Motor Cortex Representation of the Upper-Limb in Individuals Born without a Hand

The body schema is an action-related representation of the body that arises from activity in a network of multiple brain areas. While it was initially thought that the body schema developed with experience, the existence of phantom limbs in individuals born without a limb (amelics) led to the suggestion that it was innate. The problem with this idea, however, is that the vast majority of amelics do not report the presence of a phantom limb. Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) of traumatic amputees can evoke movement sensations in the phantom, suggesting that traumatic amputation does not delete movement representations of the missing hand. Given this, we asked whether the absence of a phantom limb in the majority of amelics means that the motor cortex does not contain a cortical representation of the missing limb, or whether it is present but has been deactivated by the lack of sensorimotor experience. In four upper-limb amelic subjects we directly stimulated the arm/hand region of M1 to see 1) whether we could evoke phantom sensations, and 2) whether muscle representations in the two cortices were organised asymmetrically. TMS applied over the motor cortex contralateral to the missing limb evoked contractions in stump muscles but did not evoke phantom movement sensations. The location and extent of muscle maps varied between hemispheres but did not reveal any systematic asymmetries. In contrast, forearm muscle thresholds were always higher for the missing limb side. We suggest that phantom movement sensations reported by some upper limb amelics are mostly driven by vision and not by the persistence of motor commands to the missing limb within the sensorimotor cortex. We propose that prewired movement representations of a limb need the experience of movement to be expressed within the primary motor cortex

Beyond language: The unspoken sensory-motor representation of the tongue in non-primates, non-human and human primates

The English idiom “on the tip of my tongue” commonly acknowledges that something is known, but it cannot be immediately brought to mind. This phrase accurately describes sensorimotor functions of the tongue, which are fundamental for many tongue-related behaviors (e.g., speech), but often neglected by scientific research. Here, we review a wide range of studies conducted on non-primates, non-human and human primates with the aim of providing a comprehensive description of the cortical representation of the tongue's somatosensory inputs and motor outputs across different phylogenetic domains. First, we summarize how the properties of passive non-noxious mechanical stimuli are encoded in the putative somatosensory tongue area, which has a conserved location in the ventral portion of the somatosensory cortex across mammals. Second, we review how complex self-generated actions involving the tongue are represented in more anterior regions of the putative somato-motor tongue area. Finally, we describe multisensory response properties of the primate and non-primate tongue area by also defining how the cytoarchitecture of this area is affected by experience and deafferentation

Tell it to the hand: Attentional modulation in the identification of misoriented chiral objects

Research in the field of cognitive neuroscience and neuropsychology on spatial cognition and mental imagery has increased considerably over the last few decades. While at the beginning of the XX century studying imagery was considered an object of derision \u2013 a \u2015sheer bunk\u2016 (Watson, 1928) \u2013 at the present, imagery researchers have successfully developed models and improved behavioral and neurophysiological measures (e.g., Kosslyn et al., 2006). Mental rotation constituted a major advance in terms of behavioral measures sensitive to imaginative operations executed on visual representations (i.e., Shepard & Cooper, 1982). The linearity of modulation between response times and angular disparity of the images allowed a quantitative estimate of imagery processes. The experiments described in the present thesis were motivated by the intent to continue and extend the understanding of such fascinating mental phenomena. The evolution of the present work took initial steps from the adoption of a behavioral paradigm, the hand laterality judgment task, as privileged tool for studying motor imagery in healthy individuals and brain-damaged patients. The similarity with mental rotation tasks and the implicit nature of the task made it the best candidate to test hypotheses regarding the mental simulation of body movements. In this task, response times are linearly affected by the angular departures the hand pictures are shown in, as for mental rotation, and their distributions are asymmetric between left and right hands. Drawing from these task features a widely held view posits that laterality judgment of rotated hand pictures requires participants to imagine hand-arm movements, although they receive no instruction to do so (e.g., Parsons, 1987a; Parsons, 1994). In Chapter 1, I provided a review of the relevant literature on visual and motor imagery. Particular aspects of the mental rotation literature are also explored. In Chapter 2, I examined the hand laterality task and the vast literature of studies that employed this task as means to test motor imagery processes. An alternative view to the motor imagery account is also discussed (i.e., the disembodied account). In Chapter 3, I exploited the hand laterality task, and a visual laterality task (Tomasino et al., 2010) to test motor and visual imagery abilities in a group of healthy aged individuals. In Chapter 4, I described an alternative view that has been proposed by others to explain the pattern of RTs in the hand laterality task: The multisensory integration account (Grafton & Viswanathan, 2014). In this view, hand laterality is recognized by pairing information between the seen hand's visual features and the observer's felt own hand. In Chapter 5, I tested and found evidence for a new interpretation of the particular configuration of response times in the hand laterality task. I demonstrated a spatial compatibility effect for rotated pictures of hands given by the interaction between the direction of stimulus rotation (clockwise vs. counterclockwise) and the laterality of the motor response. These effects changed by following temporal dynamics that were attributed to shifts of spatial attention. In the same chapter, I conducted other psychophysics experiments that confirmed the role of spatial attention and that ruled out the view of multisensory integration as the key aspect in determining the asymmetries of the response times' distribution. In Chapter 6, I conducted a study with patients suffering from Unilateral Neglect in which they performed the hand laterality task and a visual laterality task. The findings indicated that patients failed to integrate visual information with spatially incompatible responses irrespective of the type of task, and depending on egocentric stimulus-response spatial codes. A general discussion is presented in Chapter 7

Development and Evaluation of Tongue Operated Robotic Rehabilitation Paradigm for Stroke Survivors with Upper Limb Paralysis

Stroke is a devastating condition that may cause upper limb paralysis. Robotic rehabilitation with self-initiated and assisted movements is a promising technology that could help restore upper limb function. The objective of this research is to develop and evaluate a tongue-operated exoskeleton that will harness the intention of stroke survivors with upper limb paralysis via tongue motion to control robotic exoskeleton during rehabilitation to achieve functional restoration and improve quality of life. Specifically, a tongue operated assistive technology called the Tongue Drive System is used to harness the tongue gesture to generate commands. And, the generated command is used to control rehabilitation robot such as wrist-based exoskeleton Hand Mentor ProTM (HM) and upper limb-based exoskeleton KINARMTM. Through a pilot experiment with 3 healthy participants, we have demonstrated the functionality of an enhanced TDS-HM with pressure-sensing capability. The system can add a programmable load force to increase the exercise intensity in isotonic mode. Through experiments with healthy and stroke subjects, we have demonstrated that the TDS-KINARM system could accurately translate tongue commands to exoskeleton arm movements, quantify function of the upper limb and perform rehabilitation training. Specifically, all healthy subjects and stroke survivors successfully performed target reaching and tracking tasks in all control modes. One of the stroke patients showed clinically significant improvement. We also analyzed the arm reaching kinematics of healthy subjects in 4 modes (active, active viscous, discrete tongue, and proportional tongue) of TDS-KINARM operation. The results indicated that the proportional tongue mode was a better candidate than the discrete tongue mode for the tongue assisted rehabilitation. This study also provided initial insights into possible kinematic similarities between tongue-operated and voluntary arm movements. Furthermore, the results showed that the viscous resistance to arm motion did not affect kinematics of arm reaching movements significantly. Finally, through a 6 healthy subject experiment, we observed a tendency of a facilitatory effect of adding tongue movement to limb movement on event-related desynchronization in EEG, implying enhanced brain excitability. This effect may contribute to enhanced rehabilitation outcome in stroke survivors using TDS with motor rehabilitation.Ph.D

VALIDATION OF A MODEL OF SENSORIMOTOR INTEGRATION WITH CLINICAL BENEFITS

Healthy sensorimotor integration – or how our touch influences our movements – is critical to efficiently interact with our environment. Yet, many aspects of this process are still poorly understood. Importantly, several movement disorders are often considered as originating from purely motor impairments, while a sensory origin could also lead to a similar set of symptoms. To alleviate these issues, we hereby propose a novel biologically-based model of the sensorimotor loop, known as the SMILE model. After describing both the functional, and the corresponding neuroanatomical versions of the SMILE, we tested several aspects of its motor component through functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS). Both experimental studies resulted in coherent outcomes with respect to the SMILE predictions, but they also provided novel scientific outcomes about such broad topics as the sub-phases of motor imagery, the neural processing of bodily representations, or the extend of the role of the extrastriate body area. In the final sections of this manuscript, we describe some potential clinical application of the SMILE. The first one presents the identification of plausible neuroanatomical origins for focal hand dystonia, a yet poorly understood sensorimotor disorder. The last chapter then covers possible improvements on brain-machine interfaces, driven by a better understanding of the sensorimotor system. -- La façon dont votre sens du toucher et vos mouvements interagissent est connue sous le nom d’intégration sensorimotrice. Ce procédé est essentiel pour une interaction normale avec tout ce qui nous entoure. Cependant, plusieurs aspects de ce processus sont encore méconnus. Plus important encore, l’origine de certaines déficiences motrices encore trop peu comprises sont parfois considérées comme purement motrice, alors qu’une origine sensorielle pourrait mener à un même ensemble de symptômes. Afin d’améliorer cette situation, nous proposons ici un nouveau modèle d’intégration sensorimotrice, dénommé « SMILE », basé sur les connaissances de neurobiologie actuelles. Dans ce manuscrit, nous commençons par décrire les caractéristiques fonctionnelles et neuroanatomiques du SMILE. Plusieurs expériences sont ensuite effectuées, via l’imagerie par résonance magnétique fonctionnelle (IRMf), et la stimulation magnétique transcranienne (SMT), afin de tester différents aspects de la composante motrice du SMILE. Si les résultats de ces expériences corroborent les prédictions du SMILE, elles ont aussi mis en évidences d’autres résultats scientifiques intéressants et novateurs, dans des domaines aussi divers que les sous-phases de l’imagination motrice, les processus cérébraux liés aux représentations corporelles, ou encore l’extension du rôle de l’extrastriate body area. Dans les dernières parties de ce manuscrit, nous dévoilons quelques applications cliniques potentielles de notre modèle. Nous utilisons le SMILE afin de proposer deux origines cérébrales plausibles de la dystonie focale de la main. Le dernier chapitre présente comment certaines technologies existantes, telles que les interfaces cerveaux-machines, pourraient bénéficier d’une meilleure compréhension du système sensorimoteur

Decoding ECoG signal into 3D hand translation using deep learning

Motor brain-computer interfaces (BCIs) are a promising technology that may enable motor-impaired people to interact with their environment. Designing real-time and accurate BCI is crucial to make such devices useful, safe, and easy to use by patients in a real-life environment. Electrocorticography (ECoG)-based BCIs emerge as a good compromise between invasiveness of the recording device and good spatial and temporal resolution of the recorded signal. However, most ECoG signal decoders used to predict continuous hand movements are linear models. These models have a limited representational capacity and may fail to capture the relationship between ECoG signal and continuous hand movements. Deep learning (DL) models, which are state-of-the-art in many problems, could be a solution to better capture this relationship. In this study, we tested several DL-based architectures to predict imagined 3D continuous hand translation using time-frequency features extracted from ECoG signals. The dataset used in the analysis is a part of a long-term clinical trial (ClinicalTrials.gov identifier: NCT02550522) and was acquired during a closed-loop experiment with a tetraplegic subject. The proposed architectures include multilayer perceptron (MLP), convolutional neural networks (CNN), and long short-term memory networks (LSTM). The accuracy of the DL-based and multilinear models was compared offline using cosine similarity. Our results show that CNN-based architectures outperform the current state-of-the-art multilinear model. The best architecture exploited the spatial correlation between neighboring electrodes with CNN and benefited from the sequential character of the desired hand trajectory by using LSTMs. Overall, DL increased the average cosine similarity, compared to the multilinear model, by up to 60%, from 0.189 to 0.302 and from 0.157 to 0.249 for the left and right hand, respectively

Neurostimulation of the Rat Motor System

Ce document fait la synthèse d'un ensemble de travaux concernant la nature de la plasticité neuronale et la manière dont la neurostimulation peut être utilisée pour améliorer la récupération motrice après une atteinte neurologique. Nous commençons par les principes fondamentaux généraux des neurosciences, la structure du système nerveux moteur chez l'homme et le rat, ainsi qu'une brève discussion sur les lésions neurologiques. Les sujets sont vastes et couverts avec la brièveté nécessaire, mais ils fournissent un contexte essentiel pour les chapitres suivants, présentés sous forme d'articles scientifiques. Dans le premier article, nous passons en revue le domaine de la neurostimulation sous ses aspects fondamental et clinique avec l'Accident Vasculaire Cerebral (AVC) en tant que maladie modèle pour les lésions neurologiques. Nous classifions les interventions de stimulation en trois modèles différents d'induction de la plasticité. Notre thèse centrale est qu'une meilleure compréhension des règles sous-jacentes de la plasticité, accompagnée de progrès dans une plus grande précision spatio-temporelle, est nécessaire pour faire avancer le domaine de la neurostimulation. Dans le deuxième article, nous décrivons, étape par étape, un nouveau protocole pour évaluer l'excitabilité corticospinale chez le rongeur éveillé pendant le comportement libre, ainsi que les plateformes matérielles et logicielles associées que notre équipe a développées à cette fin. L'une de ses principale caractéristique est la possibilité d'évaluer l'excitabilité corticomotrice en boucle fermée, en fonction de l'EMG, une nouvelle façon d'accroître l'uniformité des mesures sur des animaux en comportement. Cette plateforme de développement sera utile aux neuroscientifiques intéressés par l'évaluation de l'excitabilité du système nerveux chez les rongeurs éveillés par le biais d'une interrogation électrique ou optogénétique, un intermédiaire important avant les essais chez les primates non humains et éventuellement chez les humains. Dans le troisième article, nous avons utilisé cette plateforme prototype pour étudier la stimulation électrique associative appariée et le rôle de la plasticité dépendant de la synchronisation des potentiels d'action chez des rats implantés de façon chronique, sans l'influence de l'anesthésie. Nous nous sommes concentrés sur la variation systématique de l'intervalle entre la stimulation corticale et musculaire dans notre cohorte d'animaux afin de révéler l'effet de la synchronisation relative de l'activité aux niveaux cortical et spinal. Nous n'avons pas observé de potentialisation significative dans tous les intervalles de stimulation testés, mais plutôt des tendances vers des effets de type LTD dans la plupart des conditions de synchronisation. Nous discutons des raisons possibles pour lesquelles nous avons observé ces résultats. Dans le dernier article et dans le projet en cours, nous décrivons les premiers travaux prometteurs impliquant la neurostimulation optogénétique et électrique, ainsi que la réadaptation post-AVC comme tremplin pour des recherches futures. Nous concluons par une discussion générale et nous nous projetons dans l'avenir, tant à moyen qu'à long terme. La poursuite scientifique, tant sur le plan personnel que sur celui du domaine, se poursuivra, comme il se doit. Bien que ce travail soit conçu pour être lu dans un ordre séquentiel, chaque chapitre est indépendant. Collectivement, les travaux de cette thèse posent les bases et plaident en faveur d'une meilleure compréhension de la plasticité neuronale, du développement d'outils pour l'évaluer et de l'étude de ses applications pratiques pour parvenir à une meilleure récupération motrice après une lésion neurologique.This document synthesizes a body of work concerning the nature of neural plasticity and how neurostimulation may be used to improve motor recovery after neurological insult. We begin with general foundational principles in neuroscience, the structure of the nervous and motor systems in humans and rats, and a brief discussion of neurological injury. The topics are broad and covered with the necessary brevity, but provides critical context for the following chapters. In the first paper, we review the fields of neurostimulation across the clinical and basic science domains in the service of stroke as a model disease for neurological injury, framing the field in terms of three different models of plasticity induction. Our central thesis here is that enhanced understanding of the underlying rules of plasticity, accompanied with advances in greater spatiotemporal precision is necessary to move the field of neurostimulation forward. In the second paper we describe a stable, novel step-by-step protocol to assess corticospinal excitability in the awake, freely behaving rodent, and the associated hardware and software platforms that our team has developed for this purpose. A core feature enables corticomotor excitability assessment in a closed-loop, Electromyogram (EMG)-dependent manner, a novel way of increasing consistency during free behavior in untrained animals. This development platform will be of use to neuroscientists interested in assessing the excitability of the nervous system in awake, unrestrained rodents via electrical or optogenetic interrogation, an important intermediary before trials in non-human primates and eventually humans. In the third paper, we used this prototype platform to investigate electrical paired associative stimulation and the role of spike-timing-dependent plasticity in chronically implanted rats, without the influence of anaesthesia. Our focus was on systematically varying the Inter-Stimulus Interval (ISI) between cortical and muscle stimulation in our animal cohort in order to reveal the effect of relative activity timing at both the cortical and spinal levels. We did not observe significant potentiation across all of the stimulus intervals we tested, but instead observed trends towards Long-Term Depression (LTD)-like effects in the short term across most timing conditions. We discuss possible reasons why we observed these results. In the final paper and project currently in progress, we describe early promising work involving optogenetic and electrical neurostimulation, and stroke recovery as a launchpad for future investigations. We conclude with a general discussion and peer into the future, both in the medium term and the long term. The scientific pursuit, both personally and as a field will continue, as it should. Although this work is designed to be read in sequential order, each chapter stands alone. Collectively, the work in this thesis lays the groundwork and argues for a greater understanding of neural plasticity, development of tools to assess it, and study of its practical applications to achieve enhanced motor recovery after neurological injury

Neural plasticity and the limits of scientific knowledge

Western science claims to provide unique, objective information about the world. This is supported by the observation that peoples across cultures will agree upon a common description of the physical world. Further, the use of scientific instruments and mathematics is claimed to enable the objectification of science. In this work, carried out by reviewing the scientific literature, the above claims are disputed systematically by evaluating the definition of physical reality and the scientific method, showing that empiricism relies ultimately upon the human senses for the evaluation of scientific theories and that measuring instruments cannot replace the human sensory system. Nativist and constructivist theories of human sensory development are reviewed, and it is shown that nativist claims of core conceptual knowledge cannot be supported by the findings in the literature, which shows that perception does not simply arise from a process of maturation. Instead, sensory function requires a long process of learning through interactions with the environment. To more rigorously define physical reality and systematically evaluate the stability of perception, and thus the basis of empiricism, the development of the method of dimension analysis is reviewed. It is shown that this methodology, relied upon for the mathematical analysis of physical quantities, is itself based upon empiricism, and that all of physical reality can be described in terms of the three fundamental dimensions of mass, length and time. Hereafter the sensory modalities that inform us about these three dimensions are systematically evaluated. The following careful analysis of neuronal plasticity in these modalities shows that all the relevant senses acquire from the environment the capacity to apprehend physical reality. It is concluded that physical reality is acquired rather than given innately, and leads to the position that science cannot provide unique results. Rather, those it can provide are sufficient for a particular environmental setting