Ipsilateral Silent Period Research Articles

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

ObjectiveInterhemispheric 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. MethodsThe 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. Results54 % 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. InterpretationWe 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.

Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study

BackgroundMirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue.MethodsIn 21 patients with relapsing–remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1—4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume.ResultsMS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume).ConclusionsMM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

Corpus Callosum-Mediated Interhemispheric Interactions in Cervical Spondylotic Myelopathy.

The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation. Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined. In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally. Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.

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

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. 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. 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. 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.

Yoga as an Add-on Therapy in Parkinson's Disease: A Single Group Open-label Trial.

We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson's disease (PD). We prospectively evaluated 17 patients with PD at baseline, after one month of conventional care, and after one month of supervised yoga sessions. The motor and non-motor symptoms were evaluated using the Unified Parkinson's disease Rating Scale (motor part III), Hoehn and Yahr stage, Montreal Cognitive Assessment, Hamilton depression rating scale, Hamilton anxiety rating scale, non-motor symptoms questionnaire and World Health Organization quality of life questionnaire. Transcranial magnetic stimulation was used to record resting motor threshold, central motor conduction time, ipsilateral silent period (iSP), contralateral silent period (cSP), short interval intracortical inhibition (SICI), and intracortical facilitation. The mean age of the patients was 55.5 ± 10.8 years, with a mean duration of illness of 4.0 ± 2.5 years. The postural stability of the patients significantly improved following yoga (0.59 ± 0.5 to 0.18 ± 0.4, p = 0.039). There was a significant reduction in the cSP from baseline (138.07 ± 27.5 ms) to 4 weeks of yoga therapy (116.94 ± 18.2 ms, p = 0.004). In addition, a significant reduction in SICI was observed after four weeks of yoga therapy (0.22 ± 0.10) to (0.46 ± 0.23), p = 0.004). Yoga intervention can significantly improve postural stability in patients with PD. A significant reduction of cSP and SICI suggests a reduction in GABAergic neurotransmission following yoga therapy that may underlie the improvement observed in postural stability. CTRI/2019/02/017564.

Alteration of Interhemispheric Inhibition in Patients With Lateral Epicondylalgia

Patients with lateral epicondylalgia (LE) show alterations in the primary motor cortex (M1) contralateral to the affected side. Cortical alterations have been investigated by measuring intracortical facilitation/inhibition; however, their association with pain remains controversial. Furthermore, no studies have investigated changes in interhemispheric inhibition (IHI). IHI can be assessed using the ipsilateral silent period (iSP) known as the temporary inhibition of electromyographic activity evoked by transcranial magnetic stimulation in the ipsilateral M1 of the contracting muscle. To better understand the relationship between cortical alterations and pain in LE, this observational study investigated the relationship between iSP and pain in LE. Twenty-seven healthy volunteers and 21 patients with LE were recruited. The duration of iSP in the extensor carpi radialis brevis was measured. The IHI asymmetry ratio was calculated to determine the IHI balance. Pain and disability were scored using the Japanese version of the patient-rated elbow evaluation. We observed increased inhibitory input from the ipsilateral M1 on the affected side to the contralateral M1 in LE. Additionally, the IHI balance correlated with pain severity. Hence, regulating imbalanced IHI can potentially decrease lateral elbow pain in LE. PerspectivePatients with lateral epicondylalgia (LE) experience persistent pain and cortical alterations. However, there is no established relationship between cortical alterations and pain. This study demonstrated that the interhemispheric inhibition (IHI) balance is correlated with pain. Regulating imbalanced IHI can potentially decrease lateral elbow pain in patients with LE.

Cortical excitability changes in patients of vascular parkinsonism with cognitive impairment

IntroductionVascular parkinsonism (VaP), type of lower body parkinsonism, occurs in relation to ischemic cerebrovascular disease. It can be associated with cognitive impairment. We aimed to study the cortical excitability changes in these patients using transcranial magnetic stimulation (TMS). MethodsWe included 20 patients with VaP and 22 healthy controls (HC). All subjects underwent TMS over left motor cortex with recording of resting motor threshold (RMT), central motor conduction time (CMCT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral and ipsilateral silent period (SP) along with RMT and CMCT in the contralateral lower limb. Cognitive assessments were done using Montreal cognitive assessment (MoCA) and Addenbrooke's cognitive evaluation III (ACE III). ResultsMean age of patients (63.90 ± 7.36 years) was comparable with controls (59.77 ± 6.94 years; p = 0.07). Duration of disease was 2.58 ± 2.57 years. The upper and lower limb RMT of patients (32.45 ± 4.81%; 57.20 ± 11.54%) was significantly low compared to HC (43.64 ± 7.73%; 69.18 ± 14.27%; p < 0.001). There was a significant reduction in SICI in patients (1.87 ± 2.03) compared to HC (0.38 ± 0.29; p < 0.001). In addition, there was a significant prolongation of ipsilateral SP in patients (48.49 ± 24.49) compared to controls (32.04 ± 12.26, p = 0.01). However, there was no significant difference in contralateral SP (p = 0.66) and ICF (p = 0.25) between the two groups. There was a significant prolongation of lower limb CMCT in patients (p < 0.01). There was a positive correlation of SICI with MoCA (r = 0.45, p < 0.05) and ACE-III (r = 0.33, p < 0.05) scores. ConclusionReduction in RMT and SICI in patients with VaP suggests abnormalities in GABAergic neurotransmission that may underlie cognitive impairment observed in them.

Different effects of I-wave periodicity repetitive TMS on motor cortex interhemispheric interaction.

Activity of the neural circuits in the human motor cortex can be probed using transcranial magnetic stimulation (TMS). Changing TMS-induced current direction recruits different cortical neural circuits. I-wave periodicity repetitive TMS (iTMS) substantially modulates motor cortex excitability through neural plasticity, yet its effect on interhemispheric interaction remains unclear. To explore the modulation of interhemispheric interaction by iTMS applied in different current directions. Twenty right-handed healthy young volunteers (aged 27.5 ± 5.0 years) participated in this study with three visits. On each visit, iTMS in posterior-anterior/anterior-posterior direction (PA-/AP-iTMS) or sham-iTMS was applied to the right hemisphere, with corticospinal excitability and intracortical facilitation of the non-stimulated left hemisphere evaluated at four timepoints. Ipsilateral silent period was also measured at each timepoint probing interhemispheric inhibition (IHI). PA- and AP-iTMS potentiated cortical excitability concurrently in the stimulated right hemisphere. Corticospinal excitability of the non-stimulated left hemisphere increased 10 min after both PA- and AP-iTMS intervention, with a decrease in short-interval intracortical facilitation (SICF) observed in AP-iTMS only. Immediately after the intervention, PA-iTMS tilted the IHI balance toward inhibiting the non-stimulated hemisphere, while AP-iTMS shifted the balance toward the opposite direction. Our findings provide systematic evidence on the plastic modulation of interhemispheric interaction by PA- and AP-iTMS. We show that iTMS induces an interhemispheric facilitatory effect, and that PA- and AP-iTMS differs in modulating interhemispheric inhibition.

Non-paretic leg movements can facilitate cortical drive to the paretic leg in individuals post stroke with severe motor impairment: Implications for motor priming.

Cross-education, a phenomenon where unilateral strength (or skill) training enhances strength (or skill) in the contralateral untrained limb, has been well studied in able-bodied individuals. Cross-education effect accompanies bilateral changes of corticomotor activity in the motor cortex (M1). Recent reports demonstrated greater cross-education effect in stroke survivors compared to healthy individuals, however, corticomotor responses to cross-education in stroke remains unclear. This study aimed to determine the effects of non-paretic leg movements on corticomotor excitability (CME) and reaction time of the paretic leg in severely impaired stroke survivors. Seventeen post stroke individuals with severe leg motor impairment (Fugl-Meyer lower extremity score less than 21 and absence of motor evoked potential in the paretic leg) performed three 20-min motor trainings using their non-paretic ankle: skill (targeted dynamic movements), strength (isometric resistance) and sham (sub-threshold electrical nerve stimulation). During training, verbal instructions were given to the participants to limit their movement to the non-paretic leg and this was confirmed with visual observation of the paretic leg. Transcranial magnetic stimulation measured CME of the contralateral pathways from the non-lesioned M1 to the non-paretic tibialis anterior (TA) muscle, ipsilateral pathways to the paretic TA and transcallosal inhibition (TCI) from the non-lesioned to lesioned M1. Paretic ankle reaction time was measured using a reaction time paradigm. All outcomes were measured before, immediately post, 30-min post and 60-min post priming. CME of the non-paretic TA increased after skill (.08 ± .10 mV) and strength (.06 ± .05 mV) training (p < .01). Ipsilateral CME of the paretic TA (.02 ± .01 mV) and TCI (.01 ± .01 s, ipsilateral silent period; more inhibition to the lesioned M1) increased after skill (p < .05) but not strength training. Reaction time of the paretic ankle improved after skill and strength training (-.11 ± .2 and -.13 ± .20 s, respectively; p < .05) and was sustained at 60 min. No changes were observed during the sham condition. Our findings may inform future studies for using non-paretic leg movements as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements. Conclusion: Non-paretic leg movements can be used as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements.

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

ObjectiveTo determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. MethodsWe 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). ResultsBoth 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. ConclusionTI 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. SignificanceThe results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.

Hemispheric Differences of 1 Hz rTMS over Motor and Premotor Cortex in Modulation of Neural Processing and Hand Function.

Non-invasive brain stimulation can modulate both neural processing and behavioral performance. Its effects may be influenced by the stimulated area and hemisphere. In this study (EC no. 09083), repetitive transcranial magnetic stimulation (rTMS) was applied to the primary motor cortex (M1) or dorsal premotor cortex (dPMC) of either the right or left hemisphere, while evaluating cortical neurophysiology and hand function. Fifteen healthy subjects participated in this placebo-controlled crossover study. Four sessions of real 1 Hz rTMS (110% of rMT, 900 pulses) over (i) left M1, (ii) right M1, (iii) left dPMC, (iv) right dPMC, and one session of (v) placebo 1 Hz rTMS (0% of rMT, 900 pulses) over the left M1 were applied in randomized order. Motor function of both hands (Jebsen-Taylor Hand Function Test (JTHFT)) and neural processing within both hemispheres (motor evoked potentials (MEPs), cortical silent period (CSP), and ipsilateral silent period (ISP)) were evaluated prior and after each intervention session. A lengthening of CSP and ISP durations within the right hemisphere was induced by 1 Hz rTMS over both areas and hemispheres. No such intervention-induced neurophysiological changes were detected within the left hemisphere. Regarding JTHFT and MEP, no intervention-induced changes ensued. Changes of hand function correlated with neurophysiological changes within both hemispheres, more often for the left than the right hand. Effects of 1 Hz rTMS can be better captured by neurophysiological than behavioral measures. Hemispheric differences need to be considered for this intervention.

The Transcallosal Highway: The ipsilateral silent period as a neural biomarker for impaired corpus callosum communication in multiple sclerosis

Multiple sclerosis is a neurodegenerative disease that damages myelin sheath within the central nervous system. This axonal demyelination impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in transcallosal communication impairs the coordination of movements requiring precise temporal and spatial components such as lower extremity function during gait. These bilateral movements require constant communication across the corpus callosum to excite and inhibit specific muscle groups. The ipsilateral silent period (iSP) is an indirect marker of the magnitude for transcallosal inhibition. We hypothesize that the iSP may also serve as a neural biomarker for transcallosal impairments originating from the more affected hemisphere and highlight underlying mechanisms for gait asymmetries in PwMS. Our ongoing study utilizes transcranial magnetic stimulation to assess the inhibitory capacity between the brain's hemispheres (i.e., iSPs). A focal magnetic pulse is delivered to the first dorsal interosseous resulting in a suppression of muscle activity, thus reflecting inhibitory transcallosal communication. There is a lack of research analyzing directionality data between the more and less affected hemisphere in PwMS. Therefore, we evaluate outcome metrics dependent upon the individual's more affected hemisphere. Twenty-three PwMS completed the ongoing protocol and inhibitory metrics such as depth iSP% average, duration, depth iSP% max, transcallosal conduction time, and onset latency were collected. No statistically significant differences have been found between the two hemispheres in PwMS. However, beyond directionality data, our study is investigating gait coordination with overall inhibitory capacity. Walking coordination is quantified using a metric called phase coordination index (PCI). A greater PCI value reflects poorer gait coordination. We hypothesize those who demonstrate better gait coordination (lower PCI values), will have a greater iSP. These findings will determine the potential of iSPs as a neural biomarker to address gait asymmetries and stratify participants into individualized mobility rehabilitation protocols. Multiple sclerosis is a neurodegenerative disease that damages myelin sheath within the central nervous system. This axonal demyelination impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in transcallosal communication impairs the coordination of movements requiring precise temporal and spatial components such as lower extremity function during gait. These bilateral movements require constant communication across the corpus callosum to excite and inhibit specific muscle groups. The ipsilateral silent period (iSP) is an indirect marker of the magnitude for transcallosal inhibition. We hypothesize that the iSP may also serve as a neural biomarker for transcallosal impairments originating from the more affected hemisphere and highlight underlying mechanisms for gait asymmetries in PwMS. Our ongoing study utilizes transcranial magnetic stimulation to assess the inhibitory capacity between the brain's hemispheres (i.e., iSPs). A focal magnetic pulse is delivered to the first dorsal interosseous resulting in a suppression of muscle activity, thus reflecting inhibitory transcallosal communication. There is a lack of research analyzing directionality data between the more and less affected hemisphere in PwMS. Therefore, we evaluate outcome metrics dependent upon the individual's more affected hemisphere. Twenty-three PwMS completed the ongoing protocol and inhibitory metrics such as depth iSP% average, duration, depth iSP% max, transcallosal conduction time, and onset latency were collected. No statistically significant differences have been found between the two hemispheres in PwMS. However, beyond directionality data, our study is investigating gait coordination with overall inhibitory capacity. Walking coordination is quantified using a metric called phase coordination index (PCI). A greater PCI value reflects poorer gait coordination. We hypothesize those who demonstrate better gait coordination (lower PCI values), will have a greater iSP. These findings will determine the potential of iSPs as a neural biomarker to address gait asymmetries and stratify participants into individualized mobility rehabilitation protocols.

The ipsilateral silent period and its link to cortical lesions in multiple sclerosis

The ipsilateral silent period and its link to cortical lesions in multiple sclerosis

M1-P15 as a cortical marker for transcallosal inhibition: A preregistered TMS-EEG study.

In a recently published study combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), an early component of TMS-evoked potentials (TEPs), i.e., M1-P15, was proposed as a measure of transcallosal inhibition between motor cortices. Given that early TEPs are known to be highly variable, further evidence is needed before M1-P15 can be considered a reliable index of effective connectivity. Here, we conceived a new preregistered TMS-EEG study with two aims. The first aim was validating the M1-P15 as a cortical index of transcallosal inhibition by replicating previous findings on its relationship with the ipsilateral silent period (iSP) and with performance in bimanual coordination. The second aim was inducing a task-dependent modulation of transcallosal inhibition. A new sample of 32 healthy right-handed participants underwent behavioral motor tasks and TMS-EEG recording, in which left and right M1 were stimulated both during bimanual tasks and during an iSP paradigm. Hypotheses and methods were preregistered before data collection. Results show a replication of our previous findings on the positive relationship between M1-P15 amplitude and the iSP normalized area. Differently, the relationship between M1-P15 latency and bimanual coordination was not confirmed. Finally, M1-P15 amplitude was modulated by the characteristics of the bimanual task the participants were performing, and not by the contralateral hand activity during the iSP paradigm. In sum, the present results corroborate our previous findings in validating the M1-P15 as a cortical marker of transcallosal inhibition and provide novel evidence of its task-dependent modulation. Importantly, we demonstrate the feasibility of preregistration in the TMS-EEG field to increase methodological rigor and transparency.

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.

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

ObjectiveInterhemispheric 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 MethodsWe 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). Results1372 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. ConclusionDetection of altered interhemispheric inhibition appears to be dependent on the measure of interhemispheric inhibition and the stage of recovery. SignificanceRebalancing 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.

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

ObjectiveTo 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 methods19 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. ResultsResting 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). ConclusionsSymmetric 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.

Hemisphere Asymmetry during Different Levels of Co-activation of Antagonist Muscles: a Transcranial Magnetic Stimulation Study

Contralateral and ipsilateral silent periods were recorded from first dorsal interosseous muscles of the dominant and the non-dominant hand in response to contralateral and ipsilateral transcranial magnetic stimulation (TMS) in twelve right-handed healthy volunteers during isometric index finger abduction and co-activation of antagonist muscles.&#x0D; In the dominant hand, contralateral silent period recorded during coactivation of antagonist muscles was significantly shorter than contralateral silent period recorded during isometric index finger abduction. In the nondominant hand, we did not find significant differences.&#x0D; In the dominant hand, ipsilateral silent period recorded during co-activation of antagonist muscles was significantly shorter than ipsilateral silent period recorded during isometric index finger abduction. In the non-dominant hand, we did not find significant differences.&#x0D; In conclusion, our main finding was the hemisphere asymmetry during co-activation of antagonist muscles. Both, contralateral and ipsilateral silent periods recorded from the dominant right hand were shorter in comparison to those recorded from the non-dominant hand. These findings illustrate the role of co-activation for the better and precise usage of the dominant hand.

Feasibility and Potential Value of TMS for Upper Extremity Motor Assessment at the Bedside During Acute Stroke Hospitalization

<h3>Research Objectives</h3> To assess the feasibility of collecting transcranial magnetic stimulation (TMS) measures at the bedside during acute stroke hospitalization and to associate TMS neurophysiology with upper extremity (UE) behavioral measures. <h3>Design</h3> The Stroke Motor reHabilitation and Recovery sTudy (SMaHRT; https://www.clinicaltrials.gov/ct2/show/NCT03485040?term=NCT03485040&draw=2&rank=1) is a prospective, observational cohort study <h3>Setting</h3> Inpatient neurology service, Massachusetts General Hospital, a large academic medical center. <h3>Participants</h3> Twenty-seven individuals (65.44 ± 12.52 years) with first-ever stroke resulting in UE weakness, who were 18 years or older, could follow simple commands in English and had no contraindications to receiving ipsilesional TMS were eligible for and included in this study. TMS was performed within 5.2 ± 2.2 days of stroke. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Feasibility of collecting TMS measures including motor evoked potentials (MEPs), resting motor threshold (RMT), cortical silent period (cSP) and ipsilateral silent period (iSP) at the hospital bedside was assessed. The main behavioral measures collected included upper extremity Fugl-Meyer Assessment (FMA-UE), grip strength, shoulder abduction finger extension (SAFE) score and 9-hole peg test. <h3>Results</h3> MEPs, RMT, cSP and iSP were collected in at least one hemisphere for 26/42 participants, of whom 15 participants did not receive testing due to medical and discharge factors. A mobile TMS cart facilitated efficient equipment transport. Additionally, coordination with nursing and use of hospital-bed or bedside chair positioning features maximized successful testing. Patients' whose lesioned hemisphere was MEP+ compared to MEP- at acute hospitalization had better affected FMA-UE, SAFE, 9HPT and grip strength scores (p<0.01). Lower RMT values were also associated with better affected FMA-UE (rho=-0.6, p<0.05), SAFE (rho=-0.5, p=0.07), and Grip Strength (rho=-0.4, p=0.23) scores. There were no clear linear trends between cSP or iSP and any behavioral outcome. <h3>Conclusions</h3> Several TMS measures are feasible to perform during acute stroke hospitalization. Interdisciplinary coordination, a mobile TMS cart, and participant positioning are essential to successful TMS testing at the hospital bedside. In addition to MEP, RMT has added value for relating to UE motor behavior during acute stroke hospitalization. <h3>Author(s) Disclosures</h3> See "Faculty Disclosures" task tab

Acute High-Intensity Interval Exercise Modulates Corticospinal Excitability in Older Adults.

Acute exercise can modulate the excitability of the nonexercised upper limb representation in the primary motor cortex (M1). Measures of M1 excitability using transcranial magnetic stimulation (TMS) are modulated after various forms of acute exercise in young adults, including high-intensity interval training (HIIT). However, the impact of HIIT on M1 excitability in older adults is currently unknown. Therefore, the purpose of the current study was to investigate the effects of lower limb cycling HIIT on bilateral upper limb M1 excitability in older adults. We assessed the impact of acute lower limb HIIT or rest on bilateral corticospinal excitability, intracortical inhibition and facilitation, and interhemispheric inhibition of the nonexercised upper limb muscle in healthy older adults (mean age 66 ± 8 yr). We used single and paired-pulse TMS to assess motor evoked potentials, short-interval intracortical inhibition, intracortical facilitation, and the ipsilateral silent period. Two groups of healthy older adults completed either HIIT exercise or seated rest for 23 min, with TMS measures performed before (T0), immediately after (T1), and 30 min after (T2) HIIT/rest. Motor evoked potentials were significantly increased after HIIT exercise at T2 compared with T0 in the dominant upper limb. Contrary to our hypothesis, we did not find any significant change in short-interval intracortical inhibition, intracortical facilitation, or ipsilateral silent period after HIIT. Our findings demonstrate that corticospinal excitability of the nonexercised upper limb is increased after HIIT in healthy older adults. Our results indicate that acute HIIT exercise impacts corticospinal excitability in older adults, without affecting intracortical or interhemispheric circuitry. These findings have implications for the development of exercise strategies to potentiate neuroplasticity in healthy older and clinical populations.