Cholinergic modulation of interhemispheric inhibition in the mouse motor cortex.

Interhemispheric inhibition of the homotopic motor cortex is believed to be effective for accurate unilateral motor function. However, the cellular mechanisms underlying interhemispheric inhibition during unilateral motor behavior remain unclear. Furthermore, the impact of the neuromodulator acetylcholine on interhemispheric inhibition and the associated cellular mechanisms are not well understood. To address this knowledge gap, we conducted recordings of neuronal activity from the bilateral motor cortex of mice during the paw-reaching task. Subsequently, we analyzed interhemispheric spike correlation at the cell-pair level, classifying putative cell types to explore the underlying cellular circuitry mechanisms of interhemispheric inhibition. We found a cell-type pair-specific enhancement of the interhemispheric spike correlation when the mice were engaged in the reaching task. We also found that the interhemispheric spike correlation was modulated by pharmacological acetylcholine manipulation. The local field responses to contralateral excitation differed along the cortical depths, and muscarinic receptor antagonism enhanced the inhibitory component of the field response in deep layers. The muscarinic subtype M2 receptor is predominantly expressed in deep cortical neurons, including GABAergic interneurons. These results suggest that GABAergic interneurons expressing muscarinic receptors in deep layers mediate the neuromodulation of interhemispheric inhibition in the homotopic motor cortex.

Effects of the motor cortical theta-burst transcranial-focused ultrasound stimulation on the contralateral motor cortex.

Theta-burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30 min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80 s train of active or sham tbTUS was delivered to the left M1 in 20 healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor-evoked potential (MEP) amplitudes from single-pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual-site paired-pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short-interval intracortical inhibition and intracortical facilitation (ICF) using paired-pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short-interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10 ms but not long-interval IHI at interstimulus interval of 40 ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders. KEY POINTS: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures. A repetitive TUS protocol, with an 80 s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement-related spectral power in distinct brain regions. In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1 measured with MEPs elicited by transcranial magnetic stimulation. We showed that left M1 tbTUS decreased right M1 excitability and left-to-right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1. These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research.

Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

Relationship between the interlimb transfer of a visuomotor learning task and interhemispheric inhibition in healthy humans.

The "interlimb transfer" phenomenon consists of improved performance of the trained and untrained contralateral limbs after unilateral motor practice. We here assessed whether a visuomotor learning task can be transferred from one hemisphere to the other, whether this occurs symmetrically, and the cortical neurophysiological correlates of this phenomenon, focusing on interhemispheric connectivity measures. We enrolled 33 healthy subjects (age range: 24-73 years). Participants underwent two randomized sessions, which investigated the transfer from the dominant to the nondominant hand and vice versa. Measures of cortical and intracortical excitability and interhemispheric inhibition were assessed through transcranial magnetic stimulation before and after a visuomotor task. The execution of the visuomotor task led to an improvement in motor performance with the dominant and nondominant hands and induced a decrease in intracortical inhibition in the trained hemisphere. Participants were also able to transfer the visuomotor learned skill. The interlimb transfer, however, only occurred from the dominant to the nondominant hand and positively correlated with individual learning-related changes in interhemispheric inhibition. We here demonstrated that the "interlimb transfer" of a visuomotor task occurs asymmetrically and relates to the modulation of specific inhibitory interhemispheric connections. The study results have pathophysiological, clinical, and neuro-rehabilitative implications.

Investigating the role of contextual cues and interhemispheric inhibitory mechanisms in response-selective stopping: a TMS study.

Response-selective stopping requires cancellation of only one component of a multicomponent action. While research has investigated how delays to the continuing action components ("stopping interference") can be attenuated by way of contextual cues of the specific stopping demands ("foreknowledge"), little is known of the underlying neural mechanisms. Twenty-seven, healthy, young adults undertook a multicomponent stop-signal task. For two thirds of trials, participants responded to an imperative (go) stimulus (IS) with simultaneous button presses using their left and right index fingers. For the remaining one third of trials, the IS was followed by a stop-signal requiring cancellation of only the left, or right, response. To manipulate foreknowledge of stopping demands, a cue preceded the IS that informed participants which hand might be required to stop (proactive) or provided no such information (reactive). Transcranial magnetic stimulation (TMS) assessed corticospinal excitability (CSE) as well as short- and long-interval interhemispheric inhibition (SIHI, LIHI) between the primary motor cortices. Proactive cues reduced, but did not eliminate, stopping interference relative to the reactive condition. Relative to TMS measures at cue onset, decreases in CSE (both hands and both cue conditions) and LIHI (both hands, proactive condition only) were observed during movement preparation. During movement cancellation, LIHI reduction in the continuing hand was greater than that in the stopping hand and greater than LIHI reductions in both hands during execution of multicomponent responses. Our results indicate that foreknowledge attenuates stopping interference and provide evidence for a novel role of LIHI, mediated via prefrontal regions, in facilitating continuing action components.

Impact of interhemispheric inhibition on bimanual movement control in young and old.

Interhemispheric interactions demonstrate a crucial role for directing bimanual movement control. In humans, a well-established paired-pulse transcranial magnetic stimulation paradigm enables to assess these interactions by means of interhemispheric inhibition (IHI). Previous studies have examined changes in IHI from the active to the resting primary motor cortex during unilateral muscle contractions; however, behavioral relevance of such changes is still inconclusive. In the present study, we evaluated two bimanual tasks, i.e., mirror activity and bimanual anti-phase tapping, to examine behavioral relevance of IHI for bimanual movement control within this behavioral framework. Two age groups (young and older) were evaluated as bimanual movement control demonstrates evident behavioral decline in older adults. Two types of IHI with differential underlying mechanisms were measured; IHI was tested at rest and during a motor task from the active to the resting primary motor cortex. Results demonstrate an association between behavior and short-latency IHI in the young group: larger short-latency IHI correlated with better bimanual movement control (i.e., less mirror activity and better bimanual anti-phase tapping). These results support the view that short-latency IHI represents a neurophysiological marker for the ability to suppress activity of the contralateral side, likely contributing to efficient bimanual movement control. This association was not observed in the older group, suggesting age-related functional changes of IHI. To determine underlying mechanisms of impaired bimanual movement control due to neurological disorders, it is crucial to have an in-depth understanding of age-related mechanisms to disentangle disorder-related mechanisms of impaired bimanual movement control from age-related ones.

Do Adults with Stroke have Altered Interhemispheric Inhibition? A Systematic Review with Meta-Analysis.

OBJECTIVE: Interhemispheric inhibition is an important cortical mechanism to support motor control. Altered interhemispheric inhibition has been the target of neuromodulation interventions. This systematic review investigated the evidence for altered interhemispheric inhibition in adults with unilateral neurological conditions: stroke, amyotrophic lateral sclerosis, cerebral palsy, complex regional pain syndrome, traumatic brain injury, and cerebral palsy METHODS: We pre-registered the protocol and followed PRISMA guidelines. Five databases were systematically searched to identify studies reporting interhemispheric inhibition measures in unilateral neurological conditions and healthy controls. Data were grouped according to the measure (ipsilateral silent period and dual-coil), stimulated hemisphere, and stage of the condition (subacute and chronic). RESULTS: 1372 studies were identified, of which 14 were included (n = 226 adults with stroke and 161 age-matched controls). Ipsilateral silent period-duration was longer in people with stroke than in controls (stimulation of dominant hemisphere) regardless of stroke stage. Motor evoked potential was less suppressed in people with sub-acute stroke (stimulation of the unaffected hemisphere) than controls (stimulation of dominant hemisphere) and this reversed in chronic stroke. CONCLUSION: Detection of altered interhemispheric inhibition appears to be dependent on the measure of interhemispheric inhibition and the stage of recovery. SIGNIFICANCE: Rebalancing interhemispheric inhibition using neuromodulation is considered a promising line of treatment for stroke rehabilitation. Our results did not find compelling evidence to support consistent alterations in interhemispheric inhibition in adults with stroke.

The role of interhemispheric communication during complete and partial cancellation of bimanual responses.

Precise control of upper limb movements in response to external stimuli is vital to effectively interact with the environment. Accurate execution of bimanual movement is known to rely on finely orchestrated interhemispheric communication between the primary motor cortices (M1s). However, relatively little is known about the role of interhemispheric communication during sudden cancellation of prepared bimanual movement. The current study investigated the role of interhemispheric interactions during complete and partial cancellation of bimanual movement. In two experiments, healthy young human participants received transcranial magnetic stimulation to both M1s during a bimanual response inhibition task. The increased corticomotor excitability in anticipation of bimanual movement was accompanied by a release of inhibition from both M1s. After a stop cue, inhibition was reengaged onto both hemispheres to successfully cancel the complete bimanual response. However, when the stop cue signaled partial cancellation (stopping of one digit only), inhibition was reengaged with regard to the cancelled digit, but the responding digit representation was facilitated. This bifurcation in interhemispheric communication between M1s occurred 75 ms later in the more difficult condition when the nondominant, as opposed to dominant, hand was still responding. Our results demonstrate that interhemispheric communication is integral to response inhibition once a bimanual response has been prepared. Interestingly, M1-M1 interhemispheric circuitry does not appear to be responsible for the nonselective suppression of all movement components that has been observed during partial cancellation. Instead such interhemispheric communication enables uncoupling of bimanual response components and facilitates the selective initiation of just the required unimanual movement.NEW & NOTEWORTHY We provide the first evidence that interhemispheric communication plays an important role during sudden movement cancellation of two-handed responses. Simultaneously increased inhibition onto both hemispheres assists with two-handed movement cancellation. However, this network is not responsible for the widespread suppression of motor activity observed when only one of the two hands is cancelled. Instead, communication between hemispheres enables the separation of motor activity for the two hands and helps to execute the required one-handed response.

Cortical reorganization after motor stroke: A pilot study on differences between the upper and lower limbs.

Stroke patients suffering from hemiparesis may show substantial recovery in the first months poststroke due to neural reorganization. While reorganization driving improvement of upper hand motor function has been frequently investigated, much less is known about the changes underlying recovery of lower limb function. We, therefore, investigated neural network dynamics giving rise to movements of both the hands and feet in 12 well-recovered left-hemispheric chronic stroke patients and 12 healthy participants using a functional magnetic resonance imaging sparse sampling design and dynamic causal modeling (DCM). We found that the level of neural activity underlying movements of the affected right hand and foot positively correlated with residual motor impairment, in both ipsilesional and contralesional premotor as well as left primary motor (M1) regions. Furthermore, M1 representations of the affected limb showed significantly stronger increase in BOLD activity compared to healthy controls and compared to the respective other limb. DCM revealed reduced endogenous connectivity of M1 of both limbs in patients compared to controls. However, when testing for the specific effect of movement on interregional connectivity, interhemispheric inhibition of the contralesional M1 during movements of the affected hand was not detected in patients whereas no differences in condition-dependent connectivity were found for foot movements compared to controls. In contrast, both groups featured positive interhemispheric M1 coupling, that is, facilitation of neural activity, mediating movements of the affected foot. These exploratory findings help to explain why functional recovery of the upper and lower limbs often develops differently after stroke, supporting limb-specific rehabilitative strategies.

Paradoxical facilitation alongside interhemispheric inhibition.

Neurophysiological experiments using transcranial magnetic stimulation (TMS) have sought to probe the function of the motor division of the corpus callosum. Primary motor cortex sends projections via the corpus callosum with a net inhibitory influence on the homologous region of the opposite hemisphere. Interhemispheric inhibition (IHI) experiments probe this inhibitory pathway. A test stimulus (TS) delivered to the motor cortex in one hemisphere elicits motor evoked potentials (MEPs) in a target muscle, while a conditioning stimulus (CS) applied to the homologous region of the opposite hemisphere modulates the effect of the TS. We predicted that large CS MEPs would be associated with increased IHI since they should be a reliable index of how effectively contralateral motor cortex was stimulated and therefore of the magnitude of interhemispheric inhibition. However, we observed a strong tendency for larger CS MEPs to be associated with reduced interhemispheric inhibition which in the extreme lead to a net effect of facilitation. This surprising effect was large, systematic, and observed in nearly all participants. We outline several hypotheses for mechanisms which may underlie this phenomenon to guide future research.

The modulation of short and long-latency interhemispheric inhibition during bimanually coordinated movements.

Bimanual coordination is essential for the performance of many everyday tasks. There are several types of bimanually coordinated movements, classified according to whether the arms are acting to achieve a single goal (cooperative) or separate goals (independent), and whether the arms are moving symmetrically or asymmetrically. Symmetric bimanual movements are thought to facilitate corticomotor excitability (CME), while asymmetric bimanual movements are thought to recruit interhemispheric inhibition to reduce functional coupling between the motor cortices. The influences of movement symmetry and goal conceptualisation on interhemispheric interactions have not been studied together, and not during bimanually active dynamic tasks. The present study used transcranial magnetic stimulation (TMS) to investigate the modulation of CME and short- and long-latency interhemispheric inhibition (SIHI and LIHI, respectively) during bimanually active dynamic tasks requiring different types of bimanual coordination. Twenty healthy right-handed adults performed four bimanual tasks in which they held a dumbbell in each hand (independent) or a custom device between both hands (cooperative) while rhythmically flexing and extending their wrists symmetrically or asymmetrically. Motor-evoked potentials were recorded from the right extensor carpi ulnaris. We found CME was greater during asymmetric tasks than symmetric tasks, and movement symmetry did not modulate SIHI or LIHI. There was no effect of goal conceptualisation nor any interaction with movement symmetry for CME, SIHI or LIHI. Based on these results, movement symmetry and goal conceptualisation may not modulate interhemispheric inhibition during dynamic bimanual tasks. These findings contradict prevailing thinking about the roles of CME and interhemispheric inhibition in bimanual coordination.

'Expedited Interhemispheric Inhibition': A Simple Method to Collect Additional IHI Data in the Same Amount of Time.

Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not measured, or discarded. The aim of this experiment was to investigate whether MEPs evoked from these conditioning stimuli can be utilised as non-conditioned, or 'baseline', responses, and therefore expedite IHI data collection. We evaluated short-latency (10 ms) and long-latency (40 ms) IHI bidirectionally in 14 healthy participants. There was no difference in MEP amplitudes evoked by conventional single TMS pulses randomly inserted into IHI blocks, and those evoked by the conditioning stimulus. Nor was there any significant difference in IHI magnitude when using single pulse MEPs or conditioning stimulus MEPs as baseline responses. The utilisation of conditioning stimuli dispenses with the need to insert dedicated single TMS pulses into IHI blocks, allowing for additional IHI data to be collected in the same amount of time.

Mapping the Brain-Wide Network Effects by Optogenetic Activation of the Corpus Callosum.

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.

The supplementary motor area modulates interhemispheric interactions during movement preparation.

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

Loss of GABAB -mediated interhemispheric synaptic inhibition in stroke periphery.

KEY POINTS: Recovery from the potentially devastating consequences of stroke depends largely upon plastic changes occurring in the lesion periphery and its inputs. In a focal model of stroke in mouse somatosensory cortex, we found that the recovery of sensory responsiveness occurs at the level of synaptic inputs, without gross changes of the intrinsic electrical excitability of neurons, and also that recovered responses had longer than normal latencies. Under normal conditions, one somatosensory cortex inhibits the responsiveness of the other located in the opposite hemisphere (interhemispheric inhibition) via activation of GABAB receptors. In stroke-recovered animals, the powerful interhemispheric inhibition normally present in controls is lost in the lesion periphery. By contrast, contralateral hemisphere activation selective contributes to the recovery of sensory responsiveness after stroke. ABSTRACT: Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known about the microcircuit changes underlying recovery, the extent to which perilesional plasticity occurs at synaptic input vs. spike output level, and the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extracellular and intracellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke in the neighbouring forelimb area (fS1), suggesting that, under normal conditions, they originate via horizontal connections from the neighbouring fS1. Synaptic and spike responses to forelimb stimulation in hS1 recovered to quasi-normal levels 2 weeks after stroke, without changes in intrinsic excitability and hindlimb-evoked spike responses. Recovered synaptic responses had longer latencies, suggesting a long-range origin of the recovery, prompting us to investigate the role of callosal inputs in the recovery process. Contralesional S1 silencing unmasked significantly larger responses to both limbs in controls, a phenomenon that was not observed when GABAB receptors were antagonized in the recorded area. Conversely, such GABAB -mediated interhemispheric inhibition was not detectable after stroke: callosal input silencing failed to change hindlimb responses, whereas it robustly reduced recovered forelimb responses. Thus, recovery of subthreshold responsiveness in the stroke periphery is accompanied by a loss of interhemispheric inhibition and this is a result of pathway-specific facilitatory action on the affected sensory response from the contralateral cortex.

Adaptive threshold hunting reveals differences in interhemispheric inhibition between young and older adults.

Interhemispheric inhibition between bilateral motor cortices is important for the performance of unimanual activities and may be compromised with advancing age. Conventionally, interhemispheric inhibition is assessed using paired-pulse transcranial magnetic stimulation (TMS) with constant conditioning and test stimulation parameters. Adaptive threshold hunting TMS, whereby a target motor-evoked potential amplitude is maintained in the presence of the conditioning, may provide an alternative means of assessment. Furthermore, interhemispheric inhibition may suppress late indirect-waves more so than early indirect-waves which can be preferentially elicited using anterior-posterior (AP) and posterior-anterior (PA) induced currents, respectively. The aim of this study was to assess age-related effects on interhemispheric inhibition using both conventional and threshold hunting techniques with PA- and AP-induced current. In 15 young and 15 older adults, short (10 ms) and long (40 ms) interval interhemispheric inhibition was examined in the nondominant extensor carpi radialis muscle at rest and during voluntary extension of the contralateral wrist. With the conventional technique, there were no age-related differences in short-interval interhemispheric inhibition. With threshold hunting and AP-induced current, young adults exhibited greater short-interval interhemispheric inhibition during contralateral activation compared with rest and compared with older adults. Furthermore, long-interval interhemispheric inhibition was greater in older adults compared with young for both conventional and threshold hunting techniques. Age-related differences in interhemispheric inhibition are evident with threshold hunting using PA- and AP-induced current.

Alterations in post-movement beta event related synchronization throughout the migraine cycle: A controlled, longitudinal study.

Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student's t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student's t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.

Motor Cortex Reorganization and Impaired Function in the Transition to Sustained Muscle Pain.

Primary motor cortical (M1) adaptation has not been investigated in the transition to sustained muscle pain. Daily injection of nerve growth factor (NGF) induces hyperalgesia reminiscent of musculoskeletal pain and provides a novel model to study M1 in response to progressively developing muscle soreness. Twelve healthy individuals were injected with NGF into right extensor carpi radialis brevis (ECRB) on Days 0 and 2 and with hypertonic saline on Day 4. Quantitative sensory and motor testing and assessment of M1 organization and function using transcranial magnetic stimulation were performed prior to injection on Days 0, 2, and 4 and again on Day 14. Pain and disability increased at Day 2 and increased further at Day 4. Reorganization of M1 was evident at Day 4 and was characterized by increased map excitability. These changes were accompanied by reduced intracortical inhibition and increased intracortical facilitation. Interhemispheric inhibition was reduced from the "affected" to the "unaffected" hemisphere on Day 4, and this was associated with increased pressure sensitivity in left ECRB. These data provide the first evidence of M1 adaptation in the transition to sustained muscle pain and have relevance for the development of therapies that seek to target M1 in musculoskeletal pain.

Demand on skillfulness modulates interhemispheric inhibition of motor cortices.

The role of primary motor cortex (M1) in the control of hand movements is still unclear. Functional magnetic resonance imaging (fMRI) studies of unimanual performance reported a relationship between level of precision of a motor task and additional ipsilateral M1 (iM1) activation. In the present study, we determined whether the demand on accuracy of a movement influences the magnitude of the inhibitory effect between primary motor cortices (IHI). We used transcranial magnetic stimulation (TMS) to measure active IHI (aIHI) of the iM1 on the contralateral M1 (cM1) in the premovement period of a left-hand motor task. Ten healthy participants manipulated a joystick to point to targets of two different sizes. For aIHI, the conditioning stimulus (CS) was applied to iM1, and the test stimulus (TS) to cM1, with an interstimulus interval of 10 ms. The amount of the inhibitory effect of the CS on the motor-evoked potential (MEP) of the subsequent TS was expressed as percentage of the mean MEP amplitude evoked by the single TS. Across different time points of aIHI measurements in the premovement period, there was a significant effect for target size on aIHI. Preparing to point to small targets was associated with weaker aIHI compared with pointing to large targets. The present findings suggest that, during the premovement period, aIHI from iM1 on cM1 is modulated by the demand on accuracy of the motor task. This is consistent with task fMRI findings showing bilateral M1 activation during high-precision movements but only unilateral M1 activity during low-precision movements.

Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke. This randomized, sham-controlled, double-blind study was to compare the effects of high-frequency versus low-frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements. METHODS: A total of 69 first-ever ischemic stroke patients with motor deficits were randomly allocated to receive five daily sessions of 3-Hz ipsilesional rTMS, 1-Hz contralesional rTMS or sham rTMS in addition to standard physical therapy. Outcome measures included motor deficits, neurological scores and cortical excitability, which were assessed at baseline, after the intervention and at 3-month follow-up. RESULTS: The rTMS groups manifested greater motor improvements than the control group, which were sustained for at least 3 months after the end of the treatment sessions. 1-Hz rTMS over the unaffected hemisphere produced more profound effects than 3-Hz rTMS in facilitating upper limb motor performance. There was a significant correlation between motor function improvement and motor cortex excitability change in the affected hemisphere. CONCLUSIONS: Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.