Primary Motor Cortex Excitability Research Articles

The trial-by-trial fluctuations in primary motor cortex excitability during attentional bias among smokers: A transcranial magnetic stimulation study

BackgroundA relatively new computational approach called trial-level bias score (TL-BS) has shown that attentional bias to smoking-related stimuli in smokers fluctuates temporally, trial by trial, during attention tasks. Here, we investigated the reliability of using TL-BS values to assess attentional bias and the electrophysiology mechanisms undergirding fluctuations in attentional bias among smokers. MethodIn total, 26 male smokers and 26 male non-smokers performed a dot-probe task in Experiment 1. In Experiment 2, an additional 23 male smokers and 23 male non-smokers performed the same task while undergoing single-pulse transcranial magnetic stimulation, which was used to investigate corticospinal excitability. ResultsIt showed that assessing TL-BS parameters for reaction time (RT) was more reliable than calculating the traditional mean attentional bias score; however, this superior reliability was no longer apparent after controlling for general RT variability. There was a significant difference between smokers and non-smokers in TL-BS parameters calculated for both RT and motor-evoked potential (MEP) amplitude. However, TL-BS parameters for RT and MEP amplitude were strongly correlated with general RT variability and general MEP variability, respectively. ConclusionsOur findings indicated that TL-BS parameters may not be ideal for measuring attentional bias at either the behavioral or electrophysiology level; however, larger general RT and MEP amplitude variabilities in non-smokers may indicate dysregulation of cognitive processing in smokers.

Age-Dependent Modulation of Layer V Pyramidal Neuron Excitability in the Mouse Primary Motor Cortex by D1 Receptor Agonists and Antagonists

The primary motor cortex (M1) receives dopaminergic (DAergic) projections from the midbrain which play a key role in modulating motor and cognitive processes, such as motor skill learning. However, little is known at the level of individual neurons about how dopamine (DA) and its receptors modulate the intrinsic properties of the different neuronal subpopulations in M1 and if this modulation depends on age. Using immunohistochemistry, we first mapped the cells expressing the DA D1 receptor across the different layers in M1, and quantified the number of pyramidal neurons (PNs) expressing the D1 receptor in the different layers, in young and adult mice. This work reveals that the spatial distribution and the molecular profile of D1 receptor-expressing neurons (D1+) across M1 layers do not change with age. Then, combining whole-cell patch-clamp recordings and pharmacology, we explored ex vivo in young and adult mice the impact of activation or blockade of D1 receptors on D1+ PN intrinsic properties. While the bath application of the D1 receptor agonist induced an increase in the excitability of layer V PNs both in young and adult, we identified a distinct modulation of intrinsic electrical properties of layer V D1+ PNs by D1 receptor antagonist depending on the age of the animal.

Cerebellar Transcranial Direct Current Stimulation Applied over Multiple Days Does Not Enhance Motor Learning of a Complex Overhand Throwing Task in Young Adults.

Cerebellar transcranial direct current stimulation (tDCS) enhances motor skill and learning in relatively simple motor tasks, but it is unclear if c-tDCS can improve motor performance in complex motor tasks. The purpose of this study was to determine the influence of c-tDCS applied over multiple days on motor learning in a complex overhand throwing task. In a double-blind, randomized, between-subjects, SHAM-controlled, experimental design, 30 young adults were assigned to either a c-tDCS or a SHAM group. Participants completed three identical experiments on consecutive days that involved overhand throwing in a pre-test block, five practice blocks with concurrent c-tDCS, and a post-test block. Overhand throwing endpoint accuracy was quantified as the endpoint error. The first dorsal interosseous muscle motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation was used to quantify primary motor cortex (M1) excitability modulations via c-tDCS. Endpoint error significantly decreased over the 3 days of practice, but the magnitude of decrease was not significantly different between the c-tDCS and SHAM group. Similarly, MEP amplitude slightly increased from the pre-tests to the post-tests, but these increases did not differ between groups. These results indicate that multi-day c-tDCS does not improve motor learning in an overhand throwing task or increase M1 excitability.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex.

To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

A global pause generates nonselective response inhibition during selective stopping.

Selective response inhibition may be required when stopping a part of a multicomponent action. A persistent response delay (stopping-interference effect) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. Twenty healthy human participants performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta-bursts were recorded with electroencephalography. Corticomotor excitability and short-interval intracortical inhibition in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviorally, responses in the non-signaled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that stopping-interference could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral beta-bursts occurred during stop and ignore trials. Sensorimotor response inhibition was reflected in maintenance of beta-bursts and short-interval intracortical inhibition relative to disinhibition observed during go trials. Response inhibition signatures were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.

Modulation of dorsal premotor cortex differentially influences I-wave excitability in primary motor cortex of young and older adults.

Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability in M1 of young and older adults. Twenty-two young (mean±SD, 22.9±2.9years) and 20 older (66.6±4.2years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior-anterior (PA) and anterior-posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV ; AP1mV ; PA0.5mV , early; AP0.5mV , late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P<0.05), the time course of this effect was delayed for AP1mV in older adults (P=0.001). Furthermore, while AP0.5mV , PA SICF and AP SICF were potentiated in both groups (all P<0.05), potentiation of PA0.5mV was only apparent in young adults (P<0.0001). While PMd influences early and late I-wave excitability in young adults, direct PMd modulation of the early circuits is specifically reduced in older adults. KEY POINTS: Interneuronal circuits responsible for late I-waves within primary motor cortex (M1) mediate projections from dorsal premotor cortex (PMd), but this communication probably changes with advancing age. We investigated the effects of intermittent theta burst stimulation (iTBS) to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults. We found that PMd iTBS facilitated M1 excitability assessed with posterior-anterior (PA, early I-waves) and anterior-posterior (AP, late I-waves) current TMS in young adults, with a stronger effect for AP TMS. M1 excitability assessed with AP TMS also increased in older adults following PMd iTBS, but there was no facilitation for PA TMS responses. We conclude that changes in M1 excitability following PMd iTBS are specifically reduced for the early I-waves in older adults, which could be a potential target for interventions that enhance cortical excitability in older adults.

Effects of Paired Associative Stimulation on Cortical Plasticity in Agonist–Antagonist Muscle Representations

Paired associative stimulation (PAS) increases and decreases cortical excitability in primary motor cortex (M1) neurons, depending on the spike timing-dependent plasticity, i.e., long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity, respectively. However, how PAS affects the cortical circuits for the agonist and antagonist muscles of M1 is unclear. Here, we investigated the changes in the LTP- and LTD-like plasticity for agonist and antagonist muscles during PAS: 200 pairs of 0.25-Hz peripheral electric stimulation of the right median nerve at the wrist, followed by a transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 ms (PAS-25 ms) and 10 ms (PAS-10 ms). The unconditioned motor evoked potential amplitudes of the agonist muscles were larger after PAS-25 ms than after PAS-10 ms, while those of the antagonist muscles were smaller after PAS-25 ms than after PAS-10 ms. The γ-aminobutyric acid A (GABAA)- and GABAB-mediated cortical inhibition for the agonist and antagonist muscles were higher after PAS-25 ms than after PAS-10 ms. The cortical excitability for the agonist and antagonist muscles reciprocally and topographically increased and decreased after PAS, respectively; however, GABAA and GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were less topographically decreased after PAS-10 ms. Thus, PAS-25 ms and PAS-10 ms differentially affect the LTP- and LTD-like plasticity in agonist and antagonist muscles.

Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization

Background After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. Objectives We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. Methods Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP−)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1CL reorganization was related to greater lesion volume in the MEP− group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP− but not MEP+ participants. Absence of an MEP (MEP−), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. Conclusions In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503

Language-related motor facilitation in Italian Sign Language signers.

Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.

Examining the influence of tactile imagery on primary motor cortex excitability using transcranial magnetic stimulation

Examining the influence of tactile imagery on primary motor cortex excitability using transcranial magnetic stimulation

Face emotional expressions influence interhemispheric inhibition.

The processing of face expressions is a key ability to perform social interactions. Recently, it has been demonstrated that the excitability of the hand primary motor cortex (M1) increases following the view of negative faces expressions. Interhemispheric interactions and sensory-motor integration are cortical processes involving M1, which are known to be modulated by emotional and social behaviors. Whether these processes may mediate the effects of face emotional expressions on M1 excitability is unknown. Therefore, the aim of this study was to investigate the influence of the passive viewing of face emotional expressions on M1 interhemispheric connections and sensory-motor integration using standardized transcranial magnetic stimulation (TMS) protocols. Nineteen healthy subjects participated in the study. Interhemispheric inhibition (IHI) and short-afferent inhibition (SAI) were probed in the right first dorsal interosseous (FDI) muscle 300 ms after the randomized presentation of seven different face expressions (neutral, sadness, fear, disgust, surprise and happiness). Results showed a significantly reduced IHI following the passive viewing of fearful faces compared to neutral (p=.001) and happy (p=.035) faces and following the view of sad faces compared to neutral faces (p=.008). No effect of emotional faces was detected on SAI. Data suggest that sensory-motor integration process does not mediate the increased excitability of M1 induced by the view of negative face expressions. By contrast, it may be underpinned by a depression of IHI, which from a functional point of view may promote symmetrical avoiding movements of the hands in response to aversive stimuli.

Difference between the Effects of Peripheral Sensory Nerve Electrical Stimulation on the Excitability of the Primary Motor Cortex: Examination of the Combinations of Stimulus Frequency and Duration.

Peripheral sensory nerve electrical stimulation (PES) excites the primary motor cortex and is expected to improve motor dysfunction post-stroke. However, previous studies have reported a variety of stimulus frequencies and stimulus duration settings, and the effects of these different combinations on primary motor cortex excitability are not clear. We aimed to clarify the effects of different combinations of stimulus frequency and stimulus duration of PES on the excitation of primary motor cortex. Twenty-one healthy individuals (aged &gt; 18 years, right-handed, and without a history of neurological or orthopedic disorders) were included. Each participant experienced three different stimulation frequencies (1, 10 and 50 Hz) and durations (20, 40 and 60 min). Motor-evoked potentials (MEPs) were recorded pre- and post-PES. The outcome measure was the change in primary motor cortex excitability using the MEP ratio. We used a D-optimal design of experiments and response surface analysis to define the optimal combination within nine different settings inducing more satisfying responses. The combination of stimulation frequency and stimulation time that maximized the desirability value was 10 Hz and 40 min, respectively. The results of this study may provide fundamental data for more minimally invasive and effective implementation of PES in patients with stroke.

Bilateral motor cortex functional differences in left-handed approaching-avoiding behavior.

Automatic action tendencies occur at behavioral and neurophysiological levels during task performance with the dominant right hand, with shorter reaction times (RTs) and higher excitability of the contralateral primary motor cortex (M1) during automatic vs. regulated behavior. However, effects associated with the non-dominant left-hand in approaching-avoiding behavior remain unclear. Here, we used transcranial magnetic stimulation during the performance by 18 participants of an approaching-avoiding task using the non-dominant left hand. Single-pulse transcranial magnetic stimulation was applied over left or right M1 at 150 and 300 ms after the onset of an emotional stimulus. RTs and motor-evoked potentials (MEPs) were recorded. Significant automatic action tendencies were observed at the behavioral level. Higher MEP amplitudes were detected 150 ms after stimulus onset from the right hand (non-task hand, corresponding to left M1) during regulated behavior compared with during automatic behavior. However, no significant modulation was found for MEP amplitudes from the left hand (task hand, corresponding to right M1). These findings suggested that left M1 may play a principal role in the early phase of mediating left-handed movement toward an emotional stimulus.

Gender dimorphic M1 excitability during emotional processing: a transcranial magnetic stimulation study.

BackgroundIt is widely held that emotions prime the body for action. However, the influence of gender on primary motor cortex (M1) excitability during emotional processing is not well explored.MethodsUsing single-pulse transcranial magnetic stimulation (TMS), we stimulated the right or left M1 at 150 ms and 300 ms after emotional stimulation onset (presentation of negative, neutral, and positive pictures to male and female subjects). Motor-evoked potentials (MEPs) ratio induced by single-pulse TMS was used to assess changes in corticospinal excitability.ResultsIn response to right M1 stimulation, males demonstrated higher MEP ratios following presentation of negative pictures at 150 ms while MEP ratios in response to presentation of positive pictures were greater at 300 ms. Furthermore, male subjects showed larger MEP ratios in right M1 versus left M1 at 300 ms after initiation of positive pictures, indicating lateralization of motor excitability in male subjects.ConclusionsThe current study thus provides neurophysiological evidence to support gender differences and functional lateralization of motor excitability in response to emotional stimuli.

Neurophysiological assessment of juvenile parkinsonism due to primary monoamine neurotransmitter disorders

No studies have investigated voluntary movement abnormalities and their neurophysiological correlates in patients with parkinsonism due to inherited primary monoamine neurotransmitter (NT) disorders. Nine NT disorders patients and 16 healthy controls (HCs) were enrolled. Objective measurements of repetitive finger tapping were obtained using a motion analysis system. Primary motor cortex (M1) excitability was assessed by recording the input/output (I/O) curve of motor-evoked potentials (MEP) and using a conditioning test paradigm for short-interval intracortical inhibition (SICI) assessment. M1 plasticity-like mechanisms were indexed according to MEPs amplitude changes after the paired associative stimulation protocol. Patient values were considered abnormal if they were greater or lower than two standard deviations from the average HCs value. Patients with aromatic amino acid decarboxylase, tyrosine hydroxylase, and 6-pyruvoyl-tetrahydropterin synthase defects showed markedly reduced velocity (5/5 patients), reduced movement amplitude, and irregular rhythm (4/5 patients). Conversely, only 1 out of 3 patients with autosomal-dominant GTPCH deficiency showed abnormal movement parameters. Interestingly, none of the patients had a progressive reduction in movement amplitude or velocity during the tapping sequence (no sequence effect). Reduced SICI was the most prominent neurophysiological abnormality in patients (5/9 patients). Finally, the I/O curve slope correlated with movement velocity and rhythm in patients. We provided an objective assessment of finger tapping abnormalities in monoamine NT disorders. We also demonstrated M1 excitability changes possibly related to alterations in motor execution. Our results may contribute to a better understanding of the pathophysiology of juvenile parkinsonism due to dopamine deficiency.

Motor Cortex Response to Pleasant Odor Perception and Imagery: The Differential Role of Personality Dimensions and Imagery Ability.

BackgroundNeuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil (BEO) is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor (BEO) on motor cortex using Transcranial magnetic stimulation (TMS).Materials and MethodsWe examined the primary motor cortex (M1) excitability during perception of a pleasant odor (BEO) or perception of odorless saline (experiment 1). Furthermore, we tested the effect of olfactory imagery (OI) of BEO on corticospinal excitability (experiment 2). The increase in motor evoked potential (MEP) amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability.ResultsThe results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor (BEO). The correlation analysis shows an association with neuroticism personality trait (experiment 1) and with general olfactory imagery ability (experiment 2).ConclusionBoth perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems.

Contralaterally Controlled Functional Electrical Stimulation Combined With Brain Stimulation for Severe Upper Limb Hemiplegia-Study Protocol for a Randomized Controlled Trial.

BackgroundApproximately two-thirds of stroke survivors experience chronic upper limb paresis, and of them, 50% experience severe paresis. Treatment options for severely impaired survivors are often limited. Rehabilitation involves intensively engaging the paretic upper limb, and disincentivizing use of the non-paretic upper limb, with the goal to increase excitability of the ipsilesional primary motor cortex (iM1) and suppress excitability of the undamaged (contralesional) motor cortices, presumed to have an inhibitory effect on iM1. Accordingly, brain stimulation approaches, such as repetitive transcranial magnetic stimulation (rTMS), are also given to excite iM1 and/or suppress contralesional motor cortices. But such approaches aimed at ultimately increasing iM1 excitability yield limited functional benefit in severely impaired survivors who lack sufficient ipsilesional substrate.AimHere, we test the premise that combining Contralaterally Controlled Functional Electrical Stimulation (CCFES), a rehabilitation technique that engages the non-paretic upper limb in delivery of neuromuscular electrical stimulation to the paretic upper limb, and a new rTMS approach that excites intact, contralesional higher motor cortices (cHMC), may have more favorable effect on paretic upper limb function in severely impaired survivors based on recruitment of spared, transcallosal and (alternate) ipsilateral substrate.MethodsIn a prospective, double-blind, placebo-controlled RCT, 72 chronic stroke survivors with severe distal hand impairment receive CCFES plus cHMC rTMS, iM1 rTMS, or sham rTMS, 2X/wk for 12wks. Measures of upper limb motor impairment (Upper Extremity Fugl Meyer, UEFM), functional ability (Wolf Motor-Function Test, WMFT) and perceived disability are collected at 0, 6, 12 (end-of-treatment), 24, and 36 wks (follow-up). TMS is performed at 0, 12 (end-of-treatment), and 36 wks (follow-up) to evaluate inter-hemispheric and ipsilateral mechanisms. Influence of baseline severity is also characterized with imaging.ConclusionsTargeting of spared neural substrates and rehabilitation which engages the unimpaired limb in movement of the impaired limb may serve as a suitable combinatorial treatment option for severely impaired stroke survivors.ClinicalTrials NoNCT03870672.

Cerebellar noninvasive neuromodulation influences the reactivity of the contralateral primary motor cortex and surrounding areas: a TMS-EMG-EEG study.

Understanding cerebellar-cortical physiological interactions is of fundamental importance to advance the efficacy of neurorehabilitation strategies for patients with cerebellar damage. Previous works have aimed to modulate this pathway by applying transcranial electrical or magnetic stimulation (TMS) over the cerebellum and probing the resulting changes in the primary motor cortex (M1) excitability with motor-evoked potentials (MEPs). While these protocols produce changes in cerebellar excitability, their ability to modulate MEPs has produced inconsistent results, mainly due to the MEP being a highly variable outcome measure that is susceptible to fluctuations in the excitability of M1 neurons and spinal interneurons. To overcome this limitation, we combined TMS with electroencephalography (EEG) to directly record TMS-evoked potentials (TEPs) and oscillations from the scalp. In three sessions, we applied intermittent theta-burst stimulation (iTBS), cathodal direct current stimulation (c-DC) or sham stimulation to modulate cerebellar activity. To assess the effects on M1 and nearby cortex, we recorded TMS-EEG and MEPs before, immediately after (T1) and 15min (T2) following cerebellar neuromodulation. We found that cerebellar iTBS immediately increased TMS-induced alpha oscillations and produced lasting facilitatory effects on TEPs, whereas c-DC immediately decreased TMS-induced alpha oscillations and reduced TEPs. We also found increased MEP following iTBS but not after c-DC. All of the TMS-EEG measures showed high test-retest repeatability. Overall, this work importantly shows that cerebellar neuromodulation influences both cortical and corticospinal physiological measures; however, they are more pronounced and detailed when utilizing TMS-EEG outcome measures. These findings highlight the advantage of using TMS-EEG over MEPs when assessing the effects of neuromodulation.

Corticospinal Excitability of the Lower Limb Muscles During the Anticipatory Postural Adjustments: A TMS Study During Dart Throwing.

Objective: To investigate whether the changes in the corticospinal excitability contribute to the anticipatory postural adjustments (APAs) in the lower limb muscles when performing the ballistic upper limb movement of the dart throwing.Methods: We examined the primary motor cortex (M1) excitability of the lower limb muscles [tibialis anterior (TA) and soleus (SOL) muscles] during the APA phase by using transcranial magnetic stimulation (TMS) in the healthy volunteers. The surface electromyography (EMG) of anterior deltoid, triceps brachii, biceps brachii, TA, and SOL muscles was recorded and the motor evoked potential (MEP) to TMS was recorded in the TA muscle along with the SOL muscle. TMS at the hotspot of the TA muscle was applied at the timings immediately prior to the TA onset. The kinematic parameters including the three-dimensional motion analysis and center of pressure (COP) during the dart throwing were also assessed.Results: The changes in COP and EMG of the TA muscle occurred preceding the dart throwing, which involved a slight elbow flexion followed by an extension. The correlation analysis revealed that the onset of the TA muscle was related to the COP change and the elbow joint flexion. The MEP amplitude in the TA muscle, but not that in the SOL muscle, significantly increased immediately prior to the EMG burst (100, 50, and 0 ms prior to the TA onset).Conclusion: Our findings demonstrate that the corticospinal excitability of the TA muscle increases prior to the ballistic upper limb movement of the dart throwing, suggesting that the corticospinal pathway contributes to the APA in the lower limb in a muscle-specific manner.

Long-term effect of safinamide on primary motor cortex excitability and plasticity in Parkinson's disease: A TMS study

In a recent Transcranial Magnetic Stimulation (TMS) study, we demonstrated abnormally enhanced Short-Interval Intracortical Facilitation (SICF) in patients with Parkinson's Disease (PD). These abnormalities reflect increased glutamatergic transmission in primary motor cortex (M1). A short-term treatment with safinamide at 100 mg/day can restore SICF in PD by reducing glutamatergic transmission via blockade of voltage-gated sodium channels. We here examined the long-term effect of chronic treatment with safinamide 100 mg/day on SICF and other measures of M1 excitability and plasticity in PD.