The relationship between corticospinal excitability during motor imagery and motor imagery ability

It is commonly reported that transcranial magnetic stimulation (TMS) of the motor cortex during action observation and motor imagery results in increases in the amplitude of motor evoked potentials (MEPs) in muscles specific to the observed or imagined action. This study aimed to determine whether MEP amplitude was related to the motor imagery ability of participants. Participants were 15 healthy, right-handed adults (five male), with a mean age of 29.7 years. Motor imagery ability was measured using the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) and a hand rotation task. TMS was delivered during observation and imagery of a finger-thumb opposition sequence and MEPs were measured in the abductor pollicis brevis. Significant increases in MEP amplitude, from baseline, were recorded during observation and imagery conditions. The change in amplitude to both observation and imagery was expressed as a percentage of baseline amplitude. There was a significant correlation between MEP change for the imagery condition and imagery ability, with greater change linked to more vivid images and faster response times. The relationship between MEP change for the observation condition and imagery ability was less salient. This is the first study to show that the strength of corticospinal activation during imagery, which may be a determinant of the effectiveness of imagery training, is related to imagery ability in the general population, and has implications for clinical programs.     

Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

Objective

To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise.

Larger cortical motor maps after seizures

Expansion of motor maps occurs in both clinical populations with epilepsy and in experimental models of epilepsy when the frontal lobes are involved. We have previously shown that the forelimb area of the motor cortex undergoes extensive enlargement after seizures, although the extent to which many movement representation areas are altered is not clear. Here we hypothesize that movement representations in addition to the forelimb area will be enlarged after cortical seizures. To test our hypotheses, Long Evans Hooded rats received 20 sessions of callosal (or sham) kindling, and then were subjected to intracortical microstimulation to map several movement representations including the jaw, neck, forelimb, hindlimb, trunk and tail. We found significantly larger total map areas of several movement representations, including movements that could be evoked more posterior than they are in control rats. We also show the presence of more multiple movement sites and lower movement thresholds in kindled rats, suggesting that movements not only overlap and share cortical territory after seizures, but become present in formerly non-responsive sites as they become detectable with our intracortical microstimulation methodology. In summary, several motor map areas become larger after seizures, which may contribute to the interictal motor disturbances that have been documented in patients with epilepsy.     

Topiramate selectively decreases intracortical excitability in human motor cortex

PURPOSE: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium-channel blocker, as gamma-aminobutyric acid type A (GABAA)-receptor agonist and as non-N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist. METHODS: With transcranial magnetic stimulation (TMS), we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability. In a double-blind, placebo-controlled, crossover study design, we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical silent period (CSP), and on intracortical inhibition (ICI) and intracortical facilitation (ICF) in 20 healthy subjects. RESULTS: A significant dose-dependent increase of ICI was noticed after 200 mg TPM as compared with placebo at short interstimulus intervals of 2 to 4 ms. TPM had no effect on motor thresholds or the CSP. CONCLUSIONS: We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion-channel blockade or GABAB-receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.     

Decreased input to the motor cortex increases motor cortical excitability.

OBJECTIVE: To investigate whether a short-duration reduction of input to the motor cortex affects excitability in the hand region of the motor cortex. METHODS: Subjects (n=10) received sets of transcranial magnetic stimulation of the motor cortex (TMS) and peripheral ulnar nerve stimulation. Stimuli were delivered before and after 20 min of inactivity of the test hand. The evoked compound muscle action potentials were recorded in two relaxed intrinsic hand muscles using surface EMG. RESULTS: Motor evoked potential size (MEP; expressed relative to the maximal M-wave) increased by approximately 30-40 in both hand muscles (P=0.012) following inactivity. The enlarged MEP was not associated with changes in F-wave size, a marker of motoneurone excitability, or changes in intracortical inhibition and facilitation measured with paired-pulse TMS. CONCLUSIONS: MEP growth most likely reflects an increase in motor cortical excitability. The increased excitability appears to be more associated with reduced voluntary drive to and from the motor cortex rather than reduced afferent input from the periphery. SIGNIFICANCE: These results have important implications for any investigation of motor cortical excitability in relaxed subjects. The outcome of an experimental intervention is the net result of the intervention itself and alterations in cortical excitability produced by the subjects' inactivity.     

Repetitive paired-pulse transcranial magnetic stimulation affects corticospinal excitability and finger tapping in Parkinson's disease.

OBJECTIVES: To study the effect of long trains of a recently established conditioning-test paired-pulse repetitive transcranial magnetic stimulation (rTMS) paradigm on corticospinal excitability and finger tapping speed. METHODS: We applied 900 inhibiting or facilitating paired-pulses or 900 real or sham single stimuli at 1Hz over the motor cortex contralateral to the dominant hand of 9 healthy subjects and contralateral to the more affected hand of 11 patients with Parkinson's disease. RESULTS: In both groups, motor evoked potentials (MEPs) from suprathreshold pulses were larger after facilitating paired-pulses than after inhibiting paired-pulses. After real single-pulse rTMS and after either type of paired-pulse rTMS patients showed an increase in finger tapping frequency on the stimulated hand. Tapping was unchanged contralaterally, after sham stimuli, and in controls. Tremor and tapping frequencies were not correlated, nor was the change in MEP size correlated to the change in tapping frequency. CONCLUSIONS: Repetitive paired-pulses allow selective induction of corticospinal inhibition or facilitation, but do not enhance the transient improvement of finger motility induced by conventional single-pulse rTMS.     

Scaling of motor cortical excitability during unimanual force generation

During performance of a unimanual force generation task primary motor cortices (M1s) experience clear functional changes. Here, we evaluated the way in which M1s interact during parametric increases in right wrist flexion force in healthy volunteers. We measured the amplitude and the slope of motor evoked potentials (MEP) recruitment curves to transcranial magnetic stimulation (TMS) in the left and right flexor carpi radialis (FCR) muscles at rest and during 10%, 30% and 70% of maximal wrist flexion force. At rest, no differences were observed in the amplitude and slope of MEP recruitment curves in the left and right FCR muscles. With increasing right wrist flexion force, MEP amplitudes increased in both FCR muscles, with larger amplitudes in the right FCR. We found a significant correlation between the left and right MEP amplitudes across conditions. The slope of right and left FCR MEP recruitment curve was significantly steeper at 70% of force compared to rest and 10% of force. A significant correlation between the slope of left and right FCR MEP amplitudes was found at 70% of force only. Our results indicate a differential scaling of excitability in the corticospinal system controlling right and left FCR muscles at increasing levels of unimanual force generation. Specifically, these data highlights that at strong levels of unimanual force the increases in motor cortical excitability with increasing TMS stimulus intensities follow a similar pattern in both M1s, while at low levels of force they do not.     

Zonisamide decreases cortical excitability in patients with idiopathic generalized epilepsy.

ObjectiveTo evaluate changes in cortical excitability after long-term zonisamide (ZNS) administration.MethodsFifteen drug-naïve idiopathic generalized epilepsy (IGE) patients (8 male, mean age 24.9 years) were enrolled. The transcranial magnetic stimulation (TMS) parameters obtained using two Magstim 200 stimulators were resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), and intracortical facilitation (ICF). TMS parameters were compared before and after ZNS administration.ResultsAll patients were administered ZNS monotherapy (200 mg/day) for 8 weeks. No patient reported seizures during the study period. After ZNS treatment MEP amplitudes were significantly reduced in right (−34.2%) and left hemispheres (−37.0%) (Wilcoxon’s signed rank test after Bonferroni’s correction for multiple comparisons, P < 0.05). Mean RMT, CSP, and ICI/ICF were not changed by ZNS (P > 0.05).ConclusionsThese findings suggest that ZNS decreases cortical excitability in patients with IGE and a MEP amplitude is a useful TMS parameter for evaluating changes in cortical excitability induced by ZNS.SignificanceThe findings in this study are helpful to understand how ZNS affects the excitability of the motor cortex in patients with IGE.     

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects

Objective

We studied the correlation between motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) from single-pulse TMS before and after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex (M1) in 17 healthy older participants.

Transcranial magnetic stimulation modulation of corticospinal excitability by targeting cortical I-waves with biphasic paired-pulses

Background

Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF.

Evaluation of the motor cortical excitability changes after ischemic stroke

Background:

We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).

Materials and Methods:

Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2^nd), 4^th, and 6^th week of stroke.

Results: Affected hemisphere:

MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.

Unaffected hemisphere:

MEP was recordable in all patients at baseline, and reduced significantly over time (2^nd week 43.52 ± 9.60, 4^th week 38.84 ± 7.83, and 6^th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.

Conclusion:

The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.     

Effect of therapy on motor cortical excitability in Parkinson's disease

OBJECTIVE: To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson's disease (PD). METHODS: Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later. RESULTS: Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy. CONCLUSION: These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.     

Progressive practice promotes motor learning and repeated transient increases in corticospinal excitability across multiple days

Background

A session of motor skill learning is accompanied by transient increases in corticospinal excitability(CSE), which are thought to reflect acute changes in neuronal connectivity associated with improvements in sensorimotor performance. Factors influencing changes in excitability and motor skill with continued practice remain however to be elucidated.

Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.     

Inter-hemispheric asymmetry of motor corticospinal excitability in major depression studied by transcranial magnetic stimulation

BACKGROUND: Imaging and electroencephalographic studies have reported inter-hemispheric asymmetries in frontal cortical regions associated with depression. This study aimed at comparing motor corticospinal excitability assessed by methods of transcranial magnetic stimulation (TMS) between the right and left hemispheres in patients with major depression and healthy controls. METHOD: Patients with major depression (n=35) and healthy controls (n=35) underwent a bilateral study of various motor corticospinal excitability parameters, including rest motor threshold (RMT), corticospinal silent period (CSP) duration and intra-cortical inhibition (ICI) and facilitation (ICF). Indexes of asymmetry were calculated, and the relationships between excitability parameters and clinical scores of depression were statistically analyzed. RESULTS: Depressed patients showed a reduced excitability of both excitatory (RMT, ICF) and inhibitory (CSP, ICI) processes in the left hemisphere, compared to the right hemisphere and to healthy controls. CONCLUSION: The present results confirmed the existence of inter-hemispheric asymmetries in frontal cortex activities of depressed patients in favor of a left-sided reduced excitability. This neurophysiological approach may help to guide repetitive TMS procedures in the treatment of depressive disorders.     

Central fatigue and motor cortical excitability during repeated shortening and lengthening actions

A decline in voluntary muscle activation and adaptations in motor cortical excitability contribute to the progressive decline in voluntary force during sustained isometric contractions. However, the neuronal control of muscle activation differs between isometric and dynamic contractions. This study was designed to investigate voluntary activation, motor cortex excitability, and intracortical inhibition during fatiguing concentric and eccentric actions. Eight subjects performed 143 torque motor-controlled, repeated shortening and lengthening actions of the elbow flexor muscles. Transcranial magnetic stimulation (TMS) was applied three times every 20 cycles. Magnetic evoked motor potentials (MEP), duration of the silent period (SP), and the torque increase due to TMS were analyzed. TMS resulted in a small torque increase in unfatigued actions. With repeated actions, voluntary torque dropped rapidly and the amplitude of the TMS-induced twitches increased, especially during repeated lengthening actions. MEP area of biceps brachii and brachioradialis muscles increased during repeated actions to a similar extent during lengthening and shortening fatigue. The duration of biceps and brachioradialis SP did not change with fatigue. Thus, voluntary activation became suboptimal during fatiguing dynamic actions and motor cortex excitability increased without any changes in intracortical inhibition. The apparent dissociation of voluntary activation and motor cortex excitability suggests that the central fatigue observed, especially during lengthening actions, did not result from changes in motor cortex excitability.     

Behavioural exposure and sleep do not modify corticospinal and intracortical excitability in the human motor system

ObjectiveBehavioural exposure and sleep may bidirectionally modify the excitability of cortical networks including those in the motor cortex. Here we tested whether the excitability of intracortical inhibitory and excitatory networks within the primary motor cortex exhibited changes suggestive of a time of day influence.MethodsShort-interval intracortical inhibition (SICI) and facilitation (ICF), and input–output curves (IO curves) were investigated using transcranial magnetic stimulation (TMS). Recordings were made from the resting right first dorsal interosseous (FDI) muscle in 10 healthy subjects on three occasions: 9 A.M. and 4 P.M. of the same day, and 9 A.M. of the following day.ResultsThere was no significant change in any of the measures across the three assessments.ConclusionsThese findings provide evidence that time of day does not significantly influence corticospinal and intracortical excitability in the primary motor cortex.SignificanceThese results provide no support for the hypothesis that synapses within the motor cortex undergo potentiation due to daytime use and behavioural experiences. Additionally, these findings provide evidence that measurement of motor cortical excitability is not systematically biased by time-of-day dependent variability and thus does not pose a confound in studies assessing corticospinal excitability longitudinally.     

A method to monitor motor cortical excitability in human stroke through motor evoked potentials

We describe a procedure aimed to analyse Motor Evoked Potentials (MEPs) interhemispheric differences in motor excitability in a monohemispheric subacute stroke population. This protocol has specifically been oriented to scan for any differences in MEPs amplitude at rest and during contractions from a hand muscle, Abductor Digiti Minimi (ADM), after focal Transcranial Magnetic Stimulation (TMS) in both Affected (AH) and Unaffected (UH) Hemispheres. Stroke patients can be included in the protocol if they have suffered acute stroke during the two to four month period to the admission in our rehabilitation hospital. The purpose of this protocol is to establish whether any clear pattern of interhemispheric responsiveness exists and/or to define any possible correlation between MEPs and clinical data. Disability and neurological scores are evaluated to allow a numerical comparison with electrophysiological data. Two recording sessions are planned: the first when the selected patient is admitted (T1) and the second after 8 weeks (T2). Such a period has been arbitrarily chosen because it represents a reliable time after the first recording in order to observe clinical amelioration if present. Criteria for reproducibility of experimental conditions are illustrated.     

Chronic dose effects of reboxetine on motor skill acquisition and cortical excitability

Summary Background. Enhancement of cortical excitability is thought to be beneficial for synaptic plasticity associated with motor skill acquisition. Single dose application of the selective norepinephrine reuptake inhibitor reboxetine (RBX) increases motor cortex excitability. In this study, we tested if a chronic dose application of RBX improved motor skill acquisition and modulated cortical excitability. Methods. The study was randomised, double blind and placebo-controlled. Twelve healthy subjects received four milligram RBX twice a day for four days preceded by two milligram RBX twice a day for two days. Each subject served as his own control. The time interval between the verum and the placebo session was 16 days or more. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task in each session. The task was to lift two fingers of the right hand at once while the hand was positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 sec. Between seven blocks of self-paced movements six blocks with 60 single trials at a fixed interstimulus intervall were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carry over effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris). Results. All subjects had substantial gain in performance across the selfpaced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference neither between the versions of the task nor between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carry over effect in performance. ppTMS revealed no significant differences in cortical excitability between groups. Conclusion. The newly developed skill acquisition task yields robust single subject gain of performance. As the two versions of the task do not interact, it is suitable to be used in cross-over designs. In contrast to studies using single doses of RBX, motor cortex excitability seems to be unaffected in a steady-state induced by repeated drug applications. This could explain why RBX did not modulate motor behavior.