Motor Cortex Excitability In Patients Research Articles

Search for approaches to transcranial neuromodulation in patients with post-stroke hemiparesis in real clinical practice

BACKGROUND: To increase the efficiency of motor recovery after a stroke in routine clinical practice, the search for selective biomarkers that determine the choice of the optimal strategy for noninvasive neuromodulation of the brain remains relevant. The study of interhemispheric interaction patterns can hypothetically help in determining the correct conceptual model of neuromodulation. AIM: To determine variants of interhemispheric interaction based on a correlation analysis of motor cortex excitability in patients with poststroke hemiparesis stratified by the degree of motor deficit. MATERIALS AND METHODS: This retrospective observational study involved 185 people (men, 56.2%; women, 43.8%) aged 19–88 years with verified poststroke hemiparesis and 40 healthy volunteers (men, 55.0%; women, 45.0%) aged 20–85 years. The patients underwent diagnostic transcranial magnetic stimulation in the projection of the cortical representation of m. abductor pollicis brevis and m. tibialis anterior of both brain hemispheres. The excitability level of the motor cortex and its interhemispheric asymmetry were recorded, and correlation analysis in subgroups stratified by the degree of paresis was performed. RESULTS: No interhemispheric correlation of resting motor thresholds (rMT) was found in patients with a level of muscle strength for the “hand” segment of 0–2 points (р 0.05). In the remaining subgroups, positive interhemispheric correlations of the rMT were noted (p 0.02). A positive correlation of the rMT of the damaged brain hemisphere and interhemispheric asymmetry of the motor cortex excitability for all degrees of paresis was observed when evaluating the cortical representation of the upper limb muscles. A negative correlation between the rMT of the unaffected brain hemisphere and interhemispheric asymmetry was detected for all degrees of motor deficit of the “foot” segment (p 0.02). CONCLUSION: The study did not confirm the concept of interhemispheric competition of the studied functional activity of the brain. Three authentic variants of interhemispheric interaction were identified: unidirectional hemispheric interaction with predominant reactivity of the affected hemisphere, unidirectional hemispheric interaction with predominant reactivity of the unaffected hemisphere, and functional interhemispheric dissociation. The results indicate the need to rethink some approaches to transcranial neuromodulation strategies in the analyzed cohort.

P037 Transcranial static magnetic field stimulation-induced modulation of motor cortex excitability in Parkinson’s disease

Question tSMS is a new non-pharmacological, low-cost, non-invasive brain stimulation (NIBS) technique that decreases cortical excitability in healthy subjects. The effects of tSMS in Parkinson’s disease remain unknown. We designed this study to test the ability of transcranial static magnetic field stimulation (tSMS) to modulate motor cortex excitability in patients with Parkinson’s disease. Methods We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the motor cortex of patients with Parkinson’s disease. Motor cortex excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). In a separated single-blind experimental session we evaluated the effects of tSMS on SICI and SICF. Patients were studied both after overnight withdrawal of dopaminergic therapy (OFF) medication and after an acute dose of levodopa (ON). Results tSMS significantly decreased MEP amplitudes compared to sham in patients OFF medication, but not ON medication. Furthermore, tSMS induced an increase in SICI and a reduction in SICF only in OFF condition. Conclusions These results suggest a dopamine dependency of tSMS-induced cortical changes and encourage the application of tSMS for future clinical trials in patients with Parkinson’s disease.

Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke. This randomized, sham-controlled, double-blind study was to compare the effects of high-frequency versus low-frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements. A total of 69 first-ever ischemic stroke patients with motor deficits were randomly allocated to receive five daily sessions of 3-Hz ipsilesional rTMS, 1-Hz contralesional rTMS or sham rTMS in addition to standard physical therapy. Outcome measures included motor deficits, neurological scores and cortical excitability, which were assessed at baseline, after the intervention and at 3-month follow-up. The rTMS groups manifested greater motor improvements than the control group, which were sustained for at least 3 months after the end of the treatment sessions. 1-Hz rTMS over the unaffected hemisphere produced more profound effects than 3-Hz rTMS in facilitating upper limb motor performance. There was a significant correlation between motor function improvement and motor cortex excitability change in the affected hemisphere. Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.

Neuromuscular electrical stimulation of the median nerve facilitates low motor cortex excitability in patients with spinocerebellar ataxia

The neuromodulation of motor excitability has been shown to improve functional movement in people with central nervous system damage. This study aimed to investigate the mechanism of peripheral neuromuscular electrical stimulation (NMES) in motor excitability and its effects in people with spinocerebellar ataxia (SCA). This single-blind case-control study was conducted on young control (n=9), age-matched control (n=9), and SCA participants (n=9; 7 SCAIII and 2 sporadic). All participants received an accumulated 30min of NMES (25Hz, 800ms on/800ms off) of the median nerve. The central motor excitability, measured by motor evoked potential (MEP) and silent period, and the peripheral motor excitability, measured by the H-reflex and M-wave, were recorded in flexor carpi radialis (FCR) muscle before, during, and after the NMES was applied. The results showed that NMES significantly enhanced the MEP in all 3 groups. The silent period, H-reflex and maximum M-wave were not changed by NMES. We conclude that NMES enhances low motor excitability in patients with SCA and that the mechanism of the neuromodulation was supra-segmental. These findings are potentially relevant to the utilization of NMES for preparation of motor excitability. The protocol was registered at Clinicaltrials.gov (NCT02103075).

Increased intracortical inhibition in hyperglycemic hemichorea-hemiballism.

Hemichorea-hemiballism (HC-HB) in uncontrolled diabetes mellitus is an uncommon manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC-HB is not well understood. A previous report showed increased intracortical inhibition in the motor cortex in a patient with diabetes with HC-HB. The objective of this study is to investigate motor cortex excitability in patients with hyperglycemic HC-HB. We hypothesized that intracortical inhibition measured with transcranial magnetic stimulation, which likely reflects the excitability of cortical γ-aminobutyric acid (GABA)ergic circuits, would be impaired in patients with hyperglycemic HC-HB. We studied 15 patients with mean age 71.5 years (range, 48-94 y) and 12 age-matched healthy subjects. The motor cortex contralateral to the hemichorea was tested. Transcranial magnetic stimulation measures included motor evoked potential, recruitment curve, GABAA mediated short interval intracortical inhibition, intracortical facilitation, and GABAB mediated silent period duration and long interval intracortical inhibition. No significant difference was found in motor threshold, recruitment curve response, short interval intracortical inhibition, or intracortical facilitation in both rest and active conditions between patients with hyperglycemic HC-HB and normal subjects. However, long interval intracortical inhibition was significantly increased during muscle activation but not at rest in patients with hyperglycemic HC-HB. The silent period duration is also increased in patients with hyperglycemic HC-HB. We concluded that long interval intracortical inhibition and silent period are increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC-HB, but only during muscle activation. Hemichorea-hemiballism may be associated with increased GABAB receptor-mediated inhibitory activity in the motor cortex.

Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study

BackgroundClinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD.MethodsEleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study.ResultsScores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls.ConclusionsThis study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the “Vascular depression hypothesis” at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug-induced effect on our results cannot be excluded. This study may aid the understanding of the pathogenetic differences underlying the clinical spectrum of depressive disorders.

P 248. Cortical inhibition by Retigabine in epilepsy patients: Assessment by transcranial magnetic stimulation

Introduction Transcranial magnetic stimulation (TMS) has been used to investigate the mechanism of action of several drugs. Sodium-channel blocking drugs elevate the threshold, while drugs that act on GABAergic transmission improve intracortical inhibition or prolong the silent period. While these basic studies are designed to investigate physiology and pharmacology, TMS can be suitable as biomarker in individual patients. A prospective study in newly diagnosed epilepsy demonstrated that TMS responses measured shortly after the application of an antiepileptic drug can predict long-term seizure control. ∗ Retigabine is a first-in-class antiepileptic drug that acts on potassium channels. Indirectly, changes in GABAergic synaptic transmission may contribute to its efficacy. In-vivo studies of the physiological effect of Retigabine on motor cortex excitability in patients with epilepsy could deepen our understanding of the involved mechanisms. The results of such a study may be compared with the literature on TMS-effects of classical anti-epileptic and other drugs acting on the central nervous system. Objectives The study aims to investigate the effect of Retigabine on cortical excitability measured by TMS in patients with partial onset epilepsy. If there is a change in the TMS variables after starting Retigabine, we would like to see whether this correlates with the therapeutic effect. Materials and methods This is an observational neurophysiological/neuropharmacological study. Fifteen patients with uncontrolled partial onset epilepsy, with or without secondary generalization that have an indication to initiate adjuvant treatment with Retigabine will participate. Doses of conconcurrent medication are kept constant during the study. TMS is performed before starting Retigabine, on 600 mg/day (post1), on 900/dag (post2) or after any other different maintenance dose is reached (post3). In each session resting motor threshold, short interval (2 and 5 ms) intracortical inhibition, intracortical facilitation (10 and 15 ms), long interval intracortical inhibition (250 and 300 ms) en silent period are measured. Results and conclusion At the conference preliminary results and conclusions will be presented.

Visuomotor Gain Distortion Alters Online Motor Performance and Enhances Primary Motor Cortex Excitability in Patients With Stroke

Determine if ipsilesional primary motor cortex (M1) in stroke patients processes online visuomotor discordance in gain between finger movement and observed feedback in virtual reality (VR). Chronic stroke patients flexed (N= 7) or extended (N= 1) their finger with real-time feedback of a virtual hand presented in VR. Virtual finger excursion was scaled by applying a low-gain (G(0.25) ), high-gain (G(1.75) ), or veridical (G(1.00) ) scaling factor to real-time data streaming from a sensor glove. Effects of visuomotor discordance were assessed through analysis of movement kinematics (joint excursion, movement smoothness, and angular velocity) and amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation applied to ipsilesional M1. Data were analyzed with a repeated-measures analysis of variance (significance set at 0.05). G(0.25) discordance (relative to veridical) leads to significantly larger joint excursion, online visuomotor correction evidenced by decreased trajectory smoothness, and significantly facilitated agonist MEPs. This effect could not be explained by potential differences in motor drive (background electromyographic) or by possible differences related to joint angle or angular velocity, as these variables remained invariant across conditions at the time of MEP assessment. M1 was not significantly facilitated in the G(1.75) condition. MEPs recorded in an adjacent muscle that was not involved in the task were unaffected by visual feedback in either discordance condition. These data suggest that the neuromodulatory effects of visuomotor discordance on M1 were relatively selective. Visuomotor discordance may be used to alter movement performance and augment M1 excitability in patients following stroke. Our data illustrate that visual feedback may be a robust way to selectively modulate M1 activity. These data may have important clinical implications for the development of future VR training protocols.

Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS. Three sessions of cathodal tDCS, lasting 7, 11, or 15 minutes, were performed in 10 patients and 10 healthy controls. Corticospinal excitability was measured before and after the tDCS. Cathodal tDCS induced a consistent decrease in corticospinal excitability in healthy controls, but not in ALS patients. The failure of tDCS to produce an excitability shift in the patients supports the potential diagnostic value of tDCS as a marker of upper motor neuron involvement. However, variation in corticospinal excitability measurements both inter- and intraindividually will limit its usefulness.

Modafinil reverses hypoexcitability of the motor cortex in narcoleptic patients: A TMS study

Objective Although many animal and human studies have been performed, the exact mechanisms of action whereby modafinil promotes wakefulness are still not completely understood. We aimed to investigate the functional effects of modafinil on motor cortex excitability in patients with narcolepsy by means of transcranial magnetic stimulation (TMS) techniques. Methods In a double-blind and placebo-controlled design, 24 drug-naive narcoleptic patients with cataplexy and 20 control subjects were administered modafinil or placebo over a period of 4 weeks. TMS was performed twice during the awake state before and at the end of treatment; measures of cortical excitability included central motor conduction time, resting motor threshold, short latency intracortical inhibition (SICI) and intracortical facilitation to paired-TMS. TMS measures were correlated with the conventional neurophysiological method of Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). Results As previously reported, motor threshold and SICI were significantly increased in patients with narcolepsy; modafinil reversed this cortical hypoexcitability, but only SICI differences reached statistical significance. The Spearman rank correlation analysis revealed the highest correlation between SICI and the MSLT; a positive correlation was also found between SICI and the ESS, as well as between RMT and both measures of daytime sleepiness. Conclusions This represents the first report investigating effects of modafinil on cortical excitability in human narcolepsy. Since SICI is thought to be directly related to GABA A intracortical inhibitory activity, we demonstrated that the dose of modafinil that induces a satisfactory wakefulness-promoting response in narcoleptic patients also causes decrease in GABAergic transmission.

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson’s disease

Motor cortex excitability was assessed in 12 patients with Parkinson’s disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated (“ON”) and when immobile after medication withdrawal (“OFF”). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in “ON” and “OFF” states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either “ON” or “OFF” states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.

Effects of cerebellar TMS on motor cortex of patients with focal dystonia: a preliminary report

Recent evidence suggests a role for cerebellum in pathophysiology of dystonia. Here we explored, the cerebellar modulation of motor cortex in patients with focal upper limb dystonia. Eight patients and eight controls underwent a transcranial magnetic stimulation protocol to study the cerebellar-brain-inhibition (CBI): a conditioning cerebellar stimulus (CCS) was followed 5 ms after by the contralateral motor cortex stimulation (test stimulus: TS). We explored the effects of CBI on MEP amplitude, short intracortical inhibition (SICI) and intracortical facilitation (ICF) measures. At baseline no differences in TS-MEP amplitude, SICI or ICF were found between patients and controls. Cerebellar-conditioning significantly reduced TS-MEP amplitude, increased ICF, and decreased SICI in control subjects. In contrast, no changes in these neurophysiological measures were observed in the motor cortex of patients, regardless of which side was tested. If further confirmed, these findings suggest a reduced cerebellar modulation of motor cortex excitability in patients with focal dystonia.

Altered response to rTMS in patients with Alzheimer's disease

Objective In this study, we tested the excitability of cortical motor areas in patients with Alzheimer's disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimer's disease. Methods We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5 Hz frequency and 120% rMth intensity in a group of patients with Alzheimer's disease, and age-matched controls. In a further session, rTMS was also delivered at 1 Hz frequency (trains of 10 stimuli, 120% rMth). Results Whereas in control subjects, 5 Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. Conclusions The lack of MEP facilitation reflects an altered response to 5 Hz-rTMS in patients with Alzheimer's disease. Significance Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimer's disease.

Motor cortex excitability in Alzheimer disease: one year follow-up study

Seventeen patients affected by Alzheimer disease (AD) underwent two transcranial magnetic stimulation (TMS) studies separated by an interval of 12 months, in order to monitor possible changes in motor cortex excitability. After the first examination, all patients were treated with cholinesterase inhibitor drugs. Motor threshold (MT), amplitude of motor evoked potentials and central motor conduction time were considered. After one year, the mean MT values showed a decrease significantly correlated with the severity of cognitive involvement, evaluated by means of the Mini Mental State Examination (MMSE). The difference in MT between the two recording sessions showed no significant correlation with the difference in MMSE score. One year of treatment with cholinesterase inhibitor drugs did not stop the progressive increase in motor cortex excitability. Serial analysis of TMS might represent a method to monitor the rate of change in motor cortex excitability in patients with AD.

Motor cortex excitability in patients with focal epilepsy

We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal ( n=7), extratemporal ( n=6) and focal epilepsy lateralised to one hemisphere ( n=2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2–4 ms) and facilitation (ICF, 7–15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres ( P<0.01, ANOVA) compared to the controls. In the hemisphere of seizure origin (‘abnormal’) there was a reduction of ICF ( P<0.01) and normal ICI, in the ‘normal’ hemisphere there was a reduced ICI ( P<0.01) and a slight reduction of ICF ( P<0.05). ICF on the ‘abnormal’ side was reduced ( P<0.05) compared to the ‘normal’ hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.

Motor cortex excitability in patients with cerebellar degeneration

Objectives: To study motor cortex (M1) excitability and the effect of subthreshold transcranial magnetic stimulation (TMS) in patients with cerebellar degeneration and normals performing a reaction time (RT) task. Methods: Time to wrist flexion after a visual go-signal was measured. TMS was always delivered at 90% of resting motor evoked potential (MEP) threshold. In one experiment, test TMS was delivered at various intervals after the go-signal. In half the trials priming TMS was also given with the go-signal. A second experiment examined the effect on RT of M1 and occipital priming stimulation alone. Results: M1 excitability, measured as the likelihood of producing MEPs in the wrist flexor muscles, increased immediately after the go-signal in the patients and stayed high until movement. In controls, excitability rose gradually. This difference was largely eliminated by priming TMS. RT was longer in the patient group, but improved with priming TMS. Occipital priming produced less effect on RT than M1 stimulation in both controls ( P=0.008) and patients ( P=0.0004). Conclusions: M1 excitability prior to movement in an RT task increases abnormally early in cerebellar patients. This may reflect compensation for deficient thalamocortical drive. Subthreshold TMS can partially normalize the prolonged RT and abnormal excitability rise in cerebellar patients.

Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.

2-28-07 Motor cortex excitability in patients with temporal lobe epilepsy (TLE): A transcranial magnetic stimulation study

2-28-07 Motor cortex excitability in patients with temporal lobe epilepsy (TLE): A transcranial magnetic stimulation study

Reduction of motor cortex excitability in patients with cerebellar lesion

Reduction of motor cortex excitability in patients with cerebellar lesion