The human central nervous system transmits common synaptic inputs to distinct motor neuron pools during non-synergistic digit actions.

KEY POINTS: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un-matched forces in different directions. We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control. The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire. ABSTRACT: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. Here we quantify the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles in humans during voluntary contractions. To remove confounds associated with previous studies, we used a task that required the two hand muscles to exert matched or un-matched forces in different directions. Despite the force production task consisting of uncommon digit force coordination patterns, we found that synaptic input to motor neurons is shared across all frequency bands, reflecting cortical and spinal inputs associated with force control. The coherence between discharge timings of the two pools of motor neurons was significant at the delta (0-5 Hz), alpha (5-15 Hz) and beta (15-35 Hz) bands (P < 0.05). These results suggest that correlated input to motor neurons of two hand muscles can occur even during tasks not belonging to a common behavioural repertoire and despite lack of common innervation. Moreover, we show that the extraction of activity from motor neurons during voluntary force control removes cross-talk associated with global EMG recordings, thus allowing direct in vivo interrogation of spinal motor neuron activity.

Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.

Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (≈ 45 and ≈ 55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.

Synaptic modulation by astrocytes via Ca2+-dependent glutamate release.

In the past 15 years the classical view that astrocytes play a relatively passive role in brain function has been overturned and it has become increasingly clear that signaling between neurons and astrocytes may play a crucial role in the information processing that the brain carries out. This new view stems from two seminal observations made in the early 1990s: 1. astrocytes respond to neurotransmitters released during synaptic activity with elevation of their intracellular Ca2+ concentration ([Ca2+]i); 2. astrocytes release chemical transmitters, including glutamate, in response to [Ca2+]i elevations. The simultaneous recognition that astrocytes sense neuronal activity and release neuroactive agents has been instrumental for understanding previously unknown roles of these cells in the control of synapse formation, function and plasticity. These findings open a conceptual revolution, leading to rethink how brain communication works, as they imply that information travels (and is processed) not just in the neuronal circuitry but in an expanded neuron-glia network. In this review we critically discuss the available information concerning: 1. the characteristics of the astrocytic Ca2+ responses to synaptic activity; 2. the basis of Ca2+-dependent glutamate exocytosis from astrocytes; 3. the modes of action of astrocytic glutamate on synaptic function.

Spatial localization of electrotactile stimuli on the fingertip in humans.

This study was designed to determine the extent to which sensations elicited by discrete electrotactile stimulation can be spatially localized, with a qualitative comparison to mechanical stimulation, in a 2 x 2 electrode array on the fingertip. Electrotactile stimulation was delivered in two modes: (1) same current to all locations (constant) or (2) current adjusted to perceptual threshold of each location (varied). For each stimulus location, subjects were asked to identify the location of the stimulus. Mechanical stimulation of the same locations on the fingerpad was delivered through von Frey hairs (0.07, 0.2 and 0.4 g). The percentage of accurate responses was computed for all stimulation modes. We found that the accuracy of discrimination of stimulus location in both the constant (46%) and varied (40%) electrotactile stimulation modes was significantly higher than chance level (25%; p < 0.01). Furthermore, subjects were significantly more accurate in discriminating electrotactile stimuli in the constant than in the varied mode (p < 0.05). We also found that the accuracy of spatial discrimination was dependent on stimulation site for mechanical, but not electrotactile stimulation. Finally, we found a significant difference in accuracy over the duration of the experiment only for mechanical modes, which may indicate that electrotactile stimuli are less biased over time. These results suggest that, although low in accuracy, human subjects are able to extract spatial information from electrotactile stimuli. Further research is needed to optimize the amount of the information that can be delivered through electrotactile stimulation.

Neuromuscular determinants of force coordination during multidigit grasping.

The biomechanical structure of the hand and its underlying neurophysiology contribute to the coordination of the kinematics and kinetics necessary for multidigit grasping. We recently examined the neural organization of inputs to different extrinsic finger flexors during multi-digit object hold and found moderate to strong motor unit short-term synchrony. This suggests a common neural input to the motoneurons innervating these different hand muscles/muscle compartments, which may in turn influence the coordination of grip forces. To further characterize this common input to the hand muscles during multidigit grasping, we used the frequency-based measure of coherence. Motor unit coherence provides information with regards to the oscillatory frequency of a common input, as well as the coupling of the discharges of a motor unit pair at both short and long latencies. Preliminary results indicate that a large proportion of trials are characterized by significant coherence in the 1-12 Hz frequency range, which is more pronounced in the within- than between-muscle/muscle compartment analysis. This indicates a differential organization of common oscillatory inputs to pairs of motoneurons innervating the same vs. different muscles/ muscle compartments. The functional role of the 1-12 Hz oscillatory modulation of motor unit behavior is currently being investigated.

Visual and non-visual control of landing movements in humans.

1. The role of vision in controlling leg muscle activation in landing from a drop was investigated. Subjects (n = 8) performed 10 drops from four heights (0.2, 0.4, 0.6 and 0.8 m) with and without vision. Drop height was maintained constant throughout each block of trials to allow adaptation. The aim of the study was to assess the extent to which proprioceptive and vestibular information could substitute for the lack of vision in adapting landing movements to different heights. 2. At the final stages of the movement, subjects experienced similar peak centre of body mass (CM) displacements and joint rotations, regardless of the availability of vision. This implies that subjects were able to adapt the control of landing to different heights. The amplitude and timing of electromyographic signals from the leg muscles scaled to drop height in a similar fashion with and without vision. 3. However, variables measured throughout the execution of the movement indicated important differences. Without vision, landings were characterised by 10 % larger ground reaction forces, 10 % smaller knee joint rotations, different time lags between peak joint rotations, and more variable ground reaction forces and times to peak CM displacement. 4. We conclude that non-visual sensory information (a) could not fully compensate for the lack of continuous visual feedback and (b) this non-visual information was used to reorganise the motor output. These results suggest that vision is important for the very accurate timing of muscle activity onset and the kinematics of landing.

Force synergies for multifingered grasping.

Compared with the control of precision grips involving the thumb and one or two fingers, the control of grasping using the entire hand involves a larger number of degrees of freedom that has to be controlled simultaneously, and it introduces indeterminacies in the distribution of grip forces suitable for holding an object. We studied the control of five-digit grasping by measuring contact forces when subjects lifted, held, and replaced a manipulandum. This study focused primarily on the patterns of coordination among the normal forces exerted by each of the digits, assessed by varying the center of mass of the manipulandum. The force patterns during the lift and hold phases were modulated as a function of the location of the center of mass. A frequency domain analysis revealed a consistent temporal synergy by which digits tended to exert normal forces in phase with each other across all experimental conditions. This tendency for in-phase covariations by the normal forces exerted by the digits extended over the entire functional frequency range (up to 10 Hz). When the effect of thumb force was removed, a second synergy was revealed in which forces in two fingers could be modulated 180 degrees out of phase (also prevailing throughout the range of frequencies studied). The first synergy suggests the presence of a "common drive" to all of the extrinsic finger muscles, whereas the second one suggests another input, ultimately resulting in a reciprocally organized pattern of activity of some of these muscles.

Postural hand synergies for tool use.

Subjects were asked to shape the right hand as if to grasp and use a large number of familiar objects. The chosen objects typically are held with a variety of grips, including "precision" and "power" grips. Static hand posture was measured by recording the angular position of 15 joint angles of the fingers and of the thumb. Although subjects adopted distinct hand shapes for the various objects, the joint angles of the digits did not vary independently. Principal components analysis showed that the first two components could account for >80% of the variance, implying a substantial reduction from the 15 degrees of freedom that were recorded. However, even though they were small, higher-order (more than three) principal components did not represent random variability but instead provided additional information about the object. These results suggest that the control of hand posture involves a few postural synergies, regulating the general shape of the hand, coupled with a finer control mechanism providing for small, subtle adjustments. Because the postural synergies did not coincide with grip taxonomies, the results suggest that hand posture may be regulated independently from the control of the contact forces that are used to grasp an object.

The control of timing and amplitude of EMG activity in landing movements in humans.

The control of self-initiated falls from different heights was studied. The objective of the study was to investigate in a quantitative manner the modulation of EMG timing (i.e. onset from take-off and duration from onset to touch-down) and amplitude (before and after foot contact) as a function of fall height. The muscles studied were m. soleus and m. tibialis anterior. Kinematic (ankle joint angle) and kinetic (ground reaction force) variables were also measured. Six subjects took part in the experiments that consisted of ten landings from each of five heights (0.2, 0.4, 0.6, 0.8 and 1 m) onto a force platform. We found a consistent pattern of co-contraction before and after touch-down across the fall heights studied. In both muscles, the onset of pre-landing EMG activity occurred at a longer latency following take-off when landing from greater heights. The absolute EMG duration was affected to a lesser extent by increasing fall height. These findings suggest that the onset of muscle activity of the muscles studied prior to foot contact is timed relative to the expected time of foot contact. Pre- and post-landing EMG amplitude tended to increase with height. Despite a doubling in the magnitude of ground reaction force, the amplitude of ankle joint rotation caused by the impact remained constant across heights. These findings suggest that the observed pattern of co-contraction is responsible for increasing ankle joint stiffness as fall height is increased. The attainment of an appropriate level of EMG amplitude seems to be controlled by (a) timing muscle activation at a latency timed from the expected instant of foot contact and (b) varying the rate at which EMG builds up.

Gradual molding of the hand to object contours.

Subjects were asked to reach to and to grasp 15 similarly sized objects with the four fingers opposed to the thumb. The objects' contours differed: some presented a concave surface to the fingers, others a flat one, and yet others a convex surface. Flexion/extension at the metacarpal-phalangeal and proximal interphalangeal joints of the fingers was recorded during the reaching movement. We used discriminant analysis, cluster analysis, and information theory to determine the extent to which the shape of the hand was affected by the objects' shapes along a convexity/concavity gradient. Maximum aperture of the hand was reached about midway in the reaching movement. At that time, the hand's posture was influenced by the shape of the object to be grasped but imperfectly. The information transmitted by hand posture about object shape increased gradually and monotonically as the hand approached the object, reaching a maximum at the time the object was in the grasp of the hand. We also asked subjects to shape the hand so as to grasp the object without moving the arm. Their performance was poorer on this task in the sense that hand shape discriminated among fewer objects and that trial-to-trial variability was greater than when the distal and proximal components of the motion were linked. The results indicate that the hand is molded only gradually to the contours of an object to be grasped. Because other parameters of the motion, such as movement direction, for example, already are specified fully early on in a movement, the results also suggest that the specification of diverse aspects of a movement does not evolve at a uniform rate.

Resorption of composite polymer-hydroxyapatite membranes: a time-course study in rabbit.

The histological findings in rabbit, concerning the resorption of a new composite hydroxyapatite-polymer membrane used in guided tissue regeneration are reported. The polymer appeared to be completely resorbed in about 4-6 months, while the inorganic component, hydroxyapatite, appeared to begin to resorb after the tenth month. The integrity of the membrane appeared to be unchanged after a 10-month period. No inflammatory cell infiltrate was present. This new type of membrane appeared to be relatively well tolerated by the host, had no significant adverse soft and hard tissue reaction, appeared to be easy to handle and had good space-maintaining capabilities. More research is certainly needed before clinical use in man.

Matching object size by controlling finger span and hand shape.

The ability of human subjects to accurately control finger span (distance between thumb and one finger) was studied. The experiments were performed without visual feedback of the hand and were designed to study the dependence of accuracy on object size, shape, distance, orientation and finger configuration. The effects of finger combination and sensory modality used to perceive object size (vision and haptics) were also studied. Subjects were quite proficient at this task; the small errors tended to be predominantly negative, i.e., finger span < object size. The thumb-little finger combination was less accurate than the other finger combinations, irrespective of the sensory modality used. Subjects made larger under-estimating errors when matching the size of cylinders than when matching cubes and parallelepipeds. No effect of viewing distance, object orientation and finger configuration was found. Accuracy in matching object size was not dependent on the sensory modality used. The question of how the individual degrees of freedom of the fingers and thumb contributed to the control of finger span was also addressed. Principal components analysis showed that two components could characterize the hand postures used, irrespective of object size. The amplitude of the first principal component was constant, and the amplitude of the second scaled linearly with object size. This finding suggests that all of the degrees of freedom of the hand are controlled as a unit. This result is discussed in relation to the 'virtual finger' hypothesis for grasping.

Sexual aggression by an acquaintance: methods of coping and later psychological adjustment.

The main purpose of the present study was to determine if methods of coping with sexual aggression by acquaintances were associated with psychological adjustment beyond what could be predicted by characteristics of the attack itself and beyond what could be predicted by methods of coping used to deal with other stressors. Out of 401 undergraduate women respondents (mean age = 19), 106 or 26% had been victims of sexual aggression by an acquaintance since the age of 16. Two years on average after the assault, these women reported more psychological problems on the Brief Symptom Inventory (Derogatis & Spencer, 1982) than a comparison group who had not been assaulted since age 16. Respondents who had survived sexual aggression were asked to indicate on the Coping Strategies Inventory the methods they had used to cope with this experience and the methods they had used to cope with a separate nonsexual stressful event which also had occurred since age 16. Multiple regression analyses indicated that disengagement methods of coping with sexual aggression per se accounted for unique variance in general psychological distress as measured by the Global Severity Index of the Brief Symptom Inventory and in posttraumatic stress disorder symptoms as measured by a DSM-III-R derived checklist.

Residual developmental disabilities in children with transient hypertonicity in infancy.

Developmental disabilities occurred in children who manifested transient neurologic abnormalities in early infancy. In an attempt to identify associated problems at an earlier age, the neuromotor and developmental progress of 33 children who had transient hypertonicity during early infancy was analyzed. At 2-3 years of age, various developmental abnormalities were identified in more than two-thirds of these children. Delays in speech and language development and also in fine motor/adaptive and behavioral difficulties were most frequently present. Over time, these problems persisted and other disorders also became apparent. At 5 years of age or older, learning disabilities were frequent and associated with language and perceptual problems. None of the patients had epilepsy; mental retardation was present in only 2 children. Our study demonstrates that children with transient hypertonicity in early infancy are at risk for various developmental problems which can be identified as early as 2 years of age. It also indicates that although their severity lessens over time, these developmental abnormalities tend to persist.