Sensorimotor Integration During Motor Learning: Transcranial Magnetic Stimulation Studies.

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.

Altered cortical excitability is reported in schizophrenia and depression, but findings are inconsistent. Prefrontal repetitive transcranial magnetic stimulation (TMS) induces short-term motor cortex excitability changes in healthy individuals, but its effect in schizophrenia and depression remains unexplored. Prefrontal intermittent theta burst stimulation (iTBS) improves negative symptoms in depression. Cortical excitability is a suggested biomarker for prefrontal iTBS response. We investigated if prefrontal iTBS affects motor cortex excitability in schizophrenia or depression. Secondary aims were to examine motor cortex excitability as a predictor of iTBS effect on negative symptoms in depression and to compare excitability between groups with schizophrenia, depression and healthy controls. TMS indices of cortical excitability − resting motor threshold, short-interval intracortical inhibition, intracortical facilitation and long-interval intracortical inhibition (LICI) − were pooled from previous studies, including an RCT evaluating iTBS for negative symptoms. The dataset comprised 44 patients with schizophrenia, 52 with depression, and 62 healthy controls. Regression models indicated no effect of active versus sham iTBS on any TMS index (all p ≥ .61). No baseline TMS index predicted negative symptom changes after iTBS in depression (all p ≥ .44). Patients with schizophrenia exhibited more pronounced LICI inhibition than the other groups (Mann-Whitney U = 1670, p < .001). LICI correlated with antipsychotic dose (Spearman's ρ = −0.28, p = .04). Prefrontal iTBS does not modify cortical excitability in schizophrenia or depression, nor does cortical excitability predict prefrontal iTBS effects on negative symptoms. The more pronounced LICI inhibition in schizophrenia may be related to the illness or medication.

A mild traumatic brain injury (mTBI) is a common injury that happens to people across a range of lifestyles. Rest has been regarded as the most effective remedy to restore impaired physiological functions in those who have experienced this kind of injury. However, recent data suggests that a gradual increase in physical activity post-injury can lead to quicker recovery from negative symptoms. The impact of physical activity on physiologic recovery is not completely understood and the purpose of this study was to better understand how physical activity and sleep influence physiological outcomes following a mTBI. The data collected in this study came from two groups of young adults: a healthy control (n=5) and those that had a mTBI (n = 5). The daily activity was measured using an activity monitor for a week immediately after injury. Physiological measurements of excitability and inhibition within the motor cortex and neurotransmitter concentrations were collected within 72 hours of injury and again at two months to determine if physical activity or sleep within one week after injury had an influence on physiologic recovery. Control participants had higher levels of total (d = 1.2), light (d = 1.3) and moderate physical activity (d = 0.7), and lower total sleep time (d = -1.9), compared with the mTBI group. Across the two months, relative to the control group the mTBI group showed similar changes in excitability (d = 0.13), but greater changes in inhibition (d = -0.66). Changes in the excitatory (d = 0.06) and inhibitory (d = -0.16) neurotransmitters were similar between groups. Neither physical activity, nor sleep quality were significantly associated with the change in motor cortex excitability (R 2 ≤ 0.18, p ≥ 0.22), inhibition (R 2 ≤ 0.3, p ≥ 0.08) or neurotransmitter concentrations (R 2 ≤ 0.15, p ≥ 0.20) between 72 hours and two months post-injury. These preliminary results suggest there is no direct effect of physical activity on physiological outcomes.

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

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

Transcranial magnetic stimulation was used to evaluate changes in motor cortex excitability after rapid repetitive movements in five healthy subjects aged 23-30 years, by considering the amplitude of motor evoked potentials (MEPs) at rest and after one minute of maximal frequency repetitive abduction-adduction movements of the thumb. In addition, M and F waves were evaluated by stimulating the median nerve at the wrist. All of the examined subjects showed a clear modification in post-exercise MEP amplitudes, with a mean maximal reduction of 50-60% in comparison with basal values and complete recovery after a period of about 35 minutes. The time course of this phenomenon showed a triphasic pattern: (I) a rapid decrease phase up to the fifth minute; (II) a maximal depression phase for a period of about ten minutes; (III) a slow return to basal values. No significant changes were observed in post-exercise M and F waves. These results show the existence of a reversible modulation of the excitability of the upper motor neuron after rapid repetitive movements. It is likely that this modulation takes place at the level of the motor cortex and that its anatomo-functional substrate is represented by the activation of inhibitory intracortical circuits.

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.

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.

Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

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.

Previous studies investigating the effects of somatosensory afferent inputs on cortical excitability and neural plasticity often used transcranial magnetic stimulation (TMS) of hand motor cortex (M1) as a model, but in this model it is difficult to separate out the relative contribution of cutaneous and muscle afferent input to each effect. In the face, cutaneous and muscle afferents are segregated in the trigeminal and facial nerves, respectively. We studied their relative contribution to corticobulbar excitability and neural plasticity in the depressor anguli oris M1. Stimulation of trigeminal afferents induced short-latency (SAI) but not long-latency (LAI) afferent inhibition of face M1, while facial nerve stimulation evoked LAI but not SAI. Plasticity induction was observed only after a paired associative stimulation protocol using the facial nerve. Physiological differences in effects of cutaneous and muscle afferent inputs on face M1 excitability suggest they play separate functional roles in behaviour. The lack of conventional muscle spindles in face muscles raises the question of how sensory input from the face is used to control muscle activation. In 16 healthy volunteers, we probed sensorimotor interactions in face motor cortex (fM1) using short-afferent inhibition (SAI), long-afferent inhibition (LAI) and LTP-like plasticity following paired associative stimulation (PAS) in the depressor anguli oris muscle (DAO). Stimulation of low threshold afferents in the trigeminal nerve produced a clear SAI (P<0.05) when the interval between trigeminal stimulation and transcranial magnetic stimulation (TMS) of fM1 was 15-30ms. However, there was no evidence for LAI at longer intervals of 100-200ms, nor was there any effect of PAS. In contrast, facial nerve stimulation produced significant LAI (P<0.05) as well as significant facilitation 10-30 minutes after PAS (P<0.05). Given that the facial nerve is a pure motor nerve, we presume that the afferent fibres responsible were those activated by the evoked muscle twitch. The F-wave in DAO was unaffected during both LAI and SAI, consistent with their presumed cortical origin. We hypothesize that, in fM1, SAI is evoked by activity in low threshold, presumably cutaneous afferents, whereas LAI and PAS require activity in (higher threshold) afferents activated by the muscle twitch evoked by electrical stimulation of the facial nerve. Cutaneous inputs may exert a paucisynaptic inhibitory effect on fM1, while proprioceptive information is likely to target inhibitory and excitatory polysynaptic circuits involved in LAI and PAS. Such information may be relevant to the physiopathology of several disorders involving the cranio-facial system.

IntroductionDeficits in voluntary muscle activation and altered motor cortex function are present following serious knee injury and are proposed to influence rehabilitation outcomes. It is unknown if these deficits occur...

Immediate and late modulation of interhemipheric imbalance with bilateral transcranial direct current stimulation in acute stroke.

P79-T Sensory-motor integration during a visuomotor sequence learning task

Previous studies indicated changes of motor cortex excitability in fibromyalgia (FM) patients and the positive results of transcranial stimulation techniques. The present study aimed to explore the metabolism of motor cortex in FM patients, in resting state and during slow and fast finger tapping, using functional Near-Infrared Spectroscopy (fNIRS), an optical method which detects in real time the metabolism changes in the cortical tissue. We studied 24 FM patients and 24 healthy subjects. We found a significant slowness of motor speed in FM patients compared to controls. During resting state and slow movement conditions, the metabolism of the motor areas was similar between groups. The oxyhemoglobin concentrations were significantly lower in patients than in control group during the fast movement task. This abnormality was independent from FM severity and duration. The activation of motor cortex areas is dysfunctional in FM patients, thus supporting the rationale for the therapeutic role of motor cortex modulation in this disabling disorder.