Intermanual Differences in movement-related interhemispheric inhibition

Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right-handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHI(c)) and ipsilateral (IHI(i)) to each moving finger was determined. IHI(c) was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHI(c) reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHI(i) displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity

Handedness Influences Intermanual Transfer in Chimpanzees (\u3cem\u3ePan troglodytes\u3c/em\u3e) But Not Rhesus Monkeys (\u3cem\u3eMacaca mulatta\u3c/em\u3e)

Intermanual transfer refers to an effect whereby training one hand to perform a motor task improves performance in the opposite untrained hand. We tested the hypothesis that handedness facilitates intermanual transfer in two nonhuman primate species: rhesus monkeys (N = 13) and chimpanzees (N = 52). Subjects were grouped into one of four conditions: (1) left-handers trained with the left (dominant) hand; (2) left-handers trained with the right (non-dominant) hand; (3) right-handers trained with the left (non-dominant) hand; and (4) right-handers trained with the right (dominant) hand. Intermanual transfer was measured using a task where subjects removed a Life Savers® candy (monkeys) or a washer (chimpanzees) from metal shapes. Transfer was measured with latency by comparing the average time taken to solve the task in the first session with the trained hand compared to the first session with the untrained hand. Hypotheses and predictions were derived from three models of transfer: access: benefit training with non-dominant hand; proficiency: benefit training with dominant hand; and cross-activation: benefit irrespective of trained hand. Intermanual transfer (i.e., shorter latency in untrained hand) occurred regardless of whether monkeys trained with the dominant hand or non-dominant hand, supporting the cross-activation model. However, transfer was only observed in chimpanzees that trained with the dominant hand. When handedness groups were examined separately, the transfer effect was only significant for right-handed chimpanzees, partially supporting the proficiency model. Findings may be related to neurophysiological differences in motor control as well as differences in handedness patterning between rhesus monkeys and chimpanzees

Intermanual Transfer of a Novel Writing Task in Young Adults without Disability: a Kinematic Perspective

The complexities of motor learning are an important and integral part of the practice of occupational therapy. Intermanual transfer of motor learning is a specific area of interest that has significant relevance to the specificity of clinical motor training activities utilized in therapy. The term refers to the transfer of upper extremity motor skills previously learned by one cerebral hemisphere of the brain to the other cerebral hemisphere. Understanding the complexities of motor learning is important to occupational therapists as they develop strategies to be used with applicable clients with motor disabilities. Integral to this premise is the notion that clients who have lost function in one limb may relearn motor behaviors by accessing previously learned skills from the relatively unaffected contra-lateral cerebral hemisphere. Recent research indicates an inter-hemispheric dependence for the development of upper extremity motor skills and intermanual transfer. This study investigates intermanual transfer in a group of ten right-handed subjects with no known motor disabilities. Each subject learned to perform a novel motor task that included practice, original learning, and transfer learning involving distal muscle groups The task required the writing of an alphabet letter of a foreign language. During the practice sessions, the subjects traced the letter six times either with their right or left hand. In the original learning sessions, the subjects used the same hand as in the practice sessions to reproduce the skill without the letter in view. In the transfer learning sessions, the subjects reproduced the skill with the contralateral hand. Once that protocol had been completed, subjects switched hands to begin the sessions again using the opposite hand. Movements of the pen were recorded using the search coil system to assess kinematic performance. Simultaneous electromyography (EMG) recordings of the first dorsal interosseus muscle were performed to measure distal muscle activity. EMG and kinematic data were analyzed to compare motor learning between the dominant hand transfer of learning to the non-dominant hand and the non-dominant hand transfer of learning to the dominant hand. Analysis indicates an almost full transfer of the learned motor task between hands, ranging from 80-100% for left to right and right to left conditions. Findings strongly suggest that the contralateral motor learning resulting from inter-manual transfer functions might be useful for promoting unilateral or bilateral upper extremity motor rehabilitation

Congenital mirror movements in a new Italian family

Mirror movements (MMs) occur on the contralateral side of a limb being used intentionally. Because few families with congenital MMs and no other neurological signs have been reported, the underlying mechanisms of MMs are still not entirely clear. We report on the clinical, genetic, neurophysiological and neuroimaging findings of 10 of 26 living members of a novel four-generation family with congenital MMs. DCC and RAD51 were sequenced in affected members of the family. Five of the ten subjects with MMs underwent neurophysiological and neuroimaging evaluations. The neurophysiological evaluation consisted of electromyographic (EMG) mirror recordings, investigations of corticospinal excitability, and analysis of interhemispheric inhibition using transcranial magnetic stimulation techniques. The neuroimaging evaluation included functional MRI during finger movements. Eight (all females) of the ten members examined presented MMs of varying degrees at the clinical assessment. Transmission of MMs appears to have occurred according to an autosomal-dominant fashion with variable expression. No mutation in DCC or RAD51 was identified. EMG mirror activity was higher in MM subjects than in healthy controls. Short-latency interhemispheric inhibition was reduced in MM subjects. Ipsilateral motor-evoked potentials were detectable in the most severe case. The neuroimaging evaluation did not disclose any significant abnormalities in MM subjects. The variability of the clinical features of this family, and the lack of known genetic abnormalities, suggests that MMs are heterogeneous disorders. The pathophysiological mechanisms of MMs include abnormalities of transcallosal inhibition and corticospinal decussatio

Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

It is well established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor excitability of the left non-trained hand. Subjects practiced a visuomotor tracking task engaging right digit V for 6 weeks with either progressively increasing task difficulty (PT) or no progression (NPT). Corticospinal excitability (CSE) was evaluated from the resting motor threshold (rMT) and recruitment curve parameters following application of transcranial magnetic stimulation (TMS) to the ipsilateral primary motor cortex (iM1) hotspot of the left abductor digiti minimi muscle (ADM). PT led to significant improvements in left-hand motor performance immediately after 6 weeks of training (63 ± 18%, P < 0.001) and 8 days later (76 ± 14%, P < 0.001). In addition, PT led to better task performance compared to NPT (19 ± 15%, P = 0.024 and 27 ± 15%, P = 0.016). Following the initial training session, CSE increased across all subjects. After 6 weeks of training and 8 days later, only PT was accompanied by increased CSE demonstrated by a left and upwards shift in the recruitment curves, e.g. indicated by increased MEPmax (P = 0.012). Eight days after training similar effects were observed, but 14 months later motor performance and CSE were similar between groups. We suggest that progressively adjusting demands for timing and accuracy to individual proficiency promotes motor skill learning and drives the iM1-CSE resulting in enhanced performance of the non-trained hand. The results underline the importance of increasing task difficulty progressively and individually in skill learning and rehabilitation training

Changes of hand switching costs during bimanual sequential learning

Many tasks in our daily life demand not only the use of different fingers of one hand in a serial fashion, but also to alternate from one hand to the other. Here, we investigated performance in a bimanual serial reaction time task (SRTT) with particular emphasis on learning-related changes in reaction time (RT) for consecutive button presses for homologous index- and middle fingers. The bimanual SRTT consisted of sequential button presses either with the left or right index- and middle-finger to a series of visual letters displayed on a computer screen. Each letter was assigned a specific button press with one of four fingers. Two outcome measures were investigated: (a) global sequence learning as defined by the time needed to complete a 15-letter SRTT sequence and (b) changes in hand switch costs across learning. We found that bimanual SRTT resulted in a global decrease in RT during the time course of learning that persisted for at least two weeks. Furthermore, RT to a button press showed an increase when the previous button press was associated with another hand as opposed to the same hand. This increase in RT was defined as switch costs. Hand switch costs significantly decreased during the time course of learning, and remained stable over a time of approximately two weeks. This study provides evidence for modulations of switch costs during bimanual sequence learning, a finding that might have important implications for theories of bimanual coordination and learning

Gait Asymmetry in People With Parkinson’s Disease Is Linked to Reduced Integrity of Callosal Sensorimotor Regions

Background: Individuals with Parkinson’s disease (PD) often manifest significant temporal and spatial asymmetries of the lower extremities during gait, which significantly contribute to mobility impairments. While the neural mechanisms underlying mobility asymmetries within this population remain poorly understood, recent evidence points to altered microstructural integrity of white matter fiber tracts within the corpus callosum as potentially playing a substantial role. Objectives: The purpose of this study was to quantify spatial and temporal gait asymmetries as well as transcallosal microstructural integrity of white matter fiber tracts connecting the primary and secondary sensorimotor cortices in people with PD and age-matched control participants. Methods: Spatial and temporal gait asymmetry in the levodopa off state was assessed using an instrumented walkway. On the next day, diffusion-weighted images were collected to assess white matter microstructural integrity in transcallosal fibers connecting the homologous sensorimotor cortical regions. Results: People with PD exhibited significantly more temporal and spatial gait asymmetry than healthy control subjects. Furthermore, people with PD had significantly reduced white matter microstructural integrity of transcallosal fibers connecting homologous regions of the pre-supplementary motor and supplementary motor areas (SMAs), but not the primary motor or somatosensory cortices. Finally, reduced transcallosal fiber tract integrity of the pre-SMA and S1 was associated with greater step length asymmetry in people with PD. Conclusion: People with PD showed increased step length asymmetries and decreased microstructural integrity of callosal white matter tracts connecting the higher-order sensorimotor cortices (pre-SMA and SMA). The strong association between gait asymmetries and corpus collosum integrity, supports the hypothesis that reduced transcallosal structural connectivity is a significant mechanism underlying gait asymmetries in people with PD

Investigation de l’effet du polymorphisme Val66Met du gène BDNF sur les mécanismes neurophysiologiques qui sous-tendent les apprentissages moteurs procéduraux et sensorimoteurs, de même que sur le transfert intermanuel des apprentissages

Le facteur neurotrophique dérivé du cerveau (Brain-Derived Neurotrophic Factor; BDNF), synthétisé en grande partie dans les neurones glutamatergiques en réponse à l’activité neuronale, est impliqué dans la plasticité synaptique et la croissance dendritique, en plus de jouer un rôle central dans le développement, le fonctionnement et la survie des neurones du système nerveux central. Le gène BDNF se retrouve le plus fréquemment sur sa forme Valine à Valine au codon 66 (Val66Val). Le polymorphisme à nucléotide unique Val66Met du gène BDNF, présent chez environ un tiers de la population américaine, interfère avec la recapture du BDNF par les granules de sécrétion et réduit la disponibilité du BDNF dans l’espace synaptique et les dendrites. De ce fait, le polymorphisme Val66Met est associé aux altérations de la neurotransmission excitatrice glutamatergique et inhibitrice GABA-ergique, de la synaptogénèse, ainsi qu’à des différences structurelles et fonctionnelles de plusieurs régions cérébrales comparativement aux porteurs de la variante Val66Val, par exemple au niveau de l’hippocampe. Dans le cortex moteur primaire (M1), le polymorphisme Val66Met du gène BDNF est lié à une altération de la plasticité synaptique dépendante de l’activité se répercutant entre autres dans une modulation anormale des cartes corticomotrices, de l’excitabilité corticospinale et de l’homéoplasticité synaptique. Sur le plan comportemental, les individus porteurs du polymorphisme Val66Met montrent un déficit d’apprentissage et de rétention d’habiletés visuomotrices complexes. Or, les effets potentiels du polymorphisme Val66Met sur la plasticité synaptique intracorticale impliquée dans l’apprentissage moteur et sur le transfert intermanuel de l’apprentissage, sous-tendu en grande partie par les interactions interhémisphériques, demeurent à ce jour inconnu. Dans le cadre du présent ouvrage, nous avons comparé les performances en apprentissage, en rétention et en transfert intermanuel d’habiletés motrices procédurales, par le biais de la Serial Reaction Time Task (SRTT), et en apprentissage d’habiletés sensorimotrices de base, soient la vitesse de contraction motrice, la précision de force de préhension et la dextérité manuelle fine, entre des sujets Val66Met et Val66Val droitiers, âgés de 18 à 35 ans. À l’aide de la stimulation magnétique transcrânienne, nous avons également comparé la modulation de divers mécanismes neurophysiologiques en M1 en lien avec ces phénomènes, notamment l’excitabilité corticospinale, l’inhibition intracorticale de courte latence et l’inhibition interhémisphérique. Les résultats des deux études suggèrent l’absence de différence entre les sujets Val66Val et Val66Met sur l’apprentissage de composantes sensorimotrices avec la main droite dominante et la main gauche non dominante, ainsi que sur l’apprentissage procédural d’une séquence motrice. Cependant, les résultats de l’étude 1 ont indiqué une altération du transfert intermanuel de la séquence apprise avec la main dominante vers la main non dominante non entraînée chez les sujets Val66Met, suggérant une atteinte probable des interactions interhémisphériques. De plus, les résultats de l’étude 2 ont montré une absence de modulation de l’inhibition intracorticale à courte latence en M1 bilatéral suivant la pratique sensorimotrice. Les implications potentielles de ces résultats dans l’apprentissage moteur, le transfert intermanuel et les mécanismes neurophysiologiques qui les sous-tendent sont discutées. En somme, ces résultats permettent une perspective plus précise du lien entre le polymorphisme Val66Met et ces phénomènes, en plus de suggérer des hypothèses spécifiques à étudier.Brain-derived neurotrophic factor (BDNF), which is largely synthesized in glutamatergic neurons in response to stimulation, is involved in synaptic plasticity and dendritic growth, and plays a key role in development, function, and survival of neurons in the central nervous system. The BDNF gene is most commonly found in its Valine to Valine form at codon 66 (Val66Val). The single nucleotide Val66Met polymorphism, found in approximately one third of the American population, interferes with BDNF recapture in the secretory vesicles, thus altering BDNF availability in the synaptic cleft and dendrites. Thus, the Val66Met polymorphism is associated with altered excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, synaptogenesis, and functional and structural alterations of several brain structures compared to Val66Val carriers, for instance, at the level of the hippocampus. In the primary motor cortex, the Val66Met polymorphism is linked to altered activity-dependent synaptic plasticity, which may be expressed in impaired regulation of motor cortical maps, corticospinal excitability, and synaptic homeoplasticity. At the behavioral level, Val66Met carriers display impaired learning and retention of complex visuomotor skills. However, to this day, little is known regarding the effects of the Val66Met polymorphism on intracortical plasticity mechanisms involved in motor learning, and intermanual transfer of a motor skill, which relies in part on interhemispheric interactions. In the present work, we compared learning, retention and intermanuel transfer of procedural motor skills on the Serial Reaction Time Task (SRTT), and learning of basic sensorimotor components, namely muscle contraction speed, precision grip strength, and fine manual dexterity, between Val66Val and Val66Met right-handed participants aged between 18 and 35 years old. Transcranial magnetic stimulation was used to compare the underlying neurophysiological mechanisms in M1, corticospinal excitability, short intracortical inhibition, and interhemispheric inhibition. Results of the two studies suggested the absence of difference in basic sensorimotor skill learning with the right dominant hand and the left non-dominant hand, and in procedural motor learning between Val66Val and Val66Met carriers. Further, the results in study 1 indicated an impaired intermanual transfer of procedural skills from the dominant learning hand to the non-dominant untrained hand in the Val66Met group, which likely suggests altered interhemispheric interactions. Moreover, the results in study 2 showed an absence of short-intracortical inhibition in bilateral M1 among Val66Met carriers following sensorimotor learning. Potential implications of these results in the interaction between the Val66Met polymorphism, motor learning, and the underlying neurophysiological mechanisms are discussed. In sum, these results provide a more in-depth perspective of the relationship between the Val66Met polymorphism and these processes, and specific hypotheses for future studies

L'apprentissage moteur auprès de populations avec déficits sensoriel et moteur

Apprendre de nouvelles habiletés motrices est fondamental à l'expérience humaine et à l'exécution des activités quotidiennes. L'apprentissage moteur peut être défini comme un ensemble de processus associés à la pratique ou à l'expérience menant à la capacité d'exécuter une nouvelle habileté motrice. À l'origine de ces mécanismes d'apprentissage, un contrôle moteur précis et une intégration sensorimotrice adéquate sont essentiels. De plus, la capacité d'identifier une séquence dans des évènements sériels et de reproduire avec précision la série de mouvements détectés est également importante en ce qui concerne l'apprentissage des séquences motrices présentes dans de nombreux comportements humains. Si l'un de ces processus élémentaires est compromis par une pathologie, on peut s'attendre à observer des difficultés à apprendre différentes habiletés motrices. Les études qui composent la présente thèse avaient pour objectif principal de caractériser les capacités d'apprentissage moteur dans deux populations cliniques présentant une anomalie sensorielle ou motrice avec la tâche de temps de réaction sérielle (TTRS). Dans l'article 1, les conséquences de la surdité sur l'apprentissage moteur ont été étudiées. Peu d'études ont examiné les capacités motrices chez les sourds profonds et ces quelques études ont suggéré la présence de déficits en dextérité manuelle et des retards dans la production de mouvements. Avant la publication de cet article, la capacité d'apprendre des séquences motrices complexes n'avait pas été explorée dans une population adulte sourde. L'apprentissage non-spécifique et spécifique à la séquence à la TTRS a été analysé en fonction des caractéristiques individuelles liées à la perte auditive. Les résultats ont révélé des différences significatives entre les groupes dans l'apprentissage spécifique à la séquence, les sujets sourds étant moins efficaces que les contrôles à acquérir les connaissances spécifiques à la séquence. Nous avons interprété les résultats à la lumière de la plasticité intermodale et de l'hypothèse d'échafaudage auditif. Dans l'article 2, l'apprentissage moteur, le transfert intermanuel d'une habileté motrice nouvellement acquise et la modulation du débordement moteur électrophysiologique (mouvements miroirs physiologiques; MMp) ont été évalués dans une grande famille de quatre générations avec des mutations du gène Deleted in Colorectal Cancer (DCC) et des mouvements miroirs congénitaux (MMC). Les MMC sont des contractions musculaires involontaires de l'autre côté du corps survenant lors d'un mouvement unilatéral volontaire. Ils ont été associés à une mutation dans le gène DCC, entraînant des voies cortico-spinales anormales et une inhibition interhémisphérique réduite (IIH). Comparativement aux membres de la famille sans MMC et aux contrôles sains non-apparentés, les MMp des individus avec MMC ont été significativement augmentés après l'exécution de la TTRS. L'apprentissage moteur et le transfert intermanuel ne différaient pas entre les groupes. Cependant, lorsque les participants avec la mutation DCC, avec ou sans MMC, étaient spécifiquement comparés aux participants sans la mutation DCC, l'apprentissage non-spécifique d'une séquence motrice était significativement réduit chez les personnes atteintes de la mutation DCC. Ces données suggèrent qu'une augmentation de l'activité miroir physiologique chez les patients atteints de MMC est associée à une réduction de l'IIH. De plus, les diminutions d'apprentissage moteur non-spécifique chez les porteurs de la mutation DCC pourraient être liés aux altérations de l'activité cérébelleuse et de la connectivité rapportées antérieurement. En résumé, les études comprises dans la présente thèse ont approfondi nos connaissances des capacités d'apprentissage moteur dans les contextes de déficits sensoriels ou moteurs.Learning new motor skills is essential to the human experience and to the performance of everyday activities. Motor learning can be defined as a set of processes associated with practice or experience leading to the ability to skillfully perform a new motor skill. At the root of these learning mechanisms, precise motor control and adequate sensorimotor integration are critical. Additionally, the ability to identify a sequence in serial events and accurately reproduce the series of detected movements is also important with regards to learning motor sequences that are present in many human behaviors. If any of these fundamental processes are compromised by any pathology, one can expect to observe difficulties in learning different motor skills. The studies that compose the present thesis had as a main objective to characterize the motor learning abilities in two clinical populations presenting a sensory or motor abnormality with the serial reaction time task (SRTT). In article 1, the consequences of hearing impairment on motor learning were investigated. Few studies have examined motor capacities in the profoundly deaf and these studies have suggested the presence of deficits in manual dexterity and delays in movement production. Before the publication of this article, the ability to learn complex sequential motor patterns had not been explored in a deaf adult population. Non-specific and sequence-specific learning on the SRTT were analyzed in relation to individual features related to the hearing loss. The results revealed significant differences between groups in sequence-specific learning, with deaf subjects being less efficient than controls in acquiring sequence-specific knowledge. We interpreted the results in light of cross-modal plasticity and the auditory scaffolding hypothesis. In article 2, motor learning, intermanual transfer of a newly acquired motor skill and activity-dependent modulation of electrophysiological motor overflow (physiological mirror movements; pMM) were assessed in a large, four-generational family with a Deleted in Colorectal Cancer (DCC) gene mutation and congenital mirror movements (CMM). CMM are involuntary muscle contractions in the opposite side of the body occurring during voluntary unilateral movement. They have been associated with a frameshift mutation in the DCC gene, resulting in abnormal corticospinal tracts and reduced interhemispheric inhibition (IHI). Compared with family members without CMM and unrelated healthy controls, pMM were significantly increased in CMM individuals following execution of the SRTT. Motor learning and intermanual transfer did not differ between groups. However, when participants with the DCC mutation, with or without CMM, were compared with participants without the DCC mutation, non-specific learning of a motor sequence was significantly reduced in individuals with the DCC mutation. These data suggest that increased physiological mirroring in CMM patients is associated with reduced IHI. Furthermore, impairments in non-specific motor learning in DCC mutation carriers may be related to the reported alterations in cerebellar activity and connectivity. In summary, the studies comprised in the present thesis significantly increase our knowledge of motor learning abilities in the contexts of sensory or motor deficits

Variability in bimanual coordination across the continuum of handedness.

Bimanual coordination is an essential human function requiring efficient interhemispheric communication to produce coordinated movements. Motor deficits affect a variety of clinical populations, yet a complete understanding of bimanual coordination has yet to be achieved. Previous research suggests performance variability depends on the phase demands of the coordinated task and completing bimanual tasks may result in less variability than unimanual tasks, or a bimanual advantage. Also, handedness and musical/athletic experience have also been shown to influence coordinated performance. The present study examined the existence of a bimanual advantage and potential factors influencing coordination in a tapping paradigm. Results indicated that the strong-handed individuals displayed a strong bimanual advantage; whereas, weak-handed participants had a weak bimanual advantage. Variability did not differ by musical/athletic experience. In light of the present findings, relevant studies are needed to gain further insight into bimanual coordination and the underlying processes of motor movement