Somatotopy in the ipsilateral primary motor cortex

Conflicting reports exist about the occurrence, reliability and localization of activation in the ipsilateral primary motor cortex (M1). We re-examined this issue with functional magnetic resonance imaging in 12 volunteers performing right hand, finger, wrist, elbow, foot and tongue movements in two separate sessions. Ipsilateral M1 activation was inconsistently and non-reliably present during all movements: in 54% of all hand, 50% elbow, 46% finger, 33% wrist, and in 17% of all foot experiments. When compared to contralateral M1, the volumes and maximum t-values were always smaller. The ipsilateral M1 body representation was somatotopically organized with coordinates similar to the contralateral M1. Finally, the presence of ipsilateral M1 activation depended on the global activation level in other motor-related areas, which was significantly increased, when ipsilateral M1 activation was detected.     

Influence of task-related ipsilateral hand movement on motor cortex excitability.

OBJECTIVE: The time course of the right motor cortex excitability in relation to a task-related voluntary right thumb twitch was studied using sub-threshold transcranial magnetic stimulation (TMS) to the right motor cortex. METHODS: Motor excitability was studied in 8 adult subjects who made a brief right thumb twitch to the predictable omission of every fifth tone in a series of tones 2.5 s apart. This paradigm avoided an overt sensory cue, while allowing experimental control of TMS timing relative to both movement and the cue to move. Motor excitability was characterized by several measures of motor evoked potentials (MEPs) recorded from the left thenar eminence in response to TMS over the right scalp with a 9 cm coil: probability of eliciting MEPs, incidence of MEPs and amplitude of MEPs. RESULTS: All subjects showed suppression of motor excitability immediately following a voluntary right thumb twitch (ipsilateral response), and up to 1 s after it. However, two distinctly different effects on motor excitability were observed before the response: two subjects showed excitation, beginning about 500 ms before response until 300 ms after it, followed by the post-movement suppression; 6 subjects displayed pre-movement suppression, beginning about 600 ms before the response and persisting for the duration. CONCLUSIONS: The net effect of an ipsilateral response on motor cortex can be either inhibitory or excitatory, changing with time relative to the response. These findings are compatible with two separate processes, inhibitory and excitatory, which interact to determine motor excitability ipsilateral to the responding hand.     

Contribution of the ipsilateral motor cortex to recovery after chronic stroke

It has been proposed that the intact (ipsilateral) motor cortex play a significant role mediating recovery of motor function in the paretic hand of chronic stroke patients, but this hypothesis has not been tested experimentally. Here, we evaluated the effects of transcranial magnetic stimulation (TMS) on motor performance of the paretic hand of chronic stroke patients and healthy controls. We hypothesized that, if activity in the intact hemisphere contributes to functional recovery, TMS should result in abnormal motor behavior in the paretic hand. We found that stimulation of the intact hemisphere resulted in delayed simple reaction times (RTs) in the contralateral healthy but not in the ipsilateral paretic hand, whereas stimulation of the lesioned hemisphere led to a marked delay in RT in the contralateral paretic hand but not in the ipsilateral healthy hand. RT delays in the paretic hand correlated well with functional recovery. Finger tapping in the paretic hand was affected by TMS of the lesioned but not the intact hemisphere. These results are consistent with the idea that recovered motor function in the paretic hand of chronic stroke patients relies predominantly on reorganized activity within motor areas of the affected hemisphere.     

Co-activation of primary motor cortex ipsilateral to muscles contracting in a unilateral motor task

ObjectiveThis study aims to investigate the role of the primary motor cortex ipsilateral to the movement (ipsilateral M1) in unilateral motor execution.MethodsFifteen right-handed healthy subjects underwent functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) experiments. Motor tasks were performed with the right-side limb. Subjects followed visual cues to execute movements in the scanner and independent component analysis (ICA) was applied to analyse the data. Interhemispheric inhibition (IHI), short-interval intracortical inhibition (SICI) and recruitment curves (RCs) of motor-evoked potentials (MEPs) in right M1 were measured by TMS and responses were recorded from the left flexor carpi radialis (FCR) and left anterior deltoid (AD).ResultsGroup ICA showed activations of bilateral M1s highly related to motor tasks. Additionally, TMS results showed significant increases of MEP RCs on the left FCR and left AD during right wrist flexion and right shoulder flexion. Prominent decreases of IHI and SICI were also observed under the same conditions.ConclusionsDuring unilateral muscle contraction, co-activation of the ipsilateral M1 involves additional processes modulated by intra- and interhemispheric interactions and its size of activations is specifically enhanced on the homotopic representation.SignificanceThe ipsilateral M1 plays a central role in unilateral motor executions.     

Bilateral motor resonance evoked by observation of a one-hand movement: role of the primary motor cortex

In humans, observation of movement performed by others evokes a subliminal motor resonant response, probably mediated by the mirror neurone system, which reproduces the motor commands needed to execute the observed movement with good spatial and temporal fidelity. Motor properties of the resonant response were here investigated with the ultimate goal of understanding the principles operating in the transformation from observation to internal reproduction of movement. Motor resonance was measured as the modulation of excitability of spinal motoneurones, evoked by the observation of a cyclic flexion-extension of one hand. The first two experiments showed that the observation of a one-hand movement always evoked a bimanual resonant response independent of which hand was observed and that these bilateral responses were consistently phase-linked. H-reflexes simultaneously recorded in right and left flexor carpi radialis muscles were always modulated 'in-phase' with each other. The goal of the third experiment was to define the role of primary motor cortex in the bilateral resonant response. Bilateral H-reflexes were recorded during a temporary inactivation induced by transcranial magnetic stimulation over the left cortical hand motor area of observers. The finding that such cortical depression abolished the H-reflex modulation of only the right flexor carpi radialis motoneurones, leaving it unchanged on the left side, suggested that both primary motor areas were activated by the premotor cortex and transmit the resonant activation through crossed corticospinal pathways. The data provide further evidence that the subliminal activation of motor pathways induced by movement observation is organized according to general rules shared with the control of voluntary movement.     

Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury

The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury.     

Activity in the human primary motor cortex related to ipsilateral hand movements

In two studies with positron emission tomography (PET), we found that somatosensory discrimination of length activated the ipsilateral MI, but somatosensory discrimination of shape did not. This occurred even though both tasks required the exclusive use of distal finger and hand movements which were also very similar in both tasks. The activation of the ipsilateral MI was correlated with activations of the premotor cortex in the other hemisphere, the prefrontal cortex and the posterior cingulate cortex, indicating that these areas together with the ipsilateral MI constitute a task-related active network.     

Corticostriatal input zones from the supplementary motor area overlap those from the contra- rather than ipsilateral primary motor cortex

To investigate the degree of convergence of corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA), we analyzed the extent to which corticostriatal inputs from forelimb representations of these motor-related areas spatially overlap in the macaque monkey. Of particular interest was that corticostriatal input zones from SMA overlapped those from MI of the contralateral hemisphere more extensively than from MI of the ipsilateral hemisphere.     

The role of anterior midcingulate cortex in cognitive motor control

The rostral cingulate cortex has been associated with a multitude of cognitive control functions. Recent neuroimaging data suggest that the anterior midcingulate cortex (aMCC) has a key role for cognitive aspects of movement generation, i.e., intentional motor control. We here tested the functional connectivity of this area using two complementary approaches: (1) resting‐state connectivity of the aMCC based on fMRI scans obtained in 100 subjects, and (2) functional connectivity in the context of explicit task conditions using meta‐analytic connectivity modeling (MACM) over 656 imaging experiment. Both approaches revealed a convergent functional network architecture of the aMCC with prefrontal, premotor and parietal cortices as well as anterior insula, area 44/45, cerebellum and dorsal striatum. To specifically test the role of the aMCC's task‐based functional connectivity in cognitive motor control, separate MACM analyses were conducted over “cognitive” and “action” related experimental paradigms. Both analyses confirmed the same task‐based connectivity pattern of the aMCC. While the “cognition” domain showed higher convergence of activity in supramodal association areas in prefrontal cortex and anterior insula, “action” related experiments yielded higher convergence in somatosensory and premotor areas. Secondly, to probe the functional specificity of the aMCC's convergent functional connectivity, it was compared with a neural network of intentional movement initiation. This exemplary comparison confirmed the involvement of the state independent FC network of the aMCC in the intentional generation of movements. In summary, the different experiments of the present study suggest that the aMCC constitute a key region in the network realizing intentional motor control. Hum Brain Mapp 35:2741–2753, 2014. © 2013 Wiley Periodicals, Inc .     

Unilateral grip fatigue reduces short interval intracortical inhibition in ipsilateral primary motor cortex

ObjectiveThis study was designed to examine whether exhaustive grip exercise of the left hand affected intracortical excitability in ipsilateral motor cortex.MethodsTen healthy male subjects (aged 21–24 years) participated in experiment 1 in which paired-pulse transcranial magnetic stimulation (TMS) was used to test corticospinal and corticocortical excitability in right (relaxed) first dorsal interosseous (FDI) muscle during the recovery period after exhaustive forceful grip exercise of the left hand. Seven of the same subjects participated in experiment 2, in which the intensity of the test stimulus was adjusted so that the amplitude of motor evoked potential (MEP_TEST) was kept constant throughout the measurement.ResultsIn experiment 1, MEP_TEST was slightly reduced from 5 to 15 min after exercise whilst short interval intracortical inhibition (SICI) at interstimulus interval (ISI) of 2 and 3 ms became less effective. Intracortical facilitation (ICF) was unchanged. In experiment 2 when the MEP_TEST was maintained at a constant size there was again no change in ICF, and the reduction in SICI was still present at the same intervals.ConclusionsWe conclude that unilateral exhaustive grip exercise reduced the excitability of the corticospinal output of the ipsilateral motor cortex whilst simultaneously reducing the excitability of SICI. These results would be compatible with the idea that fatigue increases the tonic level of interhemispheric inhibition from the fatigued to the non-fatigued cortex.SignificanceMuscle fatigue to the point of exhaustion has lasting effects on the excitability of intracortical circuits in the non-exercised hemisphere, perhaps via changes in the tonic levels of activity in transcallosal pathways.     

Suppression of ipsilateral motor cortex facilitates motor skill learning

The primary motor cortex (M1) plays a critical role in early aspects of motor skill learning. Given the notion of inter-hemispheric competition, unilateral disruption of M1 may increase excitability of the unaffected motor cortex and thus improve motor learning with the ipsilateral hand. We applied slow-frequency repetitive transcranial magnetic stimulation (rTMS) before the initiation of practice of a simple motor skill. Participants were randomly divided into three stimulation groups: (i) ipsilateral M1; (ii) contralateral M1; and (iii) Cz (control site). The mean execution time and error rate were recorded in four sessions distributed over 2 days. Disruption of M1 with rTMS slowed down skill acquisition with the contralateral hand, albeit non significantly, but paradoxically enhanced learning with the ipsilateral hand. This was evidenced by a significant decrease of execution time at the end of day 1 in the group that received rTMS over the ipsilateral M1 compared with both control groups (Cz and contralateral M1 stimulation). This supports the notion of inter-hemispheric competition and provides novel insights that may be applicable to neurorehabilitation.     

Periinfarct rewiring supports recovery after primary motor cortex stroke

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.     

Functional anatomy of motor recovery after early brain damage

Functional magnetic resonance imaging and transcranial magnetic stimulation were used to examine a 34 year-old right-handed patient, who, at the age of 6 years, had experienced sudden right hemiplegia, seizures, and stupor during a bout of measles encephalitis, followed by incomplete distal right motor recovery. Morphological MRI showed massive unilateral enlargement of the left ventricle, associated with extreme thinning of the white and gray matter,with partial preservation of the pyramidal tract. Functional MRI and transcranial magnetic stimulation revealed reorganization of the motor cortices, and integrity of the corticospinal pathway, respectively. Our findings indicate that complete hand motor recovery may require functional connections between the motor cortical areas and cortical-subcortical structures, in addition to the retained integrity of the primary sensorimotor area and pyramidal tract.     

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI). A subthreshold conditioning stimulus (CS) was given to PMd 2.0-5.2 ms after the TS at intensities of 50-, 70-, or 90% of TS. The CS to PMd facilitated the MEP evoked by TS over M1(HAND) at interstimulus intervals (ISI) of 2.4 or 2.8 ms. There was a second facilitatory peak at ISI of 4.4 ms. PMd-to-M1(HAND) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over lateral prefrontal cortex. Together our results indicate that our dsTMS paradigm probes a short-latency facilitatory PMd-to-M1(HAND) pathway. The temporal pattern of MEP facilitation suggests a PMd-to-M1(HAND) route that targets intracortical M1(HAND) circuits involved in the generation of indirect corticospinal volleys. This paradigm opens up new possibilities to study context-dependent intrahemispheric PMd-to-M1(HAND) interactions in the intact human brain.     

Evidence for bilateral control of skilled movements: ipsilateral skilled forelimb reaching deficits and functional recovery in rats follow motor cortex and lateral frontal cortex lesions

Unilateral damage to cortical areas in the frontal cortex produces sensorimotor deficits on the side contralateral to the lesion. Although there are anecdotal reports of bilateral deficits after stroke in humans and in experimental animals, little is known of the effects of unilateral lesions on the same side of the body. The objective of the present study was to make a systematic examination of the motor skills of the ipsilateral forelimb after frontal cortex lesions to either the motor cortex by devascularization of the surface blood vessels (pial stroke), or to the lateral cortex by electrocoagulation of the distal branches of the middle cerebral artery (MCA stroke). Plastic processes in the intact hemisphere were documented using Golgi-Cox dendritic analysis and by intracortical microstimulation analysis. Although tests of reflexive responses in forelimb placing identified a contralateral motor impairment following both cortical lesions, quantitative and qualitative measures of skilled reaching identified a severe ipsilateral impairment from which recovery was substantial but incomplete. Golgi-impregnated pyramidal cells in the forelimb area showed an increase in dendritic length and branching. Electrophysiological mapping showed normal size forelimb representations in the lesioned rats relative to control animals. The finding of an enduring ipsilateral impairment in skilled movement is consistent with a large but more anecdotal literature in rats, nonhuman primates and humans, and suggests that plastic changes in the intact hemisphere are related to that hemisphere's contribution to skilled movement.     

Highly functional ipsilateral motor control after extensive left hemispheric damage during gestation

In large early cortical lesions, one of the most devastating consequences is the impaired motor dexterity of the contralateral limb. We present the case of an 8-year-old girl with a large left hemispherical porencephaly. Unlike previous reports, the girl exhibited high dexterity of the contralateral hand with preserved independent finger movements. We performed functional MRI of hand motor functions and diffusion tensor imaging, which revealed activation of the ipsilateral motor cortex and absence of a contralateral corticospinal tract. These observations suggest that by intensive training in early life, a complete transhemispheric shift of motor control with high skills can be achieved.     

The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis

Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.     

Preferential encoding of movement amplitude and speed in the primary motor cortex and cerebellum

Voluntary movements require control of multiple kinematic parameters, a task carried out by a distributed brain architecture. However, it remains unclear whether regions along the motor system encode single, or rather a mixture of, kinematic parameters during action execution. Here, rapid event‐related functional magnetic resonance imaging was used to differentiate brain activity along the motor system during the encoding of movement amplitude, duration, and speed. We present cumulative evidence supporting preferential encoding of kinematic parameters along the motor system, based on blood‐oxygenation‐level dependent signal recorded in a well‐controlled single‐joint wrist‐flexion task. Whereas activity in the left primary motor cortex (M1) showed preferential encoding of movement amplitude, the anterior lobe of the right cerebellum (primarily lobule V) showed preferential encoding of movement speed. Conversely, activity in the left supplementary motor area (SMA), basal ganglia (putamen), and anterior intraparietal sulcus was not preferentially modulated by any specific parameter. We found no preference in peak activation for duration encoding in any of the tested regions. Electromyographic data was mainly modulated by movement amplitude, restricting the distinction between amplitude and muscle force encoding. Together, these results suggest that during single‐joint movements, distinct kinematic parameters are controlled by largely distinct brain‐regions that work together to produce and control precise movements. Hum Brain Mapp 38:5970–5986, 2017. © 2017 Wiley Periodicals, Inc.     

Seizures and recovery from experimental brain damage

The effects of the gamma-aminobutyric acid antagonist, pentylenetetrazol (PTZ), on recovery from somatosensory and motor asymmetries after unilateral sensorimotor cortex lesions were investigated. Behavior was assessed using a bilateral tactile stimulation test and a measure of forelimb motor coordination. Immediately after surgery, the PTZ-treated and saline (SAL) control groups both exhibited severe ipsilateral behavioral asymmetries. Rats receiving PTZ recovered significantly faster from somatosensory asymmetry than those receiving SAL. Recovery was complete in the PTZ group within 3 postoperative weeks, while the SAL group failed to reach a comparable level until 2 months after surgery. There was no difference between PTZ and SAL groups on recovery of forelimb motor coordination. No difference in lesion size between the SAL and the PTZ groups could be found. These data are consistent with the hypothesis that post-traumatic neuronal depression may contribute to the severity of sensorimotor deficits observed after brain damage.