Bihemispheric reorganization of neuronal activity during hand movements after unilateral inactivation of the primary motor cortex

Le cortex moteur primaire (M1) est souvent endommagé lors des lésions cérébrales telles que les accidents vasculaires cérébraux. Ceci entraîne des déficits moteurs tels qu'une perte de contrôle des membres controlatéraux. La récupération des lésions M1 s'accompagne d'une réorganisation hémodynamique dans les zones motrices intactes des deux hémisphères. Cette réorganisation est plus prononcée dans les premiers jours et semaines qui suivent la lésion. Toutefois, nous avons une compréhension limitée de la réorganisation neuronale rapide qui se produit dans ce réseau moteur cortical complexe. Ces changements neuronaux nous informent sur l’évolution possible de la plasticité subaiguë impliquée dans la récupération motrice. Par conséquent il était grand temps qu’une caractérisation de la réorganisation rapide de l'activité neuronale dans les régions motrices des deux hémisphères soit entreprise. Dans cette thèse nous avons exploré l'impact d'une lésion corticale localisée, unilatérale et réversible dans M1 sur l'activité neuronale des zones motrices des hémisphères ipsi et contralésionnel lorsque des primates non humains ont effectués des mouvements d’atteinte et de saisie. Notre modèle d'inactivation nous a permis d'enregistrer en continu des neurones isolés avant et après l'apparition des déficits moteurs. Dans une première étude, la réorganisation rapide qui se produit dans le cortex prémoteur ventral (PMv) des deux hémisphères a été étudiée (Chapitre 2). Le PMv est une zone connue pour être impliquée dans le contrôle moteur de la main et la récupération des lésions M1. Dans une seconde étude, la réorganisation rapide du M1 contralésionnel (cM1) a été étudiée et comparée à celles se produisant dans les PMv bilatérales (Chapitre 3). Le cM1 joue un rôle complexe dans la récupération des mouvements de précision de la main suite à une blessure à son homologue. Nous révélons une réorganisation neuronale importante et beaucoup plus complexe que prévu dans les deux hémisphères lors de l’apparition initiale des déficiences motrices. Nos données démontrent que les changements neuronaux survenant quelques minutes après une lésion cérébrale sont hétérogènes à la fois dans et entre les zones du réseau moteur cortical. Ils se produisent dans les deux hémisphères lors des mouvements des bras parétiques et non parétiques, et ils varient au cours des différentes phases du mouvement. Ces découvertes constituent une première étape nécessaire pour démêler les corrélats neuronaux complexes de la réorganisation au travers du réseau moteur des deux hémisphères à la suite d’une lésion cérébrale.After brain injuries such as stroke, the primary motor cortex (M1) is often damaged leading to motor deficits that include a loss of fine motor skills of the contralateral limbs. Recovery from M1 lesions is accompanied by hemodynamic reorganization in motor areas distal to the site of injury in both hemispheres that are most pronounced early after injury. However, we have limited understanding of the rapid neuronal reorganization that occurs in this complex and distributed cortical motor network. As these neural changes reflect the landscape on which subacute plasticity involved in motor recovery will take place, an exploration of the rapid reorganization in neural activity that occurs in motor regions of both hemispheres is long overdue. In the current thesis, we set out to explore the impact of a localized, unilateral and reversible cortical injury to the M1 hand area on neuronal activity in motor-related areas of both the ipsi and contralesional hemispheres as non-human primates performed a reach and grasp task. Our inactivation model allowed us to continuously record isolated neurons before and after the onset of motor deficits. In a first study, the rapid reorganization taking place in the ventral premotor cortex (PMv) of both hemispheres was investigated (Chapter 2). The PMv is an area well-known to be critically involved in hand motor control and recovery from M1 lesions. In a second study, the rapid reorganization taking place in the contralesional M1 (cM1) was studied and compared to those occurring in bilateral PMv (Chapter 3). The cM1 has a complex role in recovery of dexterous hand movements following injury to its homologue. We reveal extensive, and much more complex than expected, neuronal reorganization in both hemispheres at the very onset of motor impairments. Our data demonstrate that neuronal changes occurring within minutes after brain injury are heterogenous both within and across areas of the cortical motor network. They occur in the two hemispheres during movements of both the paretic and non-paretic arms, and they vary during different phases of movement. These findings constitute a first step in a much needed and timely effort to unravel the complex neuronal correlates of the reorganization that takes place across the distributed motor network after brain injury

EEG and TMS-EEG Studies on the Cortical Excitability and Plasticity associated with Human Motor Control and Learning

More than half of the activities of daily living rely on upper limb functions (Ingram et al., 2008). Humans perform upper limb movements with great ease and flexibility but even simple tasks require complex computations in the brain and can be affected following stroke leaving survivors with debilitating movement impairments. Hemispheric asymmetries related to motor dominance, imbalances between contralateral and ipsilateral primary motor cortices (M1) activity and the ability to adapt movements to novel environments play a key role in upper limb motor control and can affect recovery. Motor learning and control are critical in neurorehabilitation, however to effectively integrate these concepts into upper limb recovery treatments, a deeper understanding of the basic mechanisms of unimanual control is needed. This thesis aimed to investigate hemispheric asymmetries related to motor dominance, to evaluate the relative contribution of the contralateral and ipsilateral M1 during unilateral reaching preparation and finally to identify the neural correlates underlying the formation of a predictive internal model enabling to adapt movements to new environments. To this end electroencephalography (EEG), transcranial magnetic stimulation (TMS), simultaneous TMS-EEG were employed during a simple motor and a highly standardised robot-mediated task. The first study used TMS-EEG to examine differences in cortical excitability related to motor dominance by applying TMS over the dominant and non-dominant M1 at rest and during contraction. No hemispheric asymmetries related to hand dominance were found. The second study assessed the temporal dynamics of bi-hemispheric motor cortical excitability during right arm reaching preparation. TMS was applied either to the ipsilateral or contralateral M1 during different times of movement preparation. Significant bilateral M1 activation during unilateral reaching preparation was observed, with no significant differences between the contralateral and ipsilateral M1. Unimanual reaching preparation was associated with significant interactions of excitatory and inhibitory processes in both motor cortices. The third study investigated the neural correlates of motor adaptation. EEG was recorded during a robot-mediated adaptation task involving right arm reaching movements and cortical excitability was assessed by applying TMS over the contralateral M1 and simultaneously recording TMS responses with EEG before and after motor adaptation. It was found that an error-related negativity (ERN) over fronto-central regions correlated with performance improvements during adaptation, suggesting that this neural activity reflects the formation of a predictive internal model. Motor adaptation underlay significant modulations in cortical excitability (i.e. neuroplasticity) in sensorimotor regions. Finally, it was shown that native cortical excitability was linked to motor learning improvements during motor adaptation and explained the variability in motor learning across individuals. These experiments demonstrated that even unimanual motor control relies on interactions between excitatory and inhibitory mechanisms not only in the contralateral M1 but in a wider range of brain regions, shown by a bi-hemispheric activity during movement preparation, the formation of a predictive model in fronto-central regions during motor adaptation and neuroplastic changes in sensorimotor regions underlying motor adaptation during unimanual reaching

Factors influencing bilateral interactions in the human motor cortex: investigating transcallosal sensorimotor networks

All daily activities require the precise interaction and coordination of several brain regions to facilitate purposeful movements of the upper limbs. The mechanisms responsible for cross facilitation between the primary motor cortices are poorly understood and are important in understanding the neurophysiology of everyday upper limb movements and customizing task- and deficit- specific rehabilitation protocols following brain injury. Researchers have demonstrated activity-dependent changes in the primary motor cortex (M1) ipsilateral to the moving limb; however, the characteristics mediating this interaction between the hemispheres are not well understood. The aim of this thesis is to examine sensorimotor manipulations that modulate excitability of the resting M1 and determine the neural substrates that may be mediating these interactions. This thesis is comprised of 4 studies and we investigated corticomotor excitability changes of a resting upper limb muscle during (1) rhythmical movement at increasing force requirements, (2) rhythmical movement at increasing force requirements with the addition of sensory input (3) interhemispheric interactions and somatotopic relationships, and (4) convergence of multiple effectors. This dissertation identifies various sensorimotor manipulations that increase excitability of M1 and further informs the neurophysiological mechanisms that may be responsible for these interactions. Understanding the extent to which these mechanisms mediate activity between the upper limbs has implications in bimanual coordination and ultimately experience-dependent plasticity. The findings in this thesis have important applications for improving motor recovery with rehabilitation interventions post brain injury

Neuroplasticity of Ipsilateral Cortical Motor Representations, Training Effects and Role in Stroke Recovery

This thesis examines the contribution of the ipsilateral hemisphere to motor control with the aim of evaluating the potential of the contralesional hemisphere to contribute to motor recovery after stroke. Predictive algorithms based on neurobiological principles emphasize integrity of the ipsilesional corticospinal tract as the strongest prognostic indicator of good motor recovery. In contrast, extensive lesions placing reliance on alternative contralesional ipsilateral motor pathways are associated with poor recovery. Within the predictive algorithms are elements of motor control that rely on contributions from ipsilateral motor pathways, suggesting that balanced, parallel contralesional contributions can be beneficial. Current therapeutic approaches have focussed on the maladaptive potential of the contralesional hemisphere and sought to inhibit its activity with neuromodulation. Using Transcranial Magnetic Stimulation I seek examples of beneficial plasticity in ipsilateral cortical motor representations of expert performers, who have accumulated vast amounts of deliberate practise training skilled bilateral activation of muscles habitually under ipsilateral control. I demonstrate that ipsilateral cortical motor representations reorganize in response to training to acquisition of skilled motor performance. Features of this reorganization are compatible with evidence suggesting ipsilateral importance in synergy representations, controlled through corticoreticulopropriospinal pathways. I demonstrate that ipsilateral plasticity can associate positively with motor recovery after stroke. Features of plastic change in ipsilateral cortical representations are shown in response to robotic training of chronic stroke patients. These findings have implications for the individualization of motor rehabilitation after stroke, and prompt reappraisal of the approach to therapeutic intervention in the chronic phase of stroke

Reshaping cortical activity with subthalamic stimulation in Parkinson's disease during finger tapping and gait mapped by near infrared spectroscopy

Exploration of motor cortex activity is essential to understanding the pathophysiology in Parkinson's Disease (PD), but only simple motor tasks can be investigated using a fMRI or PET. We aim to investigate the cortical activity of PD patients during a complex motor task (gait) to verify the impact of deep brain stimulation in the subthalamic nucleus (DBS-STN) by using Near-Infrared-Spectroscopy (NIRS). NIRS is a neuroimaging method of brain cortical activity using low-energy optical radiation to detect local changes in (de)oxyhemoglobin concentration. We used a multichannel portable NIRS during finger tapping (FT) and gait. To determine the signal activity, our methodology consisted of a pre-processing phase for the raw signal, followed by statistical analysis based on a general linear model. Processed recordings from 9 patients were statistically compared between the on and off states of DBS-STN. DBS-STN led to an increased activity in the contralateral motor cortex areas during FT. During gait, we observed a concentration of activity towards the cortex central area in the "stimulation-on" state. Our study shows how NIRS can be used to detect functional changes in the cortex of patients with PD with DBS-STN and indicates its future use for applications unsuited for PET and a fMRI

Neurophysiological correlates of preparation for action measured by electroencephalography

The optimal performance of an action depends to a great extend on the ability of a person to prepare in advance the appropriate kinetic and kinematic parameters at a specific point in time in order to meet the demands of a given situation and to foresee its consequences to the surrounding environment. In the research presented in this thesis, I employed high-density electroencephalography in order to study the neural processes underlying preparation for action. A typical way for studying preparation for action in neuroscience is to divide it in temporal preparation (when to respond) and event preparation (what response to make). In Chapter 2, we identified electrophysiological signs of implicit temporal preparation in a task where such preparation was not essential for the performance of the task. Electrophysiological traces of implicit timing were found in lateral premotor, parietal as well as occipital cortices. In Chapter 3, explicit temporal preparation was assessed by comparing anticipatory and reactive responses to periodically or randomly applied external loads, respectively. Higher (pre)motor preparatory activity was recorded in the former case, which resulted in lower post-load motor cortex activation and consequently to lower long-latency reflex amplitude. Event preparation was the theme of Chapter 4, where we introduced a new method for studying (at the source level) the generator mechanisms of lateralized potentials related to response selection, through the interaction with steady-state somatosensory responses. Finally, in Chapter 5 we provided evidence for the existence of concurrent and mutually inhibiting representations of multiple movement options in premotor and primary motor areas.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Examination of Sex- and Limb-Specific Fatigue During Unilateral, Isometric Forearm Exercise

The purpose of this study was to examine the effects of unilateral, isometric handgrip holds to failure for the dominant (Dm) and non-dominant (NDm) limb on ipsilateral ([IPS] exercised side) and contralateral ([CON] non-exercised side) performance fatigability. Twenty individuals participated in this study (Men [n =10]; Women [n = 10; Composite Demographics: Age: 22.2 years; Height: 174.4 cm; Body Mass: 75.0 kg) and completed three visits. Two, 6 s maximal voluntary isometric contractions (MVICs) for the Dm and NDm limb were performed during visit 1, followed by a familiarization of the fatigue test. Visits 2 and 3 included an isometric, handgrip hold to failure (HTF) fatigue test at 50% MVIC for either the Dm or NDm limb using a handgrip dynamometer (iWorx Systems Inc.; Dover, NH 03820). Prior to, and immediately after the HTF, a MVIC was performed on the IPS and CON sides. The fatigue test (Dm or NDm) was randomized between visits and the side tested first (IPS and CON) was randomized for pre-and post-tests, within and between each visit. The perceptual measures of Rating of Perceived Exertion (RPE) for the Active Muscle (AM) and Overall Body (O), along with the Numerical Pain Rating (NPR) for the AM and O were taken following each MVIC and the HTF. The test-retest reliability of the Dm and NDm hand pre-HTF MVIC demonstrated ‘excellent’ reliability (Dm: ICC = 0.936; NDm: ICC = 0.938) while the Dm limb HTF demonstrated ‘fair’ reliability (ICC = 0.553) with no systematic error for either the MVIC or HTF. Men and women demonstrated similar times for the HTF (Dm limb: 130.3 ± 36.8 s; NDm limb: 112.1 ± 34.3 s; p = 0.002), despite the men (46.07 ± 10.64 kg) demonstrating a significantly greater absolute MVIC force than women (30.52 ± 6.93 kg; p ≤ 0.001). Performance fatiguability (decrease in exercise performance) and facilitation (increase in exercise performance) was calculated a via a priori planned comparisons (%D = ((pre-HTV MVIC – post-HTF MVIC) / pre-HTV MVIC)*100)). Men, collapsed across limb, demonstrated IPS limb (%D = 22.9 ± 10.8%) performance fatiguability and CON limb facilitation (%D = -6.1 ± 6.9%) following the HTF, while women demonstrated differences in performance fatiguability between the Dm and NDm limbs in IPS (Dm: %D = 28.0 ± 9.4%; NDm: %D = 32.3% ± 10.1%; p = 0.027), but no significant changes in the CON limbs (Dm: %D = -1.6 ± 5.7%; NDm: %D = 1.7 ± 5.9%). Following the HTF, men (9.2 ± 1.1) demonstrated a greater RPE-AM value than women (7.4 ± 2.2; p = 0.031), but the RPE-O, NPR-AM, NPR-O demonstrated no differences. The perceptual responses for the Pre-/Post-HTF in men demonstrated increases in RPE-AM and RPE-O in both limbs; women demonstrated increases in the IPS side only. The NPR-AM and NPR-O measures demonstrated increases for the men in both limbs and the women in the IPS side only. In this study, women demonstrated less absolute grip strength than men and demonstrated greater Dm limb strength than NDm grip strength while the men demonstrated no difference between limbs. Sex-specific training programming and body composition differences may have influenced this finding as well as the finding that the RPE-AM for a 50% MVIC HTF was higher for the men than women despite similar times to failure. The Dm limb was more fatigue resistant than the NDm limb, possibly due to continual favoring of the Dm limb in everyday tasks. Similar performance fatiguability in the IPS limb was demonstrated for men and women, however, the men demonstrated facilitation in the CON limb while there were no CON limb changes for the women. The finding of facilitation may be due to central factors, such as interhemispheric excitatory signaling from the ipsilateral to the contralateral hemisphere, and peripheral factors such as post activation potentiation (PAP) elicited from myosin light chain phosphorylation. The PAP phenomenon occurs more frequently in type II muscle fibers. Thus, the sex-dependent differences seen in facilitation and perceptual responses may be related to a greater proportion of type II fibers for the men compared to the women

Upper Limb Asymmetries of Movement Sense and Sense of Effort: The Contribution of Gender and Handedness.

Asymmetry in upper limb performances may have multiple origins. The aim of this research is to determine the contribution of sensory and motor processes to asymmetries in movement sense and sense of effort when considering gender and handedness. The distinction between gender and handedness effects, while often ignored, may shed new light on human performances. The first study investigated asymmetry in movement sense using contralateral reproductions of vibration induced illusions of movements in right (RH) and left (LH) handed young adults of both genders. Females were found more sensitive to vibratory stimulations and less asymmetric than males in movement reproduction. The asymmetry observed in males was related to handedness. Both asymmetry and sensitivity were primarily sensory in origin. The second study investigated asymmetries in the sense of effort and targeted the motor component. Both RH and LH adults were divided into three groups based on hand strength differences. A 20% MVC reference grip force was matched with the same or opposite hand (of the reference). The matching error increased with hand strength differences for RH only, suggesting that the sense of effort is a consequence of both muscle strength differences and an intrinsic asymmetry of the motor component that may vary with handedness. The last study investigated the relative contributions of efferent copy and sensory feedback to the sense of effort. Vibration was used to distort the sensory information from muscles providing the reference in the grip matching task. Visual feedback of the reference hand was also manipulated. The hand/hemisphere systems were found to differ significantly in their dependence on proprioceptive information during force reproduction, with the left hand being more feedback dependent. These findings lead us to suggest that hand preference and gender contribute to differences in movement representation, force production and sense of effort that may result from the combination of cortical structural differences and information processing specific to each hemisphere, gender and handedness group.PhDIndustrial & Operations EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99857/1/sscotlan_1.pd

Prefrontal cortex activation upon a demanding virtual hand-controlled task: A new frontier for neuroergonomics

open9noFunctional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities.openCarrieri, Marika; Petracca, Andrea; Lancia, Stefania; Basso Moro, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, ValentinaCarrieri, Marika; Petracca, Andrea; Lancia, Stefania; BASSO MORO, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentin