Cortical output modulation after rapid repetitive movements.

In patients with dystonia, abnormal movements are commonly triggered or made worse by voluntary action. By means of transcranial magnetic stimulation (TMS), we investigated changes in motor cortex excitability before the execution of wrist voluntary movements in patients with upper limb dystonia and normal control subjects. Magnetic stimulation was delivered by two Magstim 200 stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm extensor muscles. A subthreshold (80% of the rest motor threshold) conditioning stimulus was delivered 3 ms before the suprathreshold (120% of the rest motor threshold) test stimulus and the degree of inhibition of the conditioned motor evoked potentials (MEPs) was taken as an indicator of intracortical inhibition. MEPs were recorded over the forearm extensor muscles of the right arm. To study MEP amplitudes and intracortical inhibition before the onset of wrist extension in the pre-movement condition, TMS pulses were delivered from 0 ms to 100 ms after the go-signal. Besides the pre-movement condition, intracortical inhibition and the unconditioned MEP size were also investigated at rest and during tonic wrist extension. In healthy subjects studied before the wrist movement, the unconditioned MEP amplitude increased progressively and intracortical inhibition decreased significantly. Before movement in dystonic patients, the unconditioned MEP amplitude remained significantly unchanged from resting values and intracortical inhibition decreased less than it did in healthy subjects. In both groups studied during contraction, the unconditioned MEP amplitude increased and intracortical inhibition decreased from values at rest. In conclusion, these findings from reaction time tasks in patients with primary dystonia provide evidence of abnormal pre-movement motor cortex excitability. This abnormality is due to an altered release or running of motor programmes.

Motor cortex excitability can be measured by single- and paired-pulse transcranial magnetic stimulation (TMS). Repetitive transcranial magnetic stimulation (rTMS) can induce neuroplastic effects in stimulated and in functionally connected cortical regions. Due to its ability to non-invasively modulate cortical activity, rTMS has been investigated for the treatment of various neurological and psychiatric disorders. However, such studies revealed a high variability of both clinical and neuronal effects induced by rTMS. In order to better elucidate this meta-plasticity, rTMS-induced changes in motor cortex excitability have been monitored in various studies in a pre-post stimulation design. Here, we give a literature review of studies investigating motor cortex excitability changes as a neuronal marker for rTMS effects over non-motor cortical areas. A systematic literature review in April 2014 resulted in 29 articles in which motor cortex excitability was assessed before and after rTMS over non-motor areas. The majority of the studies focused on the stimulation of one of three separate cortical areas: the prefrontal area (17 studies), the cerebellum (8 studies), or the temporal cortex (3 studies). One study assessed the effects of multi-site rTMS. Most studies investigated healthy controls but some also stimulated patients with neuropsychiatric conditions (e.g., affective disorders, tinnitus). Methods and findings of the identified studies were highly variable showing no clear systematic pattern of interaction of non-motor rTMS with measures of motor cortex excitability. Based on the available literature, the measurement of motor cortex excitability changes before and after non-motor rTMS has only limited value in the investigation of rTMS related meta-plasticity as a neuronal state or as a trait marker for neuropsychiatric diseases. Our results do not suggest that there are systematic alterations of cortical excitability changes during rTMS treatment, which calls into question the practice of re-adjusting the stimulation intensity according to the motor threshold over the course of the treatment.

Prolonged changes in primary motor cortex excitability in response to combined neuromuscular electrical stimulation (NMES) and voluntary contraction with motor evoked potentials (MEPs) were investigated by transcranial magnetic stimulation and recorded by mechanomyography. Participants included 22 healthy individuals. NMES was applied to the extensor carpi radialis (ECR) by voluntary ECR contraction with 20% maximum voluntary contraction (MVC) of wrist extension. MEPs were recorded from the flexor carpi radialis (FCR) and ECR at rest with NMES, at 20% MVC with NMES (combined), and at 20% MVC alone. Significant conditional effects were revealed in ECR and FCR. In the combined condition, MEPs showed gradual enhancement, and those in FCR were more inhibited than those in the control condition. Voluntary contraction with NMES increased primary motor cortex excitability in the agonist muscle, whereas the antagonist muscle might affect reciprocal modulation in the combined condition.

The effect of sensory signals coming from skin and muscle afferents on the sensorimotor cortical networks is entitled as sensory-motor integration (SMI). SMI can be studied electrophysiologically by the motor cortex excitability changes in response to peripheral sensory stimulation. These changes include the periods of short afferent inhibition (SAI), afferent facilitation (AF), and late afferent inhibition (LAI). During the early period of motor skill acquisition, motor cortex excitability increases and changes occur in the area covered by the relevant zone of the motor cortex. In the late period, these give place to the morphological changes, such as synaptogenesis. SAI decreases during learning the motor skills, while LAI increases during motor activity. In this review, the role of SMI in the process of motor learning and transcranial magnetic stimulation techniques performed for studying SMI is summarized.

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.

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis

P 160. The “dormant potential” of the non-dominant hemisphere: In teremispheric a symmetry of cortial plasticity

Changes of cortical excitability of human motor cortex in spinocerebellar ataxia type 2: A study with paired transcranial magnetic stimulation

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions

Prestimulus cortical EEG oscillations can predict the excitability of the primary motor cortex

While task‐dependent changes in motor cortical outputs have been previously reported, the issue of whether such changes are specific for complex hand tasks remains unresolved. The aim of the present study was to determine whether cortical inhibitory tone and cortical output were greater during precision grip and power grip. Motor cortex excitability was undertaken by using the transcranial magnetic stimulation threshold tracking technique in 15 healthy subjects. The motor‐evoked potential (MEP) responses were recorded over the abductor pollicis brevis (APB), with the hand in the following positions: (1) rest, (2) precision grip and (3) power grip. The MEP amplitude (MEP amplitude REST 23.6 ± 3.3%; MEP amplitude PRECISIONGRIP 35.2 ± 5.6%; MEP amplitude POWERGRIP 19.6 ± 3.4%, F = 2.4, P < 0.001) and stimulus‐response gradient (SLOPEREST 0.06 ± 0.01; SLOPEPRCISIONGRIP 0.15 ± 0.04; SLOPE POWERGRIP 0.07 ± 0.01, P < 0.05) were significantly increased during precision grip. Short interval intracortical inhibition (SICI) was significantly reduced during the precision grip (SICI REST 15.0 ± 2.3%; SICI PRECISIONGRIP 9.7 ± 1.5%, SICI POWERGRIP 15.9 ± 2.7%, F = 2.6, P < 0.05). The present study suggests that changes in motor cortex excitability are specific for precision grip, with functional coupling of descending corticospinal pathways controlling thumb and finger movements potentially forming the basis of these cortical changes.

Assessing cortical excitability with electroencephalography: A pilot study with EEG-iTBS

Transcranial Magnetic Stimulation (TMS) serves as a crucial tool in evaluating motor cortex excitability by applying short magnetic pulses to the skull, inducing neuron depolarization in the cerebral cortex through electromagnetic induction. This technique leads to the activation of specific skeletal muscles recorded as Motor-Evoked Potentials (MEPs) through electromyography. Although various methodologies assess cortical excitability with TMS, measuring MEP amplitudes offers a straightforward approach, especially when comparing excitability states pre- and post-interventions designed to alter cortical excitability. Despite TMS's widespread use, the absence of a standardized procedure for such measurements in existing literature hinders the comparison of results across different studies. This paper proposes a standardized procedure for assessing changes in motor cortical excitability using single-pulse TMS pre- and post-intervention. The recommended approach utilizes an intensity equating to half of the MEP's maximum amplitude, thereby ensuring equal likelihood of amplitude increase or decrease, providing a consistent basis for future studies and facilitating meaningful comparisons of results.•A method for assessing changes in motor cortical excitability using single-pulse TMS before and after a specified intervention.•We recommend using an intensity equal to half of the MEP's maximum amplitude during evaluations to objectively assess motor cortical excitability changes post-intervention.

‘Direct’ and ‘crossed’ modulation of human motor cortex excitability following exercise

Phantom limb pain (PLP) affects up to 80% of amputees. Despite the lack of consensus about the etiology and pathophysiology of phantom experiences, previous evidence pointed out the role of changes in motor cortex excitability as an important factor associated with amputation and PLP. In this systematic review, we investigated changes in intracortical inhibition as indexed by transcranial magnetic stimulation (TMS) in amputees and its relationship to pain. Four electronic databases were screened to identify studies using TMS to measure cortical inhibition, such as short intracortical inhibition (SICI), long intracortical inhibition (LICI) and cortical silent period (CSP). Seven articles were included and evaluated cortical excitability comparing the affected hemisphere with the non-affected hemisphere or with healthy controls. None of them correlated cortical disinhibition and clinical parameters, such as the presence or intensity of PLP. However, most studies showed decreased SICI in amputees affected hemisphere. These results highlight that although SICI seems to be changed in the affected hemisphere in amputees, most of the studies did not investigate its clinical correlation. Thus, the question of whether they are a valid diagnostic marker remains unanswered. Also, the results were highly variable for both measurements due to the heterogeneity of study designs and group comparisons in each study. Although these results underscore the role of inhibitory networks after amputation, more studies are needed to investigate the role of a decreased inhibitory drive in the motor cortex to the cause and maintenance of PLP.