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Biomedical subjects

G Cheron

Publications and source records attributed to G Cheron.

At least 19 recordsLinked to original sources

Effect of gravity on human spontaneous 10-Hz electroencephalographic oscillations during the arrest reaction.

Electroencephalographic oscillations at 10 Hz (alpha and mu rhythms) are the most prominent rhythms observed in awake, relaxed (eye-closed) subjects. These oscillations may be considered as a marker of cortical inactivity or an index of the active inhibition of the sensory information. Different cortical sources may participate in the 10-Hz oscillation and appear to be modulated by the sensory context and functional demands. In microgravity, the marked reduction in multimodal graviceptive inputs to cortical networks participating in the representation of space could be expected to affect the 10-Hz activity. The effect of microgravity on this basic oscillation has heretofore not been studied quantitatively. Because the alpha rhythm has a functional role in the regulation of network properties of the visual areas, we hypothesised that the absence of gravity would affect its strength. Here, we report the results of an experiment conducted over the course of 3 space flights, in which we quantified the power of the 10-Hz activity in relation to the arrest reaction (i.e., in 2 distinct physiological states: eyes open and eyes closed). We observed that the power of the spontaneous 10-Hz oscillation recorded in the eyes-closed state in the parieto-occipital (alpha rhythm) and sensorimotor areas (mu rhythm) increased in the absence of gravity. The suppression coefficient during the arrest reaction and the related spectral perturbations produced by eye-opening/closure state transition also increased in on orbit. These results are discussed in terms of current theories on the source and the importance of the alpha rhythm for cognitive function.

Adult↗

Fast cerebellar oscillation associated with ataxia in a mouse model of Angelman syndrome.

Ataxia may result from various cerebellar cortex dysfunctions. It is included in the diagnostic criteria of Angelman syndrome, a human neurogenetic condition. In order to better understand the cerebellar dysfunction in this condition, we recorded in vivo cerebellar activity in a mouse model of Angelman syndrome produced by null mutation of the maternal Ube3a gene. We found fast oscillation (approximately 160 Hz) in the cerebellar cortex sustained by abnormally increased Purkinje cell firing rate and rhythmicity. This oscillation is inhibited by sensory stimulation and gap junction or GABA(A) receptor blockers. A physiologically similar oscillation was previously found in mice lacking calcium-binding proteins that also present ataxia, but never in wild-type mice. We propose that fast oscillation in the cerebellar cortex is implicated in the cerebellar symptomatology of Angelman syndrome.

Angelman Syndrome↗

Purkinje cell rhythmicity and synchronicity during modulation of fast cerebellar oscillation.

Fast (approximately 160 Hz) cerebellar oscillation has been recently described in different models of ataxic mice, such as mice lacking calcium-binding proteins and in a mouse model of Angelman syndrome. Among them, calretinin-calbindin double knockout mice constitute the best model for evaluating fast oscillations in vivo. The cerebellum of these mice may present long-lasting episodes of very strong and stable local field potential oscillation alternating with the normal non-oscillating state. Spontaneous firing of the Purkinje cells in wild type and double knockout mice largely differs. Indeed, the Purkinje cell firing of the oscillating mutant is characterized by an increased rate and rhythmicity and by the emergence of synchronicity along the parallel fiber axis. To better understand the driving role played by these different parameters on fast cerebellar oscillation, we simultaneously recorded Purkinje cells and local field potential during the induction of general anesthesia by ketamine or pentobarbitone. Both drugs significantly increased Purkinje cell rhythmicity in the absence of oscillation, but they did not lead to Purkinje cell synchronization or to the emergence of fast oscillation. During fast oscillation episodes, ketamine abolished Purkinje cell synchronicity and inhibited fast oscillation. In contrast, pentobarbitone facilitated fast oscillation, induced and increased Purkinje cell synchronicity. We propose that fast cerebellar oscillation is due to the synchronous rhythmic firing of Purkinje cell populations and is facilitated by positive feedback whereby the oscillating field further phase-locks recruited Purkinje cells onto the same rhythmic firing pattern.

Anesthetics, Dissociative↗

Role of calcium binding proteins in the control of cerebellar granule cell neuronal excitability: experimental and modeling studies.

Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin deficient mice exhibit dramatic alterations in motor coordination and in Purkinje cell firing recorded in vivo through unknown mechanisms. In the present paper, we review the results obtained with the patch clamp recording techniques in acute slice preparation. This data allow us to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of the exogenous fast calcium buffer BAPTA is infused in the cytosol to restore the calcium buffering capacity. Furthermore, we propose a mathematical model demonstrating that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium buffering capacity due to the absence of calretinin. We suggest that calcium binding proteins modulate intrinsic neuronal excitability and may therefore play a role in the information processing in the central nervous system.

Animals↗

Mono- and dual-frequency fast cerebellar oscillation in mice lacking parvalbumin and/or calbindin D-28k.

Calbindin is a fast Ca2+-binding protein expressed by Purkinje cells and involved in their firing regulation. Its deletion produced approximately 160-Hz oscillation sustained by synchronous, rhythmic Purkinje cells in the cerebellar cortex of mice. Parvalbumin is a slow-onset Ca2+-binding protein expressed in Purkinje cells and interneurons. In order to assess its function in Purkinje cell firing regulation, we studied the firing behavior of Purkinje cells in alert mice lacking parvalbumin (PV-/-), calbindin (CB-/-) or both (PV-/- CB-/-) and in wild-type controls. The absence of either protein resulted in Purkinje cell firing alterations (decreased complex spike duration and pause, increased simple spike firing rate) that were more pronounced in CB-/- than in PV-/- mice. Cumulative effects were found in complex spike alterations in PV-/- CB-/- mice. PV-/- and CB-/- mice manifested approximately 160-Hz oscillation that was sustained by Purkinje cells firing rhythmically and synchronously along the parallel fiber axis. This oscillation was dependent on GABA(A), N-methyl-D-aspartate and gap junction transmission. PV-/- CB-/- mice exhibited a dual-frequency (110 and 240 Hz) oscillation. The instantaneous spectral densities of both components were inversely correlated. Simple and complex spikes of Purkinje cells were phase-locked to one of the two oscillation frequencies. Mono- and dual-frequency oscillations presented similar pharmacological properties. These results demonstrate that the absence of the Ca2+ buffers parvalbumin and calbindin disrupts the regulation of Purkinje cell firing rate and rhythmicity in vivo and suggest that precise Ca2+ transient control is required to maintain the normal spontaneous arrhythmic and asynchronous firing pattern of the Purkinje cells.

2-Amino-5-phosphonovalerate↗

A dynamic recurrent neural network for multiple muscles electromyographic mapping to elevation angles of the lower limb in human locomotion.

This paper describes the use of a dynamic recurrent neural network (DRNN) for simulating lower limb coordination in human locomotion. The method is based on mapping between the electromyographic signals (EMG) from six muscles and the elevation angles of the three main lower limb segments (thigh, shank and foot). The DRNN is a fully connected network of 35 hidden units taking into account the temporal relationships history between EMG and lower limb kinematics. Each EMG signal is sent to all 35 units, which converge to three outputs. Each output neurone provides the kinematics of one lower limb segment. The training is supervised, involving learning rule adaptations of synaptic weights and time constant of each unit. Kinematics of the locomotor movements were recorded and analysed using the opto-electronic ELITE system. Comparative analysis of the learning performance with different types of output (position, velocity and acceleration) showed that for common gait mapping velocity data should be used as output, as it is the best compromise between asymptotic error curve, rapid convergence and avoidance of bifurcation. Reproducibility of the identification process and biological plausibility were high, indicating that the DRNN may be used for understanding functional relationships between multiple EMG and locomotion. The DRNN might also be of benefit for prosthetic control.

Adult↗

Early emergence of temporal co-ordination of lower limb segments elevation angles in human locomotion.

We analysed the co-ordination of the elevation angles of the thigh (alpha(t)), shank (alpha(s)) and foot (alpha(f)) during walking in 19 adults and 21 children (aged 11--144 months), including the very first unsupported steps in four. Cross-correlation functions (CCF) maturation of pairs of elevation angles was quantified by a global error parameter (Et((CCF))) reflecting the difference between particular CCF value of toddlers and mean adult value (Ea((CCF))). During the very first step, Et((CCF)) could be five times higher than Ea((CCF)). With walking experience, Et((CCF)) for both alpha(t)-alpha(s) and alpha(s)-alpha(f) pairs evolved following a biexponential profile, with a fast time constant below 6 months. Adult-like CCF parameters were reached earlier for alpha(s)-alpha(f) than alpha(t)-alpha(s), indicating disto-proximal maturation of the temporal co-ordination of the lower limb segments in human locomotion.

Adult↗

Development of a kinematic coordination pattern in toddler locomotion: planar covariation.

The purpose of this study is to analyze the coordination patterns of the elevation angles of lower limb segments following the onset of unsupported walking in children and to look for the existence of a planar covariation rule as previously described in adult human locomotion. The kinematic patterns of locomotion were recorded in 21 children (11-144 months of age) and 19 adults. In 4 children we monitored the very first unsupported steps. The extent to which the covariation of thigh, shank, and foot angles was constrained on a plane in 3D space was assessed by means of orthogonal regression and statistically quantified by means of principal component analysis. The orientation of the covariation plane of the children was compared with the mean value of the adults' plane. Trunk stability with respect to the vertical was assessed in both the frontal (roll) and sagittal (pitch) planes. The evolution with walking experience of the plane orientation and trunk oscillations demonstrated biexponential profiles with a relatively fast time constant (< 6 months after the onset of unsupported locomotion) followed by a much slower progression toward adult values. The initial fast changes of these walking parameters did not parallel the slow, monotonic maturation of anthropometric parameters. The early emergence of the covariation plane orientation and its correlation with trunk vertical stability reflect the dynamic integration of postural equilibrium and forward propulsion in a gravity-centered frame. The results support the view that the planar covariation reflects a coordinated, centrally controlled behavior, in addition to biomechanical constraints. The refinement of the planar covariation while morphological variables drastically change as the child grows implies a continuous update of the neural command.

Aging↗

Distinct multi-joint control strategies in spastic diplegia associated with prematurity or Angelman syndrome.

Spastic diplegia is commonly due to periventricular leucomalacia associated with premature birth. It is also a feature of Angelman syndrome (AS), a neurogenetic disorder with developmental delay, absent speech and mirthful behaviour. We studied the kinematics and kinetics of the squatting movement and associated electromyographic (EMG) activities in 20 children with spastic diplegia associated with periventricular leucomalacia (SDPL) or AS and 18 unimpaired children. While movement of normal subjects consisted of vertical translation of most body segments, the movement of SDPL children was operated around the fixed knee with backward shift of the hip, and AS children performed a forward flexion of the trunk over the thigh. Trunk stability was correlated with movement velocity in both pathological groups. In normal subjects, anticipatory EMG pattern consisted of silencing of hamstring muscle tonic activity prior to movement onset. This deactivation was not present in spastic diplegia. In SDPL, anticipatory overactivation of ankle joint actuators was recorded and tonic co-contraction persisted throughout the movement. In AS, rhythmic EMG bursting was seen during the movement. Shoulder, hip and knee trajectories in the sagittal plane showed marked within-group stereotypies in orientation, shape and length. The patterns in both pathological groups were therefore distinctive. We speculate that they reflect corticospinal impairment in SDPL and combined corticospinal and cerebellar dysfunction in AS.

Angelman Syndrome↗

Effect of intrathecal baclofen on gait control in human hereditary spastic paraparesis.

The covariation between thigh, shank and foot elevation angles during locomotion was analysed by means of orthogonal planar regression in a patient with pure hereditary spastic paraparesis before and after an intrathecal bolus of baclofen and in seven healthy subjects. The size, shape and spatial orientation of the loop defining patient's planar covariation (thigh angle vs. shank angle vs. foot angle) significantly differed from the controls' before baclofen, whereas these features resumed normal characteristics after baclofen injection. This shows that alteration of the control of phase coupling for the co-ordination of lower limb segments in human gait by increased spinal reflexes can be reversed by intrathecal baclofen injection.

Adult↗

Head stability during whole body movements in spastic diplegia.

Head angular stability is essential for postural control in whole body movement. Using the opto-electronic ELITE system, we have studied head orientation during the movements of squatting from the standing position and straightening-up from the squatting position in 12 children with spastic diplegia and 12 age-matched controls. Although no instruction was given regarding the head, diplegic children consistently performed excessive neck flexion in the squatting movement and excessive hyperextension in the straightening-up movement, whereas normal children maintained the initial orientation throughout both movements. We discuss pathophysiological implications.

Cerebral Palsy↗

Intrathecal baclofen normalizes motor strategy for squatting in familial spastic paraplegia: a case study.

We aimed to assess whether intrathecal baclofen could alter the motor strategy for squatting of a patient with pure familial spastic paraplegia. Before baclofen injection and two, four and six hours after it, the patient was evaluated as follows: self-report of walking stiffness and movement initiation; muscle tone with the Ashworth scale; and kinematic and electromyographic analysis of the squatting movement using the opto-electronic ELITE system. The patient's subjective improvement and decrease in muscle tone were dramatic after baclofen injection. Kinematic analysis of squatting showed gradual improvement. Before the injection, the movement was performed with loss of trunk verticality, backward shift of the hip, multiphasic ascending phase of the knee angular velocity and dynamic ankle stiffening. After baclofen injection, the movement was made with vertical translation of body segments and monophasic ascending phase of the knee angular velocity. The effect was maximal six hours after the injection. Electromyographic activities showed a non-specific co-contraction pattern before the injection, and a reciprocal pattern two hours after it. Moreover, a physiological anticipatory deactivation of the hamstring muscles appeared two hours after the injection. In this study of a single patient with familial spastic paraplegia, intrathecal baclofen has facilitated the emergence of normal, supraspinally determined movement patterns.

Adult↗

Sensory and motor interfering influences on somatosensory evoked potentials.

The interfering influences by which the different components of the early somatosensory evoked potentials are modified are reviewed from both neurophysiologic and clinical perspectives. Special consideration is given to the specific differences between sensory and motor interferences. In this context, the specific effect of the mental movement simulation task on the frontal N30 component is discussed in relation to the involvement of this evoked wave as a physiologic index of the dopaminergic motor pathways. Relevant interfering approaches, including concurrent events ranging from tactile stimulation to locomotion, are reviewed and discussed insofar as these data provide insights into the neurophysiologic processes of interaction between competing internal models controlling motor acts and sensory information.

Afferent Pathways↗

Impaired motor coordination and Purkinje cell excitability in mice lacking calretinin.

In the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium concentration ([Ca2+]i). Ca2+ binding proteins are enriched in the cerebellum, but their role in information processing is not clear. Here, we show that mice deficient in calretinin (Cr-/-) are impaired in tests of motor coordination. An impairment in Ca2+ homeostasis in Cr-/- Purkinje cells was supported by the high Ca2+-saturation of calbindin-D28k in these cells. The firing behavior of Purkinje cells is severely affected in Cr-/- alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause. In contrast, in slices, transmission at parallel fiber- or climbing fiber-Purkinje cell synapses is unaltered, indicating that marked modifications of the firing behavior in vivo can be undetectable in slice. Thus, these results show that calretinin plays a major role at the network level in cerebellar physiology.

Aging↗

Does the coordination between posture and movement during human whole-body reaching ensure center of mass stabilization?

The whole-body center of mass (CoM) has been classically regarded as the stabilized reference value for human voluntary movements executed upon a fixed base of support. Axial synergies (opposing displacements of head and trunk with hip segments) are believed to minimize antero-posterior (A/P) CoM displacements during forward trunk movements. It is also widely accepted that anticipatory postural adjustments (APAs) create forces of inertia that counteract disturbances arising from the moving segment(s). In the present study, we investigated CoM stabilization by axial synergies and APAs during a whole-body reaching task. Subjects reached towards an object placed on the ground in front of them in their sagittal plane using a strategy of coordinated trunk, knee, and hip flexion. The reaching task imposed constraints on arm-trajectory formation and equilibrium maintenance. To manipulate equilibrium constraints, differing conditions of distance and speed were imposed. The comparison of distance conditions suggested that axial synergies were not entirely devoted to CoM stabilization: backward A/P hip displacements reduced as head and trunk forward A/P displacements increased. Analysis of upper- and lower-body centers of mass in relation to the CoM also showed no strict minimization of A/P CoM displacements. Mechanical analysis of the effects of APAs revealed that, rather than acting to stabilize the CoM, APAs created necessary conditions for forward CoM displacement within the base of support in each condition. The results have implications for the CoM as the primary stabilized reference for posture and movement coordination during whole-body reaching and for the central control of posture and voluntary movement.

Adolescent↗