Integrating Cortical Sensorimotor Representations Across Spatial Scales and Task Contexts

Our understanding of how brains function is stratified between two very different scales: mesoscale (what function a given cortical area performs), measured with tools like fMRI; and microscale (what a given neuron does), measured with implanted microelectrodes. While extensive research has been done to characterize brain activity at both of these spatial scales, describing relationships between these two domains has proven difficult. Identifying ways to integrate findings between these scales is valuable for both research and clinical applications, but is particularly important for intracortical brain-computer interfaces (BCIs), which aim to restore motor function after paralysis or amputation. In humans, the brain is much larger than the available microelectrode arrays, so determining where to place the arrays is a critical aspect of ensuring optimal performance. BCIs preferentially target primary motor and somatosensory cortices, due to their direct relationship to motor control and critical role in skilled and dexterous movements. However, despite these areas displaying a relatively ordered spatial organization, it is difficult to accurately predict the behavior of neurons recorded from a given area for several reasons. Mesoscale activity is overlapping, with activity relating to multiple different movements observed in a single area. Additionally, neurons have flexible behavior, displaying different “tuning” to similar behavior under different contexts. Here I present my research integrating neuroimaging-based cortical mapping with directly-recorded neural activity in human sensorimotor cortex. First, I examine how the large-scale organization of sensorimotor representations measured with fMRI is affected by contextual sensory information. I then examine how spatially separate neural populations recorded with intracortical microelectrode arrays encode different types of movement. Finally, I examine whether how population encoding changes to reflect contextual sensory information using the same task as in the fMRI study. Together, these results provide a foundation for reconciling neural activity across spatial scales and task contexts, and will inform the design and placement of more capable BCI systems

A low-dimensional representation of arm movements and hand grip forces in post-stroke individuals

Characterizing post-stroke impairments in the sensorimotor control of arm and hand is essential to better understand altered mechanisms of movement generation. Herein, we used a decomposition algorithm to characterize impairments in end-effector velocity and hand grip force data collected from an instrumented functional task in 83 healthy control and 27 chronic post-stroke individuals with mild-to-moderate impairments. According to kinematic and kinetic raw data, post-stroke individuals showed reduced functional performance during all task phases. After applying the decomposition algorithm, we observed that the behavioural data from healthy controls relies on a low-dimensional representation and demonstrated that this representation is mostly preserved post-stroke. Further, it emerged that reduced functional performance post-stroke correlates to an abnormal variance distribution of the behavioural representation, except when reducing hand grip forces. This suggests that the behavioural repertoire in these post-stroke individuals is mostly preserved, thereby pointing towards therapeutic strategies that optimize movement quality and the reduction of grip forces to improve performance of daily life activities post-stroke

Reaching for the light: The prioritization of conspicuous visual stimuli for reflexive target-directed reaching

The degree to which something stands out against the background of its environment communicates important information. The phenomenon of camouflage is a testament of the degree to which visual salience and probability of survival tend to overlap. Salient stimuli often elicit fast, reflexive movements in order to catch prey or avoid a predator. The overarching goal of the work presented in this thesis is to investigate how the physical salience of visual stimuli influence the programming and execution of reaching movements. I approached this question by recording kinematics and muscle responses during reaching movements. Broadly, this thesis investigates the effect of the physical salience of targets on the magnitude and latency of involuntary, spatially tuned muscle responses toward those targets. In Chapters 2 and 3, subjects reached toward an array of potential targets on a touchscreen. The final target was cued only after the reaching movement was initiated. From trial to trial, targets differed in their numerosity (i.e., how many on the left versus the right) and in their salience (i.e., their relative contrast with the background). Different amounts of delay were introduced between the appearance of the targets and the cue to move. The results from these two studies demonstrate that the physical salience of (i.e., the luminance contrast differences between) targets influences the timing and the magnitude of involuntary deviations toward the most salient target(s) during reaching movements. At the level of individual subjects, the degree to which someone involuntarily reached toward the salient stimulus was predicted by the relationship between processing speeds for the different target contrasts. In Chapter 4, subjects reached toward individual targets that varied in luminance contrast. Muscle activity in the right pectoralis major was recorded with intramuscular electrodes. Consistent with past studies, there was a consistent muscle response that was time-locked to the appearance of the target, regardless of the reaction time for the ensuing reaching movement. The same processing speed differences and magnitude modulations observed in Chapters 2 and 3 (due to different luminance contrast values of the targets) were observed in these stimulus-locked muscle responses. Further testing revealed that stimulus-locked responses were elicited by a delayed, spatially uninformative go-cue

Biomechanics

Biomechanics is a vast discipline within the field of Biomedical Engineering. It explores the underlying mechanics of how biological and physiological systems move. It encompasses important clinical applications to address questions related to medicine using engineering mechanics principles. Biomechanics includes interdisciplinary concepts from engineers, physicians, therapists, biologists, physicists, and mathematicians. Through their collaborative efforts, biomechanics research is ever changing and expanding, explaining new mechanisms and principles for dynamic human systems. Biomechanics is used to describe how the human body moves, walks, and breathes, in addition to how it responds to injury and rehabilitation. Advanced biomechanical modeling methods, such as inverse dynamics, finite element analysis, and musculoskeletal modeling are used to simulate and investigate human situations in regard to movement and injury. Biomechanical technologies are progressing to answer contemporary medical questions. The future of biomechanics is dependent on interdisciplinary research efforts and the education of tomorrow’s scientists

A randomized controlled trial on the effects induced by robot-assisted and usual-care rehabilitation on upper limb muscle synergies in post-stroke subjects

Muscle synergies are hypothesized to reflect connections among motoneurons in the spinal cord activated by central commands and sensory feedback. Robotic rehabilitation of upper limb in post-stroke subjects has shown promising results in terms of improvement of arm function and motor control achieved by reassembling muscle synergies into a set more similar to that of healthy people. However, in stroke survivors the potentially neurophysiological changes induced by robot-mediated learning versus usual care have not yet been investigated. We quantified upper limb motor deficits and the changes induced by rehabilitation in 32 post-stroke subjects through the movement analysis of two virtual untrained tasks of object placing and pronation. The sample analyzed in this study is part of a larger bi-center study and included all subjects who underwent kinematic analysis and were randomized into robot and usual care groups. Post-stroke subjects who followed robotic rehabilitation showed larger improvements in axial-to-proximal muscle synergies with respect to those who underwent usual care. This was associated to a significant improvement of the proximal kinematics. Both treatments had negative effects in muscle synergies controlling the distal district. This study supports the definition of new rehabilitative treatments for improving the neurophysiological recovery after stroke

Dynamic landscapes and human dispersal patterns : tectonics, coastlines, and the reconstruction of human habitats

Studies of the impact of physical environment on human evolution usually focus on climate as the main external forcing agent of evolutionary and cultural change. In this paper we focus on changes in the physical character of the landscape driven by geophysical processes as an equally potent factor. Most of the landscapes where finds of early human fossils and artefacts are concentrated are ones that have been subjected to high levels of geological instability, either because of especially active tectonic processes associated with faulting and volcanic activity or because of proximity to coastlines subject to dramatic changes of geographical position and physical character by changes of relative sea level. These processes can have both beneficial effects, creating ecologically attractive conditions for human settlement, and deleterious or disruptive ones, creating barriers to movement, disruption of ecological conditions, or hazards to survival. Both positive and negative factors can have powerful selective effects on human behaviour and patterns of settlement and dispersal. We consider both these aspects of the interaction, develop a framework for the reconstruction and comparison of landscapes and landscape change at a variety of scales, and illustrate this with selected examples drawn from Africa and Arabia

Effects of overground walking with a robotic exoskeleton on lower limb muscle synergies

Les exosquelettes robotisés de marche (ERM) représentent une intervention prometteuse dans le domaine de la réadaptation locomotrice. Sur le plan clinique, les ERM facilitent la mise en application de principes de neuroplasticité. Jusqu'à présent, la majorité des études analysant les effets de l’ERM a été menée avec des ERM fournissant une assistance robotique complète le long d’une trajectoire de mouvements prédéfinie des membres inférieurs (MI) de façon à reproduire la marche de façon quasi parfaite à très basse vitesse. La nouvelle génération d’ERM, maintenant disponible sur le marché, propose de nouveaux modes de contrôles qui permettent, entre autres, une liberté de mouvement accrue aux MIs (c.-à-d. trajectoire non imposée) et une possibilité d’offrir une assistance ou résistance aux mouvements de différentes intensités surtout pendant la phase d’oscillation du cycle de marche. Cependant, les effets de ces modes de contrôles sur la coordination musculaire des MI pendant la marche au sol avec l’ERM, caractérisé via l’extraction de synergies musculaires (SM), restent méconnus. Cette thèse mesure et compare les caractéristiques des SM (c.-à-d. nombre, profils d’activation, composition musculaire et contribution relative des muscles) pendant la la marche au sol sans ou avec un ERM paramétré avec six différents modes de contrôle chez des individus en bonne santé (articles #1 et #2) et d’autres ayant une lésion médullaire incomplète (LMI) (article #3). Les signaux électromyographiques (EMG) des différents muscles clés des MI, enregistrés lors de la marche, ont été utilisés afin d’extraire les SM avec un algorithme de factorisation matricielle non négative. La similarité des cosinus et les coefficients de corrélation ont caractérisé les similitudes entre les caractéristiques des SM. Les résultats montrent que: 1) les profils d'activation temporelle et le nombre de SM sont modifiés en fonction de la vitesse de marche avec, entre autres une augmentation de la vitesse de marche entrainant une fusion de SM, chez les individus en bonne santé marchant sans ERM ; 2) lorsque ces derniers marchent avec un ERM, les différents modes de contrôle testés ne dupliquent pas adéquatement les SM retrouvées lors de la marche sans ERM. En fait, uniquement le mode de contrôle libérant la contrainte de trajectoire de mouvements des MIs dans le plan sagittal lors de la phase d’oscillation reproduit les principales caractéristiques des SM retrouvées pendant la marche sans ERM ; 3) le nombre et la composition musculaire des SM sont modifiés pendant la marche sans ERM chez les personnes ayant une LMI. Cependant, parmi tous les modes de contrôle étudiés, seul le mode de contrôle libérant le contrôle de la trajectoire de mouvements des MI et assistant l’oscillation du MIs (c.-à-d. HASSIST) permets l’extraction de SM similaire à celles observées chez des individus en santé lors d'une marche sans ERM. Dans l’ensemble, cette thèse a mis en évidence le fait que différentes demandes biomécaniques liées à la marche (c.-à-d. vitesse de marche, modes de contrôle de l’ERM) modifient le nombre et les caractéristiques de SM chez les personnes en santé. Cette thèse a également confirmé que la coordination musculaire, mise en évidence via l’analyse de SM, est altérée chez les personnes ayant une LMI et a tendance à se normaliser lors de la marche avec l’ERM paramétré dans le mode de HASSIST. Les nouvelles preuves appuieront les professionnels de la réadaptation dans le processus de prise de décision concernant la sélection du mode de contrôle des MIs lors de l’entrainement locomoteur utilisant avec un ERM.Wearable robotic exoskeletons (WRE) represent a promising rehabilitation intervention for locomotor rehabilitation training that aligns with activity-based neuroplasticity principles in terms of optimal sensory input, massed repetition, and proper kinematics. Thus far, most studies that investigated the effects of WRE have used WRE that provide full robotic assistance and fixed trajectory guidance to the lower extremity (L/E) to generate close-to-normal walking kinematics, usually at very slow speeds. Based on clinicians’ feedback, current commercially-available WRE have additional control options to be able to integrate these devices into the recovery process of individuals who have maintained some ability to walk after an injury to the central nervous system. In this context, WRE now offer additional degrees of movements for the L/E to move freely and different strategies to assist or resist movement, particularly during the gait cycle’s swing phase. However, the extent that these additional WRE control options affect L/E neuromuscular control during walking, typically characterized using muscle synergies (MSs), remains unknown. This thesis measures and compares MSs characteristics (i.e., number, temporal activation profile, and muscles contributing to a specific synergy [weightings]) during typical overground walking, with and without a WRE, in six different control modes, in abled-bodied individuals (Articles #1 and #2) and individuals with incomplete spinal cord injury (iSCI; Article #3). Surface EMG of key L/E muscles were recorded while walking and used to extract MSs using a non-negative matrix factorization algorithm. Cosine similarity and correlation coefficients characterized, grouped, and indicated similarities between MS characteristics. Results demonstrated that: 1) the number of MSs and MS temporal activation profiles in able-bodied individuals walking without WRE are modified by walking speed and that, as speed increased, specific MSs were fused or merged compared to MSs at slow speeds; 2) In able-bodied individuals walking with WRE, few WRE control modes maintained the typical MSs characteristics that were found during overground walking without WRE. Moreover, freeing the L/E swing trajectory imposed by the WRE best reproduced those MSs characteristics during overground walking without the WRE; and 3) After an iSCI, alterations to the number and the composition of MSs were observed during walking without WRE. However, of all WRE control modes that were investigated, only HASSIST (i.e., freeing WRE control over L/E swing trajectory while assisting the user’s self-selected trajectory) reproduced the number and composition of MSs found in abled-bodied individuals during overground walking without WRE. Altogether, the results of this thesis demonstrated that different walking-related biomechanical demands (i.e., walking speed) and most of the WRE control modes can alter some MSs, and their characteristics, in able-bodied individuals. This research also confirmed that impaired muscle coordination, assessed via MSs, can adapt when walking with a WRE set with specific control options (e.g., HASSIST). These MS adaptations mimicked typical MS characteristics extracted during overground walking. The evidence generated by this thesis will support the decision-making process when selecting specific L/E control options during WRE walking, allowing rehabilitation professionals to refine WRE locomotor training protocols