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.

Age-related decline in GABAergic intracortical inhibition can be counteracted by long-term learning of balance skills.

Ageing induces a decline in GABAergic intracortical inhibition, which seems to be associated not only with decremental changes in well-being, sleep quality, cognition and pain management but also with impaired motor control. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. Therefore, the present study investigated whether age-related cortical dis-inhibition could be reversed after 6 months of balance learning and whether improvements in postural control correlated with the extent of reversed dis-inhibition. The results demonstrated that intracortical inhibition can be upregulated in elderly subjects after long-term balance learning and revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition and may therefore be seminal for many pathologies in which the equilibrium between inhibitory and excitatory neurotransmitters is disturbed. KEY POINTS: Ageing induces a decline in GABAergic intracortical inhibition. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. After 6 months of balance learning, intracortical inhibition can be upregulated in elderly subjects. The results of this study also revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition.

Caffeine and cortical excitability, as measured with paired-pulse transcranial magnetic stimulation.

INTRODUCTION/AIMS: The transcranial magnetic stimulation tests of short-interval intracortical inhibition (SICI) by both conventional amplitude measurements (A-SICI) and threshold-tracking (T-SICI) are important methods to investigate intracortical inhibitory circuits, and T-SICI has been proposed to aid the diagnosis of amyotrophic lateral sclerosis. Beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability. The aim of this study was to determine whether these SICI tests are affected by caffeine. METHODS: Twenty-four healthy subjects (13 females, 11 males, aged from 19 to 31, mean: 26.2 ± 2.4 years) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo ingested as chewing gum. A-SICI and T-SICI, using parallel tracking (T-SICIp), were performed before and after chewing gum. RESULTS: There was no significant change in SICI parameters after placebo in A-SICI (p > .10) or T-SICIp (p > .30), and no significant effect of caffeine was found on A-SICI (p > .10) or T-SICIp (p > .50) for any of the interstimulus intervals. DISCUSSION: There is no need for caffeine abstention before measurements of SICI by either the T-SICI or A-SICI measurements.

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 GABAA 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 GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA 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 GABAA receptor activity, long-interval intracortical inhibition representing GABAB 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 GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA 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 GABAA 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.

Reliability of transcranial magnetic stimulation-evoked responses on knee extensor muscles during cycling.

Transcranial magnetic stimulation (TMS) measures the excitability and inhibition of corticomotor networks. Despite its task-specificity, few studies have used TMS during dynamic movements and the reliability of TMS paired pulses has not been assessed during cycling. This study aimed to evaluate the reliability of motor evoked potentials (MEP) and short- and long-interval intracortical inhibition (SICI and LICI) on vastus lateralis and rectus femoris muscle activity during a fatiguing single-leg cycling task. Nine healthy adults (2 female) performed two identical sessions of counterweighted single-leg cycling at 60% peak power output until failure. Five single pulses and ten paired pulses were delivered to the motor cortex, and two maximal femoral nerve stimulations (Mmax) were administered during two baseline cycling bouts (unfatigued) and every 5 min throughout cycling (fatigued). When comparing both baseline bouts within the same session, MEP·Mmax-1 and LICI (both ICC: >0.9) were rated excellent while SICI was rated good (ICC: 0.7-0.9). At baseline, between sessions, in the vastus lateralis, Mmax (ICC: >0.9) and MEP·Mmax-1 (ICC: 0.7) demonstrated good reliability; LICI was moderate (ICC: 0.5), and SICI was poor (ICC: 0.3). Across the fatiguing task, Mmax demonstrated excellent reliability (ICC > 0.8), MEP·Mmax-1 ranged good to excellent (ICC: 0.7-0.9), LICI was moderate to excellent (ICC: 0.5-0.9), and SICI remained poorly reliable (ICC: 0.3-0.6). These results corroborate the cruciality of retaining mode-specific testing measurements and suggest that during cycling, Mmax, MEP·Mmax-1, and LICI measures are reliable whereas SICI, although less reliable across days, can be reliable within the same session.

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

OBJECTIVE: We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson's disease (PD). METHODS: 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. RESULTS: 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). CONCLUSION: 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. CLINICALTRIALSGOV IDENTIFIER: CTRI/2019/02/017564.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Adults.

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults. MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation. RESULTS: The participants' age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability. CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

The value of corticospinal excitability and intracortical inhibition in predicting motor skill improvement driven by action observation.

The observation of other's actions represents an essential element for the acquisition of motor skills. While action observation is known to induce changes in the excitability of the motor cortices, whether such modulations may explain the amount of motor improvement driven by action observation training (AOT) remains to be addressed. Using transcranial magnetic stimulation (TMS), we first assessed in 41 volunteers the effect of action observation on corticospinal excitability, intracortical inhibition, and transcallosal inhibition. Subsequently, half of the participants (AOT-group) were asked to observe and then execute a right-hand dexterity task, while the controls had to observe a no-action video before practicing the same task. AOT participants showed greater performance improvement relative to controls. More importantly, the amount of improvement in the AOT group was predicted by the amplitude of corticospinal modulation during action observation and, even more, by the amount of intracortical inhibition induced by action observation. These relations were specific for the AOT group, while the same patterns were not found in controls. Taken together, our findings demonstrate that the efficacy of AOT in promoting motor learning is rooted in the capacity of action observation to modulate the trainee's motor system excitability, especially its intracortical inhibition. Our study not only enriches the picture of the neurophysiological effects induced by action observation onto the observer's motor excitability, but linking them to the efficacy of AOT, it also paves the way for the development of models predicting the outcome of training procedures based on the observation of other's actions.

Cortico-cortical paired associative stimulation (ccPAS) over premotor-motor areas affects local circuitries in the human motor cortex via Hebbian plasticity.

Transcranial magnetic stimulation (TMS) studies have shown that cortico-cortical paired associative stimulation (ccPAS) can strengthen connectivity between the ventral premotor cortex (PMv) and the primary motor cortex (M1) by modulating convergent input over M1 via Hebbian spike-timing-dependent plasticity (STDP). However, whether ccPAS locally affects M1 activity remains unclear. We tested 60 right-handed young healthy humans in two studies, using a combination of dual coil TMS and ccPAS over the left PMv and M1 to probe and manipulate PMv-to-M1 connectivity, and single- and paired-pulse TMS to assess neural activity within M1. We provide convergent evidence that ccPAS, relying on repeated activations of excitatory PMv-to-M1 connections, acts locally over M1. During ccPAS, motor-evoked potentials (MEPs) induced by paired PMv-M1 stimulation gradually increased. Following ccPAS, the threshold for inducing MEPs of different amplitudes decreased, and the input-output curve (IO) slope increased, highlighting increased M1 corticospinal excitability. Moreover, ccPAS reduced the magnitude of short-interval intracortical inhibition (SICI), reflecting suppression of GABA-ergic interneuronal mechanisms within M1, without affecting intracortical facilitation (ICF). These changes were specific to ccPAS Hebbian strengthening of PMv-to-M1 connectivity, as no modulations were observed when reversing the order of the PMv-M1 stimulation during a control ccPAS protocol. These findings expand prior ccPAS research that focused on the malleability of cortico-cortical connectivity at the network-level, and highlight local changes in the area of convergent activation (i.e., M1) during plasticity induction. These findings provide new mechanistic insights into the physiological basis of ccPAS that are relevant for protocol optimization.

Reliability of corticospinal excitability and intracortical inhibition in biceps femoris during different contraction modes.

This study aimed to determine the test-retest reliability of a range of transcranial magnetic stimulation (TMS) outcomes in the biceps femoris during isometric, eccentric and concentric contractions. Corticospinal excitability (active motor threshold 120% [AMT120%] and area under recruitment curve [AURC]), short- and long-interval intracortical inhibition (SICI and LICI) and intracortical facilitation (ICF) were assessed from the biceps femoris in 10 participants (age 26.3 ± 6.0 years; height 180.2 ± 6.6 cm, body mass 77.2 ± 8.0 kg) in three sessions. Single- and paired-pulse stimuli were delivered under low-level muscle activity (5% ± 2% of maximal isometric root mean squared surface electromyography [rmsEMG]) during isometric, concentric and eccentric contractions. Participants were provided visual feedback on their levels of rmsEMG during all contractions. Single-pulse outcomes measured during isometric contractions (AURC, AMT110%, AMT120%, AMT130%, AMT150%, AMT170%) demonstrated fair to excellent reliability (ICC range, .51 to .92; CV%, 21% to 37%), whereas SICI, LICI and ICF demonstrated good to excellent reliability (ICC range, .62 to .80; CV%, 19 to 42%). Single-pulse outcomes measured during concentric contractions demonstrated excellent reliability (ICC range, .75 to .96; CV%, 15% to 34%), whereas SICI, LICI and ICF demonstrated good to excellent reliability (ICC range, .65 to .76; CV%, 16% to 71%). Single-pulse outcomes during eccentric contractions demonstrated fair to excellent reliability (ICC range, .56 to .96; CV%, 16% to 41%), whereas SICI, LICI and ICF demonstrated good to excellent (ICC range, .67 to .86; CV%, 20% to 42%). This study found that both single- and paired-pulse TMS outcomes can be measured from the biceps femoris muscle across all contraction modes with fair to excellent reliability. However, coefficient of variation values were typically greater than the smallest worthwhile change which may make tracking physiological changes in these variables difficult without moderate to large effect sizes.

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions.

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors. Fourteen healthy adults performed three sets of 10 ECC and CON right elbow flexor contractions at 75% of respective maximum on separate days. Elbow flexor maximal voluntary isometric contraction (MVIC) torques were measured before and after exercise, and responses to single- and paired-pulse TMS were recorded from the non-exercised left and exercised right biceps brachii. Pre-exercise and post-exercise responses for ECC and CON were compared by repeated measures analyses of variance (ANOVAs). MVIC torque of the exercised arm decreased (p < 0.01) after CON (-30 ± 14%) and ECC (-39 ± 13%) similarly. For the non-exercised left biceps brachii, resting motor threshold (RMT) decreased after CON only (-4.2 ± 3.9% of maximum stimulator output [MSO], p < 0.01), and intracortical facilitation (ICF) decreased (-15.2 ± 20.0%, p = 0.038) after ECC only. For the exercised right biceps, RMT increased after ECC (8.6 ± 6.2% MSO, p = 0.014) but not after CON (6.4 ± 8.1% MSO, p = 0.066). Thus, unilateral ECC and CON elbow flexor exercise modulated excitability differently for the non-exercised hemisphere. These findings suggest that responses after a single bout of exercise may not reflect longer term adaptations.

The effects of transcutaneous auricular vagal nerve stimulation on cortical GABAergic and cholinergic circuits: A transcranial magnetic stimulation study.

Neurophysiological evidence that transcutaneous auricular vagal nerve stimulation (taVNS) affects neuronal signalling at the cortical level is sparse. We used transcranial magnetic stimulation to assess the effect of taVNS on the excitability of intracortical GABAergic and cholinergic circuits. In this within-subject, double-blind study on 30 healthy participants, we used TMS paradigms to assess the effect of a single session of taVNS at 100 Hz and sham earlobe VNS (sVNS) on short-interval intracortical inhibition (SICI) curve and short-latency afferent inhibition (SAI). Control experiment was performed on additional 15 participants using the same experimental settings, but delivering no stimulation (xVNS). Bayesian statistics were used to assess the differences, producing % values that reflect the certainty that the values of interest were decreased during or after stimulation compared with baseline. taVNS increased SICI (96.3%), whereas sVNS decreased SICI (1.2%). SAI was not affected by taVNS, although it was decreased during sVNS (1.34% and 9.1%, for interstimulus intervals 20 and 24 ms, respectively). The changes in TMS parameters detected during sVNS were present in the same direction in the control experiment with no stimulation. Our study provides evidence that taVNS increases the activity of cortical GABAAergic system, leaving cortical cholinergic circuits unaffected. Changes in intracortical cortical excitability during sVNS, which were also observed in the control experiment with no stimulation were likely the effect of expectation related to participation in an interventional study.

Cortical Disinhibition Drives Freezing of Gait in Parkinson's Disease and an Exploratory Repetitive Transcranial Magnetic Stimulation Study.

BACKGROUND: Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD). OBJECTIVE: The aim was to reveal the mechanisms of "OFF-period" FOG (OFF-FOG) and "levodopa-unresponsive" FOG (ONOFF-FOG) in PD. METHODS: We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in "ON" and "OFF" medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients. RESULTS: In "OFF" condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in "ON" condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI. CONCLUSIONS: Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients correlated with the their reduced SICI insensitive to dopaminergic medication. SICI can serve as an indicator of the severity of impaired gait characteristics in FOG and reflect treatments efficacy for FOG in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Altitude-induced effects on neuromuscular, metabolic and perceptual responses before, during and after a high-intensity resistance training session.

PURPOSE: We tested if an acute ascending to 2320 m above sea level (asl) affects corticospinal excitability (CSE) and intracortical inhibition (SICI) measured with transcranial magnetic stimulation (TMS) at rest, before, during and after a traditional hypertrophy-oriented resistance training (RT) session. We also explored whether blood lactate concentration (BLa), ratings of perceived exertion (RPE), perceived muscular pain and total training volume differed when the RT session was performed at hypoxia (H) or normoxia (N). METHODS: Twelve resistance-trained men performed eight sets of 10 repetitions at 70% of one repetition maximum of a bar biceps curl at N (SpO2 = 98.0 ± 0.9%) and H (at 2320 asl, SpO2 = 94.0 ± 1.9%) in random order. Before each session, a subjective well-being questionnaire, the resting motor threshold (rMT) and a single pulse recruitment curve were measured. Before, during and after the RT session, BLa, RPE, muscle pain, CSE and SICI were measured. RESULTS: Before the RT session only the rMT differed between H (- 5.3%) and N (ES = 0.38). RPE, muscle pain and BLa increased through the RT session and were greater at H than N (12%, 54% and 15%, respectively) despite a similar training volume (1618 ± 468 kg vs. 1638 ± 509 kg). CSE was reduced during the RT session (~ 27%) but recovered ten minutes after, regardless of the environmental condition. SICI did not change after any RT session. CONCLUSIONS: The data suggest that acute exposure to moderate hypoxia slightly increased the excitability of the most excitable structures of the corticospinal tract but did not influence intracortical or corticospinal responses to a single RT session.

Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study.

BACKGROUND: Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording provides information on both intracortical reorganization and networking, and that information could yield new insights into post-stroke neuroplasticity. However, a comprehensive investigation using both concurrent TMS-EEG and motor-evoked potential-based outcomes has not been carried out in patients with chronic stroke. Therefore, this study sought to investigate the intracortical and network neurophysiological features of patients with chronic stroke, using concurrent TMS-EEG and motor-evoked potential-based outcomes. METHODS: A battery of motor-evoked potential-based measures and concurrent TMS-EEG recording were performed in 23 patients with chronic stroke and 21 age-matched healthy controls. RESULTS: The ipsilesional primary motor cortex (M1) of the patients with stroke showed significantly higher resting motor threshold (P = 0.002), reduced active motor-evoked potential amplitudes (P = 0.001) and a prolonged cortical silent period (P = 0.007), compared with their contralesional M1. The ipsilesional stimulation also produced a reduction in N100 amplitude of TMS-evoked potentials around the stimulated M1 (P = 0.007), which was significantly correlated with the ipsilesional resting motor threshold (P = 0.011) and motor-evoked potential amplitudes (P = 0.020). In addition, TMS-related oscillatory power was significantly reduced over the ipsilesional midline-prefrontal and parietal regions. Both intra/interhemispheric connectivity and network measures in the theta band were significantly reduced in the ipsilesional hemisphere compared with those in the contralesional hemisphere. CONCLUSIONS: The ipsilesional M1 demonstrated impaired GABA-B receptor-mediated intracortical inhibition characterized by reduced duration, but reduced magnitude. The N100 of TMS-evoked potentials appears to be a useful biomarker of post-stroke recovery.

Is it possible to compare inhibitory and excitatory intracortical circuits in face and hand primary motor cortex?

Face muscles are important in a variety of different functions, such as feeding, speech and communication of non-verbal affective states, which require quite different patterns of activity from those of a typical hand muscle. We ask whether there are differences in their neurophysiological control that might reflect this. Fifteen healthy individuals were studied. Standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods were used to compare intracortical inhibitory (short interval intracortical inhibition (SICI); cortical silent period (CSP)) and excitatory circuitries (short interval intracortical facilitation (SICF)) in two typical muscles, the depressor anguli oris (DAO), a face muscle, and the first dorsal interosseous (FDI), a hand muscle. TMS threshold was higher in DAO than in FDI. Over a range of intensities, resting SICF was not different between DAO and FDI, while during muscle activation SICF was stronger in FDI than in DAO (P = 0.012). At rest, SICI was stronger in FDI than in DAO (P = 0.038) but during muscle contraction, SICI was weaker in FDI than in DAO (P = 0.034). We argue that although many of the difference in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting SICI in DAO, may reflect fundamental differences in the physiology of the two muscle groups. KEY POINTS: Transcranial magnetic stimulation (TMS) single- and paired-pulse protocols were used to investigate and compare the activity of facilitatory and inhibitory intracortical circuits in a face (depressor anguli oris; DAO) and hand (first dorsal interosseous; FDI) muscles. Several TMS intensities and interstimulus intervals were tested with the target muscles at rest and when voluntarily activated. At rest, intracortical inhibitory activity was stronger in FDI than in DAO. In contrast, during muscle contraction inhibitory activity was stronger in DAO than in FDI. As many previous reports have found, the motor evoked potential threshold was higher in DAO than in FDI. Although many of the differences in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting short interval intracortical inhibition in DAO, may reflect fundamental differences in the physiology of the two muscle groups.

The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study.

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior-anterior (PA) and anterior-posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI.

Effects of short-term upper limb immobilization on sensory information processing and corticospinal excitability.

Several studies have reported the effects of short-term immobilization of the upper limb on the excitability of the primary motor cortex. In a report examining the effects of upper limb immobilization on somatosensory information processing using somatosensory-evoked potentials (SEPs), short-term upper limb immobilization reduced the amplitude and increased the latency of the P45 component recorded over the contralateral sensorimotor cortex of SEPs. However, the effects of upper limb immobilization on other regions involved in somatosensory information processing are unknown. Therefore, we investigated the effects of short-term right upper limb immobilization on sensory information processing, particularly in motor-related areas, by measuring the cortical components of SEPs. We also evaluated the excitability of the primary motor cortex and corticospinal tract as well as motor performance (visual simple reaction time and pinch force) related to these areas. All subjects were divided into two groups: the SEP group, in which the effects of upper limb immobilization on the excitability of somatosensory processing were investigated, and the transcranial magnetic stimulation (TMS) group, in which the effects of upper limb immobilization on the excitability of the corticospinal tract and primary motor cortex were investigated. Motor performance was evaluated in all subjects. We showed that 10-h right upper limb immobilization increased the cortical component of SEPs (N30) in the SEP group and decreased the excitability of the corticospinal tract, but not of the primary motor cortex, in the TMS group. The pinch force decreased after upper limb immobilization. However, the visual simple reaction time did not change between pre- and post-immobilization. The supplementary motor area and premotor cortex are believed to be the source of the N30. Therefore, these results suggest that upper limb immobilization affected somatosensory information processing in motor-related areas. Moreover, 10-h right upper limb immobilization reduced the excitability of corticospinal tracts but not that of the primary motor cortex, suggesting that circuits outside the M1, such as the intra- and inter-hemispheric inhibitory and facilitatory circuits rather than circuits within the M1, may be responsible for the reduced excitability of the central nervous system after restraint.

Effects of lower limb segmental muscle vibration on primary motor cortex short-latency intracortical inhibition and spinal excitability in healthy humans.

We examined the effects of lower limb segmental muscle vibration (SMV) on intracortical and spinal excitability in 13 healthy participants (mean age: 34.9 ± 7.8 years, 12 males, 1 female). SMV at 30 Hz was applied to the hamstrings, gastrocnemius, and soleus muscles for 5 min. Paired-pulse transcranial magnetic stimulation protocols were used to investigate motor-evoked potential (MEP)  amplitude, short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) from the abductor hallucis muscle (AbdH). These assessments were compared to the results of a control experiment (i.e., non-vibration) in the same participants. F-waves were evaluated from the AbdH on the right (vibration side) and left (non-vibration side) sides, and we calculated the ratio of the F-wave amplitude to the M-response amplitude (F/M ratio). These assessments were obtained before, immediately after, and 10, 20, and 30 min after SMV. For SICI, there was no change immediately after SMV, but there was a decrease over time (before vs. 30 min after, p = 0.021; immediately after vs. 30 min after, p = 0.015). There were no changes in test MEP amplitude, SICF, or the F/M ratio. SMV causes a gradual decrease in SICI over time perhaps owing to long-term potentiation. The present results may have implications for the treatment of spasticity.

Intracortical facilitation and inhibition in human primary motor cortex during motor skill acquisition.

The primary motor cortex (M1) is critical for movement execution, but its role in motor skill acquisition remains elusive. Here, we examine the role of M1 intracortical circuits during skill acquisition. Paired-pulse transcranial magnetic stimulation (TMS) paradigms of short-interval intracortical facilitation (SICF) and inhibition (SICI) were used to assess excitatory and inhibitory circuits, respectively. We hypothesised that intracortical facilitation and inhibition circuits in M1 would be modulated to support acquisition of a novel visuomotor skill. Twenty-two young, neurologically healthy adults trained with their nondominant hand on a skilled and non-skilled sequential visuomotor isometric finger abduction task. Electromyographic recordings were obtained from the nondominant first dorsal interosseous (FDI) muscle. Corticomotor excitability, SICF, and SICI were examined before, at the midway point, and after the 10-block motor training. SICI was assessed using adaptive threshold-hunting procedures. Task performance improved after the skilled, but not non-skilled, task training, which likely reflected the increase in movement speed during training. The amplitudes of late SICF peaks were modulated with skilled task training. There was no modulation of the early SICF peak, SICI, and corticomotor excitability with either task training. There was also no association between skill acquisition and SICF or SICI. The findings indicate that excitatory circuitries responsible for the generation of late SICF peaks, but not the early SICF peak, are modulated in motor skill acquisition for a sequential visuomotor isometric finger abduction task.