Short-interval Intracortical Inhibition Research Articles

Abstract TMP35: Short Interval Intracortical Inhibition is Associated With Leg Motor Function in Chronic Stroke

Objective: Stroke disrupts inhibitory and excitatory networks in the brain. To develop better therapies, we need to understand the role of inhibitory and excitatory systems. Paired-pulse transcranial magnetic stimulation (ppTMS) allows for evaluation of these inhibitory and excitatory systems. Our objective was to explore the relationship between Short Interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) ppTMS measures for tibialis anterior (TA) and measures of lower limb motor function in chronic stroke. Methods: Lower limb motor function was evaluated with Fugl-Meyer for Lower Limb (FM), gait speed (max and preferred), Timed-up-and-go (TUG), Functional Gait Assessment (FGA) and Gait Assessment and Intervention Tool (GAIT). SICI was collected with interstimulus interval of 2ms and ICF with 10ms. The conditioning stimulus was 90% and test stimulus was 120% of active motor threshold. Motor evoked potentials (MEPs) were collected for both paretic or non-paretic TAs while volitionally activated to 20% of maximum effort. SICI and ICF were calculated as percent of test stimulus (TS) amplitude. Analysis included descriptive statistics and linear models controlling for age, months post-stroke, and gender. TUG test time was log-transformed. Results: Study participants (n=34) were 66±8 years old, 4.9±4 years after stroke and 76% male. Mean±SD FM was 25.1±3.7 and preferred gait speed was 0.52±0.30 m/s. Relative to TS amplitude, SICI was 107±27% and ICF was 175±71% for paretic leg and, for non-paretic leg, SICI was 108±42% and ICF was 159±66%. For paretic leg after controlling for ICF, a 10% lower SICI was associated with the following: 0.89 point better FM (95% CI: 0.37-1.42), 14% better TUG (95% CI: 3-23%), 0.08 m/s faster max speed (95% CI: 0.02-0.14), and 0.05 m/s faster preferred walking speed (95% CI: 0.01-0.10). For non-paretic limb, a 10% lower SICI was associated with a 0.43 point better FGA (95% CI: 0.11-0.76) while a 10% lower ICF was associated with a 0.73 point better GAIT (95% CI: 0.37-1.10). Conclusion: Greater inhibition with paired pulse of both paretic and non-paretic limbs was predictive better motor abilities. These findings are related to previous work and warrant future investigations.

Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study.

The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function. A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery. Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles ( P < 0.001), lower resting motor threshold (-10.5% of the stimulator output, 95% CI: -16.8 to -4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (-1.1, 95% CI: -1.7 to -0.5, P = 0.001, Cohen d = 0.915). Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.

Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition.

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial

BackgroundTranscranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI).MethodsThis study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase.DiscussionThe study’s findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment.Trial registrationChinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

Relationship between transcranial magnetic stimulation markers of motor control and clinical recovery in obsessive compulsive disorder/Gilles de la Tourette syndrome: a proof of concept case study.

Obsessive compulsive disorder (OCD) and Gilles de la Tourette syndrome (GTS) are neurodevelopmental disorders characterized by difficulties in controlling intrusive thoughts (obsessions) and undesired actions (tics), respectively. Both conditions have been associated with abnormal inhibition but a tangible deficit of inhibitory control abilities is controversial in GTS. Here, we examined a 25 years-old male patient with severe OCD symptoms and a mild form of GTS, where impairments in motor control were central. Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) to elicit motor-evoked potentials (MEPs) during four experimental sessions, allowing us to assess the excitability of motor intracortical circuitry at rest as well as the degree of MEP suppression during action preparation, a phenomenon thought to regulate movement initiation. When tested for the first time, the patient presented a decent level of MEP suppression during action preparation, but he exhibited a lack of intracortical inhibition at rest, as evidenced by reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). Interestingly, the patient's symptomatology drastically improved over the course of the sessions (reduced obsessions and tics), coinciding with feedback given on his good motor control abilities. These changes were reflected in the TMS measurements, with a significant strengthening of intracortical inhibition (SICI and LICI more pronounced than previously) and a more selective tuning of MEPs during action preparation; MEPs became even more suppressed, or selectively facilitated depending on the behavioral condition in which they we probed. This study highlights the importance of better understanding motor inhibitory mechanisms in neurodevelopmental disorders and suggests a biofeedback approach as a potential novel treatment.

Probing intrahemispheric interactions with a novel dual-site TMS setup

ObjectiveUsing dual-site transcranial magnetic stimulation (dsTMS), the effective connectivity between the primary motor cortex (M1) and adjacent brain areas such as the dorsal premotor cortex (PMd) can be investigated. However, stimulating two brain regions in close proximity (e.g., ±2.3 cm for intrahemispheric PMd–M1) is subject to considerable spatial restrictions that potentially can be overcome by combining two standard figure-of-eight coils in a novel dsTMS setup. MethodsAfter a technical evaluation of its induced electric fields, the dsTMS setup was tested in vivo (n = 23) by applying a short-interval intracortical inhibition (SICI) protocol. Additionally, the intrahemispheric PMd–M1 interaction was probed. E-field modelling was performed using SimNIBS. ResultsThe technical evaluation yielded no major alterations of the induced electric fields due to coil overlap. In vivo, the setup reliably elicited SICI. Investigating intrahemispheric PMd–M1 interactions was feasible (inter-stimulus interval 6 ms), resulting in modulation of M1 output. ConclusionsThe presented dsTMS setup provides a novel way to stimulate two adjacent brain regions with fewer technical and spatial limitations than previous attempts. SignificanceThis dsTMS setup enables more accurate and repeatable targeting of brain regions in close proximity and can facilitate innovation in the field of effective connectivity.

Reliability of intracortical inhibiton measured using threshold tracking technique

Background. Paired-pulse transcranial magnetic stimulation allows assessing intracortical inhibition. However, a high variability of motor evoked potential (MEP) amplitude is a limitation of its use. Therefore, a new threshold tracking technique became of particular interest, which is based on the measurement not of the amplitude, but of the change of test stimulus intensity required to induce a MEP of a given amplitude.Aim. The assessment of absolute and relative reliability of short-interval intracortical inhibition (SICI) using threshold tracking technique in healthy volunteers.Materials and methods. All healthy volunteers included into the study (n = 12) underwent diagnostic paired-pulse transcranial magnetic stimulation in two consecutive days. The procedure included registration of passive motor threshold; the registration of 30 MEPs with supra-threshold intensity and determination of SICI using threshold tracking technique. At the first day the procedure was performed twice (T1, T2), at the second day – once (T3). Standard error of the measurement (SEM) and SEM% were calculated to assess absolute reliability, and intra-class correlation coefficient – for the assessment of relative reliability.Results. A good or excellent relative reliability were observed for SICI averaged at intervals 1.0–3.0 ms and 1.0–7.0 ms when assessed within a day or at different days. Relative reliability of SICI at separate interstimulus intervals varied in a wide range. SEM% was more than 10 % both for averaged SICI and SICI at all interstimulus intervals. Motor threshold had excellent reliability both assessed within a day and at different days, and low SEM values (5.6 % for Т1–Т2 and 4.39 % for Т1–Т3). High SEM and SEM% were observed for average MEP amplitude, it also had a moderate relative reliability when assessed within a day and a poor one – at different days.Conclusion. Calculation of averaged SICI can be recommended in further studies because of its high reliability values.

Corticomotor Control of Lumbar Erector Spinae in Postural and Voluntary Tasks: The Influence of Transcranial Magnetic Stimulation Current Direction.

Lumbar erector spinae (LES) contribute to spine postural and voluntary control. Transcranial magnetic stimulation (TMS) preferentially depolarizes different neural circuits depending on the direction of electrical currents evoked in the brain. Posteroanterior current (PA-TMS) and anteroposterior (AP-TMS) current would, respectively, depolarize neurons in the primary motor cortex (M1) and the premotor cortex. These regions may contribute differently to LES control. This study examined whether responses evoked by PA- and AP-TMS are different during the preparation and execution of LES voluntary and postural tasks. Participants performed a reaction time task. A Warning signal indicated to prepare to flex shoulders (postural; n = 15) or to tilt the pelvis (voluntary; n = 13) at the Go signal. Single- and paired-pulse TMS (short-interval intracortical inhibition-SICI) were applied using PA- and AP-TMS before the Warning signal (baseline), between the Warning and Go signals (preparation), or 30 ms before the LES onset (execution). Changes from baseline during preparation and execution were calculated in AP/PA-TMS. In the postural task, MEP amplitude was higher during the execution than that during preparation independently of the current direction (p = 0.0002). In the voluntary task, AP-MEP amplitude was higher during execution than that during preparation (p = 0.016). More PA inhibition (SICI) was observed in execution than that in preparation (p = 0.028). Different neural circuits are preferentially involved in the two motor tasks assessed, as suggested by different patterns of change in execution of the voluntary task (AP-TMS, increase; PA-TMS, no change). Considering that PA-TMS preferentially depolarize neurons in M1, it questions their importance in LES voluntary control.

Examining short interval intracortical inhibition with different transcranial magnetic stimulation-induced current directions in ALS

ObjectiveTo establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker. MethodsThreshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex. ResultsAt group level, SICI3ms-PA (AUROC = 0.7), SICI3ms-AP (AUROC = 0.8) and SICI1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI1ms-PA and SICI3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROC = 0.50). ConclusionsSICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS. SignificanceExamining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.

Effects of Clozapine on Cortical Inhibition

Abstract Background Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. Methods Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. Results Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. Conclusions This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.

Effect of home-based transcranial direct current stimulation combined with nutritional counseling therapy on binge eating disorder symptoms: A randomized pilot trial.

To examine the effect of nutritional counseling therapy (NCT) combined with transcranial direct current stimulation (tDCS) on Binge Eating Disorder (BED) symptoms. 40 women with BED were randomly (ratio of 2:2:2) allocated to one of the groups: active tDCS (a-tDCS), NCT, sham tDCS (s-tDCS) with NCT, and a-tDCS with NCT. Home-based tDCS was applied to the dorsolateral prefrontal cortex for 28 sessions. A mixed analysis of variance showed no main effect between groups or a time × group interaction. However, a significant main effect was found for time on the primary outcome: Binge Eating Scale (p = 0.001; eta2p= 0.325), which tended to decrease during treatment and follow-up. A significant main effect was found on the secondary outcome: short-interval intracortical inhibition (SICI) (p = 0.02; eta2p= 0.112), a measure of inhibitory function, which increased from baseline to the final period in the a-tDCS group, without significant differences between groups. These findings reveal that the combined therapy did not have a synergic effect on BED symptoms. Since this is a pilot study and this is a promising area, we provide data to plan future larger-scale studies investigating the effects of tDCS and behavioral interventions in BED treatment.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study

Introduction: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABA_A receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. Methods: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [¹¹C]flumazenil positron emission tomography to assess GABA_A receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABA_A receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABA_A receptor activity, long-interval intracortical inhibition representing GABA_B receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. Results: No significant differences in baseline GABA_A receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABA_A receptor availability and TMS outcomes. Changes in GABA_A receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. Conclusion: We found that a change in GABA_A receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Effects of sleep deprivation on cortical excitability: A threshold-tracking TMS study and review of the literature

ObjectiveInsufficient sleep is linked to several health problems. Previous studies on the effects of sleep deprivation on cortical excitability using conventional transcranial magnetic stimulation (TMS) included a limited number of modalities, and few inter-stimulus intervals (ISIs) and showed conflicting results. This study aimed to investigate the effects of sleep deprivation on cortical excitability through threshold-tracking TMS, using a wide range of protocols at multiple ISIs. MethodsFifteen healthy subjects (mean age ± SD: 36 ± 3.34 years) were included. The following tests were performed before and after 24 h of sleep deprivation using semi-automated threshold-tacking TMS protocols: short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) at 11 ISIs between 1 and 30 ms, short interval intracortical facilitation (SICF) at 14 ISIs between 1 and 4.9 ms, long interval intracortical inhibition (LICI) at 6 ISIs between 50 and 300 ms, and short-latency afferent inhibition (SAI) at 12 ISIs between 16 and 30 ms. ResultsNo significant differences were observed between pre- and post-sleep deprivation measurements for SICI, ICF, SICF, or LICI at any ISIs (p < 0.05). As for SAI, we found a difference at 28 ms (p = 0.007) and 30 ms (p = 0.04) but not at other ISIs. ConclusionsSleep deprivation does not affect cortical excitability except for SAI. SignificanceThis study confirms some of the previous studies while contradicting others.

Does lower-limb osteoarthritis alter motor cortex descending drive and voluntary activation? A systematic review and meta-analysis.

The aim of the study was to quantify motor cortex descending drive and voluntary activation (VA) in people with lower-limb OA compared to controls. A systematic review and meta-analysis according to the PRISMA guidelines was carried out. Seven databases were searched until 30 December 2022. Studies assessing VA or responses to transcranial magnetic stimulation (TMS; i.e. motor evoked potential, intracortical facilitation, motor threshold, short-interval intracortical inhibition, and silent period) were included. Study quality was assessed using Joanna Briggs Institute criteria and evidence certainty using GRADE. The meta-analysis was performed using RevMan inverse variance, mixed-effect models. Eighteen studies were included, all deemed low-quality. Quadriceps VA was impaired with knee OA compared to healthy controls (standardised mean difference (SMD) = 0.84, 95% CI = -1.12-0.56, low certainty). VA of the more symptomatic limb was impaired (SMD = 0.42, 95% CI = -0.75-0.09, moderate certainty) compared to the other limb in people with hip/knee OA. As only two studies assessed responses to TMS, very low-certainty evidence demonstrated no significant difference between knee OA and healthy controls for motor evoked potential, intracortical facilitation, resting motor threshold or short-interval intracortical inhibition. Low-certainty evidence suggests people with knee OA have substantial impairments in VA of their quadriceps muscle when compared to healthy controls. With moderate certainty we conclude that people with hip and knee OA had larger impairments in VA of the quadriceps in their more painful limb compared to their non-affected/other limb.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability.

Cortical myoclonus is produced by abnormal neuronal discharges within the sensorimotor cortex, as demonstrated by electrophysiology. Our hypothesis is that the loss of cerebellar inhibitory control over the motor cortex, via cerebello-thalamo-cortical connections, could induce the increased sensorimotor cortical excitability that eventually causes cortical myoclonus. To explore this hypothesis, in the present study we applied anodal transcranial direct current stimulation over the cerebellum of patients affected by cortical myoclonus and healthy controls and assessed its effect on sensorimotor cortex excitability. We expected that anodal cerebellar transcranial direct current stimulation would increase the inhibitory cerebellar drive to the motor cortex and therefore reduce the sensorimotor cortex hyperexcitability observed in cortical myoclonus. Ten patients affected by cortical myoclonus of various aetiology and 10 aged-matched healthy control subjects were included in the study. All participants underwent somatosensory evoked potentials, long-latency reflexes and short-interval intracortical inhibition recording at baseline and immediately after 20 min session of cerebellar anodal transcranial direct current stimulation. In patients, myoclonus was recorded by the means of surface EMG before and after the cerebellar stimulation. Anodal cerebellar transcranial direct current stimulation did not change the above variables in healthy controls, while it significantly increased the amplitude of somatosensory evoked potential cortical components, long-latency reflexes and decreased short-interval intracortical inhibition in patients; alongside, a trend towards worsening of the myoclonus after the cerebellar stimulation was observed. Interestingly, when dividing patients in those with and without giant somatosensory evoked potentials, the increment of the somatosensory evoked potential cortical components was observed mainly in those with giant potentials. Our data showed that anodal cerebellar transcranial direct current stimulation facilitates-and does not inhibit-sensorimotor cortex excitability in cortical myoclonus syndromes. This paradoxical response might be due to an abnormal homeostatic plasticity within the sensorimotor cortex, driven by dysfunctional cerebello-thalamo-cortical input to the motor cortex. We suggest that the cerebellum is implicated in the pathophysiology of cortical myoclonus and that these results could open the way to new forms of treatment or treatment targets.

Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans

BackgroundThe basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. Objective/HypothesisThe main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. MethodsWe combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). ResultsRegression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. ConclusionsTaken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Intracortical and interhemispheric excitability changes in arm amputees: A TMS study

ObjectiveTo evaluate cortical circuits and excitability of the motor cortex in the hemisphere contralateral to the affected (AH) and to the unaffected arm (UH), in upper limb amputees. MethodsMotor evoked potentials (MEP) were recorded in 17 subjects who had upper limb amputation: 11 trans-radial (TR) and 6 trans-humeral (TH). Motor thresholds (MT), short interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI) in the available arm muscles of the stump were evaluated. ResultsThere was no significant difference in MT between hemispheres. SICI was preserved in TR but not in TH group. Additionally, in the TR group, the MEP amplitudes in AH were higher than in UH. A significant IHI was observed in the whole sample but not in each hemisphere or patient group. ConclusionsIn our population of TR amputees, we found increased corticospinal excitability in the AH with preserved intracortical inhibition. This finding was not observed in the TH population. SignificanceUnderstanding the changes in intracortical excitability in amputees may enhance knowledge of the functional reorganization of the brain in the post-amputation phase, bringing useful information for prosthetic rehabilitation.