due to the second stimulus through intracortical inhibition. However, if the first stimulus of a threshold pair exceeded approximately 65% of resting motor threshold it became responsible for the spinal action-potential initiation. The subsequent second stimulus served as a ”booster” for the ongoing intracortical I-wave activity, making it impossible to observe the intracortical inhibition evoked by the first stimulus.
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    Experimental brain research 129 (1999), S. 378-390 
    ISSN: 1432-1106
    Keywords: Key words Manual tracking ; Microgravity ; Visuomotor transformation ; Adaptation ; Human ; Spaceflight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.
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  • 52
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    Keywords: Key words Spasticity ; Gait ; Spinal cord ; Human ; Clonidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the effect of the intrathecal (i.t.) injection of clonidine (30, 60 and 90 µg) on the polysynaptic spinal reflexes (PSR) elicited by electrical stimulation of flexor reflex afferents (FRA), monosynaptic reflex and gait of 11 subjects with spinal cord injuries. The effect of clonidine administration on gait velocity, stride amplitude and duration was measured in eight subjects who were able to walk. Five subjects were able to walk after intrathecal injection of clonidine and three were not able to stand up. Three subjects improved their gait velocity after clonidine administration; one (S6) increased his stride amplitude; the two others decreased their cycle durations. The tibialis anterior seemed to be more regularly activated during gait. Spasticity was reduced dramatically (P〈0.0001) after i.t. clonidine injection, but there was no statistically significant difference in the soleus H reflex (no effect on Hmax/Mmax). Clonidine administration decreased the amplitude of the early PSR (90–120 ms, N=4) and the threshold and maximal integrated EMG corresponding to the late response (140–450 ms, N=7). This effect was dose dependent (30, 60 and 90 µg). Placebo injection (N=4) caused no change. The changes in spinal reflexes, with a large reduction in spasticity, no change in motoneurone excitability and a large decrease in PSR, suggest that clonidine acts at a premotoneuronal level, possibly by presynaptic inhibition of group II fibres. The increase in gait velocity in three subjects could have been due to reduced spasticity or activation of spinal circuitry.
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  • 53
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    Experimental brain research 128 (1999), S. 353-368 
    ISSN: 1432-1106
    Keywords: Key words Multijoint arm ; Simulations ; Muscle torques ; Kinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Adults are able to reach for an object for the first time with appropriate direction, speed, and accuracy. The rules by which the nervous system is able to set muscle activities to accomplish these outcomes are still debated and, indeed, the sensitivity of kinematics to variations in muscle torques is unknown for complex arm movements. As a result, this study used computer simulations to characterize the effects of change in muscle torque on initial hand path. The same change was applied to movements towards 12 directions in the horizontal plane, and changes were systematically manipulated such that: (1) torque amplitude was changed at one joint, (2) timing of torque was changed at one joint, and (3) amplitude and/or timing was changed at two joints. Results showed that simultaneous changes in torque amplitude at shoulder and elbow joints affected initial speed uniformly across direction. These results add to conclusions from previous experimental and modeling work that the simplest rule to produce a desired change in speed for any direction is to scale torque amplitude at both joints. In contrast, all simulations showed nonuniform effects on initial path direction. For some regions of the workspace, initial path direction was little affected by either a ±30% change in amplitude or a ±100-ms change in timing, whereas for other regions the same changes produced large effects on initial path direction. These findings suggest that the range of possible torque solutions to achieve a particular initial path direction varies within the workspace and, consequently, the requirements for an accurate initial path will vary within the workspace.
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  • 54
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    Experimental brain research 125 (1999), S. 109-114 
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Visual pathways ; Illusions ; Prehension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This partial dissociation is discussed in terms of its implications for streams of visual processing.
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  • 55
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    Experimental brain research 126 (1999), S. 289-306 
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Trajectory formation ; Coordination ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The degrees of freedom problem is often posed by asking which of the many possible degrees of freedom does the nervous system control? By implication, other degrees of freedom are not controlled. We give an operational meaning to ”controlled” and ”uncontrolled” and describe a method of analysis through which hypotheses about controlled and uncontrolled degrees of freedom can be tested. In this conception, control refers to stabilization, so that lack of control implies reduced stability. The method was used to analyze an experiment on the sit-to-stand transition. By testing different hypotheses about the controlled variables, we systematically approximated the structure of control in joint space. We found that, for the task of sit-to-stand, the position of the center of mass in the sagittal plane was controlled. The horizontal head position and the position of the hand were controlled less stably, while vertical head position appears to be no more controlled than joint motions.
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  • 56
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    Experimental brain research 126 (1999), S. 536-544 
    ISSN: 1432-1106
    Keywords: Key words Magnetic brain stimulation ; Afferent input ; Motor cortex ; Plasticity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peri- pheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.
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  • 57
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    Experimental brain research 124 (1999), S. 42-52 
    ISSN: 1432-1106
    Keywords: Key words Ocular tracking ; Oculomanual coordination ; Electromyography ; Internal model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  When the eyes and arm are involved in a tracking task, the characteristics of each system differ from those observed when they act alone: smooth pursuit (SP) latency decreases from 130 ms in external target tracking tasks to 0 ms in self-moved target tracking tasks. Two models have been proposed to explain this coordination. The common command model suggests that the same command be addressed to the two sensorimotor systems, which are otherwise organized in parallel, while the coordination control model proposes that coordination is due to a mutual exchange of information between the motor systems. In both cases, the interaction should take into account the dynamic differences between the two systems. However, the nature of the adaptation depends on the model. During self-moved target tracking a perturbation was applied to the arm through the use of an electromagnetic brake. A randomized perturbation of the arm increased the arm motor reaction time without affecting SP. In contrast, a constant perturbation produced an adaptation of the coordination control characterized by a decrease in arm latency and an increase in SP latency relative to motor command. This brought the arm-to-SP latency back to 0 ms. These results support the coordination control model.
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  • 58
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    Experimental brain research 124 (1999), S. 287-294 
    ISSN: 1432-1106
    Keywords: Key words Magnetoencephalography ; V1 cortex ; V2 cortex ; V6 complex ; Horizontal meridian ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We recorded whole-scalp magnetoencephalographic (MEG) responses to black-and-white checkerboards to study whether the human cortical responses are quantitatively similar to stimulation of the lower and upper visual field at small, 0–6°, eccentricities. All stimuli evoked strongoccipital responses peaking at 50–100 ms (mean 75 ms). The activation was modeled with a single equivalent current dipole in the contralateral occipital cortex, close to the calcarine fissure, agreeing with an activation of the V1/V2 cortex. The dipole was, on average, twice as strong to lower than to upper field stimuli. Responses to hemifield stimuli that extended to both lower and upper fields resembled the responses to lower field stimuli in source current direction and strength. These results agree with psychophysical data, which indicate lower visual field advantage in complex visual processing. Parieto-occipital responses in the putative V6 complex were similar to lower and upper field stimuli.
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  • 59
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    Experimental brain research 128 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Eye-hand coordination ; Human ; Saccade ; Vision ; Bimanual coordination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300±39 ms for the predictive condition versus 394±53 ms for the non-predictive condition, P〈0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.
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  • 60
    ISSN: 1432-1106
    Keywords: Key words Reaching movements ; Grasping movements ; Prehension ; Manual control ; Computational model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Reaching and grasping an object can be viewed as the solution of a multiple-constraint satisfaction problem. The constraints include contact with the object with the appropriate effectors in the correct positions as well as generation of a collision-free trajectory. We have developed a computational model that simulates reaching and grasping based on these notions. The model, rendered as an animation program, reproduces many basic features of the kinematics of human reaching and grasping behavior. The core assumptions of the model are: (1) tasks are defined by flexibly organized constraint hierarchies; (2) manual positioning acts, including prehension acts, are first specified with respect to goal postures and then are specified with respect to movements towards those goal postures; (3) goal postures are found by identifying the stored posture that is most promising for the task, as determined by the constraint hierarchy, and then by generating postures that are more and more dissimilar to the most-promising stored posture until a deadline is reached, at which time the best posture that was found during the search is defined as the goal posture; (4) depending on when the best posture was encountered in the search, the deadline for the search in the next trial is either increased or decreased; (5) specification of a movement to the goal posture begins with straight-line interpolation in joint space between the starting posture and goal posture; (6) if an internal simulation of this default movement suggests that it will result in collision with an obstacle, the movement can be reshaped until an acceptable movement is found or until time runs out; (7) movement reshaping occurs by identifying a via posture that serves as a body position to which the actor moves from the starting posture and then back to the starting posture, while simultaneously making the main movement from the starting posture to the goal posture; (8) the via posture is identified using the same posture-generating algorithm as used to identify the goal posture. These processes are used both for arm positioning and, with some elaboration, for prehension. The model solves a number of problems with an earlier model, although it leaves some other problems unresolved.
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  • 61
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    Experimental brain research 128 (1999), S. 539-542 
    ISSN: 1432-1106
    Keywords: Key words Silent period ; Transcranial magnetic stimulation ; Motor cortex ; Epidural recordings ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.
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  • 62
    ISSN: 1432-0851
    Keywords: Key words In vitro immunisation ; MUC1 ; Human ; antibodies ; Phage display ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently described an efficient method to study the human humoral immune response in vitro and to generate isotype-switched, antigen-specific human B cells, which has allowed us to produce high-affinity IgG antibodies against different peptides. In an attempt to study the in vitro immune response against self-antigens, such as tumour-associated antigens, this protocol was used to immunise resting human peripheral blood B cells with a peptide epitope from the human-adenocarcinoma-associated antigen, MUC1. After the two-step in vitro immunisation, the secondary immunised cultures were tested for MUC-1-specific antibodies by enzyme-linked immunosorbent assay (ELISA). Phage molecular libraries were subsequently constructed, using the variable parts of Ig genes derived from cells taken from ELISA-positive wells. The libraries were selected on the MUC1 core peptide. Antigen-specific Fab fragments, specific for the self antigen MUC1, were found in the library of secondary immunised IgG+ B cells and these antibodies were evaluated by BIAcore analysis. The specific Fab fragments exhibited an unusually rapid dissociation rate constant and the overall response frequency was lower, as compared to other antibodies generated by this protocol, which might be explained by the repetitive nature of the core peptide used for immunisation.
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  • 63
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    Journal of comparative physiology 185 (1999), S. 297-304 
    ISSN: 1432-1351
    Keywords: Key words Odor coding ; Learning ; Enhanced sensitivity ; Rabbit ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The olfactory system is faced with a particular problem – the high dimensionality and inherent unpredictability of the chemical world. Most natural odorants encountered in everyday life are complex mixtures of many different volatiles. This means that from the outset the olfactory system has to contend with a great and often unpredictable diversity of molecules, making it difficult for stable primary features of the chemical world to be mapped onto the sensory surface. One solution to such unpredictability is provided by learning. Learning confers flexibility, enabling individuals of a given species to acquire and make use of the most appropriate information in a particular environment. Two examples of this are presented: learning of maternal odors in neonatal rabbits, including evidence that the sensory surface itself may be influenced by environmental conditions so as to enhance sensitivity to molecules of particular ecological relevance, and cross-cultural human studies suggesting that experience with everyday odors influences not only the way these are evaluated, but also their perceived intensity. It is concluded that an adequate understanding of odor coding and olfactory function will not be possible without taking such experience-dependent factors into account.
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  • 64
    ISSN: 1615-2573
    Keywords: Smooth muscle cell ; Heterogeneity ; Coronary artery ; Human ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The arterial media is composed of a heterogeneous population of smooth muscle cells (SMCs). Recently, the properties of SMCs were observed to be heterogeneous not only among individual cells but also among arteries of the same vascular bed. To test the hypothesis that a site-specific heterogeneity exists in the SMCs of human coronary arteries, we examined the expression of desmin, vimentin, calponin, and high-molecular-weight (h-) caldesmon in arteries of various sizes. Specimens of arteries were obtained at autopsy from 12 patients: 6 adults (67 ± 4 years old); 3 younger adults (26 ± 2 years old); and 3 neonates. The size of the arteries was estimated by the number of SMC layers of the media. The expression was compared in SMCs of large arteries (〉10 layers in adults, 〉5 layers in neonates), medium-sized arteries (5–10 layers in adults, 3–5 SMC layers in neonates), and small arteries (〈3 layers). In adults, the percentage of arteries positive for desmin was lower in the small (17% ± 3%) and medium-sized arteries (44% ± 12%) than in the large arteries (94% ± 6%) (P 〈 0.01). The percentage of arteries positive for calponin was also lower in the small (18% ± 2%) and medium-sized arteries (66% ± 5%) than in the large arteries (100%) (P 〈 0.01). The percentage for vimentin and h-caldesmon did not differ among large, medium-sized, and small arteries. These observations in adults were similar to those in younger adults or neonates. The phenotypes of medial SMCs are vessel sizedependent in human coronary arteries. This finding should be important for understanding the site-specific characteristics of vascular function in the regulation of myocardial perfusion or those of vascular responses to environmental changes.
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  • 65
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    Archives of dermatological research 291 (1999), S. 247-252 
    ISSN: 1432-069X
    Keywords: Key words T cell activation ; Nickel ; Human ; Interferon-gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Contact hypersensitivity to nickel is the most common form of allergic contact dermatitis. To gain insight into the induction of this frequent disease, T cell reactivity towards nickel was investigated in “nonallergic” individuals defined as those with no skin manifestations and a negative patch test towards NiSO4. Surprisingly, we found that nickel induced proliferation of peripheral blood mononuclear cells (PBMC) from 16 of 18 adult individuals tested. This activation was specific, and no stimulation of PBMC was observed using control stimulants at equimolar concentrations. Furthermore, the NiSO4-induced activation required the presence of professional antigen-presenting cells. To describe the functional capacity of the nickel-inducible T cells, cytokine release was investigated in both nickel-allergic and nonallergic individuals. The T cells from both groups released interferon-γ but no interleukin-4 upon stimulation with nickel, suggesting that the functional capacities of these cell populations were similar in nickel-allergic and nonallergic individuals. Thus, at this level, no qualitative differences could be demonstrated between T cells obtained from nickel-allergic and nonallergic individuals.
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  • 66
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    European journal of clinical pharmacology 55 (1999), S. 349-352 
    ISSN: 1432-1041
    Keywords: Key words Ischaemic stroke ; Vinpocetine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: To determine whether vinpocetine decreases short- and long-term case fatality and proportion of dependent survivors if administered within 2 weeks of stroke onset. Methods: All published and unpublished trials were attempted to be identified using the standard search strategy of the Cochrane Collaboration Stroke Review Group, using MEDLINE searches performed with all known manufacturer code names and trade names of vinpocetine and by contacting manufacturers of vinpocetine to give information of all randomised controlled trials on vinpocetine in stroke. Researchers who participated in trials on vinpocetine in Hungary were asked for further information. Only truly randomised, unconfounded clinical trials that compared the effect of vinpocetine to either placebo or another reference treatment for acute stroke where treatment started no later than 14 days after stroke onset were eligible for inclusion. Data synthesis and analysis was performed using the Cochrane Review Manager software (RevMan version 3.0). Results: Among the identified studies on vinpocetine in stroke, only one fulfilled the selection criteria for inclusion in the review. No death occurred in the study groups and no statistically significant difference was found in dependency between the treatment and the placebo groups. No adverse effects were reported. Conclusions: Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke.
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  • 67
    ISSN: 1432-0533
    Keywords: Key words Amantadine ; Human ; N-methyl-d-aspartate ; Phencyclidine ; Postmortem brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer’s, Parkinson’s or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment.
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  • 68
    ISSN: 1432-1912
    Keywords: Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K+ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca2+ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca2+-induced contractions in human arteries.
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  • 69
    ISSN: 1432-2072
    Keywords: Key words Cannabinoids ; THC ; Dronabinol ; Binocular depth inversion ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic Δ9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The time-course of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.
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  • 70
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    Psychopharmacology 143 (1999), S. 339-346 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Smoking ; Naltrexone ; Opiates ; Mechanism ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. Objective: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. Methods: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. Results: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. Conclusions: The blockade of nicotine’s effects by naltrexone supports a role for opioid mechanisms in cigarette smoking.
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  • 71
    ISSN: 1432-2072
    Keywords: Key words Alternative reinforcers ; Heroin ; Human ; Intranasal ; Intravenous ; Opioids ; Performance ; Progressive ratio ; Reinforcing effect ; Self-administration ; Subjective effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., “I feel a good drug effect,”“I feel high”), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.
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  • 72
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Naloxone ; Dose ratio ; Opiate dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.
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  • 73
    ISSN: 1432-2072
    Keywords: Key words Aggression ; Tryptophan ; Serotonin ; Human ; Diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Some studies have shown that sharp reduction of L-tryptophan (Trp) concentration in plasma results in increases in laboratory-measured aggression. Conversely, raising plasma Trp has blunted aggression. These effects are presumably due to impaired or enhanced serotonin synthesis and neurotransmission in the brain. In this study, the laboratory-measured aggressive behavior of eight men under both Trp depletion (T-) and Trp loading (T+) conditions was compared to their aggressive behavior under food-restricted control conditions (overnight fast without an amino acid beverage). Subjects were provoked by periodic subtraction of money which was attributed to a fictitious other participant, and aggression was defined as the number of retaliatory responses the subject made ostensibly to reduce the earnings of the (fictitious) other participant. Following ingestion of the T- beverage, aggressive responding was significantly elevated relative to the food-restricted control condition, and this increased aggressive behavior became more pronounced across behavioral testing sessions on a time-course which paralleled previously documented decreases in plasma Trp concentrations. In contrast, no changes were observed in aggressive responding under T+ conditions relative to food-restricted conditions. These within-subject behavioral changes under depleted plasma Trp conditions support earlier indications of a role of serotonin in regulating aggression.
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  • 74
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    Psychopharmacology 147 (1999), S. 200-209 
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Flumazenil ; Precipitated withdrawal ; Antagonist ; Physical dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Preclinical studies of the benzodiazepine antagonist flumazenil (Romazicon®) have contributed to the understanding of the physical dependence associated with chronic benzodiazepine use; when administered to animals chronically pretreated with benzodiazepines, flumazenil precipitates a withdrawal syndrome. However, few controlled clinical studies have been conducted. Objectives: The objective was to characterize the effects of flumazenil in long-term users of therapeutic doses of benzodiazepines. Methods: The acute physiological, participant-rated, and observer-rated effects of intravenously administered flumazenil (1 mg/70 kg) and caffeine (300 mg/70 kg; active drug control) were evaluated in an experimental group of 13 long-term users (mean 4.6 years) of low therapeutic doses (mean 11.2 mg/day diazepam equivalent) relative to a matched group of 13 volunteers without prior exposure to benzodiazepines in a double-blind, placebo-controlled, mixed design. Results: Whereas the experimental group did not differ from the control group with respect to the effects of placebo, and both groups showed some changes in response to caffeine (e.g., increased blood pressure and anxiety scores), only the experimental group showed considerable changes in physiological measures, participant ratings (e.g., increased ratings of dizziness, blurred vision, heart pounding, feelings of unreality, pins and needles, nausea, sweatiness, noises louder than usual, jitteriness, things moving, sensitivity to touch), and observer ratings in response to flumazenil; in addition, four participants developed panic attacks. Conclusions: This study clearly demonstrates that flumazenil can precipitate symptoms commonly associated with benzodiazepine withdrawal in chronic low-dose benzodiazepine users.
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  • 75
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    Psychopharmacology 147 (1999), S. 266-273 
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Lorazepam ; Human ; Memory ; Auditory priming ; Visual priming ; Explicit memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Lorazepam has been repeatedly shown to impair both explicit memory and perceptual priming, a form of implicit memory, in the visual domain. However, the effects of this benzodiazepine on priming in other perceptual domains, such as auditory priming, have never been explored. Objective:The present study investigated whether the deleterious effects of lorazepam on perceptual priming are restricted to the visual domain, or if they could be extended to the auditory domain. Methods: Thirty-two healthy volunteers were randomly assigned to two parallel groups, placebo and lorazepam 0.038 mg/kg. The drug was administered orally, following a double-blind procedure. In the same subjects, perceptual priming was assessed in the auditory and visual domains using similar word-stem completion tasks, and explicit memory was explored using a free- recall task. Results: Lorazepam markedly reduced free-recall performance for visually and auditorily presented words. Lorazepam equally impaired visual and auditory priming. In the auditory word-stem completion task, prior presentation of a word facilitated perception of its stem in the placebo group. This facilitation effect was not observed in the lorazepam group. The lorazepam-induced impairment of priming was not due to sedation or explicit contamination. Conclusion: These results indicate that the deleterious effects of lorazepam on priming are not restricted to the visual modality, but extend to the auditory modality.
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  • 76
    ISSN: 1432-2072
    Keywords: Key words MDMA ; Ecstasy ; Human ; EEG ; Power ; Coherence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. Objective: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Methods: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject’s consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. Results: MDMA use was positively correlated with absolute power in the alpha (8–12 Hz) and beta (12–20 Hz) frequency bands, but not with the delta (1–3 Hz) or theta (4–7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Conclusions: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs.
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  • 77
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Human ; Self-administration ; D1 agonist ; Subjective effect ; Craving ; Cardiovascular effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Data in laboratory animals suggest that D1 receptor agonists may have potential utility for the treatment of cocaine abuse. Objective: The effects of ABT-431, a selective agonist at the dopamine D1 receptor, on the reinforcing, cardiovascular and subjective effects of cocaine were investigated in humans. Method: Nine experienced cocaine smokers (8M, 1F), participated in nine self-administration sessions while residing on an inpatient research unit: three doses of ABT-431 (0, 2, 4 mg IV) were each given in combination with three doses of smoked cocaine (0, 12, 50 mg). ABT-431 was intravenously administered over a 1-h period immediately prior to cocaine self-administration sessions. A six-trial choice procedure (cocaine versus $5 merchandise vouchers) was utilized, with sessions consisting of: (a) one sample trial, where participants received the cocaine dose available that day, and (b) five choice trials, where participants chose between the available cocaine dose and one merchandise voucher. Results: ABT-431 did not affect the number of times participants chose to smoke each dose of cocaine, but produced significant dose-dependent decreases in the subjective effects of cocaine, including ratings of “High,”“Stimulated,” dose liking, estimates of dose value, “Quality,” and “Potency.” Furthermore, there was a trend for ABT-431 (4 mg) to decrease cocaine craving. ABT-431 also increased heart rate, while decreasing systolic and diastolic pressure at each dose of cocaine. Conclusions: These data suggest that D1 agonists may have potential utility for the treatment of cocaine abuse.
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  • 78
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    Psychopharmacology 145 (1999), S. 39-51 
    ISSN: 1432-2072
    Keywords: Key words Zaleplon ; Triazolam ; Benzodiazepine ; Hypnotics ; Learning ; Memory ; Abuse potential ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition site on the GABAA benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ1 (ω1) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect, and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam.
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  • 79
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Alprazolam ; Placebo ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8–30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.
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  • 80
    ISSN: 1432-2072
    Keywords: Key words Marijuana ; Human ; THC ; Withdrawal ; Dependence ; Tolerance ; Subjective effect ; Performance ; Food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral Δ9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915–1700 hours), and in the evening engaged in private or social recreational activities (1700–2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1–3, 8–11, and 16–19. Active THC was administered on days 4–7 (20 mg qid) and on days 12–15 (30 mg qid). Both active doses of THC increased ratings of “High,”“Good Drug Effect,” and “Willingness to Take Dose Again” compared to baseline (days 1–3). THC also increased food intake by 35–45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of “Anxious,”“Depressed,” and “Irritable,” decreased the reported quantity and quality of sleep, and decreased food intake by 20–30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.
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  • 81
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    Psychopharmacology 141 (1999), S. 395-404 
    ISSN: 1432-2072
    Keywords: Key words Marijuana ; Dependence ; Withdrawal ; Human ; Tolerance ; Subjective effect ; Performance ; Residential laboratory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Symptoms of withdrawal after oral Δ9-tetrahydrocannabinol (THC) administration have been reported, yet little is known about the development of dependence on smoked marijuana in humans. In a 21-day residential study, marijuana smokers (n = 12) worked on five psychomotor tasks during the day (0915–1700 hours), and in the evening engaged in recreational activities (1700–2330 hours); subjective-effects measures were completed 10 times/day. Food and beverages were available ad libitum from 0830 to 2330 hours. Marijuana cigarettes (0.0, 1.8, 3.1% THC) were smoked at 1000, 1400, 1800, and 2200 hours. Placebo marijuana was administered on days 1–4 . One of the active marijuana doses was administered on days 5–8, followed by 4 days of placebo marijuana (days 9–12). The other concentration of active marijuana cigarettes was administered on days 13–16, followed by 4 days of placebo marijuana (days 17–20); the order in which the high and low THC-concentration marijuana cigarettes were administered was counter-balanced between groups. Both active doses of marijuana increased ratings of “High,” and “Good Drug Effect,” and increased food intake, while decreasing verbal interaction compared to the placebo baseline (days 1–4). Abstinence from active marijuana increased ratings such as “Anxious,”“Irritable,” and “Stomach pain,” and significantly decreased food intake compared to baseline. This empirical demonstration of withdrawal from smoked marijuana may suggest that daily marijuana use may be maintained, at least in part, by the alleviation of abstinence symptoms.
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  • 82
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Drug discrimination ; Training conditions ; Testing conditions ; Three-choice procedure ; Subjective effect ; Human ; Smoking status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discrimination of a drug’s interoceptive stimulus effects often depends substantially on training and testing conditions. Objectives: We examined changes in nicotine discrimination behavior in humans as a function of lowering the training dose and of varying the discrimination testing procedure. Methods: Smokers and never-smokers (n=10 each) were initially trained to discriminate 20 µg/kg nicotine by nasal spray from placebo (0) and tested on generalization of discrimination responding across a range of doses from 0 to 20 µg/kg. Each subsequently learned to reliably discriminate progressively smaller doses of nicotine from placebo until his or her threshold dose for discrimination was identified (mean=2.7 µg/kg). A repeat testing of generalization responding across 0–20 µg/kg was then conducted, using placebo and the subject’s threshold dose as training doses. Generalization testing involved both two-choice and three-choice (novel response option) quantitative procedures. Results: A significant shift to the left was seen in nicotine-appropriate responding in the two-choice procedure when the nicotine training dose was lowered (i.e. from the first to the second test of generalization). In the three-choice procedure, however, there was no such leftward shift. Instead, in never-smokers, a flattening of nicotine-appropriate responding occurred with a lowering of the training dose, while novel-appropriate responding significantly increased. The subjective effects of ”head rush” and, in never-smokers only, ”jittery” also showed a shift to the left in their relationship with nicotine generalization dose when the training dose was lowered. Conclusions: These results confirm the importance of training and testing conditions on discrimination behavior and subjective drug responses within subjects and demonstrate the utility of the novel-response, three-choice procedure for assessing qualitatively different stimulus effects of novel drug doses.
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  • 83
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    Psychopharmacology 145 (1999), S. 162-174 
    ISSN: 1432-2072
    Keywords: Key words Opioid blockade ; Buprenorphine ; Naltrexone ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy. Objective: This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation compared to naltrexone and placebo. Methods: Opioid-experienced volunteers (n = 8) participated in this 10-week, inpatient, double-blind, within-subject, crossover study. Five randomized conditions [buprenorphine (2 and 8 mg, sublingually), naltrexone (25 and 100 mg, PO) and placebo] were each examined during a 2-week period; the test drug was given for 7 days followed by a 7-day placebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice-weekly corresponding with treatment and wash-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measures were collected. Results: Buprenorphine alone produced dose-related prototypic agonist effects during induction (i.e., positive mood, respiratory depression, miosis); tolerance developed only to the subjective effects. Buprenorphine 2 mg partially attenuated the effects of hydromorphone, while nearly complete attenuation was observed with 8 mg that lasted up to 72 h after discontinuation. Both naltrexone doses produced complete hydromorphone blockade after a single dose; blockade of the behavioral, but not physiological, effects persisted for 5 days after discontinuation of 100 mg. Conclusions: These data suggest that 2 mg buprenorphine is a sub-therapeutic maintenance dose, both buprenorphine 8 mg and naltrexone produce immediate and efficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.
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  • 84
    ISSN: 1434-0879
    Keywords: Key words Alpha-1-microglobulin ; Calcium oxalate ; Crystallization ; ELISA ; Human ; Urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the past few years, alpha-1-microglobulin (α1m) has been copurified from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have purified α1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was purified with an anti-α1m antibodies CNBr-activated sepharose column. Two molecular species of α1m of respectively 30 and 60 kDa were purified. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-α1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the first test, the presence of α1m of 30 kDa (8 μg/ml) in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM Ox(NH4)2 inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of α1m of 30 kDa in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modification of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary α1m concentration was significantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 ± 0.29 vs 5.34 ± 1.08 mg/l respectively, P = 0.01). The decreased concentration of α1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.
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  • 85
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 370-372 
    ISSN: 1434-4726
    Keywords: Key words Gastroesophageal reflux disease ; Human ; papilloma virus ; Laryngeal papillomatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hallmark of gastroesophageal reflux disease (GERD) is an increased exposure of esophageal and laryngeal mucosa to gastric juice. This exposure can cause complications such as chronic laryngitis or chronic respiratory diseases. We report our experience in managing three pediatric patients with severe recurrent juvenile laryngeal papillomatosis (JLP) associated with GERD. All patients showed a high rate of recurrence requiring multiple laser surgeries. Systemic αinterferon therapy over a period of more than 1 year and photodynamic therapy with dihematoporphyrin produced no improvement. However, after therapy for GERD, the rate of recurrence of JLP decreased significantly. Although the course of respiratory papillomatosis is known to fluctuate, our findings suggest that gastroesophageal reflux may have a role in aggravating papillomatosis.
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  • 86
    ISSN: 1432-2307
    Keywords: Key words p21 ; p53 ; Colon ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.
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  • 87
    ISSN: 1432-2307
    Keywords: Key words Peroxisomes ; Hepatocellular tumors ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A significant reduction of catalase activity, a peroxisomal marker enzyme, occurs in human hepatic neoplasias, but no information is available on other peroxisomal proteins. We have studied by means of immunohistochemistry four specific proteins of peroxisomes (catalase and three enzymes of lipid β-oxidation) in human hepatocellular tumors of various differentiation grades from adenoma to anaplastic carcinoma. In all tumors, except the adenomas, the tumor cells contained fewer peroxisomes than extrafocal hepatocytes and the reduction of antigenic sites in the tumor types generally correlated with the degree of tumor dedifferentiation as assessed by classical histopathological criteria. Two poorly differentiated tumors had no detectable peroxisomes at all. There were no major differences in the intensities of the immunocytochemical staining for all four studied peroxisomal antigens in different tumors, suggesting that the neoplastic transformation affects the biogenesis of the entire organelle and not merely the individual peroxisomal enzyme proteins. Some tumors exhibited a distinct peripheral distribution of peroxisomes. In cases with associated liver cirrhosis, the hepatocytes in the adjacent liver showed marked peroxisome proliferation, forming large perinuclear aggregates, occupying occasionally the entire cytoplasm. Taken together, our observations indicate that peroxisomes are significantly altered in both hepatocellular tumors and liver cirrhosis and, thus, could be responsible for some of the metabolic derangements observed in those disease processes.
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  • 88
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Craving ; Cytidine ; CDP-choline ; Human ; Medication ; Drug dependent ; Citicoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The administration of cytidine-5′-diphosphate choline (CDP-choline, citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either citicoline or placebo. Subjects did not experience any side effects and citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.
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  • 89
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    Psychopharmacology 142 (1999), S. 149-157 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Craving ; Smoking ; Rapid smoking ; Cigarette ; Self-report ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior.
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  • 90
    ISSN: 1432-2072
    Keywords: Key words MDMA (3 ; 4-methylenedioxymethamphetamine) ; Serotonin ; Psychopathology ; Human ; Rat ; Prepulse inhibition ; Habituation ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. Objective: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. Methods: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. Results: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. Conclusions: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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  • 91
    ISSN: 1432-2072
    Keywords: Key words Methadone maintenance treatment ; Chiral analysis ; Methadone ; Plasma ; Urine ; Abused drug ; Daily variation ; Rating scales ; Dose-adjustment ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: One of the major problems in methadone maintenance treatment is to find optimal individual doses for the patients. Objective: The present study investigated whether the use of rating scales together with enantioselective analysis of l-methadone might facilitate dose adjustments in a clinical situation. Methods: Rating scales were used to evaluate subjective and objective signs of well-being in relation to plasma methadone concentrations in two groups of patients receiving methadone maintenance treatment. The first group (n = 25) was well-adjusted according to clinical observations and were satisfied with their methadone doses (86.2 ± 4.3 mg). The second group (n = 25) was in need of the methadone dose adjustment; they complained of low dosing, despite a dose level of 69.2 ± 4.0 mg/day. Results: Results indicated a significant correlation between dose and methadone concentration among dissatisfied patients only. The trough levels of d,l-methadone and l-methadone, as well as their elimination rates, were similar in the two groups of patients. There was a variable predominance of l- over d-methadone in plasma (ratio ≈1.2; range 0.7–3.6). Illicit use of drugs by the patients was related to the methadone dose and to satisfaction with the dose received. Increased illicit drug use among dissatisfied patients was successfully eliminated by raising the methadone dose. Subjective and objective ratings of the satisfied patients were quite stable throughout the evaluation period, whereas the ratings of the dissatisfied patients were unstable. These patients seemed to be more sensitive to low trough levels of methadone than the satisfied patients. Associations between the subjective and objective ratings and plasma methadone, along with background characteristics, were characterized by multiple regression analyses. The plasma concentrations of l-methadone were one of the most important explanatory variables in these analyses. Associations between well-being and methadone concentrations in plasma were stronger for l-methadone than for d,l-methadone. Conclusions: Selective measurements of the active isomer and the use of rating scales should be of clinical value when monitoring methadone maintenance treatment patients.
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  • 92
    ISSN: 1432-2072
    Keywords: Key words Alcohol effect ; Impulsivity ; Working memory ; Executive function ; High-risk ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Impulsivity is associated with increased risk for alcoholism. Alcohol also may increase impulsive behavior, although little is known about the processes underlying this effect. Objectives: This study tested a model proposing that the executive processes of working memory (WM) and conditional associative learning (CAL) modulate behavioral inhibition. Subjects had either a positive (FHP) or a negative (FHN) family history of alcoholism. Hypotheses were that alcohol would increase Go/No-Go impulsive responding but only in subjects with low working memory capacity (low-WM), low-CAL ability, or FHP for alcoholism. The model also predicted that WM and CAL modulate inhibitory responses to contingency reversal on a Go/No-Go task. Methods: A Go/No-Go learning task with a midway contingency reversal was administered to 71 FHP and 78 FHN subjects when sober and after drinking one of two moderate doses of alcohol. WM (digits backward) and CAL (conditional spatial association task) were also assessed when sober. Results: Alcohol resulted in more false alarms but only in low-WM subjects. Both WM and CAL modulated learning to inhibit behavior after contingency reversal, suggesting separate modulation mechanisms for WM and CAL. Subjects with low- capacity WM and subjects with low-capacity CAL ability had more difficulty learning response inhibition after contingency reversal. FHPs and FHNs did not differ in their response to alcohol. Conclusions: The results support our model of the modulatory role of WM and CAL in the ongoing regulation of behavioral inhibitory systems. The results also suggest that individuals with low capacity WM are more susceptible to alcohol’s effect of increasing impulsive behavior, suggesting that alcohol reduces the capacity of working memory to modulate response inhibition.
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  • 93
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    Psychopharmacology 146 (1999), S. 111-118 
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Heroin dependence ; Opioid dependence ; Human ; Opioid withdrawal ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown. Objectives: To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication. Methods: Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21–22 days. Self report and observer measures were taken at 24-h intervals. Results: No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed. Conclusions: These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.
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  • 94
    ISSN: 1432-0533
    Keywords: Key words Purkinje cell ; Cerebellum ; Development ; Inositol 1 ; 4 ; 5-triphosphate type 1 receptor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.
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  • 95
    ISSN: 1432-069X
    Keywords: Key words Chronic diabetic wounds ; Human ; fibroblasts ; Wound healing ; Cell culture ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with diabetes mellitus experience impaired wound healing often resulting in chronic foot ulcers. Hospital discharge data indicate that 6–20% of all diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower extremity ulcer. Maintaining glucose levels at acceptable levels (below 10 mmol/l) is considered to be an important part of the clinical treatment, but the exact mechanism by which diabetes delays wound repair is not yet known. We studied this phenomenon by determining the potential of fibroblasts isolated from the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to proliferate in vitro. Controls were fibroblasts isolated from normal skin of the upper leg of five healthy age-matched volunteers and of six non-insulin-dependent diabetes patients. Proliferative capacity was analysed by evaluation of plates after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was studied by light and transmission electron microscopy. Diabetic ulcer fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly more slowly than the nonlesional control fibroblasts (P 〈 0.00047) and age-matched control fibroblasts (P 〈 0.00003). After culturing the fibroblasts for a prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e. physiological) medium, this difference in proliferation rate between diabetic ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P 〈 0.0001 for high-glucose and P 〈 0.0009 for low-glucose on day 7). Fibroblast proliferation in all three groups was slightly lower in high-glucose than in low-glucose medium, although not significantly at any time-point. Light microscopy showed diabetic ulcer fibroblasts to be large and widely spread. Transmission electron microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin fibroblasts revealed a large dilated endoplasmic reticulum, a lack of microtubular structures and multiple lamellar and vesicular bodies. These results show a diminished proliferative capacity and abnormal morphology of fibroblasts derived from diabetic ulcers of non-insulin-dependent diabetes patients.
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  • 96
    ISSN: 1432-069X
    Keywords: Key words ORS cells ; Melanocytes ; Human ; Organotypic cultures ; Melanosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred “through racial barriers”. Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.
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  • 97
    ISSN: 1437-1596
    Keywords: Key words Poisoning ; Benfuracarb ; Carbofuran ; Human ; Blood ; Urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract We describe here three cases involving acute fatalities due to benfuracarb ingestion and the forensic toxicological implications. Benfuracarb, a carbamate insecticide and its main metabolite carbofuran, were detected using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS) after extraction with ethyl acetate and then quantified using gas chromatography (GC) equipped with NPD. The blood levels of benfuracarb and carbofuran were in the range of 0.30∼2.32 μg/ml and 1.45∼1.47 μg/ml, respectively. Benfuracarb was not detected in urine, but carbofuran was detected in the range of 0.53∼2.66 μg/ml.
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  • 98
    Electronic Resource
    Electronic Resource
    Springer
    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 177-183 
    ISSN: 1433-7347
    Keywords: Key words Knee joint ; Human ; Anterior knee pain ; Innervation ; Substance-P fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract The etiology of pain in anterior knee pain syndrome is a matter of controversy. The normal, articular cartilage is aneural, so defects in the surface are not thought to produce pain. Some authors have sought the origin of the pain in soft tissue structures around the knee. Knowledge of the distribution of nociceptive nerve fibers around the knee would provide insight for treating anterior knee pain syndrome. Twenty consecutive patients (28 knees), all women, with anterior knee pain syndrome (group I) participated in the study. For comparison we used two groups of patients: 20 patients with an osteoarthritic knee (group II) and 20 patients with anterior cruciate ligament rupture or meniscal lesion with no history of pain in the anterior compartment (group III). Immunohistochemical techniques using a monoclonal antibody to substance-P (SP) were employed to identify nociceptive fibers. For statistical analyses we used the one-way ANOVA test, which was corrected with the LSD test, at the level of significance P 〈 0.05. Results of the study demonstrate that SP-immunoreactive nerve fibers are widespread within the soft tissues around the knee. These tissues include the retinaculum, synovium, fat pad and, in some circumstances, bone. In cases of anterior knee pain, the presence of neuropeptide-containing fibers was statistically significant in the medial retinaculum (P 〈 0.005) and in the fat pad (P 〈 0.001) compared to group III, and compared to group II (P 〈 0.05 and P 〈 0.007, respectively). For lateral retinaculum this relationship was not so statistically strong (P 〈 0.02) and was equal in comparison between anterior knee pain patients (group I) and group II or group III. There were no statistically significant differences in the distribution of substance-P nerve fibers in the fat pad, lateral and medial retinaculum or synovium between groups II and III. The results of this study provide immunohistochemical evidence suggesting that pain may originate in the fat pad and medial retinaculum of many patients with anterior knee pain syndrome.
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  • 99
    ISSN: 1573-6792
    Keywords: EEG ; Alpha activity ; Spatial segmentation techniques ; Wakefulness ; Sleep onset ; REM sleep ; Dream imagery ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous alpha activity clearly present in relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and REM sleep was studied with spatial segmentation methods in order to determine if the brain activation state would be modulating the alpha spatial microstates composition and duration. These methods of spatial segmentation show some advantages: i) they extract topographic descriptors independent of the chosen reference (reference-free methods), and ii) they achieve spatial data reduction that are more data-driven than dipole source analysis. The results obtained with this study revealed that alpha activity presented a different spatio-temporal pattern of brain electric fields in each arousal state used in this study. These differences were reflected in a) the mean duration of alpha microstates (longer in relaxed wakefulness than in drowsy period and REM sleep), b) the number of brain microstates contained in one second (drowsiness showed more different microstates than did relaxed wakefulness and REM state), and c) the number of different classes (more abundant in drowsiness than in the rest of brain states). If we assume that longer segments of stable brain activity imply a lesser amount of different information to process (as reflected by a higher stability of the brain generator), whereas shorter segments imply a higher number of brain microstates caused by more different steps of information processing, it is possible that the alpha activity appearing in the sleep onset period could be indexing the hypnagogic imagery self-generated by the sleeping brain, and a phasic event in the case of REM sleep. Probably, REM-alpha bursts are associated with a brain microstate change (such as sleep spindles), as demonstrated by its phasic intrusion in a desynchronized background of brain activity. On the other hand, alpha rhythm could be the “baseline” of brain activity when the sensory inputs are minimum and the state is relaxed wakefulness.
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  • 100
    ISSN: 1573-6792
    Keywords: Magnetoencephalography ; Human ; Words ; Tones ; Cerebral dominance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer while right-handed subjects (N = 15) were engaged in either an auditory word- or a tone-recognition task. Sources of the recorded magnetic fields were modeled as equivalent current dipoles at 4 ms intervals and the number of sources in the later portion of the magnetic response was used as an index of the degree of brain activation. Significantly more sources were found in the left as compared to the right hemisphere in the word but not the tone task on a group basis. On an individual basis, 13/15 subjects had more sources in the left as compared to the right hemisphere during the word task, while in the tone task 3/10 subjects showed this pattern. Sources of activity were found in the left superior and middle temporal gyri in all subjects with available MRI scans. Sources were also found in the supramarginal gyrus and in medial temporal areas, including the hippocampus, in the majority of cases. MEG appears to be a promising tool for detecting activity in cerebral areas specialized for language and memory function.
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