Cortical output modulation after rapid repetitive movements

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 anatomofunctional substrate is represented by the activation of inhibitory intracortical circuits.

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Sommario Abbiamo valutato mediante Stimolazione Magnetica Transcranica eventuali modificazioni dell'eccitabilità della corteccia motoria dopo movimenti rapidi ripetitivi. Sono stati studiati 5 soggetti sani di età compresa tra i 23 e 30 anni valutando l'ampiezza del potenziale evocato motorio (PEM) a riposo e dopo movimento ripetitivo di abduzione-adduzione del pollice sostenuto per 1 minuto a frequenza massimale. Sono stati inoltre valutati l'onda M e l'onda F da stimolazione del nervo mediano al polso. In tutti i soggetti esaminati è stata riscontrata una chiara modificazione dell' ampiezza del PEM dopo esercizio con una riduzione media massimale del 50–60% rispetto le condizioni basali e recupero completo entro 35 minuti circa. La sequenza temporale di questo fenomeno aveva un andamento trifasico: (1) rapido decremento entro il 5° minuto, (II) depressione massimale della durata di 10 min circa, (III) lento ritorno ai valori basali. Non sono state invece riscontrate modificazioni dell'onda M e dell'onda F. I dati ottenuti dimostrano l'esistenza di una modulazione reversibile dell'eccitabilità del I neurone di moto dopo movimenti rapidi ripetitivi. è verosimile che tale modulazione si realizzi a livello della corteccia motoria e che abbia come substrato anatomo-funzionale l'attivazione di circuiti intracorticali inibitori.

     

脑卒中患者病灶周围运动功能的重组

Perilesional reorganization is an important recovery mechanism for stroke patients because it yields good motor outcomes. However, perilesional reorganization remains poorly understood. The scientific basis for stroke rehabilitation can be established when detailed mechanisms of recovery are clarified. In addition, studies at the subcortical level remain in the early stages. Therefore, the present study suggested that additional investigations should focus on perilesional reorganization at the subcortical level, identifying the critical period for this mechanism and determining treatment strategies and modalities to facilitate development. The present study reviews literature focused on perilesional reorganization in stroke patients with regard to demonstration, clinical characteristics, and rehabilitative aspects, as well as previous studies of perilesional reorganization at cortical and subcortical levels.     

Transcranial Magnetic Stimulation as an Investigative Tool for Motor Dysfunction and Recovery in Stroke: An Overview for Neurorehabilitation Clinicians

Rationale: An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis. Scope: Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been used in conjunction with other existing diagnostic tools to investigate motor pathophysiology in stroke patients. Since TMS emerged more than two decades ago, its application in clinical and basic neuroscience has expanded worldwide. TMS can quantify the corticomotor excitability properties of clinically affected and unaffected muscles and can probe local cortical networks as well as remote but functionally related areas. This provides novel insight into the physiology of neural circuits underlying motor dysfunction and brain reorganization during the motor recovery process. This important tool needs to be used with caution by clinical investigators, its limitations need to be understood, and the results should to be interpreted along with clinical evaluation in this patient population. Summary: In this review, we provide an overview of the rationale, implementation, and limitations of TMS to study stroke motor physiology. This knowledge may be useful to guide future rehabilitation treatments by assessing and promoting functional plasticity.     

Effect of Consecutive Application of Paired Associative Stimulation on Motor Recovery in a Rat Stroke Model: A Preliminary Study

This study investigated the changes in motor evoked potential (MEP) amplitude and motor behavior index when paired associative stimulation (PAS), a conjoint stimulation of a peripheral nerve and the motor cortex, was applied in a rat stroke model. The PAS was applied to 19 rats and sham stimulation was applied to 15 rats. One part of PAS consisted of peripheral electrical stimulation of the soleus muscle and the other part was transcranial magnetic stimulation of the motor cortex. The stimulation was repeated for 30 min with a frequency of 0.05 Hz. Five sessions of PAS were applied over 5 consecutive days. The motor behavior index was higher in the PAS group than in the sham stimulation group at 7 d after ischemic brain injury. There was no lasting difference between the PAS animals and the sham stimulation group in MEP amplitude although MEP amplitude was increased immediately after PAS. MEP amplitude can be increased by the PAS paradigm in rats as well as in humans and PAS has potential therapeutic value for motor recovery after brain injury.     

Motor cortex stimulation for levodopa-resistant akinesia: case report.

We treated a patient with levodopa-resistant akinesia with motor cortex stimulation (MCS), and she showed dramatic improvement more than 1 year. On admission, the patient presented severe akinesia and gait disturbance without tremor and rigidity, and did not respond to levodopa test. The patient was suspected pure akinesia and progressive supranuclear palsy. First, high-frequency rTMS of primary motor cortex was examined, and showed the dramatic improvement. Next, chronic subdural electrodes were implanted over the motor cortex bilaterally. One year after surgery, the Unified Parkinson's Disease Rating Scale had improved remarkably, and she could walk four times faster than before. The H2 15O PET study showed a significant increase of rCBF in the left SMA and right dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative treatment for patients with akinesia, including those with PD, and particularly for levodopa-resistant patients, who respond well to rTMS.     

Repetitive transcranial magnetic stimulation of language function in patients with refractory epilepsy A preliminary functional magnetic resonance imaging study

To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.     

经颅重频磁刺激对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响

目的 观察经颅重频磁刺激（rTMS）对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响。方法测定Wistar大鼠右后肢运动阚值（MT）．制作左侧大脑中动脉栓塞（MCAO）再灌流模型．给予rTMS（1次／d）。再灌流72h处死取脑。比较大鼠MCAO再灌流损伤不同时间MT、神经功能评分，脑梗死体积的变化及rTMS的影响。结果MCAO再灌流损伤使大鼠出现局灶性梗死灶，MT升高；神经功能障碍且其程度随损伤时间延长而愈加明显．表现为功能评分升高；rTMS可改善大鼠MCAO再灌流损伤72h的MT和功能障碍程度。减小梗死体积。尤其改善神经功能障碍的程度与对照组比较差异有显著性（P=0．004）。结论rTMS可能对早期缺血脑组织有保护作用．对缺血性脑卒中有进一步研究、应用前景。     

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 418–424, 1997.     

Cortical silent period duration and its implications for surround inhibition of a hand muscle

Surround inhibition is a neural mechanism that assists in the focusing of excitatory drive to muscles responsible for a given movement (agonist muscles) by suppressing unwanted activity in muscles not relevant to the movement (surround muscles). The purpose of the study was to determine the contribution of γ‐aminobutyric acid_B receptor‐mediated intracortical inhibition, as assessed by the cortical silent period (CSP), to the generation of surround inhibition in the motor system. Eight healthy adults (five women and three men, 29.8 ± 9 years) performed isometric contractions with the abductor digiti minimi (ADM) muscle in separate conditions with and without an index finger flexion movement. The ADM motor evoked potential amplitude and CSP duration elicited by transcranial magnetic stimulation were compared between a control condition in which the ADM was activated independently and during conditions involving three phases (pre‐motor, phasic, and tonic) of the index finger flexion movement. The motor evoked potential amplitude of the ADM was greater during the control condition compared with the phasic condition. Thus, the presence of surround inhibition was confirmed in the present study. Most critically, the CSP duration of the ADM decreased during the phasic stage of finger flexion compared with the control condition, which indicated a reduction of this type of intracortical inhibition during the phasic condition. These findings indicate that γ‐aminobutyric acid_B receptor‐mediated intracortical inhibition, as measured by the duration of the CSP, does not contribute to the generation of surround inhibition in hand muscles.     

Similar effect of intermittent theta burst and sham stimulation on corticospinal excitability: A 5‐day repeated sessions study

Despite accumulating evidence of inter and intraindividual variability in response to theta burst stimulation, it is widely believed that in therapeutic applications, repeated sessions can have a “build‐up” effect that increases the response over and above that seen in a single session. However, strong evidence for this is lacking. Therefore, we examined whether daily administration of intermittent theta burst stimulation (iTBS) over the primary motor cortex induces cumulative changes in transcranial magnetic stimulation measures of cortical excitability, above the changes induced by sham stimulation. Over five consecutive days, 20 healthy participants received either active iTBS or sham stimulation. Each day, baseline measures of cortical excitability were assessed before and up to 30 min after the intervention. There was no significant difference in the rate of response between iTBS and sham stimulation on any of the 5 days. There was no iTBS specific cumulative increase of corticospinal excitability. The likelihood that an individual would remain a responder from day‐to‐day was low in both groups, implying high within‐subject variability of both active and sham iTBS after‐effects. In contrast, we found a high within‐subject repeatability of resting and active motor threshold, and baseline motor‐evoked potential amplitude. In summary, sham stimulation has similar effect to active iTBS on corticospinal excitability, even when applied repeatedly for 5 days. Our results might be relevant to research and clinical applications of theta burst stimulation protocols.     

Amphetamine enhances training-induced motor cortex plasticity

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.     

Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke

Background: Repetitive transcranial magnetic stimulation (rTMS) is a simple and non‐invasive method of augmenting motor recovery after stroke, probably mediated by restoring inter‐hemispheric activation balance. This placebo‐controlled pilot study examined the possible benefit of stimulating the lesioned hemisphere (5‐Hz rTMS) or inhibiting the contra‐lesional hemisphere (1‐Hz rTMS) on clinical recovery of motor function in patients with ischaemic stroke and assessed the sustainability of the response. Methods: Sixty patients with ischaemic stroke (>1 month from onset) with mild‐to‐moderate hemiparesis were randomized to receive 10 daily sessions of either sham rTMS, 5‐Hz ipsi‐lesional rTMS or 1‐Hz contra‐lesional rTMS, in addition to a standard physical therapy protocol. Serial assessments were made over a period of 12 weeks by the thumb‐index finger tapping test (FT), Activity Index (AI) score and the modified Rankin Scale (mRS). Results: In contrast to control patients, those receiving active rTMS as ipsi‐lesional 5‐Hz stimulation or 1‐Hz contra‐lesional stimulation showed statistically significant improvement on the FT test, AI scores and mRS score at 2 weeks, and the effect was sustained over the 12‐week observation period. No significant adverse events were observed during treatment in either group. Conclusions: Repetitive TMS has beneficial effects on motor recovery that can be translated to clinically meaningful improvement in disability in patients with post‐stroke hemiparesis, with a well‐sustained effect. The similarity of inhibitory and stimulatory rTMS in producing these effects supports the inter‐hemispheric balance hypothesis and encourages further research into their use in long‐term neurorehabilitation programmes of patients with stroke.