Interhemispheric inhibition is different during arm cycling than a position- and intensity-matched tonic contraction.

Task-dependent changes in inhibition may explain why supraspinal excitability is higher during arm cycling than an intensity- and position-matched tonic contraction. The present study investigated whether interhemispheric inhibition (IHI) associated with biceps brachii activity was different during arm cycling, a locomotor output, compared to a tonic contraction. IHI was quantified using an ipsilateral silent period (iSP) evoked via transcranial magnetic stimulation (TMS) of the ipsilateral motor cortex. TMS was delivered at 120% resting motor threshold during the mid-elbow flexion phase of arm cycling (6 o'clock position, made relative to a clock face) and during a position- and intensity-matched tonic contraction. In total, 36 participants took part in the study. However, only 14 participants demonstrated IHI during arm cycling and 10 participants during tonic contraction. Of these participants, eight displayed clear iSPs during arm cycling and tonic contraction. The iSP duration was longer during arm cycling than tonic contraction (p < 0.05), while iSP EMG amplitude and area were not different between tasks (p > 05 for both comparisons). The main finding from this study is that IHI appears to be stronger during arm cycling than an intensity- and position-matched tonic contraction. This does not support previous findings of higher supraspinal excitability during arm cycling.

Comparison of Transcallosal Inhibition Between Hemispheres and Its Relationship with Motor Behavior in Patients with Severe Upper Extremity Impairment After Subacute Stroke.

OBJECTIVE: To compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior. MATERIALS AND METHODS: 19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed. RESULTS: Resting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045). CONCLUSIONS: Symmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke.

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.

Time course of the effects of low-intensity transcranial ultrasound on the excitability of ipsilateral and contralateral human primary motor cortex.

Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique that can modulate the excitability of cortical and deep brain structures with a high degree of focality. Previous human studies showed that TUS decreases motor cortex (M1) excitability measured by transcranial magnetic stimulation (TMS), but whether the effects appear beyond sonication and whether TUS affects the excitability of other interconnected cortical areas is not known. The time course of M1 TUS on ipsilateral and contralateral M1 excitability was investigated in 22 healthy human subjects via TMS-induced motor-evoked potentials. With sonication duration of 500 ms, we found suppression of M1 excitability from 10 ms before to 20 ms after the end of sonication, and the effects were stronger with blocked design compared to interleaved design. There was no significant effect on contralateral M1 excitability. Using ex-vivo measurements, we showed that the ultrasound transducer did not affect the magnitude or time course of the TMS-induced electromagnetic field. We conclude that the online-suppressive effects of TUS on ipsilateral M1 cortical excitability slightly outlast the sonication but did not produce long-lasting effects. The absence of contralateral effects may suggest that there are little tonic interhemispheric interactions in the resting state, or the intensity of TUS was too low to induce transcallosal inhibition.

Pathophysiological associations of transcallosal dysfunction in ALS.

AIM: Involvement of the corpus callosum has been identified as a feature of amyotrophic lateral sclerosis (ALS), particularly through neuropathological studies. The aim of the present study was to determine whether alteration in transcallosal function contributed to the development of ALS, disease progression and thereby functional disability. METHODS: Transcallosal function and motor cortex excitability were assessed in 17 ALS patients with results compared to healthy controls. Transcallosal inhibition (interstimulus intervals (ISI) of 8-40 ms), short interval intracortical facilitation (SICF) and inhibition (SICI) were assessed in both cerebral hemispheres. Patients were staged utilising clinical and neurophysiological staging assessments. RESULTS: In ALS, there was prominent reduction of transcallosal inhibition (TI) when recorded from the primary and secondary motor cortices compared to controls (F = 23.255, p < 0.001). This reduction of TI was accompanied by features indicative of cortical hyperexcitability, including reduction of SICI and increase in SICF. There was a significant correlation between the reduction in TI and the rate of disease progression (R = -0.825, p < 0.001) and reduction in muscle strength (R = 0.54, p = 0.031). CONCLUSION: The present study has established that dysfunction of transcallosal circuits was an important pathophysiological mechanism in ALS, correlating with greater disability and a faster rate of disease progression. Therapies aimed at restoring the function of transcallosal circuits may be considered for therapeutic approaches in ALS.

The modulatory effects of bilateral arm training (BAT) on the brain in stroke patients: a systematic review.

OBJECTIVE: To systematically review the modulatory effects of bilateral arm training (BAT) on the brain of stroke patients in contrast to unilateral arm training (UAT) or regular motor training. METHODS: We conducted a literature search using PubMed, EMBASE, MEDLINE, and Science Citation Index Expanded databases from the inception to March 2019 for identifying any relevant studies. Two authors independently screened the literature, extracted data, and qualitatively described the included studies. RESULTS: Eleven studies with a total of 225 stroke patients were included in this review. 156 out of those participants received neuroimaging or neurophysiological examinations. Six studies reported enhanced activation of the ipsilesional primary motor area (M1) induced by BAT, as measured by MEP and fMRI. Beyond the M1, three studies showed that supplementary motor area (SMA) was activated, and three studies found the primary sensory cortex area (S1) was activated by BAT in stroke patients, as measured by fMRI. One article showed that the inter-/intra-hemispheric functional connections of the sensorimotor network were more highly strengthened after BAT than regular motor training, in particular the functional connectivity between the SMA and the M1 in the bi-hemispheres. Three studies reported that BAT increased the inhibitory flow from the ipsilesional hemisphere to the contralesional hemisphere, as measured by interhemispheric transcallosal inhibition (IHI). However, the superiority of BAT in inducing a symmetric IHI than UAT was controversial. CONCLUSION: BAT is potentially more effective than UAT in improving upper limb recovery after stroke by activating the ipsilesional primary motor area (M1), supplementary motor area (SMA), and primary sensory cortex (S1) and enhancing the intra-hemispheric and interhemispheric connectivity within the sensorimotor network and the cortical motor system.

Neurophysiological signatures of hand motor response to dual-transcranial direct current stimulation in subacute stroke: a TMS and MEG study.

BACKGROUND: Dual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors. METHODS: We conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2-4 weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2 mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS. RESULTS: Stroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in α-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS. CONCLUSIONS: Task-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related α-activity.

Developmental profile of motor cortex transcallosal inhibition in children and adolescents.

Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.

An acute bout of exercise modulates both intracortical and interhemispheric excitability.

Primary motor cortex (M1) excitability is modulated following a single session of cycling exercise. Specifically, short-interval intracortical inhibition and intracortical facilitation are altered following a session of cycling, suggesting that exercise affects the excitability of varied cortical circuits. Yet we do not know whether a session of exercise also impacts the excitability of interhemispheric circuits between, and other intracortical circuits within, M1. Here we present two experiments designed to address this gap in knowledge. In experiment 1, single and paired pulse transcranial magnetic stimulation (TMS) were used to measure intracortical circuits including, short-interval intracortical facilitation (SICF) tested at 1.1, 1.5, 2.7, 3.1 and 4.5 ms interstimulus intervals (ISIs), contralateral silent period (CSP) and interhemispheric interactions by measuring transcallosal inhibition (TCI) recorded from the abductor pollicus brevis muscles. All circuits were assessed bilaterally pre and two time points post (immediately, 30 min) moderate intensity lower limb cycling. SICF was enhanced in the left hemisphere after exercise at the 1.5 ms ISI. Also, CSP was shortened and TCI decreased bilaterally after exercise. In Experiment 2, corticospinal and spinal excitability were tested before and after exercise to investigate the locus of the effects found in Experiment 1. Exercise did not impact motor-evoked potential recruitment curves, Hoffman reflex or V-wave amplitudes. These results suggest that a session of exercise decreases intracortical and interhemispheric inhibition and increases facilitation in multiple circuits within M1, without concurrently altering spinal excitability. These findings have implications for developing exercise strategies designed to potentiate M1 plasticity and skill learning in healthy and clinical populations.

Transcallosal conduction in paroxysmal kinesigenic dyskinesia.

OBJECTIVES: Detecting whether a possible disequilibrium between the excitatory and inhibitory interhemispheric interactions in paroxysmal kinesigenic dyskinesia (PKD) exists. METHODS: This study assessed measures of motor threshold, motor evoked potential latency, the cortical silent period, the ipsilateral silent period and the transcallosal conduction time (TCT) in PKD patients. Data were compared between the clinically affected hemisphere (aH) and the fellow hemisphere (fH). RESULTS: The transcallosal conduction time from the aH to the fH was 11.8 ms (range = 2.3-20.7) and 13.6 ms (range = 2.8-67.7) from the fH to the aH. The difference in TCT in the affected side was significant (p = .019). CONCLUSION: The findings demonstrated that, although inhibitory interneurons act normally and symmetrically between the motor cortices and transcallosal inhibition was normal and symmetrical between both sides, the onset of transcallosal inhibition was asymmetrical. The affected hemisphere's inhibition toward the unaffected hemisphere is faster compared to the inhibition provided by the fellow hemisphere. These results are consistent with an inhibitory deficit in the level of interhemispheric interactions. SIGNIFICANCE: This study revealed a defect in inhibition of the motor axis could be responsible in the pathological mechanisms of kinesigenic dyskinesia.

Trait- and state-dependent cortical inhibitory deficits in bipolar disorder.

OBJECTIVES: Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. METHODS: Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. RESULTS: During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. CONCLUSIONS: The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits.

Lateralization of brain activity pattern during unilateral movement in Parkinson's disease.

We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug-naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum-cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination.

Exploring the specific time course of interhemispheric inhibition between the human primary sensory cortices.

The neurophysiological mechanism of interhemispheric inhibition (IHI) between the human primary sensory cortices (S1s) is poorly understood. Here we used a paired median nerve somatosensory evoked potential protocol to observe S1-S1 IHI from the dominant to the nondominant hemisphere with electroencephalography. In 10 healthy, right-handed individuals, we compared mean peak-to-peak amplitudes of five somatosensory evoked potential components (P14/N20, N20/P25, P25/N30, N30/P40, and P40/N60) recorded over the right S1 after synchronous versus asynchronous stimulation of the right and left median nerves. Asynchronous conditioning + test stimuli (CS+TS) were delivered at interstimulus intervals of 15, 20, 25, 30, and 35 ms. We found that, in relation to synchronous stimulation, when a CS to the left S1 preceded a TS to the right S1 at the short intervals (15 and 20 ms) the amplitude of the cortical N20/P25 complex was significantly depressed, whereas at the longer intervals (25, 30, and 35 ms) significant inhibition was observed for the thalamocortical P14/N20 as well as the cortical N20/P25 components. We conclude that the magnitude of S1 IHI appears to depend on the temporal asynchrony of bilateral inputs and the specific timing is likely reflective of a direct transcallosal mechanism. Employing a method that enables direct S1 IHI to be reliably quantified may provide a novel tool to assess potential IHI imbalances in individuals with neurological damage, such as stroke.

RAD51 deficiency disrupts the corticospinal lateralization of motor control.

Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.

A neurophysiological approach to mirror movements in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate mirror activity in amyotrophic lateral sclerosis (ALS) patients, using a simple paradigm of signal quantification. METHODS: Patients were asked to perform a brief isometric maximum contraction of the abductor digiti minimi (ADM) or tibialis anterior (TA) on one side, while relaxing the contralateral side of the body. Both sides were investigated. Signals were stored and analyzed offline, for quantification of electromyographic signal. Clinical signs of upper motor neuron (UMN) dysfunction, transcranial magnetic stimulation (TMS) for the upper (UL) and lower limbs (LL), the ADM ipsilateral cortical silent period (iSP) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) cognitive scale were also investigated. RESULTS: 42 ALS patients were included. In the 4 investigated muscles the amount of mirror activity was significantly higher than in the matched healthy group. The amount of mirror activity was similar between sides, but significantly higher in UL and LL with abnormal TMS results for ADM (p = 0.005) and TA (p = 0.002), as well as in UL with abnormal iSP values (p = 0.009). No association was found between mirror activity and clinical signs of UMN involvement. CONCLUSIONS: Mirror activity is a common phenomenon in ALS. Mirror activity intensity corresponds to the severity of UMN dysfunction, as measured by TMS, and probably derives from the abnormal transcallosal inhibition as mirrored by iSP abnormality. SIGNIFICANCE: Mirror activity is increased in ALS and is associated with abnormal transcallosal inhibition and UMN dysfunction.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.

OBJECTIVE: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates. METHODS: The demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups. RESULTS: 54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables. INTERPRETATION: We found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.

The distribution of transcallosal inhibition to upper extremity muscles is altered in chronic stroke.

OBJECTIVE: To determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. METHODS: We examined thirteen healthy controls and sixteen mildly to moderately impaired chronic stroke patients. We used transcranial magnetic stimulation (TMS) to probe TI from the contralesional onto ipsilesional hemisphere (assigned in controls). We recorded the ipsilateral silent period in the paretic biceps (BIC) and first dorsal interosseous (FDI). We measured TI strength, distribution gradient (TI difference between muscles), and motor impairment (Fugl-Meyer Assessment). RESULTS: Both groups had stronger TI acting on their FDIs than BICs (p < 0.001). However, stroke patients also had stronger TI acting on their BICs than controls (p = 0.034), resulting in a flatter distribution of inhibition (p = 0.028). In patients, stronger FDI inhibition correlated with less hand impairment (p = 0.031); BIC inhibition was not correlated to impairment. CONCLUSION: TI is more evenly distributed to the paretic FDI and BIC in chronic stroke. The relative increase in proximal inhibition does not relate to better function, as it does distally. SIGNIFICANCE: The results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.

Reliability of transcallosal inhibition measurements for the lower limb motor cortex in stroke.

Transcallosal inhibition (TCI) is a measure of between-hemisphere inhibitory control that can be evaluated with the ipsilateral silent period (iSP) transcranial magnetic stimulation (TMS) paradigm. The study of iSP for the lower extremity has been limited possibly due to the close orientation of the lower extremity motor representations. Change in TCI can provide insights into pathophysiological mechanisms underlying the asymmetry in corticomotor excitability in stroke. Here, we describe a method for iSP quantification and report reliability of iSP parameters for the tibialis anterior (TA) muscle in stroke. 26 individuals with stroke attended three sessions where single pulse TMS was used to measure TCI from the lesioned to non-lesioned hemisphere. A double cone coil was used for stimulating the ipsilateral motor cortex while the participant maintained an isometric contraction of the non-paretic TA. Absolute and relative reliability were computed for iSP latency, duration and area. iSP latency showed the lowest measurement error (absolute reliability) and iSP latency, duration and area showed good relative reliability (intraclass correlation coefficients > 0.6). This study suggests that iSP parameters for the tibialis anterior are reliable and attempts to provide a guideline for evaluating TCI for the lower extremity in stroke and other clinical populations.

Existence of Interhemispheric Inhibition between Foot Sections of Human Primary Motor Cortices: Evidence from Negative Blood Oxygenation-Level Dependent Signal.

Interhemispheric inhibition (IHI) between the left and right primary motor cortices (M1) plays an important role when people perform an isolated unilateral limb movement. Moreover, negative blood oxygenation-level dependent signal (deactivation) obtained from the M1 ipsilateral to the limb could be a surrogate IHI marker. Studies have reported deactivation in the hand section of the ipsilateral M1 during simple unilateral hand movement. However, deactivation in the foot section during unilateral foot movement has not been reported. Therefore, IHI between the foot sections of the bilateral M1s has been considered very weak or absent. Thirty-seven healthy adults performed active control of the right foot and also passively received vibration to the tendon of the tibialis anterior muscle of the right foot, which activates the foot section of the contralateral M1, with brain activity being examined through functional magnetic resonance imaging. The vibration and active tasks significantly and non-significantly, respectively, deactivated the foot section of the ipsilateral M1, with a corresponding 86% and 60% of the participants showing decreased activity. Thus, there could be IHI between the foot sections of the bilateral M1s. Further, our findings demonstrate between-task differences and similarities in cross-somatotopic deactivation.

Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients.

BACKGROUND: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. METHODS: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). RESULTS: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. CONCLUSIONS: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.