Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing. © 2004 Elsevier Inc. All rights reserved.

Neural Prosthetics and Parietal Cortex

In the last decade, research efforts into directly interfacing with the neurons of individuals with motor deficits have increased. The goal of such research is clear: Enable individuals affected by paralysis or amputation to regain control of their environments by manipulating external devices with thought alone. Though the motor cortices are the usual brain areas upon which neural prosthetics depend, research into the parietal lobe and its subregions, primarily in non-human primates, has uncovered alternative areas that could also benefit neural interfaces. Similar to the motor cortical areas, parietal regions can supply information about the trajectories of movements. In addition, the parietal lobe also contains cognitive signals like movement goals and intentions. But, these areas are also known to be tuned to saccadic eye movements, which could interfere with the function of a prosthetic designed to capture motor intentions only. In this thesis, we develop and examine the functionality of a neural prosthetic with a non-human primate model using the superior parietal lobe to examine the effectiveness of such an interface and the effects of unconstrained eye movements in a task that more closely simulates clinical applications. Additionally, we examine methods for improving usability of such interfaces.

The parietal cortex is also believed to contain neural signals relating to monitoring of the state of the limbs through visual and somatosensory feedback. In one of the world’s first clinical neural prosthetics based on the human parietal lobe, we examine the extent to which feedback regarding the state of a movement effector alters parietal neural signals and what the implications are for motor neural prosthetics and how this informs our understanding of this area of the human brain.

The influence of drug-induced dyskinesias on manual tracking in Parkinson's disease

The influence of peak-dose drug-induced dyskinesia (DID) on manual tracking (MT) was examined in 10 dyskinetic patients (OPO), and compared to 10 age/gendermatched non-dyskinetic patients (NDPD) and 10 healthy controls. Whole body movement (WBM) and MT were recorded with a 6-degrees of freedom magnetic motion tracker and forearm rotation sensors, respectively. Subjects were asked to match the length of a computer-generated line with a line controlled via wrist rotation. Results show that OPO patients had greater WBM displacement and velocity than other groups. All groups displayed increased WBM from rest to MT, but only DPD and NDPO patients demonstrated a significant increase in WBM displacement and velocity. In addition, OPO patients exhibited excessive increase in WBM suggesting overflow DID. When two distinct target pace segments were examined (FAST/SLOW), all groups had slight increases in WBM displacement and velocity from SLOW to FAST, but only OPO patients showed significantly increased WBM displacement and velocity from SLOW to FAST. Therefore, it can be suggested that overflow DID was further increased with increased task speed. OPO patients also showed significantly greater ERROR matching target velocity, but no significant difference in ERROR in displacement, indicating that significantly greater WBM displacement in the OPO group did not have a direct influence on tracking performance. Individual target and performance traces demonstrated this relatively good tracking performance with the exception of distinct deviations from the target trace that occurred suddenly, followed by quick returns to the target coherent in time with increased performance velocity. In addition, performance hand velocity was not correlated with WBM velocity in DPO patients, suggesting that increased ERROR in velocity was not a direct result of WBM velocity. In conclusion, we propose that over-excitation of motor cortical areas, reported to be present in DPO patients, resulted in overflow DID during voluntary movement. Furthermore, we propose that the increased ERROR in velocity was the result of hypermetric voluntary movements also originating from the over-excitation of motor cortical areas.

Visual feedback alters the variations in corticospinal excitability that arise from rhythmic movements of the opposite limb

Augmented visual feedback can have a profound bearing on the stability of bimanual coordination. Indeed, this has been used to render tractable the study of patterns of coordination that cannot otherwise be produced in a stable fashion. In previous investigations (Carson et al. 1999), we have shown that rhythmic movements, brought about by the contraction of muscles on one side of the body, lead to phase-locked changes in the excitability of homologous motor pathways of the opposite limb. The present study was conducted to assess whether these changes are influenced by the presence of visual feedback of the moving limb. Eight participants performed rhythmic flexion-extension movements of the left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback of wrist displacement was provided in relation to a target amplitude, defined by the mean movement amplitude generated during the immediately preceding no feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of the right limb by magnetic stimulation of the left motor cortex. Consistent with our previous observations, MEP amplitudes were modulated during the movement cycle of the opposite limb. The extent of this modulation was, however, smaller in the presence of visual feedback of the moving limb (FCR omega(2) =0.41; ECR omega(2)=0.29) than in trials in which there was no visual feedback (FCR omega(2)=0.51; ECR omega(2)=0.48). In addition, the relationship between the level of FCR activation and the excitability of the homologous corticospinal pathway of the opposite limb was sensitive to the vision condition; the degree of correlation between the two variables was larger when there was no visual feedback of the moving limb. The results of the present study support the view that increases in the stability of bimanual coordination brought about by augmented feedback may be mediated by changes in the crossed modulation of excitability in homologous motor pathways.

Neural Modeling and Imaging of the Cortical Interactions Underlying Syllable Production

This paper describes a neural model of speech acquisition and production that accounts for a wide range of acoustic, kinematic, and neuroimaging data concerning the control of speech movements. The model is a neural network whose components correspond to regions of the cerebral cortex and cerebellum, including premotor, motor, auditory, and somatosensory cortical areas. Computer simulations of the model verify its ability to account for compensation to lip and jaw perturbations during speech. Specific anatomical locations of the model's components are estimated, and these estimates are used to simulate fMRI experiments of simple syllable production with and without jaw perturbations.

Acute inactivation of the contralesional hemisphere for longer durations improves recovery after cortical injury

Au cours des dernières années, des méthodes non-invasives de stimulations permettant de moduler l’excitabilité des neurones suivant des lésions du système nerveux central ont été développées. Ces méthodes sont maintenant couramment utilisées pour étudier l’effet de l’inhibition du cortex contralésionnel sur la récupération motrice à la suite d’un accident vasculocérébral (AVC). Bien que plusieurs de ces études rapportent des résultats prometteurs, les paramètres permettant une récupération optimale demeurent encore inconnus. Chez les patients victimes d'un AVC, il est difficile de débuter les traitements rapidement et d'initier l’inhibition dans les heures suivant la lésion. L'impact de ce délai est toujours inconnu. De plus, aucune étude n’a jusqu’à maintenant évalué l’effet de la durée de l’inhibition sur la récupération du membre parétique. Dans le laboratoire du Dr Numa Dancause, nous avons utilisé un modèle bien établi de lésion ischémique chez le rat pour explorer ces questions. Nos objectifs étaient d’évaluer 1) si une inactivation de l’hémisphère contralésionnel initiée dans les heures qui suivent la lésion peut favoriser la récupération et 2) l’effet de la durée de l’inactivation sur la récupération du membre parétique. Suite à une lésion dans le cortex moteur induite par injections d’un vasoconstricteur, nous avons inactivé l’hémisphère contralésionnel à l’aide d’une pompe osmotique assurant l’infusion continue d’un agoniste du GABA (Muscimol). Dans différents groupes expérimentaux, nous avons inactivé l’hémisphère contralésionnel pour une durée de 3, 7 et 14 jours suivant la lésion. Dans un autre groupe, le Muscimol a été infusé pour 14 jours mais à un débit moindre de façon à pouvoir étudier le lien entre la fonction du membre non-parétique et la récupération du membre parétique. Les données comportementales de ces groupes ont été comparées à celles d’animaux ayant récupéré de façon spontanée d'une lésion similaire. Nos résultats indiquent que l’augmentation de la durée de l’inactivation (de 3 à 14 jours) accélère la récupération du membre parétique. De plus, les deux groupes ayant reçu une inactivation d'une durée de 14 jours ont montré une plus grande récupération fonctionnelle que le groupe n’ayant pas reçu d’inactivation de l’hémisphère contralésionnel, le groupe contrôle. Nos résultats suggèrent donc que l’inactivation de l’hémisphère contralésionnel initiée dans les heures suivant la lésion favorise la récupération du membre parétique. La durée d’inhibition la plus efficace (14 jours) dans notre modèle animal est beaucoup plus longues que celles utilisées jusqu’à maintenant chez l’homme. Bien qu’il soit difficile d’extrapoler la durée idéale à utiliser chez les patients à partir de nos données, nos résultats suggèrent que des traitements de plus longue durée pourraient être bénéfiques. Finalement, un message clair ressort de nos études sur la récupération fonctionnelle après un AVC: dans le développement de traitements basés sur l’inhibition de l’hémisphère contralésionnel, la durée de l’inactivation est un facteur clef à considérer.

Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.

Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society.

Cortical control of facial expression.

The present topical review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human non-verbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be both voluntarily or emotionally controlled. Recent studies in non-human primates and humans revealed that the motor control of facial expressions has a distributed neural representation. At least 5 cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and, finally, the rostral and caudal cingulate cortex. The results of studies in humans and non-human primates suggest that the innervation of the face is bilaterally controlled for the upper part, and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cortex, the ventral lateral premotor cortex, and the supplementary motor area are essential for the voluntary control of facial expressions. In contrast, the cingulate cortical areas are important for emotional expression, since they receive input from different structures of the limbic system. This article is protected by copyright. All rights reserved.

Leading role of thalamic over cortical neurons during postinhibitory rebound excitation

The postinhibitory rebound excitation is an intrinsic property of thalamic and cortical neurons that is implicated in a variety of normal and abnormal operations of neuronal networks, such as slow or fast brain rhythms during different states of vigilance as well as seizures. We used dual simultaneous intracellular recordings of thalamocortical neurons from the ventrolateral nucleus and neurons from the motor cortex, together with thalamic and cortical field potentials, to investigate the temporal relations between thalamic and cortical events during the rebound excitation that follows prolonged periods of stimulus-induced inhibition. Invariably, the rebound spike-bursts in thalamocortical cells occurred before the rebound depolarization in cortical neurons and preceded the peak of the depth-negative, rebound field potential in cortical areas. Also, the inhibitory-rebound sequences were more pronounced and prolonged in cortical neurons when elicited by thalamic stimuli, compared with cortical stimuli. The role of thalamocortical loops in the rebound excitation of cortical neurons was shown further by the absence of rebound activity in isolated cortical slabs. However, whereas thalamocortical neurons remained hyperpolarized after rebound excitation, because of the prolonged spike-bursts in inhibitory thalamic reticular neurons, the rebound depolarization in cortical neurons was prolonged, suggesting the role of intracortical excitatory circuits in this sustained activity. The role of intrathalamic events in triggering rebound cortical activity should be taken into consideration when analyzing information processes at the cortical level; at each step, corticothalamic volleys can set into action thalamic inhibitory neurons, leading to rebound spike-bursts that are transferred back to the cortex, thus modifying cortical activities.

Specialization in pyramidal cell structure in the sensory-motor cortex of the vervet monkey (Cercopethicus pygerythrus)

Recent studies have revealed systematic differences in the pyramidal cell structure between functionally related cortical areas of primates. Trends for a parallel in pyramidal cell structure and functional complexity have been reported in visual, somatosensory, motor, cingulate and prefrontal cortex in the macaque monkey cortex. These specializations in structure have been interpreted as being fundamental in determining cellular and systems function, endowing circuits in these different cortical areas with different computational power. In the present study we extend our initial finding of systematic specialization of pyramidal cell structure in sensory-motor cortex in the macaque monkey [Cereb Cortex 12 (2002) 1071] to the vervet monkey. More specifically, we investigated pyramidal cell structure in somatosensory and motor areas 1/2, 5, 7, 4 and 6. Neurones in fixed, flat-mounted, cortical slices were injected intracellularly with Lucifer Yellow and processed for a light-stable 3,3'-diaminobenzidine reaction product. The size of, number of branches in, and spine density of the basal dendritic arbors varied systematically such that there was a trend for increasing complexity in arbor structure with progression through 1/2, 5 and 7. In addition, cells in area 6 were larger, more branched, and more spinous than those in area 4. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

Specialization in pyramidal cell structure in the sensory-motor cortex of the chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species. (c) 2005 Wiley-Liss, Inc.

Ipsilateral corticocortical projections to the primary and middle temporal visual areas of the primate cerebral cortex: area-specific variations in the morphology of connectionally identified pyramidal cells

We quantified the morphology of over 350 pyramidal neurons with identified ipsilateral corticocortical projections to the primary (V1) and middle temporal (MT) visual areas of the marmoset monkey, following intracellular injection of Lucifer Yellow into retrogradely labelled cells. Paralleling the results of studies in which randomly sampled pyramidal cells were injected, we found that the size of the basal dendritic tree of connectionally identified cells differed between cortical areas, as did the branching complexity and spine density. We found no systematic relationship between dendritic tree structure and axon target or length. Instead, the size of the basal dendritic tree increased roughly in relation to increasing distance from the occipital pole, irrespective of the length of the connection or the cortical layer in which the neurons were located. For example, cells in the second visual area had some of the smallest and least complex dendritic trees irrespective of whether they projected to V1 or MT, while those in the dorsolateral area (DL) were among the largest and most complex. We also observed that systematic differences in spine number were more marked among V1-projecting cells than MT-projecting cells. These data demonstrate that the previously documented systematic differences in pyramidal cell morphology between areas cannot simply be attributed to variable proportions of neurons projecting to different targets, in the various areas. Moreover, they suggest that mechanisms intrinsic to the area in which neurons are located are strong determinants of basal dendritic field structure.

Investigations of attentional processing in parietal and occipital human cortical regions with magnetoencephalography

Attention defines our mental ability to select and respond to stimuli, internal or external, on the basis of behavioural goals in the presence of competing, behaviourally irrelevant, stimuli. The frontal and parietal cortices are generally agreed to be involved with attentional processing, in what is termed the 'fronto-parietal' network. The left parietal cortex has been seen as the site for temporal attentional processing, whereas the right parietal cortex has been seen as the site for spatial attentional processing. There is much debate about when the modulation of the primary visual cortex occurs, whether it is modulated in the feedforward sweep of processing or modulated by feedback projections from extrastriate and higher cortical areas. MEG and psychophysical measurements were used to look at spatially selective covert attention. Dual-task and cue-based paradigms were used. It was found that the posterior parietal cortex (PPC), in particular the SPL and IPL, was the main site of activation during these experiments, and that the left parietal lobe was activated more strongly than the right parietal lobe throughout. The levels of activation in both parietal and occipital areas were modulated in accordance with attentional demands. It is likely that spatially selective covert attention is dominated by the left parietal lobe, and that this takes the form of the proposed sensory-perceptual lateralization within the parietal lobes. Another form of lateralization is proposed, termed the motor-processing lateralization, the side of dominance being determined by handedness, being reversed in left- relative to right-handers. In terms of the modulation of the primary visual cortex, it was found that it is unlikely that V1 is modulated initially; rather the modulation takes the form of feedback from higher extrastriate and parietal areas. This fits with the idea of preattentive visual processing, a commonly accepted idea which, in itself, prevents the concept of initial modulation of V1.

Investigating the human mirror neuron system by means of cortical synchronization during the imitation of biological movements

The human mirror neuron system (MNS) has recently been a major topic of research in cognitive neuroscience. As a very basic reflection of the MNS, human observers are faster at imitating a biological as compared with a non-biological movement. However, it is unclear which cortical areas and their interactions (synchronization) are responsible for this behavioural advantage. We investigated the time course of long-range synchronization within cortical networks during an imitation task in 10 healthy participants by means of whole-head magnetoencephalography (MEG). Extending previous work, we conclude that left ventrolateral premotor, bilateral temporal and parietal areas mediate the observed behavioural advantage of biological movements in close interaction with the basal ganglia and other motor areas (cerebellum, sensorimotor cortex). Besides left ventrolateral premotor cortex, we identified the right temporal pole and the posterior parietal cortex as important junctions for the integration of information from different sources in imitation tasks that are controlled for movement (biological vs. non-biological) and that involve a certain amount of spatial orienting of attention. Finally, we also found the basal ganglia to participate at an early stage in the processing of biological movement, possibly by selecting suitable motor programs that match the stimulus.