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Notes: Summary The effect of caffeine (single oral doses of 200 mg and 400 mg) on the CNS was tested under resting conditions and while performing a concentration performance test in a placebo-controlled pilot study on ten healthy males. The EEG was evaluated quantitatively by spectral analysis with a Computer Aided Topographical Electro En-cephalo Metry system. Comparison of the averaged frequency content revealed a clear difference between the change in the functional state of the brain due to the mental arithmetics, on the one hand, and the caffeine effect, on the other. Both states of altered brain activity were reflected in a particular topographical distribution of the frequency change with respect to a frontal-occipital accentuation. Comparison of the two periods of mental arithmetics in the absence or presence of caffeine showed a tendency to concentration-dependent differences from each other. Administration of 200 mg and 400 mg caffeine in the relaxed state effected the decrease in spectral power in the theta and alpha ranges. The concentration performance test without caffeine effected decreases in power in the alpha range in frontal to parietal cortex and enhanced theta power in frontal and occipital regions and the alpha power in occipital cortex. The caffeine-dependent decrease in theta power and the decrease in delta power seen under relaxation conditions after 400 mg are not observed during the concentration performance test in the presence of caffeine.

Notes: Summary Two subjects were rotated eccentrically in the manner described previously. In contrast to a normal control group, settings of a luminous line to the subjective vertical were almost unrelated to the gravitoinertial vector before, and totally so shortly after, space flight. Only 3 days postflight did a clear relation to the gravitoinertial vector re-establish itself in the one subject who actually flew. The correspondence became normal 5 days after the flight. Since there were no clinical abnormalities evident in the subjects, it is suggested that both subjects suppressed their vestibular information, presumably as an effect of vestibular deconditioning training before the flight. In addition, as a consequence of the flight experience one subject continued to ignore it several days after the flight.

Notes: Summary The narcotic agent etomidate and the antimycotic drug ketoconazole are known to block steroid biosynthesis in man. To study the different effects of these imidazole derivatives on human adrenal steroid biosynthesis we incubated slices of human adrenal glands with 3H-labeled precursors and increasing concentrations of etomidate or ketoconazole (0-2000 μM). After extraction the labeled metabolites were separated by thin-layer chromatography and quantified by scintillation counting. Etomidate inhibited most potently 11β-hydroxylase activity by suppressing the formation of corticosterone from 11-deoxycorticosterone to 1 % of control [50% inhibitory concentration (IC50) 0.03 μM] while ketoconazole suppressed 11β-hy-droxylase to only 39% of control activity (IC50 15 μM). Ketoconazole however, most potently blocked the conversion of 17α-hydroxy-proges-terone to androstenedione by C17,20-desmolase to about 15% of control activity (IC50 1 μM) while etomidate showed a much weaker effect on this enzyme with a suppression to 50% of C17,20-desmolase control activity at a concentration of 380 μM. Both imidazole drugs showed a similar strong inhibitory effect on the activity of 17α-hy-droxylase (IC50 6-18 μM) and 16α-hydroxylase (IC50 4–8 μM) and did not affect 21-hydroxylase. These in vitro data indicate a predominant inhibitory effect of etomidate on corticosteroid biosynthesis by relative selective inhibition of 11β-hydroxylase and of ketoconazole on the adrenal androgen biosynthesis by a predominant inhibition of C17,20-desmolase. This differential inhibitory effect of etomidate and ketoconazole on human steroid biosynthesis may be of clinical importance for a possible therapeutic use of these imidazole derivatives in endocrine disorders.

Notes: Summary The collagen fibres of rabbit and human ureter were exposed by digestion with trypsin and hyaluronidase. The fibre structure was examined using an SEM and examples of the inner and outer fibre structures are shown together with the effects of different types of mechanical strain. An interesting difference between the arrangements of the inner fibres of human and rabbit was seen where the human ureter had a cross-ply structure while in the rabbit it was helical.

Notes: Summary A pathological study was conducted on an autopsied patient who had undergone amputation of the right arm at the level of the shoulder 38 years prior to death. The numbers of anterior horn cells, spinal ganglion cells and myelinated fibers in the anterior and posterior spinal roots at the cervical segments were examined quantitatively and compared with those of age-matched control subjects. On the amputation side, anterior horn cells, spinal ganglion cells and large myelinated fibers of the anterior and posterior roots were decreased in number. In addition, on the spared side, the medium-sized neurons of Rexed's lamina IX were shrunken, or decreased in number, and the number of small- and medium-sized myelinated fibers in the anterior roots was decreased. These findings indicate that the long-term effects of axonal amputation induce retrograde degeneration of the anterior horn and spinal ganglion cells on the amputation side, resulting in atrophy and a decrease of medium-sized neurons in the anterior horn even on the contralateral, spared side.

Notes: Summary Ultrastructural development of the stomach was studied by light, scanning electron and transmission electron microscopy, using 19 human embryos at Carnegie stages from 14 to 23 (6.8–28.0 mm in crown-rump length, 5 to 8 weeks of gestation). The precise time of appearance of differentiated characteristic structures was examined electron microscopically. The first gastric pit, with radially arranged epithelial cells beneath which the basement membrane bulged into the mesenchyme, was observed on the lesser curvature at stage 22. Although the mesenchymal condensation which would develop into the inner circular muscle layer appeared at stage 18 onward, cytoplasmic myofibrils were not observed until stage 22. Nerve fibers were first observed at stage 16, and at later stages they gathered into bundles to form a nerve plexus external to the developing inner circular muscle layer. On the basis of accurate timing of the appearance and the mode of development of these structures, possible relations between developing gastric layers were discussed. Histocytochemically, glycogen or other carbohydrates were demonstrated in the cytoplasm of the gastric epithelium throughout the stages examined. These carbohydrates were localized mainly in vacuole-like spaces in the basal part of the epithelial cells. This subcellular localization, and the amount of carbohydrate, did not change significantly during the observed embryonic period. In the serosa, carbohydrates were not detected at stages 14 and 15, but observed consistently within the vacuoles in the cytoplasm from stage 17 onward. No other layer of the embryonic stomach had detectable carbohydrates. These observations suggest that carbohydrates in the gastric epithelium at an early developmental stage are not directly related to the developing mucin secretory activity of the epithelium, but may serve as an energy source for cell growth and differentiation of the epithelium and/or for mesenchyme-epithelial interactions.

Notes: Abstract Evidence is accumulating that nerve growth factor receptor (NGF-R or p75NGFR) can mediate cell growth and differentiation of non-neuronal cells. NGF-R expression was studied in developing teeth of human embryos and fetuses between the 6th and 18th weeks of gestation, using a monoclonal mouse-anti-human NGFR antibody. In contrast to earlier findings in rodents, the NGF-R expression of the human dental papilla was found to be transient. NGF-R was present in the condensing ecto-mesenchymal cells of the dental papilla in the early cap stage tooth germ. In later developmental stages, a shift of the NGF-R expression from the papilla to the cytoplasmic membrane of the inner enamel epithelium (IEE) was demonstrated. As in rodent odontogenesis, the NGF-R immunoreactivity of the IEE remained until the odontoblasts started secretion of predentinal matrix in the late bell state. The mitotic activity in the IEE was detected by an antibody against proliferating cell nuclear antigen (PCNA) and showed that the NGFR expression of the IEE decreased as the cell proliferation ceased. We propose that NGF-R may, be involved in differentiational and/or proliferative events of human odontogenesis.

Notes: Summary The medical literature concerning neuropathological changes caused by hydrocephalus is reviewed. In both humans and experimental animals the ependyma suffers focal destruction, cerebral blood vessels are distorted and capillaries collapse, there is damage to axons and myelin in the periventricular white matter, and occasionally neurons suffer injury. The damage appears to result from mechanical distortion of the brain combined with impaired cerebral blood flow. If ventriculomegaly develops very early, foci of cortical dysgenesis may be the result. The character and distribution of pathological changes are dependent on the age at which hydrocephalus develops, the rate and magnitude of ventricular enlargement, and the duration of hydrocephalus. Diversionary shunting of cerebrospinal fluid can only incompletely reverse the damage and the potential for reversal diminishes as the duration of hydrocephalus increases.

Notes: Summary We describe a detailed study of fluoride distribution with age in the human cortical rib bone. Human ribs were obtained from 110 subjects (M:68,F;42) aged 20–93 years. The fluoride distribution from the periosteal to endosteal surfaces of the ribs was determined by sampling each specimen using an abrasive micro-sampling technique, and the samples were analyzed using the fluoride electrode, as described by Weatherell et al. [1]. The concentration of fluoride was highest in the periosteal region, decreased gradually towards the interior of the tissue where the concentration of fluoride tended toward the plateau, and then rose again towards the endosteal surface. Patterns of fluoride distribution changed with age, and the difference between periosteal and endosteal fluoride levels increased with age. Although average fluoride concentrations increased with age in both sexes, there was a significant difference between males and females at the age of about 55 years (P〈0.05).

Notes: Summary The role of transforming growth factor β (TGF-β) in fracture healing has previously been investigated in a rodent model, but not in human material. We investigated TGF-β1 gene expression in specimens of callus from normally healing human fractures, using in situ hybridization to a cDNA TGF-β1 probe and an autoradiographic disclosure system. TGF-β1 mRNA was present in areas of proliferation of mesenchymal tissue, bone, and cartilage. Levels of expression were lower in cells in the fracture hematoma and in differentiated (hypertrophic) chondrocytes. These results are compatible with those found in various animal models using immunohistochemistry and support the view that locally produced TGF-β1 is a regulator of fracture repair in humans from the early (mesenchymal proliferation) stage to the stage of remodeling of woven bone. They also indicate that, for TGF-β1, animal models accurately reflect human bone repair.

Notes: Summary Omeprazole is an inhibitor of gastric H+, K+-ATPase. Although the major proton transport of osteoclast is mediated by a vacuolar-type H+-ATPase which is different from the gastric H+, K+-ATPase,in vitro studies have demonstrated that omeprazole inhibits bone resorption. In this study, the effect of omeprazole on bone resorption was evaluated in patients who had a history of gastric ulcer and were treated with maintenance doses of H2 blocker without any gastric complaints at the study time. H2 blocker administration was changed to omeprazole treatment in the study group and to no treatment in the control group. Urinary excretion of hydroxyproline and calcium decreased after omeprazole treatment in the study group. Serum intact PTH, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase (TRAP) increased in this group. In the control group, there were not any changes in these parameters. The discrepancy between serum TRAP and urinary excretion of hydroxyproline and calcium in the study group was thought to be due to the suppression of bone resorption by omeprazole, which probably interfered the acidification at resorption lacunae and resulted in the inactivation of TRAP and other lysosomal enzymes. The results of our study suggest the possibility that the specific inhibitors of the osteoclastic proton pump (such as bafilomycins) will more effectively suppress bone resorption and be useful for the treatment of metabolic bone diseases with increased bone resorption.

Notes: Abstract Objective To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). Design Prospective clinical investigation. Setting Medical intensive care unit of a university hospital. Patients 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and —in some cases — hemodialysis. Measurements and results Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84±1.52 pmol·ml−1) than in healthy controls (1.77±0.18 pmol·ml−1,p〈0.0001), in septicemia patients without circulatory failure (3.28±0.36 pmol·ml−1,p〈0.005) or in patients with hyperkinetic non-septic shock (3.6±0.7 pmol·ml−1,p〈0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. Conclusion These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Notes: Abstract In order to find out whether human vergence eye movements are influenced by simultaneous hand tracking movements, vergence was studied when sinusoidal (expressed in vergence angles) target movements were tracked. The target motion was externally generated and the target actually moved in depth. Tracking was done by the eyes alone or by the eyes and hand together, in both light and dark viewing conditions. Our data show that the target motion was tracked by the eyes with a short delay (on average 48 ms), independent of the tracking condition. This suggests that vergence modeling should include some predictive mechanism similar to that proposed for the smooth pursuit subsystem. Furthermore, in contrast to effects on smooth pursuit, simultaneous hand tracking movements did not influence vergence eye movements. From this, we argue that the balance between smooth pursuit and saccadic eye movements is adjustable and can be adapted to the requirements of different tasks.

Notes: Abstract The H-reflex technique has been used to evaluate the time-course of the effects evoked by transcranial clockwise magnetic stimuli in flexor or extensor carpi radialis motoneurones. In six subjects, magnetic stimulation was applied over the scalp in the focus for the motor response of those muscles. At intensities below motor threshold, a facilitation of the H-reflex started at a conditioning-test interval of -4 ms (i.e. when the magnetic stimulus lagged the test stimulus by 4 ms), reached a peak at about -2 ms and rapidly decayed. At about -1 ms, the decay attained a local minimum, which in three subjects had values indicating the presence of an inhibition. Thereafter, a second facilitatory phase peaked at about +1 ms. By matching the time course with the latency of the cortical muscle action potential (CMAP) evoked by suprathreshold magnetic stimulation, it is inferred that the motoneuronal discharge coincides with the second peak of facilitation and is preceded by 3–4 ms of subliminal excitation. This early effect could be brought to threshold by convergence of a subliminal Ia EPSP, leading to a reduction of the CMAP latency. The early excitatory effects reported above are as fast as those described as following transcranial electrical stimulation, and should likewise be considered as monosynaptic.

Notes: Abstract During chewing, a small part of the observed muscle activity is needed for the basic open-close movements of the mandible, and additional muscle activity (AMA) is needed to overcome the resistance of the food. The AMA consists of two contributions: a large peripherally induced contribution, starting after food contact and a small anticipating contribution, starting before food contact. We investigated whether the latencies of these contributions depend on the expected or actual bolus size. Subjects made rhythmic open-close movements near their natural chewing frequency controlled by a metronome. This frequency was determined while the subjects were chewing gum. Food resistance was simulated by an external force, acting on the jaw in a downward direction during part of the closing movement. Bolus size was simulated by the jaw gape at which the force started. Jaw movement and surface EMG of the masseter and anterior temporal muscles on both sides and the suprahyoid muscles were recorded during experiments in which the jaw gape at which the force started was varied. The peripherally induced contribution to the AMA started about 20 ms after the onset of the force, irrespective of the jaw gape at which the force started. It is concluded thatthe onset of this contribution depends solely on food contact in the actual cycle. The function of the observed mechanism for jaw elevator muscle control may be to enable a highly automatic control of the muscle activity required to overcome the resistance of food of different hardness and different size. The onset of the anticipating contribution to the AMA showed neither a relationship with the actual jaw gape at which force onset occurred nor with the expected jaw gape of force onset. It is suggested that the onset of the anticipating AMA is related to the jaw gape at the onset of closing. The function of this contribution may be the regulation of the mechanical response of the jaw after an expected disturbance of the closing movement by food contact, by tuning the muscle stiffness to the expected hardness of the food.

Notes: Abstract Humans do not confound the motion of shadows cast upon a surface with the motion of the surface itself, although schemes that propose recombination of orientation-selective motion signals into a rigid motion percept of two-dimensional patterns would predict that they should do so. We propose a simple scheme that avoids recombination and instead attributes perception of two-dimensional pattern motion to the activation of orientation-selective end-stopped units that operate on the logarithm of the luminance. The proposed units respond to the change of contrast along a line, which typically occurs at an intersection. They are not active, however, when a shadow border intersects the edge of an object, because contrast does not change along either of these edges. Thus, end-stopped units signal the motion of transparent intersections weakly or not at all, and the independent motions of the shadow border and the object prevail. We tested two implications of this scheme, using plaids with variable intersection luminance. First, when the intersection luminance was such that it kept the contrast along the intersecting lines nearly constant, the sensitivity for the rigid plaid's direction of motion was minimal, and the sliding motion of the components prevailed. This occurred for light bars on dark backgrounds and for dark bars on light backgrounds. Thus, the effect of the intersection's luminance on the balance between the percepts of rigid-plaid motion and the motion of sliding components was independent of contrast inversion of bar and background. Secondly, when thin lines with the same luminance as the bars covered the borders of the intersection, the intersection's luminance did not affect the rigid-plaid motion percept very much, even when it corresponded to a transparent intersection. This indicates that, when the edges of the intersection and those of the bars were not collinear, the nulling of the endstopped units did not occur. This result is in line with physiological studies, which showed that the response of an end-stopped cell to a line is only partially inhibited when a similar line is presented non-collinearly with the first in the inhibitory end-zone of its receptive field. Our results are consistent with a scheme in which a second stage of motion detectors combines signals of orientation-selective end-free and orientation-selective end-stopped units for perception of the rigid motion of two-dimensional patterns.

Notes: Abstract We examined whether internally triggered saccades made to a nonjumping target (I-saccades) could be adapted independently from externally triggered saccades induced by a jumping target (E-saccades). Five subjects made I-saccades between two fixed targets, one placed straight ahead and the other one positioned at an eccentricity of 17.5°. The peripheral target was displaced to an eccentricity of 8.75° during the saccadic movements toward this target. Amplitudes of the I-saccades made from the central to the peripheral target before and after adaptation were compared with each other. Saccadic amplitudes after adaptation were between 10% and 42% smaller than those before adaptation. E-saccades induced by a single target which jumped from straight ahead to the same peripheral target position as was used for the I-saccades were also measured before and after the adaptation of I-saccades. Amplitudes of E-saccades before and after adaptation were hardly different from each other except in one subject. The mean decreases in amplitude of the two types of saccades, averaged over all subjects, were 21% for I-saccades and 5% for E-saccades. These results show that I-saccades can be adapted to changed visual conditions while E-saccades remain unadapted. We conclude from this finding that I-saccades and E-saccades are generated by at least partially different neural mechanisms.

Notes: Abstract Naive human subjects were tested in three different tasks: (1) a visuomotor mental rotation task, in which the subjects were instructed to move a cursor at a given angle from a stimulus direction; (2) a visual mental rotation task, in which the subjects had to decide whether a displayed letter was normal or mirror image regardless of its orientation in the plane of presentation; and (3) a visuomotor memory scanning task, in which a list of two to five stimuli directions were presented sequentially and then one of the stimuli (test stimulus), except the last one, was presented again. Subjects were instructed to move a cursor in the direction of the stimulus that followed the test stimulus in the previous sequence. The processing rate of each subject in each task was estimated using the linear relation between the response time and the angle (mental rotation tasks) or the list length (memory scanning task). We found that the processing rates in the mental rotation tasks were significantly correlated but that neither correlated significantly with the processing rate in the memory scanning task. These results suggest that visuomotor and visual mental rotations share common processing constraints that cannot be ascribed to general mental processing performances.

Notes: Abstract Fatigue of voluntary muscular effort is a complex and multifaceted phenomenon. Fatigue of peripheral nervous system components, including the contractile apparatus and the neuromuscular junction, has been well studied. Central nervous system components also fatigue, but studies have lagged for want of objective methods. Transcranial magnetic stimulation is a relatively new technique that can be used to assess central nervous system excitability from the motor cortex to the alpha-motoneuron. In six normal volunteers, including four of the investigators, the amplitudes of motor evoked potentials elicited by transcranial magnetic stimulation were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The decrease in amplitude was associated with a feeling of fatigue. The mechanism of this phenomenon is apparently decreased efficiency in the generation of the motor command in the motor cortex.

Notes: Abstract Two superimposed gratings, which differ in orientation and move independently, combine into a coherently moving plaid if the component gratings are similar. The effect on the plaid motion percept of the addition of texture to each grating was investigated. The texture disambiguates the motion of each component grating. Under the assumption of recombination of first-stage motion detectors into a second stage, which becomes available to perception, one would expect the perceived motion direction of the plaid to change as a result of texture addition. Subjects perceived the oblique motion direction of textured bars of a single orientation correctly. This occurred for texture details with dimensions down to the resolution limit in the fovea (1 min of arc). Two bar patterns with fine texture (1 min of arc details) which differ in orientation were perceived to cohere into a plaid. The plaid's motion direction, however, was independent of the parallel motion components of the bars. For coarser textures (2 and 4 min of arc details) the bar patterns were perceived to slide past one another. In addition, we found that the plaid motion percept occurred less frequently for longer motion sequences, wider bars and for a combination of the component textures at the intersections which is compatible with partial transparency of the bars. These results do not support the two-stage model of Adelson and Movshon (1982), where only the motion component perpendicular to each grating orientation is encoded and where the perception of the plaid motion results from “recombination” of these perpendicular motion components. The data are more in line with a model where first-stage motion detectors are orientation selective but without the restriction that their preferred direction of motion is perpendicular to their preferred orientation. In the second stage it is proposed that combination occurs across the orientation dimension only. This preserves the direction of motion “labels” at the output of the second stage and allows for representation of transparent as well as coherent plaid motion at this stage of processing.

Notes: Abstract Saccadic reaction times and amplitudes were determined in four human subjects and two rhesus monkeys when they made saccades to visual targets appearing in different spatial or temporal contexts. Two stimuli were presented at different positions, either simultaneously (global condition) or in random order (range condition). Both the gap and the overlap paradigm were used. The characteristics of different groups of saccades defined by the separate peaks in the distribution of the saccadic reaction times as express and regular saccades, were analysed and compared. It is shown that, in man and monkey, the amplitudes of express saccades undergo the same or even stronger context-dependent changes as do those of regular saccades. Furthermore, the presence or absence of the fixation point also influences the saccadic amplitudes, at least for the express saccades. We conclude that the neural mechanisms that determine the amplitudes of the express saccades are more strictly under the control of the physical and physiological conditions of the stimulus situation, whereas regular saccades have greater — although not complete — dependence on the psychological context and, in particular, the subject's effort.

Notes: Abstract With subjects standing on a treadmill moving sinusoidally backward and forward, recordings of electromyographic (EMG) leg and trunk muscle activity, head and joint movements and platform torque were made with the subjects' eyes open or closed. The sinusoidal frequency was changed, stepwise and randomly, between 0.5, 0.3 and 0.25 Hz. The amplitude of the deflection was constant at ±12 cm. During an adapted sinus cycle, the maximum leg muscle EMG activity was recorded in the tibialis anterior around the posterior turning point and in the gastrocnemius around the anterior turning point in the treadmill cycle. This activity was associated with a forward inclination of the body around the posterior point and a straightening of the body at the anterior point. Both the degree of body inclination and the corresponding EMG activity were dependent upon the sinusoidal frequency. The programmed adjustment of the body inclination was such that the result of inertial and gravitational forces acting on the body coincided with the axis of the body at the posterior turning point. At the anterior point, the adjustment was achieved mainly by strong activation of the leg extensors. The latencies of the compensatory muscle responses to a change in treadmill frequency were significantly shorter at the posterior point for the gastrocnemius than for the tibialis anterior, and at the anterior point for the tibialis anterior than for the gastrocnemius. No correlated changes were seen in the corresponding head and joint movements. The difference in latency can best be attributed to the different body postures during the sinusoid. Early activation of the gastrocnemius is required due to the forward-directed impulse to the inclined body at the posterior point, and of the tibialis anterior muscle due to the backward-directed impulse to the erect body at the anterior point. It is suggested that afferent input from extensor load receptors provides information about the position of the body's centre of gravity relative to the support surface and determines the generation of the EMG responses. Adaptation of both the EMG and biomechanical patterns to a new sinusoidal frequency of the treadmill occurred within four cycles after the change. Biomechanically, this was reflected as a change in the body posture. Vision did not significantly affect these changes. In conclusion, standing on a sinusoidally moving platform, the nervous system acts to control the position of the body's centre of gravity relative to the feet. Body posture is adjusted in such a way that the forces acting on the body during the treadmill movements become minimised. After adaptation, body equilibrium becomes predominantly controlled by positive feedback from programmed leg muscle activation.

Notes: Abstract Previous work on multifunctional muscle has suggested that motor unit recruitment during a combined force task is the result of an interactive effect of weighted inputs acting simultaneously on the motoneuron pool. The present study shows that a similar effect describes motor unit activation in a two-joint muscle as forces are combined at both proximal and distal attachments. The recruitment thresholds of single motor units in medial gastrocnemius muscle were determined during combined knee flexion and plantarflexion isometric contractions. Slow isometric ramp contractions in knee flexion were produced while maintaining various background levels of plantarflexion force. The combination of knee flexion and plantarflexion forces at which a motor unit initially discharged was used to characterize recruitment as represented by the slope of the regression line fit to the individual data points. Each subject completed two experiments; one at each of two knee joint angles, with the ankle joint fixed at 90°. The effect of knee angle was assessed by comparing the slopes of the regression lines that characterized motor unit recruitment at each knee angle. Motor units in medial gastrocnemius were recruited when the linear sum of the forces exerted in plantarflexion and knee flexion exceeded a certain threshold of combined force. Specifically, the apparent force threshold of recruitment in knee flexion decreased as the level of force maintained in plantarflexion increased. Further, evidence is provided indicating that the linear relationship describing recruitment in two-joint muscle is dependent upon joint angle. The basis for the alteration in force threshold is thought to be related to changes in muscle length and mechanical advantage which might adjust the relative weighting of inputs that determine muscle activation patterns. These results indicate a possible common strategy employed by the nervous system in coordinating the activation of motor units to perform a specific task.

Notes: Abstract In the present study, we investigated topographical differences between monocularly and binocularly evoked potential fields related to the retinal location and spatial frequency of grating stimuli. Electrical brain activity was recorded in 18 healthy adults using an array of 21 electrodes over the occipital areas. Vertical black-and-white grating patterns of different spatial frequencies were presented with central fixation or lateralized to the left or right hemiretina. Computation of global field power determined component latency. Topographic characteristics of the field distributions were examined at the individual component latency for each subject using statistical comparisons between experimental conditions. The strength of the potential fields was significantly larger with binocular stimuli, whereas no effects were observed when comparing component latencies. Pronounced differences occurred in the spatial distribution of electrical brain activity: with 2.5 cycles/deg, large, significant topographic differences between monocularly and binocularly evoked activity were obtained. The potential fields showed a more anterior and more lateralized component distribution with binocular than monocular stimuli. In addition, when the gratings were presented binocularly, significant topographic differences were observed when low and high spatial frequency stimuli were compared. Our results suggest that the relationship between the topography of evoked components and retinal stimulus location and spatial frequency is different for monocular and binocular stimuli, indicating that binocular information processing triggers different neuronal processes in the human visual cortex.

Notes: Abstract Muscle activity patterns in some complex human jaw muscles appear to be task sensitive. However, it is presently uncertain how changes in motor task affect motor unit (MU) behaviour in the human temporalis muscle. In this study, activity was recorded from 40 MUs in the anterior region of the muscle. The lowest sustainable firing frequency (LSFF) was reached by slow increases and decreases in firing rate, then firing was maintained at the lowest possible rate without significant pauses. An array of consecutive interspike intervals (ISI) were sampled digitally and used to measure the LSFF for each task associated with the MU. In a controlled paradigm, MU reflex inhibition was measured during the performance of different tasks. Single electrical pulses of non-noxious intensity were delivered to the gingiva near the maxillary canine tooth. During continuous MU firing at a controlled firing frequency of 10 Hz, series of pulses were delivered with increasing delays, after preselected spikes. The MUs fired continuously during the performance of 1–4 postural and tooth-contact tasks. There were significant differences in LSFFs between tasks in those MUs associated with multiple tasks. In the reflex study, all MUs were inhibited, but the magnitude of the inhibition was highly task dependent. Thus, both LSFF and reflex inhibition of temporalis MUs appear to vary with the motor task and are sensitive to the position of the jaw and the direction and location of tooth contact along the tooth row. This behaviour most likely reflects task-related changes in output from orofacial and muscle afferents.

Notes: Abstract This study investigated changes in myoelectric and mechanical variables for movements made “as fast as possible” as a function of practice in the context of the dual-strategy hypothesis of motor control (Gottlieb et al. 1989b). Five male subjects made 1400 rapid elbow flexion movements in ten blocks of 20 trials over seven experimental sessions. Improved performance was defined as increased peak movement velocity, decreased peak velocity variability, increased acceleration and deceleration, a proportionately greater increase in peak deceleration than peak acceleration, and greater consistency in terminal location. The changes observed over experimental sessions were very similar to (but larger and more consistent than) those seen for the first experimental session, with the partial exception of the timing of the antagonist electromyogram (EMG). In general, the increases in the values of the measured mechanical variables covary with myoelectric measures in the same way as when subjects are asked to intentionally change speed in accordance with the rules of the speed-sensitive strategy (Corcos et al. 1989). However, there are differences between subjects in the extent to which speed changes can be attributable to the agonist muscle, the antagonist muscle, or in the timing between the muscles. In one of the five subjects, the latency of the antagonist EMG decreased over blocks on the 1st day but increased over experimental sessions and was consequently activated proportionately later in the movement. This suggests that extended practice can give at least some subjects flexibility in modifying the motor programs that underlie movement.

Notes: Abstract We attempted to demonstrate convergence onto human spinal Ia inhibitory interneurons from Ia afferents and from fast conducting corticospinal axons. Stimulation of the common peroneal nerve at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H-reflex, attributed to reciprocal inhibition. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the soleus H-reflex, including a short latency-inhibition. To test for convergence, the two stimuli were given together so that the two inhibitions coincided.When each stimulus alone produced clear inhibition, the inhibition produced by both stimuli was less than expected, implying an interaction between the two volleys, for example, occlusion occurring in interneurons or motoneurons.When the H-reflex was relatively unaffected by one or other conditioning volley, the inhibition produced by the combined stimulation was greater than expected, as might be expected with convergence onto a common pool of interneurons.

Notes: Abstract We examined the time-varying dynamics of the human triceps surae stretch reflex before, during, and after a large stretch was imposed upon the ankle joint, during a constant voluntary contraction of 15% of maximum voluntary contraction. Stretch reflex dynamics were estimated by superimposing a small stochastic displacement on many such stretches and using an “ensemble-based” time-varying identification procedure to compute impulse response functions relating the perturbation to the evoked electromyogram (EMG) at each point throughout the task. We found that stretch reflex magnitude (relating joint velocity to EMG) varied directly with baseline EMG activity during steady-state conditions before and after the large imposed stretch. Following the large stretch and the reflex activity it evoked, both background EMG and stretch reflex magnitude declined for up to 100 ms; changes in the stretch reflex were substantially greater in magnitude and followed a different time course from the corresponding changes in background EMG, however, indicating that stretch reflex properties were modulated independently of motoneuron pool activation level. Based on timing and the invariance of stretch reflex dynamics across time, it is argued that this behavior is largely mediated via peripheral neural mechanisms. This peripheral modulation of the stretch reflex presumably supplements various descending influences to adjust reflex properties.

Notes: Abstract The size of the soleus H-reflex was measured after a slow (17 deg/s) passive stretch of ankle plantarflex ors and compared to its control size without muscle stretch in ten neurologically healthy subjects and in six spastic spinal-cord-injured patients. Two seconds after the end of the stretch, the size of the H-reflex was reduced to about 30% of its pre-stretch size in the healthy sub jects. The depression remained for 10–15 s. In the spastic, spinal-cord-injured patients, stretch caused significantly less reduction in the size of the H-reflex. The H-reflex also regained its pre-stretch size much faster than in healthy subjects. We suggest that the smaller depression of the H-reflex observed in spastic patients may be involved in the pathophysiology of spasticity.

Notes: Abstract Synchronous activity was studied in relation to the contractile properties of pairs of motor units (MUs) recorded with independent microelectrodes in the right extensor digitorum communis muscle (EDC) of human subjects during isometric finger extension. MU contrac tile properties were characterized in terms of the rise time and amplitude of twitch tensions extracted by spike-trig gered averages of the extension force. Synchronization of MU discharges appeared in the form of narrow central peaks in the cross-correlograms of 35 of 50 pairs of MUs, suggesting the contribution of common last-order neu rons. Synchronization peaks tended to be briefer and higher among pairs of MUs with slower and smaller twitches than among pairs of MUs with faster and larger twitches. The higher peaks of slow-contracting MUs sug gest a greater effectiveness of the common synaptic in puts. The broader peaks of fast-contracting MUs might reflect an additional synchronization of the inputs to fast MUs at high force levels. The areas of the cross-correlo gram peaks were similar for both groups and suggest that under our conditions, about three motoneurons would discharge synchronously for a given motoneuron spike. To test whether the amount of MU synchronization could be altered voluntarily, four subjects attempted to increase or decrease synchrony, using as feedback clicks triggered by coincident firings of the recorded MUs. In nine of 15 conditioning sessions, the magnitudes of the synchronization peaks showed significant changes in the intended direction. These results imply that supraspinal centers can control the relative amount of inputs that contribute to the synchronization of motoneuron dis charges during voluntary contraction of EDC.

Notes: Abstract To determine age-related changes in oculomotor function we measured vestibuloocular (VOR), optokinetic (OKN), and visual-vestibular responses in a large group of normal subjects over the age of 75 years and compared the results with those from a group of young adults. Compared with the young subjects, older subjects had: (1) an amplitude-dependent decrease in VOR gain, (2) a shorter dominant VOR time constant, (3) a lower OKN slow-phase velocity saturation, and (4) a decreased ability to enhance and suppress the VOR with vision. These functional changes in older subjects are presumably secondary to well-documented, age-related changes in the sensory and neural elements of the visualvestibulooculomotor pathways. They may be a contributory factor to the common complaints of dizziness and dysequilibrium in people over the age of 75 years.

Notes: Summary The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.

Notes: Abstract We have examined the time variations of stretch reflex dynamics throughout rapid voluntary changes in the isometric contraction level of the human triceps surae muscles. This was achieved by superimposing a small stochastic displacement upon many such changing contractions and then identifying the time-varying relationship between the perturbation and the evoked electromyograms (EMGs). An “ensemble” time-varying system identification technique was used to estimate these input-output dynamics as a set of impulse response functions, one for each time before, during, and after the change in contraction level, with a temporal resolution equal to the data acquisition rate. Three main findings resulted. First, stretch reflex gain (relating joint velocity to EMG) was significantly modulated during changes in voluntary contraction level, increasing as the subject contracted the muscles and decreasing as the subject relaxed. Second, stretch reflex dynamics did not change with contraction level, even when its gain varied substantially. Third, the time course of the gain changes closely followed the level of the EMG, even though the subjects used rather different activation and deactivation patterns. These results suggest that, for the behavior studied (i.e., rapid changes in isometric contraction level), stretch reflex gain and motoneuron pool activation level were controlled by a common descending command rather than being independently specified.

Notes: Abstract Upright standing and walking tasks require the integration of several sources of sensory information. In a normal and highly predictable environment, locomotor synergies involving several muscles may take place at lower spinal levels with neural circuitry tuned by local loops of assistance or self-organizing processes generated in coordinative networks. When ongoing regulation of gait is necessary (obstacles, changes in direction) supraspinal involvement is necessary to perform movements adapted to the environment. Using a classical information processing framework and a dual-task methodology, it is possible to evaluate the attentional demands for performing static and dynamic equilibrium tasks. The present experiment evaluates whether the attentional requirements for a control sitting condition and for standing and walking conditions vary with the intrinsic balance demands of the tasks. The results show that standing and walking conditions required more attention than sitting in a chair. The attentional cost for walking was also significantly greater than for standing. For the walking task, reaction times when subjects were in singlesupport phase (small base of support) were significantly longer than those in double-support phase, suggesting that the attentional demands increased with an increase in the balance requirements of the task. Balance control requires a continuous regulation and integration of sensory inputs; increasing balance demands loads the higher level cognitive system.

Notes: Abstract Detection thresholds to step indentations applied to touch domes were measured and compared with threshold values obtained on adjacent areas of hairy skin. The mean of the detection thresholds determined on touch domes for five subjects was 504±27 μm (SEM). The detection thresholds found off the touch domes (2–3 mm away) were somewhat higher in all ten cases (two studies per subject), with a mean value of 587±28 μm, which was significant at the 0.01 level. These thresholds are an order of magnitude greater than those that elicit responses in touch-dome-associated slowly adapting type I (SAI) fibres in cats, and, together with the small difference between the detection thresholds determined on and off touch domes, indicate that the activity of single touch dome SAI fibres does not mediate the detection of steady indentation in the hairy skin.

Notes: Abstract The abilities of human subjects to perform reach and grasp movements to remembered locations/ orientations of a cylindrical object were studied under four conditions: (1) visual presentation of the object — reach with vision allowed; (2) visual presentation — reach while blindfolded; (3) kinesthetic presentation of the object-reach while blindfolded and (4) kinesthetic presentation-reach with vision. The results showed that subjects were very accurate in locating the object in the purely kinesthetic condition and that directional errors were low in all four conditions; but, predictable errors in reach distance occurred in conditions 1,2, and 4. The pattern of these distance errors was similar to that identified in previous research using a pointing task to a small target (i.e., overshoots of close targets, undershoots of far targets). The observation that the pattern of distance errors in condition 4 was similar to that of conditions 1 and 2 suggests that subjects transform kinesthetically defined hand locations into a visual coordinate system when vision is available during upper limb motion to a remembered kinesthetic target. The differences in orientation of the upper limb between target and reach positions in condition 3 were similar in magnitude to the errors associated with kinesthetic perceptions of arm and hand orientations in three-dimensional space reported in previous studies. However, fingertip location was specified with greater accuracy than the orientation of upper limb segments. This was apparently accomplished by compensation of variations in shoulder (arm) angles with oppositely directed variations in elbow joint angles. Subjects were also able to transform visually perceived object orientation into an appropriate hand orientation for grasp, as indicated by the relation between hand roll angle and object orientation (elevation angle). The implications of these results for control of upper limb motion to external targets are discussed.

Notes: Abstract This study assessed the reach to grasp movement and its adaptive response to a perturbation of object size. In blocked trials, subjects (n = 12) were instructed to reach 35 cm to grasp and lift a small- (0.7 cm) or large-diameter (8 cm) cylinder. Under an unconstrained condition (condition 1), no instructions as to the type of grasp to adopt were given. Subjects thus naturally used a precision grip (PG) for the small cylinder and whole hand prehension (WHP) for the large cylinder. Under condition 2, subjects were instructed to utilize a PG for grasps of both the large and small cylinders. For condition 3, the instruction was to use WHP irrespective of object size. Kinematic organization was determined with analysis of the recordings of active markers placed on the wrist, thumb, and three fingers. For condition 1 the results showed a temporal arrangement of both components (transport and manipulation) which differed from that of conditions 2 and 3. In perturbed trials, illumination shifted from the small to large cylinder or vice versa. With condition 1, subjects automatically switched from one grasp to another with no or little increase of movement duration. This was generally achieved by an earlier temporal setting of peak wrist deceleration. For conditions 2 and 3, where a change of aperture was required, movement duration was prolonged without adaptation of earlier transport component parameters. It is concluded that the adaptive responses to a change of distal patterning also affect the organization of the proximal component. Assessment of grasps constrained by instructions may lead to interpretations of central control of the reach to grasp movement which differ from those obtained by assessing more natural prehensile patterns.

Notes: Abstract Horizontal and vertical optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) provided by a partial-field, binocular optokinetic stimulator were recorded in one astronaut before, during, and after a 25-day space flight. A ground-based study was performed on six control subjects. During the flight experiment, performed on flight days 5, 18, 19, and 21, the subject either had their feet attached to the deck or was free-floating. Vertical OKN gain only slightly increased in weightlessness compared with ground data, but the center of interest (CI) during vertical OKN, evaluated by the eye position in the saggital plane at the end of the fast phases relative to the straight-ahead direction, was found to be significantly changed during long-term exposure to weightlessness. The horizontal CI showed very little change in-flight, but the gain was increased. The time constant for the astronaut was small for vertical OKAN, but there was an increase in slow-phase velocity (SPV) by the end of the flight, which returned to normal postflight. These results partly confirm the data obtained during head-tilt studies on the ground and are in accordance with the hypothesis of a gravity-dependent control of vertical gaze direction during orientation reflexes.

Notes: Abstract Most studies of rapid orienting gaze shifts generated by combined eye and head movements have focused on an experimental condition in which gaze displacements are started with the subject's eyes in the normal straight-ahead position in the orbit. Such an experimental approach does not permit a clear identification of the input signal to the head motor system, because target offset angle is the same for both the eye and head. We have studied gaze shifts in human subjects which began with the visual axis straight ahead relative to the body (i.e., gaze or line of sight aligned with body sagittal plane) and with head offset from straight ahead at various angular positions. In our experimental conditions, the amplitude of head movement during a gaze shift was nearly equal to the angular distance between the target position and the starting head position (target-re-head), even though subjects were not specifically instructed to move their heads. This observation contrasts with other published reports in the literature showing considerable varibility amongst subjects in the amplitude of head rotation within a given task and between tasks. The difference may be related to the initial conditions which required subjects to align the eye and head on specific starting targets, since others have shown that requiring head alignment enhances head displacement. The amplitude of the saccadic eye movement was not determined by either the target's position relative to the starting eye or head positions. The value that best described the eye movement amplitude was the eye position in the orbit at the end of the saccade. This was nearly equal to target-rehead until a saturation eye position in the orbit was attained.

Notes: Abstract Non-invasive transcranial magnetic stimulation (TMS) of motor cortex induces motor evoked potentials in contralateral muscles which are thought to be conducted by the corticospinal tract. Furthermore, inhibitory actions can be elicited by TMS which appear directly after the motor evoked potential (postexcitatory inhibition, PI) and can be visualized by blockade of tonic voluntary EMG activity. It was the aim of the present study to answer the questions of whether this inhibitory action is mainly of cortical or of spinal origin, which brain area generates this inhibition, and whether the duration of PI differs between proximal and distal muscles. Experiments were performed on a total of 34 healthy volunteers. Brain stimuli were delivered with a Novametrix Magstim 200HP with a maximum output of 2.0 T, and stimulation was performed during tonic voluntary activation of the muscle under study. Stimulation strength was 1.5 times threshold level. Duration of PI was defined as the time from the onset of the motor evoked potential to the reoccurrence of the EMG background activity. PI was found more pronounced in distal hand muscles than in proximal arm and leg muscles. The largest PI values were observed when the primary motor cortex was stimulated. To test the excitability of the spinal motoneurones during PI, cortical double stimulation at various intervals was performed and the soleus H-reflex was evoked at different intervals after cortical stimulation. Neither test revealed a decrease in the excitability of the spinal motoneurones during PI. These findings imply that spinal segmental inhibitory action cannot account for PI and that, most probably, inhibitory actions within the motor cortex play a major role in the genesis of PI.

Notes: Abstract In order to study the roles of muscle mechanics and reflex feedback in stabilizing movement, experiments were conducted in which healthy human subjects performed targeted wrist movements under conditions where the damping of the wrist was reduced with a load having the property of negative viscosity. If the movement speed and negative viscosity were sufficiently high, the wrist oscillated for several hundred milliseconds about the final target position. Subjects increased the activation of both wrist flexor and extensor muscles to increase joint stiffness to damp the oscillations. With practice, both the tendency to oscillate and the level of muscle activation were reduced. A small bias torque in either direction, added to the negative viscosity, enhanced the oscillations as well as the amount of flexor and extensor muscle activation during the stabilization phase of fast movements. The tendency for the wrist to oscillate was also seen during slow movements where the oscillations were superimposed upon the voluntary movement. We suggest that this reduction in mechanical stability is primarily of reflex origin. As wrist stiffness increases, the natural frequency of the wrist also increases, which in turn produces an increase in the phase lag of the torque generated by the myotatic reflex with respect to wrist angular velocity, effectively reducing damping. The oscillation frequency was often close to a critical frequency for stability at which torque, due to the myotatic reflex, lagged angular velocity by 180° (6–7.5 Hz). Nevertheless, subjects were able to damp these oscillations, probably because the torque due to intrinsic muscle stiffness (in phase with position and hence lagging velocity by only 90°) dominated the torque contribution of the myotatic reflex. Increasing stiffness with declining oscillation amplitude may also have contributed significantly to damping.

Notes: Abstract Human subjects pointed, without seeing their arm, at visual targets presented in repeated sequences in a frontal plane. Required movement direction could change within the sequence by 0, 45, 90, 135 or 180°. Hand position was recorded contact-free in three dimensions (3D). From the recordings, the pointing errors towards each target were transformed into a Cartesian coordinate system with the x-axis representing the mean direction of all movements towards that target. We then investigated the relationship between successive errors by applying linear regression analysis separately to the three Cartesian error components. For the x-component, we found that successive errors were positively correlated throughout the experiment, which confirms our previous finding that errors in sequential pointing tend to accumulate (Bock and Eckmiller 1986; Bock et al. 1990). Correlation dropped by nearly 50% following a direction change of 90° or more, suggesting that accumulation is reduced but not abolished by large changes in movement direction. The slope of the regression line averaged 0.6, which indicates the existence of a complementary trend towards error correction, contributing about 40% towards motor performance. Changes of movement direction affected slope and correlation in a closely similar way, suggesting that reduced accumulation is paralleled by increased correction. For the y- and z-components, we found that successive errors were positively correlated as well, but were not reduced following even large direction changes. This apparent discrepancy can be resolved by assuming separate neural mechanisms for amplitude and for direction control, differing in their sensitivity to direction changes. We discuss our findings in the context of the two predominant motor control hypotheses, the amplitude and the position control models.

Notes: Abstract We measured torsional vestibular and optokinetic eye movements in human subjects with the head and trunk erect, with the head supine and the trunk erect, and with the head and trunk supine, in order to quantify the effects of otolithic and proprioceptive modulation. During active head movements, the torsional vestibulo-ocular reflex (VOR) had significantly higher gain with the head upright than with the head supine, indicating that dynamic otolithic inputs can supplement the semicircular canal-ocular reflex. During passive earth-vertical axis rotation, torsional VOR gain was similar with the head and trunk supine and with the head supine and the trunk erect. This finding implies that static proprioceptive information from the neck and trunk has little effect upon the torsional VOR. VOR gain with the head supine was not increased by active, self-generated head movement compared with passive, whole body rotation, indicating that the torsional VOR is not augmented by dynamic proprioceptive inputs or by an efference copy of a command for head movement. Viewing earth-fixed surroundings enhanced the torsional VOR, while fixating a chair-fixed target suppressed the VOR, especially at low frequencies. Torsional optokinetic nystagmus (OKN) evoked by a full-field stimulus had a mean slow-phase gain of 0.22 for 10°/s drum rotation, but gain fell to 0.06 for 80°/s stimuli. Despite this fall in gain, mean OKN slow-phase velocities increased with drum speed, reaching maxima of 2.5°/s–8.0°/s in our subjects. Optokinetic afternystagmus (OKAN) was typically absent. Torsional OKN and OKAN were not modified by otolithic or proprioceptive changes caused by altering head and trunk position with respect to gravity. Torsional velocity storage is negligible in humans, regardless of head orientation.

Notes: Abstract Within-arm somatotopy was identified in multiple motor areas of six normal human subjects who performed a visuomotor tracking task during positron emission tomography (PET) measurement of relative cerebral blood flow (relCBF). A randomly moving target, presented on a computer monitor, was continuously followed with the index finger (movement at the metacarpopha-langeal joint), thumb, fist (movement at the wrist), forearm (movement at the elbow), elbow (movement at the shoulder), and eyes alone (control task) during sequential imaging. Segmental limb movements were associated with relCBF responses in the contralateral motor, supplementary motor, cingulate, and parietal cortex, and in the ipsilateral cerebellum. Localization of responses after stereotaxic transformation into Talairach atlas space, as well as within-subject analysis without anatomic deformations, demonstrated an overlapping somatotopic distribution in the motor cortex, with thumb responses most ventrolateral and shoulder responses most dorsomedial. Proximal limb movements induced relCBF responses of greater magnitude than distal movements. Somatotopy was also identified in the supplementary motor area, with index finger responses dorsal and anterior to shoulder responses. An additional set of somatotopic responses were located in the cingulate cortex, also with finger responses anterior to shoulder responses. Somatotopy was not identified in the anterior cerebellum. The distribution of relCBF responses is concordant with electrophysiologic studies in nonhuman primates that demonstrate a fractured somatotopy on a fine scale and a general somatotopic scheme of the limb on a large scale in multiple discrete motor areas.

Notes: Abstract A new conceptual and theoretical framework for studying the human postural control system is introduced. Mathematical techniques from statistical mechanics are developed and applied to the analysis and interpretation of stabilograms. This work was based on the assumption that the act of maintaining an erect posture could be viewed, in part, as a stochastic process. Twenty-five healthy young subjects were studied under quiet-standing conditions. Center-of-pressure (COP) trajectories were analyzed as one-dimensional and two dimensional random walks. This novel approach led to the extraction of repeatable, physiologically meaningful parameters from stabilograms. It is shown that although individual stabilograms for a single subject were highly variable and random in appearance, a consistent, subject-specific pattern emerged with the generation of averaged stabilogram-diffusion plots (mean square COP displacement vs time interval). In addition, significant inter-subject differences were found in the calculated results. This suggests that the steady-state behavior of the control mechanisms involved in maintaining erect posture can be quite variable even amongst a population of age-matched, anthropometrically similar, healthy individuals. These posturographic analyses also demonstrated that COP trajectories could be modelled as fractional Brownian motion and that at least two control systems — a shortterm mechanism and a long-term mechanism — were operating during quiet standing. More specifically, the present results suggest that over short-term intervals open-loop control schemes are utilized by the postural control system, whereas over long-term intervals closed-loop control mechanisms are called into play. This work strongly supports the position that much can be learned about the functional organization of the postural control system by studying the steady-state behavior of the human body during periods of undisturbed stance.

Notes: Abstract We examined the manner in which the keystroke kinematics of the hand and the fingers varied with the mean rate of typing by trained typists. We used words and phrases in which only one letter was typed with the right hand and all of the remaining letters were typed using the left hand. We varied the typing rate over a threefold range (intervals between keypresses ranging from 150 ms to 500 ms) with the aid of a metronome. The results from four subjects, and three letters (n, u, and o) were analyzed. We did not find a simple scaling that could account for variations in the velocity profiles with typing rate. For some subjects and some letters, the velocities were independent of typing rate. In other instances, the kinematics did depend on typing rate, but to a much greater extent prior to the time of keypress than afterward. Sometimes the velocity profiles of all of the fingers and of the hand changed in a similar manner as the interval between keypresses was varied. In other instances only the focal movement of the hand and the finger used to press the key depended on the interval, whereas the motions of the other fingers did not. We suggest that the consistencies in the velocity profiles which we observed may simplify the problem of arranging a temporally ordered sequence of goal-directed movements.

Notes: Abstract The ability to make accurate reaching movements toward proprioceptively defined target locations was studied in seven normal subjects who were trained to reach to five different targets in a horizontal plane, with no vision of hand or target. The task consisted of moving a handle from a fixed origin to each target location, fast and accurately. Target locations were learned in training sessions that utilized acoustic cuing. Most movements were rapid, with a bell-shaped velocity profile. The error in target reproduction, which constituted the difference between the position consciously identified as the correct target location and the real target location, was calculated in each trial. This was compared with the error in preprogrammed reaching, which constituted the difference between the point in space where the initial fast movement toward the target ended and the target location. The absence of significant differences between these two error types indicated that the transformation from an internal representation of target location into a motor program for reaching to it did not introduce an additional reaching error. Learning of target locations was done only with the right hand, yet, reaching of both hands was tested. This allowed a comparison between the subjects' ability to utilize a transformed spatial code (reaching with the untrained hand) and their ability to use a direct sensory-motor code (reaching with the trained hand). While transformation of the spatial code was found to reduce it's accuracy, utilization of this code in motor programming again did not appear to introduce an additional error.

Notes: Abstract This article describes the results of the “ellipses” experiment conducted during the second French-Soviet spaceflight (project Aragatz). The realization of oriented motor tasks, on the basis of internal body representation and without visual feedback, was chosen as a paradigm for studying the determinants of spatial orientation under weightlessness. The process of drawing ellipses in the air, using arm movements with axes parallel or perpendicular to the longitudinal body axis, was studied under normal gravity and in weightlessness, and recorded using a video computer motion-analyzing system (Kinesigraph). On Earth, the experiments were performed in standing and lying positions, and in flight, in the erect position with the feet fixed to the floor. In general, performance of the task in microgravity was not disturbed. Under conditions of spaceflight, the longitudinal ellipse was inclined forward in accordance with the inclination of the whole body relative to the fixed feet. On Earth, the angle between the long axes of longitudinal and transverse ellipses deviated from 90° by 20–30°. The same deviation persisted under microgravity conditions. The distinctive features of ellipses traced by individual subjects were also preserved. It is concluded that an egocentric reference system ensures normal performance of sensorimotor tasks in the absence of a gravitational reference.

Notes: Abstract When restraining a mechanically “active” object (one that exerts unpredictable changes in loading forces) with a precision grip of the digits, we maintain a stable grasp by modulating our grip force using somatosensory information related to the loading forces. The response to ramp load increases consists of an initial fast rise in grip force (“catch-up”) followed by a secondary response that steadily increases the grip force in parallel with the load force (“tracking”). The sizes of these response components scale in proportion to the loading rate. However, maintaining a stable grasp without employing an exceedingly large grip force may require further scaling of this load to grip sensorimotor transformation based on two additional factors: (1) the friction at the digit-object interface and (2) the grip force present at the start of the load increase. The present experiments sought to determine whether such scaling occurs and to characterize its control. Subjects restrained a manipulandum held between the tips of the thumb and index finger. At unpredictable times a pulling force appeared, directed away from the subject's hand. Each pull had a trapezoidal load profile beginning and ending at 0 N with 4-N/s ramps; each ramp was 1 s in duration. The texture of the gripped surfaces varied among sandpaper, suede, and rayon, which represented increasingly slippery surfaces. The grip force at the start of the load ramp (intertrial grip force), and the amplitudes of the catch up and secondary grip responses scaled in proportion to the inverse friction. We interpret these results to indicate a uniform scaling of the transformations controlling the intertrial grip force, the catch up response, and the secondary response. Initial state information from tactile cues available upon object contact appeared to update the frictional scaling value. This conclusion is based on observations of immediate changes in the intertriai grip force upon contact with a new surface, and because differences in force-rate profiles appeared virtually by the onset of the catch-up response. Similarly, the intertriai grip force also constituted initial state information. The size of the catch-up and secondary grip force responses varied inversely with the size of the intertrial grip force. These scalings of the load to grip force sensorimotor transformation for friction and intertrial grip force level appear to be functionally adaptive, because they contribute to a stable grasp (prevent object slips) while avoiding exceedingly large safety margins.

Notes: Summary Ten right-hand-dominant subjects completed a series of unsighted, goal-directed, arm flexion movements under three different mechanical loading conditions: an inertial load, an elastic spring load, and a stretched-spring load. Subjects completed a series of inertial load training trials followed by random application of one of the three loads. Three time intervals of the first agonist pulse were considered for analysis: the time from initiation of agonist activity to the onset of movement, the interval from movement initiation to the end of the agonist pulse, and the duration of the entire agonist pulse. Analyses revealed that load type did not affect the duration of any of the time intervals studied. The results suggest the presence of a regulatory control process which temporally organizes an invariant agonist pulse even when the movement is perturbed by external loads possessing different mechanical characteristics.

Notes: Abstract In order to investigate whether the mandibular stretch (jaw-jerk) reflex is modulated in a task-dependent manner, jaw-jerk reflexes were elicited in eight subjects during clenching with unilateral and bilateral tooth support, respectively. The reflexes were examined in the electromyographic (EMG) activity recorded by means of surface electrodes and were elicited by means of small transient jaw displacements at a constant value of 80 μm. Low levels of background EMG were applied ranging from 1 to 30% maximal voluntary contraction (MVC) as controlled by means of visual feedback. Linear relationships were observed between reflex amplitude and level of background EMG. The slope in these relationships served as a measure of reflex gain. For the masseter as well as the anterior temporal muscles, the reflex gain, averaged over both sides, was larger during clenching with unilateral tooth support than with bilateral tooth support (P 〈 0.05). Furthermore, the gain was larger on the side without tooth support during unilateral clenching and larger on the side without visual feedback of elevator muscle activity during bilateral clenching. It can be concluded that the jaw-jerk reflex is modulated to subserve the stabilization of the mandible, with the reflex sensitivity being larger the more that alternative stabilizing factors such as mechanical tooth contact, visual feedback and feedback from periodontal pressure receptors around the teeth are lacking. The reflex modulation may be of functional importance in stabilizing the mandible during its movement in the chewing process, as the food is predominantly placed unilaterally between the antagonistic teeth during individual chewing cycles.

Notes: Abstract The objective of this study was to characterize the mechanical behavior of the elbow joint during voluntary movement, for different speeds of movement and under different loading conditions. Torque pulses of 50 ms duration were applied at movement onset and at peak velocity on random trials. The displacement away from the unperturbed trajectory was used as an indicator of the relative compliance of the elbow under different conditions. We found that both the displacement and the time taken to return to the unperturbed trajectory decreased if the overall speed of the movement increased or if a viscous resistive load was added, implying lower joint compliance. It was possible to account qualitatively for differences in mechanical behavior from observed muscle activation patterns.

Notes: Abstract To produce accurate goal-directed arm movements, subjects must determine the precise location of target object. Position of extracorporeal objects can be determined using: (a) an egocentric frame of reference, in which the target is localized in relation to the position of the body; and/or (b) an allocentric system, in which target position is determined in relation to stable visual landmarks surrounding the target (Bridgeman 1989; Paillard 1991). The present experiment was based on the premise that (a) the presence of a structured visual environment enables the use of an allocentric frame of reference, and (b) the sole presence of a visual target within a homogeneous background forces the registration of the target location by an egocentric system. Normal subjects and a deafferented patient (i.e., with an impaired egocentric system) pointed to visual targets presented in both visual environments to evaluate the efficiency of the two reference systems. For normals, the visual environment conditions did not affect pointing accuracy. However, kinematic parameters were affected by the presence or absence of a structured visual surrounding. For the deafferented patient, the presence of a structured visual environment permitted a decrease in spatial errors when compared with the unstructured surrounding condition (for movements with or without visual feedback of the trajectory). Overall, results support the existence of an egocentric and an allocentric reference system capable of organizing extracorporeal space during arm movements directed toward visual targets.

Notes: Abstract The retinal periphery of nine healthy subjects was stimulated with computer-generated random-dot kinematograms. These stimuli provided almost isolated visual motion information and minimal position cues. Pattern-reversal stimuli at the same location in the visual field were used for control. Stimulus-related electrical brain activity was recorded from 29 scalp electrodes. Total mean and individual data were analyzed with a spatiotemporal multiple dipole model. The scalp potentials showed a different spatial distribution for motion and pattern stimulation in the time range of 160–200 ms. In this epoch, the predominant motion-related source activity was localized in the region of the contralateral occipital-temporal-parietal border. A significant ipsilateral source activity was not found. The predominant source activity related to the pattern stimulus occurred in the same epoch. The corresponding equivalent dipole was localized more medially and deeper in the brain. The orientation of these major dipole activities was markedly different. These dipoles appeared to represent activity of distinct extrastriate areas, in contrast to earlier activity which was modelled by more posterior dipoles in the occipital lobe. The latter dipoles were at comparable contralateral locations and had similar peak activities around 100 ms, suggesting an origin in the striate cortex.

Notes: Abstract Neuromagnetic responses were recorded with a 24 SQUID magnetometer in two “oddball” experiments to determine whether mismatch responses to changes in single stimulus features are additive. In experiment 1, the one feature deviants differed from standards in interstimulus interval (ISI) or frequency, and the two feature deviants in both ISI and frequence. In experiment 2, deviants differed in duration, frequency, or both. All deviants evoked a mismatch field (MMF) with sources close to each other in the supratemporal auditory cortex. Except for the ISI deviants, the MMF sources were about 1 cm anterior to the source of the 100ms response, N100m, to the standards. In the two experiments, MMFs obtained in response to the two feature deviants resembled closely the sum of MMFs in response to one feature deviants. The results suggest that the standards leave a multiple neuronal representation in the human auditory cortex. The particular neuronal traces of the representation react independently to changes in different features of sound stimuli.

Notes: Abstract We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and visual-vestibular interaction in five patients with markedly elevated vestibulo-ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth pursuit, decreased initial slow phase velocity of OKN, and impaired ability to suppress the VOR with real or imagined targets. OKN slow phase velocity gradually built up over 25–45 s, reaching normal values for low stimulus velocities (≤30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN was normal. These findings can be explained by models that include separate velocity storage and variable gain elements shared by the vestibular and optokinetic systems.

Notes: Abstract When a first saccade is made in response to a single, suddenly appearing stimulus it often misses the target. The retinal error may be very large, in particular in those cases where the subject anticipates the target location and initiates a saccade to a wrong position. We have analyzed the time of the occurrence of the secondary saccades by which the subject corrects these errors. Using the gap task with random target locations we found that large errors after anticipatory saccades — especially those after direction errors — can be corrected very fast. The latencies of these corrective saccades (being measured from target onset, not from the end of the primary saccade) form bimodal distributions with a first peak at 100 ms. It is therefore concluded that large errors can be corrected by express secondary saccades.

Notes: Abstract Two monkeys were trained to make an arm movement with an orthogonal bend, first up and then to the left (⌝), following a waiting period. They held a two-dimensional manipulandum over a spot of light at the center of a planar working surface. When this light went off, the animals were required to hold the manipulandum there for 600–700 ms and then move the handle up and to the left to receive a liquid reward. There were no external signals concerning the “go” time or the trajectory of the movement. It was hypothesized that during that period signs of directional processing relating to the upcoming movement would be identified in the motor cortex. Following 20 trials of the memorized movement trajectory, 40 trials of visually triggered movements in radially arranged directions were performed. The activity of 137 single cells in the motor cortex was recorded extracellularly during performance of the task. It was found that 62.8% of the cells changed activity during the memorized waiting period. During the waiting period, the population vector (Georgopoulos et al. 1983, 1984) began to grow approximately 130 ms after the center light was turned off; it pointed first in the direction of the second part of the memorized movement (←) and then rotated clockwise towards the direction of the initial part of the movement (↑). These findings indicate processing of directional information during the waiting period preceding the memorized movement. This conclusion was supported by the results of experiments in ten human subjects, who performed the same memorized movement (⌝). In 10% of the trials a visual stimulus was shown in radially arranged directions in which the subjects had to move; this stimulus was shown at 0, 200, and 400 ms from the time the center light was turned off. We found that as the interval increased the reaction time shortened for the visual stimulus that was in the same direction as the upward component of the memorized movement.

Notes: Abstract There are several parameters associated with motoneuron size, among which are the conduction velocity of the axon as well as the size of the excitatory postsynaptic potential (EPSP) induced by stimulation of Ia afferents in the corresponding muscle nerve. In particular, it has been established in animal experiments that small motoneurons with a low conduction velocity exhibit large Ia EPSPs, whereas large motoneurons with a high conduction velocity show small Ia EPSPs. Thus small motoneurons are recruited earlier than large ones. In this study, we investigated whether such a relationship between motoaxon conduction velocity and size of the Ia EPSPs could also be found for human soleus motoneurons. In total, 36 motor units from six healthy volunteers were activated by a slight voluntary contraction and exposed to 200 stimuli of the tibial nerve in the popliteal fossa. Stimuli were delivered using a special stimulus protocol ensuring a constant pre-stimulus spike density along with a constant rate of discharge of the investigated unit. From the stimulus-correlated spike train data a measure of Ia-EPSP amplitude was obtained, along with the single-unit H-reflex latency. Additionally, for each unit, the so-called surface macro EMG was recorded, which measures the complete electrical activity attributable to the unit investigated. From the macro EMG, the intramuscular delay from arrival of each action potential at the soleus muscle and the detection of the muscle-fiber action potential picked up by the recording needle electrode were measured. All single-unit H-reflex latencies were corrected for the corresponding intramuscular delays. From the corrected latencies, single-unit conduction velocities were obtained. It was found that there was a highly significant negative correlation between the estimate of the single-unit conduction velocity and the inferred size of the Ia EPSP. Thus, it was found that Ia-EPSP amplitudes in human soleus motoneurons follow the size principle.

Notes: Abstract The stiffness of the human elbow joint was investigated during targeted, 1.0-rad voluntary flexion movements at speeds ranging from slow (1.5 rad/s) to very fast (6.0 rad/s). A torque motor produced controlled step position errors in the execution of the movements. The steps began at the onset of movement, rose to an amplitude of 0.15 rad in 100 ms, and had a duration equal to movement duration. The net joint torque (muscle torque) resisting the step perturbation was computed from the applied torque, the joint acceleration, and the limb inertia. Subjects resisted the imposed step changes with approximately step changes in the net muscle torque. The mean resistance torque divided by the step amplitude was computed and is referred to as the stiffness. The stiffness increased with the voluntary movement speed, over the range of speeds (1.5–6 rad/s). The stiffness increased linearly with the magnitude of the net muscle torque on the unperturbed trials (referred to as “background torque”). The stiffness changed by only 20% when the step amplitude ranged from 0.05 to 0.15 rad. The mechanical resonant frequency (f r), estimated from the average stiffness estimates, ranged from 0.8 to 3.0 Hz. The resonant frequency approximately equaled the principal frequency component of the movement f m. On average: f r = 0.96 f m+0.46. During the fixed, 100-ms rise time of the step, the resistance was not linearly related to the background torque. At slower speeds the resistance was relatively greater during this rise time. However, when the imposed step perturbation was modified so that its rise time occurred in a time proportional to the movement duration (rather than in the fixed, 100-ms, time), the muscle torque resisting the motor during this rise time was proportional to the background torque. When these modified step responses were plotted on a time scale normalized to the movement duration, they all had approximately the same shape. Apparently the muscle viscosity scaled with the stiffness so as to maintain the constant response shape (constant damping ratio). The observed “tuning” of the mechanical properties to the movement speed is suggested to be important in the robust generation of smooth stereotyped voluntary movements.

Notes: Abstract The role of reflexes in the control of stiffness during human elbow joint movement was investigated for a wide range of movement speeds (1.5–6 rad/s). The electromyographic (EMG) responses of the elbow joint muscles to step position errors (step amplitude 0.15 rad; rise time 100 ms) imposed at the onset of targeted flexion movements (1.0 rad amplitude) were recorded. For all speeds of movement, the step position disturbance produced large modulations of the usual triphasic EMG activity, both excitatory and inhibitory, with an onset latency of 25 ms. In the muscles stretched by the perturbation, the early EMG response (25–60 ms latency) magnitude was greater than 50% of the activity during the unperturbed movements (background activity). In all muscles the EMG responses integrated over the entire movement were greater than 25% of the background activity. The responses were relatively greater for slower movements. Perturbations assisting the movement caused a short-latency (25–60 ms) reflex response (in the antagonist muscle) that increased with movement speed and was constant as a percentage of the background EMG activity. In contrast, perturbations resisting the movement caused a reflex response (in the agonist muscle) that was of the same absolute magnitude at all movement speeds, and thus decreased with movement speed as a percentage of the background EMG activity. There was a directional asymmetry in the reflex response, which produced an asymmetry in the mechanical response during slow movements. When the step perturbation occurred in a direction assisting the flexion movement, the antagonist muscle activity increased, but the main component of this response was delayed until the normal time of onset of the antagonist burst. When the step perturbation resisted the movement the agonist muscles responded briskly at short latency (25 ms). A reflex reversal occurred in two of six subjects. A fixed reflex response occurred in the antagonist muscle, regardless of the perturbation direction. For the extension direction perturbations (resisting movement), this response represented a reflex reversal (50 ms onset latency) and it caused the torque resisting the imposed step (stiffness) to drop markedly (below zero for one subject). Reflex responses were larger when the subject was prevented from reaching the target. That is, when the perturbation remained on until after the normal time of reaching the target, the EMG activity increased, with a parallel increase in stiffness. Similarly, when the perturbations prevented the subject from reaching the target during a 1-rad voluntary cyclic movement, the EMG and stiffness increased markedly. Coactivation of the antagonist muscle with the agonist muscle was not prominent (〈30% of antagonist activity) during unperturbed movements. The perturbations were resisted with reciprocal activity, and thus reflex action did not increase the coactivation. However, as a result of the low-pass properties of muscle, substantial cocontraction of the agonist and antagonists muscle forces may have occurred during rapid movements, thus leading to increased stiffness. As the relative changes in normal EMG activity produced by the perturbation were often comparable with the changes in mean muscle torque (stiffness) reported in the first paper of this series, we conclude that the action of reflexes produced a significant portion of the resistance to perturbations. This reflexive portion was greater for slower movements, it was greater when the subject neared the target, and it was variable according to the perturbation direction and the particular subject. Given that the perturbations were of similar frequency content to the movement itself (though of smaller amplitude) and that the reflexes contributed substantially to the resistance to these perturbations, we suggest that in normal unperturbed movements the observed EMG is likewise substantially determined by the reflex activity.

Notes: Abstract The amplitude of the Hoffmann reflex (H-reflex) of the human soleus muscle is modulated in a cyclical way during walking. This paper addresses two questions associated with the neural mechanisms that might generate this modulation: (1) Does the amplitude of the H-reflex simply rise and fall as a function of the background excitability of the soleus motoneuron pool? (2) Is the modulation of the H-reflex dependent on events associated with activation of the antagonist muscle? The amplitude of the soleus H-reflex was compared under three conditions: natural walking, walking without activating the tibialis anterior muscle, and walking with activation of the soleus muscle in the swing phase. Human subjects were able to perform these three tasks with minimal training. The results indicated that the soleus H-reflex remained very depressed in the swing phase of walking, even when a voluntary contraction of the soleus muscle was superimposed during this time. Moreover, the presence of tibialis anterior activity had a very minor effect on the amplitude of the soleus H-reflex during walking. It is concluded that modulation of the soleus H-reflex is not simply a reflection of the background excitability of the motoneuron pool, and the modulation is not dependent on activation of the antagonist muscle. Other more powerful mechanisms are acting to modulate the reflex, most likely presynaptic inhibition of the primary afferents.

Notes: Abstract Several psychophysical procedures have been used to measure cyclovergence but none has been adequately validated with respect to an objective measure. Scleral search coils were used to measure cyclovergence induced by dichoptic textured patterns which cyclorotated in antiphase through 6° at frequencies between 0.05 and 2 Hz. In one psychophysical procedure subjects nulled the apparent oscillatory motion of radial nonius lines superimposed on a small black disc at the center of a large cyclorotating display. In the second, subjects nulled the apparent inclination in depth of a vertical line displayed in the same way. The amplitude of cyclovergence measured objectively and the magnitude of oscillation of the nonius lines were similar at low stimulus frequencies. At higher frequencies of cyclorotation, both amplitudes declined but the nonius amplitude exceeded that of cyclovergence. The apparent inclination of the vertical test line, as indicated by the nulling procedure, also declined with increasing frequency of cyclorotation, but not at the same rate. At low frequencies, the apparent inclination of the test line was greater than that corresponding to the cyclodisparity induced into the line and almost as great as that corresponding to the relative disparity between the oscillating pattern and the line. The implications of these results for measuring cyclovergence and for an understanding of stimuli driving cyclovergence and perceived inclination in depth are discussed.

Notes: Abstract This study was aimed at complementing the existing knowledge about vestibular perception of self-motion in humans. Both goal-directed vestibulo-ocular reflex and vestibular memory-contingent saccade (VM-CS) tasks were used, respectively as concurrent and retrospective magnitude estimators for passive whole-body rotation. Rotations were applied about the earth-vertical and earth-horizontal axes to study the effect of the otolith signal in self-rotation evaluation, and both in yaw and pitch to examine the horizontal and vertical semi-circular canals. Two different magnitudes of constant angular acceleration (50°/s2 and 100°/s2) were used. The main findings were (1) strong correlation between both oculomotor responses of both tasks, (2) greater accuracy with rotations about the earth-vertical than the earth: -horizontal axis, (3) greater accuracy for yaw than for pitch rotations, (4) greater accuracy for high acceleration than for low, and (5) no effect of the delay (2s or 12s) in the VMCS task. Adequacy of both tasks as subjective magnitude estimators of vestibular perception of self-motion is discussed.

Notes: Abstract It is well known that during volitional sinusoidal tracking the long-latency reflex modulates in parallel with the volitional EMG activity. In this study, a series of experiments are reported demonstrating several conditions in which an uncoupling of reflex from volitional activity occurs. The paradigm consists of a visually guided task in which the subject tracked a sinusoid with the wrist. The movement was perturbed by constant torque or controlled velocity perturbations at 45° intervals of the tracking phase. Volitional and reflex-evoked EMG and wrist displacement as functions of the tracking phase were recorded. The relationship of both short-latency (30–60 ms) and longer-latency (60–100 ms) reflex components to the volitional EMG was evaluated. In reflex tracking, the peak reflex amplitude occurs at phases of tracking which correspond to a maximum of wrist joint angular velocity in the direction of homonymous muscle shortening and a minimum of wrist compliance. Uncoupling of the reflex and volitional EMG was observed in three situations. First, during passive movement of the wrist through the sinusoidal tracking cycle perturbation-evoked long-latency stretch reflex peak is modulated as for normal, volitional tracking. However, with passive joint movement the volitional EMG modulation is undetectable. Second, a subset of subjects demonstrate a normally modulated and positioned long-latency reflex with a single peak. However, these subjects have distinct bimodal peaks of volitional EMG. Third, the imposition of an anti-elastic load (positive position feedback) shifts the volitional EMG envelope by as much as 180° along the tracking phase when compared with conventional elastic loading. Yet the long-latency reflex peak remains at its usual phase in the tracking cycle, corresponding to the maximal velocity in the direction of muscle shortening. Furthermore, comparison of the results from elastic and anti-elastic loads reveals a dissociation of short- and long-latency reflex activity, with the short-latency reflex shifting with the volitional EMG envelope. Comparable results were also obtained for controlled velocity perturbations used to control for changes in joint compliance. The uncoupling of the reflex and volitional EMG activity in the present series of experiments points to a flexible relationship between reflex and volitional control systems, altered by peripheral input and external load.

Notes: Summary In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex.

Notes: Summary The saccadic eye movements of 20 naive adults, 7 naive teenagers, 12 naive children, and 4 trained adult subjects were measured using two single target saccade tasks; the gap and the overlap task. In the gap task, the fixation point was switched off before the target occurred; in the overlap task it remained on until the end of each trial. The target position was randomly selected 4° to the left or 4° to the right of the fixation point. The subjects were instructed to look at the target when it appeared, not to react as fast as possible. They were not given any feedback about their performance. The results suggest that, in the gap task, most of the naive subjects exhibit at least two (the teenagers certainly three) clearly separated peaks in the distribution of the saccadic reaction times. The first peak occurs between 100 and 135 ms (express saccades), the second one between 140 and 180 ms (fast regular), and a third peak may follow at about 200 ms (slow regular). Other subjects did not show clear signs of two modes in the range of 100 to 180 ms, and still others did not produce any reaction times below 135 ms. In the overlap task as well three or even more peaks were obtained at about the same positions along the reaction time scale of many, but not all subjects. Group data as well as those of individual subjects were fitted by the superposition of three gaussian functions. Segregating the reaction time data into saccades that over- or undershoot the target indicated that express saccades almost never overshoot. The results are discussed in relation to the different neural processes preceding the initiation of visually-guided saccades.

Notes: Abstract In order to explore the nature and amount of information in the optic array used by subjects required to carry out one-handed catching actions, the optical expansion pattern (using a deflating ball) and the duration of viewing time (using liquid crystal spectacles) of the ball were varied. Subjects were required to catch luminous balls (two of constant physical size and one of changing physical size during approach) attached to a pendulum in a totally dark room, while the liquid spectacles were closed at 0, 100, 200 or 300 ms before hand-ball contact. The results confirmed previous findings that the timing of the catching action is based on retinal expansion information and that conclusion was strengthened when an additional dependent variable (time of the maximal opening velocity of the grasp) was used. Further, for the viewing time duration manipulations, the time of the maximal closing velocity of the hand was later, while no effect was found on the time of the maximal opening velocity, when the last 300 ms of the trajectory of the ball was occluded. Adjustments to the catching action in response to the different ball sizes under the 0 ms condition differed significantly from the adjustments under the 300 ms condition. Both findings point to the importance of relative optical expansion information, available between 300 and 200 ms before ball-hand contact, in maintaining a (relatively) continuous perception-action coupling in the act of catching.

Notes: Abstract The control of mandibular posture has been related to the activity of the anterior temporal muscles, whereas the masseter muscles have been viewed mainly as force producers. However, these groups of muscles, especially in the deep layers, are highly endowed with muscle spindles, so that a difference in function should imply a difference in the reflex sensitivity. By studying the jaw-jerk reflex by means of bipolar surface electromyogram, the reflex sensitivity was determined from relationships between reflex amplitude and jaw displacement from both groups of muscles in eight subjects. At a constant level of background muscle activity, and hence with a constant excitability of the alpha motoneurons, the reflex sensitivity can be determined from these relationships in terms of gain and threshold. In order to account for differences in thickness of the soft tissues overlying the various muscles studied, the reflex amplitude was normalized with respect to the level of maximal voluntary contraction (MVC). In experiments where the inter-electrode distance was 18 mm over both groups of muscles, the reflex gain of the anterior temporal muscles was larger than that of the masseter muscles (P 〈 0.05). The threshold value did not differ significantly from zero for either group of muscles. Normalization of the reflex amplitude with respect to MVC can be carried out correctly only if the reflexly activated muscle fibres are distributed uniformly within the muscle. In order to gain an insight into this distribution, control experiments were performed with three subjects in which the inter-electrode distance was varied, thus influencing the depth in the muscle from which active muscle fibres were recorded. The reflex gain of the masseter muscle with an inter-electrode distance of 22 mm, which records from deeper layers of the muscle as well as superficial ones, was larger than with a distance of 11 mm (P 〈 0.01–0.10 in the various subjects). No such differences were found for the anterior temporal muscle. It was concluded that the afferents of the spindles in the jaw-elevator muscles do not project uniformly upon the motoneurons, but involve mainly fibres in the deeper layers of the muscle. The difference in gain found between the masseter and the anterior temporal muscles with the same inter-electrode distance of 18 mm is likely to be due to a larger distance of the reflexly activated muscle fibres in the masseter muscle with respect to the electrodes rather than to a difference in reflex sensitivity between the muscles. Hence, the masseter as well as the anterior temporal muscles could be involved in mandibular stabilization.

Notes: Abstract We examined the somatosensory perceptions evoked by stimulation of rolandic and parietal brain regions in 40 epileptic patients undergoing a presurgical investigation with intracerebral electrodes. Bipolar stimulation trains were delivered in an incremental sequence at medial and/or lateral contact pairs of stereotaxically implanted, multi-contact electrodes, while monitoring stimulus afterdischarge propagation with electrodes in frontal and temporal lobes. Rolandic stimulation evoked contralateral sensations, whereas sensations from either side were evoked in the opercular region. Stimulation of lateral posterior parietal cortex evoked only few sensations and these were restricted to the supramarginal gyrus. Contralateral sensations were evoked in the posterior cingulate gyrus, whereas ipsilateral sensations were evoked in the vicinity of the cingulate sulcus. Complex proprioceptive sensations in the form of bilateral feelings of levitation were elicited in a medial parietal region around the subparietal sulcus and not at any other site. These perceptions were not accompanied by any movement, tactile, or vestibular sensations, suggesting that the human sub-parietal sulcus region is linked to the proprioceptive processing system.

Notes: Abstract The main purpose of this study was to investigate the development of the head stabilization in space strategy (HSSS) during various locomotor tasks in 3- to 8-year-old children and adults. The contribution of visual factors to the HSSS was also examined by applying peripheral visual restriction, stroboscopic visual motion cue restriction, and darkness. The kinematics of the head and trunk rotations (pitch, yaw, and roll) were analyzed by means of an optical TV-image processor (ELITE system). For each of the three angular components, an appropriate “head anchoring index” was defined in order to compare the HSSS with a head stabilization on the trunk strategy. Head-trunk correlation rates were also calculated for each angular component in order to evaluate the head-trunk stiffness. The development of head-trunk coordinations during locomotion under normal vision can be said to involve at least three main periods. The first period occurs from the age of 3 to 6 years, when the HSSS is adopted only while walking on the flat ground. While walking on narrow supports, children in this age-group rather tend to increase the head-trunk stiffness, especially at 6 years of age. The second period includes 7- to 8-year-old children. Children of this age become able to adopt the HSSS while walking on narrow supports. During this period, the HSSS is associated with a large decrease in the head-trunk correlations. Lastly, in adulthood the HSSS is commonly adopted but specifically involves the roll component associated with the lateral body oscillations while walking. Vision was found to have little influence on children's HSSS while walking, whatever their age. Moreover, darkness induces an increase in the efficiency of the HSSS in adults. This confirms that the HSSS is the most appropriate strategy available for dealing with an increase in the level of equilibrium difficulty and may reflect a “top-down” organization of the postural control while walking. These results also suggest that the HSSS may be mainly of vestibular origin and presumably serves to facilitate the visual input processing, particularly that of the motion and peripheral visual cues which are involved in the control of body equilibrium during locomotion.

Notes: Abstract Earlier recordings of eye position in three dimensions have revealed that Listing's law is obeyed in reasonable approximation, both statically and dynamically. This implies that all eye positions are confined to a plane when using a rotation vector or quaternion representation. The orientation of the angular velocity axis is crucial in order to preserve the law. For a single-axis rotation, the eye's angular velocity axis has to tilt out of Listing's plane, otherwise the law cannot be preserved in eccentric saccades. Experimental work has confirmed that normal, visually-guided saccades resemble single-axis rotations whose angular velocity axis tilts by the right amount. We investigated how well the saccadic system implements Listing's law when the trajectory of the eyes is more complicated, as in a non-single-axis rotation where the angular velocity vector depends on instantaneous eye position. Eye position was measured in three dimensions using the magnetic scleral search coil method for five subjects. Non-single-axis rotations of the eye were evoked with a double-step paradigm. We found that Listing's law is obeyed equally well during fixations, single-axis saccades and in non-single-axis saccades. Some deviations from the law were found in both curved and single-axis eye movements, but we demonstrated that the net torsional component of eye position of these saccades is negligible compared to that expected if the angular velocity axis did not tilt at all. In addition, analysis of the angular velocity signals in the curved movements showed strong similarity to the computed signal required for implementing Listing's law. Our results show that the observed deviations from Listing's law reflect only minor failures in the mechanism underlying its dynamic implementation. We conclude that single-axis rotations are not a necessary condition for the implementation of Listing's law in saccades. Our results are compatible with the notion that the implementation of Listing's law relies upon internal feedback. Various suggestions of how models can be reconciled with recent data on the three-dimensional control of saccades are discussed.

Notes: Abstract Application of a small (around 1 mA), constant electric current between the mastoid processes (galvanic stimulation) of a standing subject produces enhanced body sway in the approximate direction of the ear behind which the anode is placed. We examined the electromyographic (EMG) responses evoked by such stimulation in the soleus and in the triceps brachii muscles. For soleus, subjects stood erect, with their eyes closed, leaning slightly forward. The head was turned approximately 90° to the right or left relative to the feet. In averaged records (n=40), current pulses of 25 ms or longer modulated the EMG in a biphasic manner: a small early component (latency 62±2.4 ms, mean ± SEM) was followed by a larger late component (latency 115±5.2ms) of opposite sign, which was appropriate to produce the observed body sway. The early component produced no measurable body movement. Lengthening the duration of the stimulus pulse from 25 to 400 ms prolonged the late component of the response but had little effect on the early component. Short- and long-latency EMG responses were also evoked in the triceps brachii muscle if subjects stood on a transversely pivoted platform and had to use the muscle to maintain their balance in the anteroposterior plane by holding a fixed handle placed by the side of their hip. The latency of the early component was 41±2.6 ms; the latency of the late component was 138±4.3 ms and was again of appropriate sign for producing the observed body sway. Galvanic stimulation evoked no comparable responses in either triceps brachii or soleus muscles if these muscles were not being used posturally. The responses were most prominent if vestibular input provided the dominant source of information about postural stability, and were much smaller if subjects lightly touched a fixed support or opened their eyes. The difference in latency between the onset of the early component of the response in arm and leg muscles suggests that this part of the response uses a descending pathway which conducts impulses down the spinal cord with a velocity comparable with that of the fast conducting component of the corticospinal tract. The late component of the EMG response occurs earlier in the leg than the arm. We suggest that it forms part of a patterned, functional response which is computed independently of the early component.

Notes: Abstract Previous experiments have suggested that the analysis of visual images could be a gravity-dependent process. We investigated this hypothesis using a mental rotation paradigm with pictures of three-dimensional objects during a 26-day orbital flight aboard the Soviet MIR station. The analysis of cosmonauts' response times showed that the mental rotation task is not greatly impaired in weightlessness. On the contrary, there are indications of a facilitation as: (1) the average rotation time per degree was shorter inflight than on the ground; (2) this difference seemed to be particularly marked for stimuli calling for roll axis rotations. However several factors may be responsible for this difference which was not obvious in one subject. Further experiments will have to test if this effect is really due to exposure to microgravity.

Notes: Abstract Fatigue is often associated with increased clumsiness. One possible explanation for this is that the proprioceptive signals from receptors in and around muscles change during muscle fatigue. Thirteen human subjects were tested for their ability to match the elbow angle of one arm with the contralateral arm, before and after a fatiguing contraction of one arm. Contractile fatigue was induced by a series of maximal voluntary contractions of the elbow flexors of the dominant arm. While fatigue of either the target arm or the matching arm usually changed the ability of individual subjects to match arm position, this effect varied markedly from one subject to another and no consistent pattern was discerned. In particular, there was no reciprocal change when the fatigued arm was the matching arm compared with when the nonfatigued arm was the matching arm. The absence of a consistent reciprocal effect indicates that the fatigue-related changes in the ability to match arm position are not solely due to changes in proprioceptive signals and that central fatigue processes are probably involved.

Notes: Abstract In the following experiments, we examined parallels between properties of A-delta high-threshold mechanoreceptors (HTMs; mechanonociceptors, MN, and intense pressure receptors, IPR) innervating the goat mucosa and human mucosal pain report. As suggested in previous studies, activation thresholds of afferents which are generally considered to be mechanical nociceptors are far below mechanical pain thresholds. It was determined that classification of nociceptors by frequency thresholds, i.e., the pressure at which HTMs maintained a minimum frequency (97 g/mm2 and 117 g/mm2 for IPRs and MNs respectively) brings afferent reactivity into alignment with perceptual events. The range of reactivity of the nociceptor pool paralleled pain report from “faintweak” (142 g/mm2) to “strong-intense” (277 g/mm2). It is suggested that coding of intense mechanical pain from compressive forces is likely to arise from both individual afferents, whose reactivity spanned the range, and from recruitment of afferent populations with progressively higher thresholds.

Notes: Abstract The perception of viscosity was studied using the contralateral limb-matching procedure in which subjects adjusted the viscosity of a motor connected to the wrist of one (matching) arm until it was perceived to be the same as that of the motor attached to the other (reference) arm. Two servo-controlled electromagnetic linear motors with computer-controlled viscosity were used to present viscosities ranging in amplitude from 2 to 1024 N · s/m to 11 subjects. Ten different viscosities were matched by subjects, and there were ten repetitions of each stimulus amplitude. The psychophysical function relating the reference to matching viscosity was linear (99% variance accounted for), and the accuracy with which the viscosities were matched (slope of 0.88) paralleled that reported previously for force, limb position and stiffness. The Weber fraction for viscosity was 0.34, which is 50% larger than that measured for stiffness and over twice that reported for force. An analysis of the movements and forces generated to perceive the reference viscosity revealed that subjects did not vary the amplitude of the movements and typically made very small excursions of the forearm, but that both the velocity of the movements and force changed significantly as a function of the reference viscosity. These findings were interpreted as indicating that the human proprioceptive system is capable of integrating information regarding force and movement velocity so as to perceive the viscosity of a mechanical system connected to the limbs, but that its sensitivity to changes in viscosity is much less than would be predicted from its capacity to detect variations in muscle force and limb movement.

Notes: Abstract The initiation of coupled eye and arm movements was studied in six patients with mild cerebellar dysfunction and in six age-matched control subjects. The experimental paradigm consisted of 40 deg step-tracking elbow movements made under different feedback conditions. During tracking with the eyes only, saccadic latencies in patients were within normal limits. When patients were required to make coordinated eye and arm movements, however, eye movement onset was significantly delayed. In addition, removal of visual information about arm versus target position had a pronounced differential effect on movement latencies. When the target was extinguished for 3 s immediately following a step change in target position, both eye and arm onset times were further prolonged compared to movements made to continuously visible targets. When visual information concerning arm position was removed, onset times were reduced. Eye and arm latencies in control subjects were unaffected by changes in visual feedback. The results of this study clearly demonstrate that, in contrast to earlier reports of normal saccadic latencies associated with cerebellar dysfunction, initiation of both eye and arm movements is prolonged during coordinated visuomotor tracking thus supporting a coordinative role for the cerebellum during oculo-manual tracking tasks.

Notes: Abstract In this study, the possible influence of the transport on the grasp component of prehension movements was investigated. The first phase of the transport (acceleration phase) and of the grasp (finger aperture phase) kinematics were studied under conditions of visual and non-visual object presentation (prehension experiment). In the non-visual condition, object size was estimated by haptics and object position was estimated by proprioception. Eight subjects were required to reach and grasp three objects of different size located at two distances. An additional experiment (matching experiment) was carried out to control the scaling of object size in the two conditions. The results showed that in the matching experiment size estimation for large objects was similar in the two conditions, whereas small stimuli were underestimated in the haptic condition. In the prehension experiment, maximal finger aperture and velocity of finger aperture were greater in the non-visual than in the visual condition, and the difference was greater for small than for large stimuli. Moreover, in both conditions, finger opening was larger for prehension movements directed to the far than to the near objects, but only for smaller stimuli. Hand trajectory variability increased in the non-visual condition and with the distance, whereas finger opening variability was only affected by the non-visual condition. For smaller stimuli, increased finger opening with distance was positively correlated with the increase in wrist variability in the visual condition, but not in the non-visual condition. Furthermore, increased finger opening between visual and non-visual conditions was correlated with the increase in wrist variability, for smaller objects at the near object location. No positive correlations were found between finger opening and grip variability. These results are interpreted in favour of the dependence of finger opening on transport, when control requirements during reaching increase.

Notes: Abstract The previous paper in this series showed that changes both within and between experimental sessions can be understood in the framework of the dual-strategy hypothesis of motor control, with a modification sometimes required for the timing of the antagonist muscle. The present paper extends these findings by determining how practicing movements at one distance generalizes to changes in performance at other distances. Five subjects made elbow flexion movements over five different distances (pretest). They then performed 1400 movements (seven sessions of ten blocks of 20 trials) at only one of those distances. The subjects then repeated the flexion movements over the five different distances (posttest). On the posttest, subjects decreased their average movement time by 20 ms. In addition, their movements became less variable. The electromyographic pattern of the faster movements was characterized by a more rapidly rising electromyogram, for three of the subjects, and an antagonist latency that decreased.

Notes: Abstract In this paper, we examine grip forces and load forces during point-to-point arm movements with objects grasped with a precision grip. We demonstrate that grip force is finely modulated with load force. Variations in load force arise from inertial forces related to movement; grip force rises as the load force increases and falls as load force decreases. The same finding is observed in vertical and horizontal movements performed at various rates. In vertical movements, maximum grip force coincides in time with maximum load force. The maxima occur early in upward and later in downward movements. In horizontal movements, where peaks in load force are observed during both the acceleratory and deceleratory phases, grip force rises at the beginning of the movement and remains high until the end. The results suggest that when moving an object with the hand the programming of grip force is an integral part of the planning process.

Notes: Abstract Two paradigms of memory-guided saccades were studied in 14 patients with focal vascular lesions affecting either the frontal eye field (FEF), or the supplementary eye field (SEF) or Brodmann's area 46 in the prefrontal cortex (PFC), and in 13 age-matched control subjects. In the first paradigm, the subject had to remember the position of a visual target with the body immobile and, in the second, the position towards which gaze was directed before a body rotation, i.e. with a vestibular input. In control subjects, the percentage of error in saccade accuracy (horizontal component) was greater in the second than in the first paradigm (37% and 14% on average, respectively). Compared with controls, amplitude error was significantly increased in the FEF group for the first paradigm only, in the SEF group for the second paradigm only, and in the PFC group for both paradigms. These results are consistent with (1) the PFC providing an improvement in the utilization by the saccade system of the visual and vestibular signals used in the two paradigms, and (2) the FEF and SEF providing an improvement in the utilization of visual signals in the first paradigm and vestibular signals in the second paradigm, respectively. Furthermore, from these findings and experimental data, it may be hypothesized (1) that the PFC is a part of the network contributing to short-term memorization of both visual and vestibular signals, and (2) that the FEF and SEF control two different types of memory-guided saccades, with separate calculation modes to determine their amplitude.

Notes: Abstract This paper is devoted to the results of the “tactile matrix” experiment performed during the second French-Soviet spaceflight (project Aragatz). The perception of the orientation of complex tactile stimuli (letters and digits) applied to different skin areas under varied conditions was studied. The task of interpretation of complex tactile stimuli was not affected by the absence of the gravitational vertical, although this task is closely associated with mechanisms for the perception of body configuration, as well as the spatial orientation of different body parts. The number of errors made under conditions of weightlessness was often even less than on Earth. The results confirm the high stability of the egocentric reference system and provide evidence that this system is based on a body scheme which cannot be easily modified by changing external conditions.

Notes: Abstract Modification of somatosensory processing depending on the behavioral setting was studied. Active alternating movements of the fingers, passive tactile stimuli to the hand, and active exploration of objects were performed during recording of somatosensory evoked potentials (SEPs). SEPs were elicited by compound electrical median nerve stimulation and electrical stimulation at detection threshold of cutaneous median nerve fascicles identified by microneurography. Electrical stimulation was not time-locked to the studied condition. In comparison with SEPs at rest there was attenuation of early cortical potentials up to 25 ms post-trigger in all nonresting conditions. In stimulation of the compound median nerve as well as of isolated cutaneous fascicles of a hand actively exploring an object there was an additional increased negativity, peaking at 28 ms. This facilitory effect was independent of attentional focusing and was absent during exploration using the ipsilateral, non-electrically stimulated hand. In patients with parietal lesions the facilitatory effect was diminished on the affected side. Spline interpolated brain maps at this latency based on 32channel recordings in healthy volunteers showed a shift of local contralateral positive maximum from frontal to parietal during exploration, indicating enhancement of a tangential dipole. It is suggested that in conditions involving close sensorimotor interaction such as exploratory hand movements there is preactivation of a cortical area which is located in the central sulcus and receives cutaneous somatosensory inputs.

Notes: Abstract Horizontal eye movements were recorded in eight healthy subjects during super-slow trunk rotation with respect to the space-stationary head. In some trials, subjects simultaneously indicated their perception of selfmotion by means of a joystick. Over the frequency range employed (0.007–0.05 cycles per second, ±20°), all subjects perceived the relative motion of head and trunk as a head rotation with respect to the stationary trunk. Eye movements were observed which were in phase with imaginary head rotation; their amplitude exceeded the amplitude of actual body rotation. The grasping of a rigid ground-based handle (1) produced a sensation of trunk rotation in space, (2) suppressed the sensation of imaginary head rotation in space and (3) gave rise to a significant decrease in amplitude of eye movements. The grasping of a stiff rod with non-zero compliance did not produce these effects. It is concluded that eye movements in response to body rotation with respect to the fixed head are not purely reflex reactions, but are influenced by the internal representation of body motion.

Notes: Abstract When a temporal gap is introduced between the offset of a central fixation point and the onset of a peripheral sacccadic target, normal subjects generate an increased number of short latency (90–150 ms) saccades, termed express saccades, and the profile of express saccade frequency across different gap sizes for any individual subject, even if untrained in the task, shows a high test-retest reliability. In patients with schizophrenia, the generation of express saccades was also normal for gap sizes of 200–300 ms or in an overlap task (gap = 0 ms). However, for temporal gaps of 50–150 ms, the generation of express saccades was significantly impaired in the schizophrenic subjects. This selective deficit appeared to be independent of the patients' neuroleptic medication status and did not correlate with the severity of schizophrenic symptoms. It is postulated that the successful execution of an express saccade requires that the cognitive operations of disengagement of visual attention and selection of the appropriate motor command to generate a saccade both be commenced or completed during the temporal gap between fixation offset and peripheral target onset. Our results suggest that, in schizophrenia, there is an impairment in the cortical/subcortical neural network that generates express saccades and controls these cognitive operations. Potential sites for such dysfunction in schizophrenia include the parietal cortex and the GABA-ergic function of the superior colliculus.

Notes: Abstract Chronic loss of vestibular function modifies the role of neck afferents in human perception of self-motion. We characterized this change by comparing the self-motion perception of patients with chronic vestibular loss (Ps) to that of normal subjects (Ns). Stimuli consisted of sinusoidal horizontal rotations (0.025–0.4 Hz) of the trunk relative to the head (neck stimulation) and/or of the head in space (vestibular stimulation). Perception of head rotation relative to the trunk, of trunk rotation in space, or of head rotation in space was assessed in terms of gain and phase (veridical perception, G=1 and ϕ=0°) as well as detection threshold using a pointing procedure. (1) Perception of head rotation relative to the trunk (neck proprioception). Ps' detection threshold of head-to-trunk rotation was normal (i.e. similar to that of Ns) across all frequencies tested. Also, with peak angular velocities above 5°/s, the gain of their perception was approximately normal. When peak velocity was decreased below this value, however, either by lowering stimulus frequency with peak displacement kept constant (±8°) or by decreasing peak displacement at constant frequency (0.05 Hz), the gain increased above unity, unlike in Ns. In contrast, the phase remained normal (approximately 0°). (2) Perception of trunk rotation in space. Ps perceived their trunks as stationary during neck stimulation and all vestibular-neck combinations at medium to low frequencies. At 0.4 Hz, however, Ps consistently perceived the trunk rotation, conceivably due to somatosensory selfmotion cues arising from high body acceleration. In contrast, Ns perceive a trunk-in-space rotation with the neck stimulation and most of the stimulus combinations across the whole frequency range tested. Ns perceived their trunks as stationary only during head rotation on the stationary trunk (presumed to reflect a mutual cancellation of neck and vestibular signals). (3) Perception of head rotation in space. In Ps, unlike Ns, this perception always resembled that of head rotation relative to the trunk. (4) When Ps were presented with a visual or somatosensory space reference (not motion cues), their perception of trunk and head rotation in space became approximately normal. (5) We suggest that there are basically two changes in the neck induced self motion perception associated with chronic vestibular loss. First, neck proprioception shows a non linear gain that overemphasizes low stimulus velocities, for unknown reasons. Second, the neck signal which normally is used for the perception of trunk rotation in space is suppressed (Ps in the dark, deprived of any space reference, resort to the notion that their trunks are stationary). The change in Ps' perception of head rotation in space is attributed to the former two changes (assuming that they superimposed their notion of head on trunk rotation on that of a stationary trunk).

Notes: Abstract Aggressive, escape and point-maintained operant responding of male marijuana smokers were measured during six 25-min sessions conducted over an 8-h experimental day. Aggressive responding ostensibly subtracted points exchangeable for money from another subject. Escape responding protected the subject's counter from point subtractions initiated by the other subject for some period of time. Aggressive and escape responding were engendered by subtracting points from the subjects and maintained by initiation of intervals free of point subtractions. Point subtractions presented to the subjects were attributed to other persons. Subjects earned points exchangeable for money on a third response option. Subjects participated in one session prior to smoking and five sessions after smoking. Subjects smoked placebo or three different potencies of active marijuana cigarettes. Marijuana smoking effects on escape responding were not significant and depended upon the frequency of provocation. Point-maintained responding was decreased after marijuana smoking. Aggressive responding was increased for the first hour after smoking and returned to placebo levels later in the day. These effects of marijuana smoking on aggressive responding are discussed in terms of subject characteristics, particularly drug use history.

Notes: Abstract Melatonin (10, 20, 40, or 80 mg, PO) or placebo was administered at 1145 hours on five separate occasions to 20 healthy male volunteers and the effects on serum melatonin levels, mood, performance, and oral temperature were monitored. Subjects were studied between 0930 and 1700 hours. A battery of interactive computer tasks designed to assess performance and mood was completed, oral temperature was measured, and blood samples were taken for serum melatonin radioimmunoassay. The areas under the time-melatonin concentration curve (AUC) varied significantly in proportion to the various melatonin doses. Compared with placebo treatment, all melatonin doses significantly decreased oral temperature, number of correct responses in auditory vigilance, response latency in reaction time, and self-reported vigor. Melatonin also increased self-reported fatigue, confusion, and sleepiness.

Notes: Abstract The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D1-dopamine receptors. This striatal uptake was displaced by high doses of the selective D1-antagonist SCH 23390 (2 mg/kg) but not by the 5HT2-antagonist ketanserin (1.5 mg/kg) or the selective D2-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [11C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [11C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [11C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [11C]NNC 756 the ratio was about 5. This ratio of 5 for [11C]NNC 756 is the highest obtained so far for PET radioligands for the D1-dopamine receptor.

Notes: Abstract We examined the urinary excretion of S-benzyl-N-acetylcysteine (SBAC) of toluene sniffers using capillary gas chromatography. SBAC was extracted from 10 ml urine with chloroform and backextracted into 1 M sodium bicarbonate solution. After acidification, the aqueous solution was reextracted with ethyl acetate, and then derivatized to its methyl ester (ME). The peak appearing in the gas chromatogram was identified as SBAC-ME by mass spectrometry. The calibration curve was constructed by plotting the peak height ratio of SBAC-ME and internal standard (S-phenethyl-N-acetylcysteine)-ME against analyte concentration using 10 ml toluene unexposed urine. It showed good linearity over the range of 0.05–3.0 mg/l (r = 0.99). We have applied this technique to urine samples from toluene sniffers. SBAC was detected in all urinary samples of sniffers (n = 30, 0.11–47.13 mg/l), but not at all in the urine of toluene unexposed subjects (n = 60). These results prove that SBAC is also formed from toluene by human metabolism, and detection of SBAC is considered a useful marker for inhalation of toluene.

Notes: Abstract Androgen insensitivity syndromes represent one cause of human male pseudohermaphroditism related to defects in the androgen receptor. The formation of a biologically active androgen receptor complex with testosterone and 5α-dihydrotestosterone is required for normal androgen action during fetal development and fifferentiation of the internal accessory sex glands and external genitalia. Cloning of the human androgen receptor complementary DNA and genetic screening of human subjects with the clinical and biochemical features of androgen insensitivity using the polymerase chain reaction, denaturing gradient gel electrophoresis and nucleotide sequencing techniques have led to the identification of molecular defects in the androgen receptor. The complexity of phenotypic presentation by affected subjects with the complete or partial forms of androgen insensitivity is represented by the heterogeneity of androgen receptor gene mutations which include deletions and point mutations, with the latter causing, inappropriate splicing of RNA, premature termination of transcription and amino acid substitutions. The naturally occurring mutations in the androgen receptor of subjects with androgen insensitivity represent a base upon which we can increase our understanding of the structure and function of the androgen receptor in normal physiology, and disease.

Notes: Abstract Intracellular Ca2+ ([Ca2+]i) was measured in single isolated human umbilical vein smooth muscle cells. Stimulation with histamine, in the absence of external Ca2+, mobilised Ca2+ from intracellular stores. When repeated brief applications of agonist were used, the time to onset, amplitude and rate of rise of the Ca2+ transients were found to change. Two components could often be discerned in the rising phase of the transients, an initial slow “pacemaker” and a second faster and larger component. Following the first histamine-activated transient the basal level of [Ca2+]i was invariably lower than that prior to stimulation. This lower value was maintained whilst the cell remained in Ca2+-free solution, but could be returned to a higher level if the cell was exposed to external Ca2+. When the mobilisation of the intracellular store was reduced to undetectable levels, re-exposure to Ca2+-containing medium reactivated responses. In the absence of external Ca2+, continuous application of histamine activated a series of transient increases in intracellular Ca2+, which decreased progressively in amplitude and rate of rise. The interval between transients also increased. These findings are discussed in terms of the activation of inositol trisphosphate-sensitive intracellular Ca2+ stores and their sensitivity to cytoplasmic Ca2+ and intrasarcoplasmic reticulum Ca2+.

Notes: Summary Changes in tension were monitored isometrically on helical strips from both femoral and saphenous human veins obtained during autopsy and during surgical removal of varicose veins respectively. Both venous tissues contracted in response to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and 8-hydroxy2-(di-n-propylamino) tetralin (8-OH-DPAT). While 5-HT was about 2 times more potent in saphenous (pD2 = 7.35) than in femoral veins (pD2 = 7.04), 5-CT stimulated the saphenous vein (pD2 = 7.62) at about 20 times lower concentrations than were required for stimulation of the femoral vein (pD2 = 6.27). 8-OH-DPAT induced venoconstriction only when used at very high concentrations and pD2 values could not be determined. These data suggested different subtypes and/or distribution of 5-HT receptors in both venous preparations. Further evidence for this was obtained by the observation that spiperone (a 5-HT receptor blocker with high affinity for 5-HT2 and 5-HT1A sites) produced a parallel shift to the right of the 5-HT curve in femoral veins but elicited a biphasic displacement of the 5-HT curve in saphenous veins. In the femoral vein, spiperone showed a pA2 value of 9.20±0.08, statistically not different from that calculated for the spiperone sensitive 5-HT effect in saphenous vein (pA2 = 9.14±0.08). The results suggest that regional variations in the distribution of 5-HT receptor subtypes do exist, human femoral veins possessing mainly 5-HT2 receptors whereas in human saphenous veins both 5-HT1-like and 5-HT2 receptors are present.

Notes: Summary The effect of pinacidil on the contractile response to stepwise increases of the extracellular K+ concentration ([K+]0) was investigated in isolated segments of human pial and mesenteric arteries and rabbit basilar and mesenteric arteries. The [K+]O eliciting half maximum contraction (EC50) was lower in human pial (18 mM) and rabbit basilar (27 mM) arteries than in human (33 mM) and rabbit (32 mM) mesenteric arteries, respectively. The α-adrenoceptor blocker, prazosin, increased the EC50 value for K+ from 27 to 40 mM and reduced the maximum response in rabbit mesenteric arteries, but had no effect on the K+-induced contraction in rabbit basilar arteries, indicating a substantial noradrenergic component of the K+ response in the former arteries. Removal of the endothelium decreased the EC50 value for K+ from 27 to 15 mM in rabbit basilar arteries, whereas the K+ sensitivity was unaffected in rabbit mesenteric arteries. Pinacidil shifted the K+ concentration-response curve to the right in human and rabbit cerebral and mesenteric arteries. In rabbit basilar arteries, but not in mesenteric arteries, the shift was larger in the absence than in the presence of an intact endothelium. When endothelium-denuded rabbit arteries were compared, the inhibitory effect of pinacidil was larger in basilar than in mesenteric arteries. Thus, pinacidil inhibits K+-induced contractions in both cerebral and mesenteric arteries, but appears to act preferentially on endothelium-denuded rabbit basilar arteries. Provided that endothelial damage and depolarization-induced vasoconstriction are of pathophysiological importance in cerebrovascular disorders such as stroke and cerebral ischemia secondary to vasospasm after subarachnoid hemorrhage, pinacidil may have a therapeutic potential.

Notes: Abstract The localization of neuropeptide Y (NPY) and atrial natriuretic peptide (ANP) in the endothelial cells of human umbilical blood vessels was studied using the pre-embedding peroxidase-antiperoxidase (PAP) technique for electron microscopy and avidin-biotin-complex (ABC) immunostaining for endothelial cells cultured from umbilical vein. Subpopulations of NPY- and ANP-immunoreactive endothelial cells were present in term umbilical vein and artery. The umbilical vein contained more positive cells than the artery. The percentage of NPY- and ANP-immunoreactive umbilical vein cells in culture was 32% and 44%, respectively, out of a total of 3013 cells examined. The possibility that these potent vasoactive substances located in the endothelial cells of the non-innervated umbilical vessels are involved in the local regulation of blood flow is discussed.

Notes: Abstract The heterogeneity of endothelial cell surface antigen expression was studied in 5 human full-term placentae by means of indirect immunohistochemistry using 9 monoclonal antibodies and by staining with fluorescent-conjugated Ulex europaeus lectin, both of which are widely used endothelial cell markers. (1) A highly specific, homogeneous staining of fetal and maternal placental vessels of all sizes and anatomical regions was observed by the monoclonal antibodies PAL-E, QBEND10 and 1F10. These antibodies were even more specific than Ulex europaeus lectin, factor VIII antibody and von Willebrand factor antibody, which cross-reacted with some non-endothelial cells and structures. The reactivity of PAL-E, QBEND10 and 1F10 with residual surface cells of the basal plate strongly suggests an endothelial origin of these cells. (2) In contrast to other organs, PAL-E, QBEND10 and HM 15/3 strongly stained endothelial cells of the macrovascular system in the human placenta. This might indicate an organ-associated heterogeneity of fetal endothelial cells. (3) Monoclonal antibodies against receptors for transferrin and IgG (FcγRII) labeled the endothelial cells of fetal placental vessels with increasing intensity distal to the insertion of the umbilical cord. The vessels of the umbilical cord itself were unreactive. This might suggest a heterogeneity of macro- and microvascular endothelial cells.

Notes: Abstract Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the occurrence and distribution in human nasal mucosa of endothelin, a potent vasoconstrictor peptide, by immunocytochemistry and the effect of systemic administration of endothelin-1 on vascular perfusion of rabbit nasal mucosa by laser Doppler flowmetry. Endothelin-like immunoreactivity was demonstrated within vascular endothelial cells in both developing and mature human mucosa. Nasal epithelial cells and some connective tissue cells, presumed to be macrophages, also displayed specific immunostaining. In rabbits injected with endothelin-1, a potent and prolonged nasal vasoconstriction was observed. It is suggested that endothelin released locally may participate in the regulation of nasal blood flow via paracrine mechanisms. Since endothelin has growth-promoting actions on several cell types, it is also tentatively proposed that this regulatory peptide may play a role during development of the nose.

Notes: Abstract The present study describes the dynamic process of both acellular extrinsic (AEFC) and acellular/cellular intrinsic fiber cementum (AIFC/CIFC) matrix production on growing human teeth. Selected erupting maxillary and mandibular premolars with roots grown to about 70%–95% of their final length were placed in organ culture immediately following extraction. Twelve teeth for short-time labeling were pulse-incubated for 15 min in medium containing 3H-proline and chased for various times in order to follow the migration and secretion of the tracer. Eight teeth for long-time incubation were labeled continuously for 5 h before being chased for 1–8 days in order to label cementum matrix accumulation. After decalcification in ethylene diaminetetraacetic acid (EDTA), their roots were subdivided into about 20 slices each. Epon-embedded sections were prepared for light- and electron-microsopic as well as autoradiographic examination. During CIFC-formation, cementoblasts revealed high intracytoplasmic silver grain concentrations within the first hour after 3H-proline administration. The release of the tracer occurred between 60 to 120 min after administration. After 2 h, cementoblasts and the cementum matrix appeared to be labeled about equally. After 5 h, most of the labeled proteins appeared to be localized in the cementoid. Silver grains increased in number over the cementum matrix from 5–24 h. Very high intracellular grain concentrations within very large cementoblasts corresponded to regions of rapid cementum formation. Tracer-halos around entrapped cells lend support to a multipolar mode of matrix production during CIFC-initiation. The fate of the tracer during the development of early AEFC-matrix was less clear. However, fibroblasts revealed dense intracytoplasmic grain accumulations within the first hour after 3H-proline administration. Thereafter, the tracer localization was vague. This indistinct grain localization reflected the particular mode of AEFC-matrix production characterized by addition of new fibril segments to pre-existing fibers of a collagenous fringe.

Notes: Abstract Trophoblast cells were cultured on microporous membrane filters. After incubation at different times with gold-conjugated ligands, the cells were processed for electron microscopy. Gold particles indicating the presence of both IgG and LDL appeared in a time-dependent manner in coated pits and coated vesicles. LDL-gold appeared primarily within lysosomes whereas approximately 50% of the internalized IgG-gold appeared within vesicles (diameters ranging from 35 to 80 nm) near the basal regions of the cell. These vesicles may be the protective mechanism which prevents IgG breakdown during transcytosis across trophoblast cells, thus allowing transport of the intact molecule to the fetus.