Elsevier

Neuroscience Research

Volume 92, March 2015, Pages 29-38
Neuroscience Research

Task-specific brain reorganization in motor recovery induced by a hybrid-rehabilitation combining training with brain stimulation after stroke

https://doi.org/10.1016/j.neures.2014.10.004Get rights and content

Highlights

  • We developed a new hybrid-rehabilitation combining rTMS and motor training for stroke.

  • We investigated the task-specific multi-regional brain reorganization induced by it.

  • We found reduced activities in ipsilesional SMC, contralesional CMC and PMC after it.

  • The findings were shown only for the trained movements but not for the untrained ones.

  • The clinical improvements were associated with the amount of activation change.

Abstract

Recently, we have developed a new hybrid-rehabilitation combining 5 Hz repetitive transcranial magnetic stimulation and extensor motor training of the paretic upper-limb for stroke patients with flexor hypertonia. We previously showed that the extensor-specific plastic change in M1 was associated with beneficial effects of our protocol (Koganemaru et al., 2010). Here, we investigated whether extensor-specific multiregional brain reorganization occurred after the hybrid-rehabilitation using functional magnetic resonance imaging. Eleven chronic stroke patients were scanned while performing upper-limb extensor movements. Untrained flexor movements were used as a control condition. The scanning and clinical assessments were done before, immediately and 2 weeks after the hybrid-rehabilitation. As a result, during the trained extensor movements, the imaging analysis showed a significant reduction of brain activity in the ipsilesional sensorimotor cortex, the contralesional cingulate motor cortex and the contralesional premotor cortex in association with functional improvements of the paretic hands. The activation change was not found for the control condition. Our results suggested that use-dependent plasticity induced by repetitive motor training with brain stimulation might be related to task-specific multi-regional brain reorganization. It provides a key to understand why repetitive training of the target action is one of the most powerful rehabilitation strategies to help patients.

Introduction

Use-dependent plasticity is a neurophysiological basis of functional recovery in neuro-rehabilitation (Butefisch et al., 1995, Dimyan and Cohen, 2011, Hummelsheim, 1999, Masiero and Carraro, 2008, Nudo and Milliken, 1996, Nudo et al., 1996a, Nudo et al., 1996b, Richards et al., 2008). Repeating a specific motor training induces use-dependent plasticity in the primary motor cortex (M1) through long-term potentiation (LTP)-like changes of specific corticospinal motoneurons for the trained task (Butefisch et al., 2000, Classen et al., 1998, Rossini and Pauri, 2000).

Patients with chronic stroke, with moderate-to-severe hemiparesis, often suffer from motor deficits associated with flexor hypertonia, as well as motor weakness. In order to facilitate use-dependent plasticity for extensor function which counteracts flexor hypertonia, we have developed a new hybrid-rehabilitation combining 5 Hz repetitive transcranial magnetic stimulation (rTMS) given over the ipsilesional M1 area and extensor motor training aided by electrical neuromuscular stimulation for the paretic upper-limb. It led to a functional recovery with reduction of flexor hypertonia, attributable to the extensor-specific change in M1 (Koganemaru et al., 2010). In our previous study, neuromuscular stimulation of our protocol had little influence on hypertonia (Koganemaru et al., 2010). In previous reports, its effects are still controversial on reduction of hypertonia of paretic upper limbs (Dewald et al., 1996, Fujiwara et al., 2009, Hines et al., 1993, Hummelsheim et al., 1997).

Neuroimaging studies demonstrated that multi-regional brain reorganization occurred in several motor-related regions including bilateral M1, premotor cortices (PMC), cingulate motor cortex (CMC), basal ganglia and cerebellum in process of recovery after stroke insults (Carey et al., 2002, Jang et al., 2003, Jang et al., 2005, Johansen-berg et al., 2002a, Luft et al., 2004, Nelles et al., 2001, Ward et al., 2003a, Ward et al., 2003b, Ward et al., 2004, Ward and Cohen, 2004). Over-activity of non-M1 regions in an acute stage was progressively decreased with an improvement of motor performance of the hemiparetic limbs (Calautti et al., 2001, Small et al., 2002, Ward et al., 2003a, Ward et al., 2003b). In a chronic stage, the magnitude of brain activity in the non-M1 regions was negatively correlated with the clinical outcome (Ward et al., 2003a, Ward et al., 2003b) and positively correlated with the extent of damage in corticospinal function (Ward et al., 2006) probably due to the compensatory mechanism of secondary motor areas (Feydy et al., 2002, Ward et al., 2003a, Ward et al., 2003b). However, if any repetitive motor training could induce task-specific enhancement of the ipsilesional M1 function, a compensatory drive from secondary motor areas would be reduced when the trained task was performed.

In order to investigate whether extensor-specific multi-regional brain reorganization was induced by the hybrid-rehabilitation, we performed the fMRI scanning in chronic subcortical stroke patients. We hypothesized that the hybrid-rehabilitation would reduce brain activity of non-M1 regions specific for an extension-related task if it could recover residual corticospinal function from the ipsilesional M1 involved in paretic extensor function. Furthermore, we expected that extensor-specific activity change would be related to functional improvement of the paretic upper-limbs.

Section snippets

Subjects

We investigated 11 post-stroke patients (eight men and three women) aged 54–68 years (mean ± standard deviation, 60.8 ± 5.3), who were all right-handed according to the Edinburgh Handedness Inventory (Oldfield, 1971), and had experienced their first-ever subcortical stroke (seven with infarction and four with hemorrhage) >6 months ago (31.0 ± 30.5). The lesions were documented by MRI (T1- and T2-weighted images). All of the patients had no pharmacological treatment of spasticity, epilepsy, depression

Results

No patients experienced side effects during the experiments. The stimulus intensity was 21.9 ± 1.47 mA for electrical neuromuscular stimulation. The behavioral and neurophysiological assessments were confirmed to be performed in the same way in the pre- and post-intervention.

Discussion

The present study showed that the hybrid-rehabilitation combining 5 Hz-rTMS and extensor motor training of the paretic upper-limb induced a functional recovery such as an increase of active ROM in extension and grip power with reduction of spasticity, resulting in an improved daily use of the affected upper-limbs in chronic subcortical stroke patients as our previous study reported (Koganemaru et al., 2010). In a neurophysiological assessment, the active MT from the paretic EDC muscles was

Acknowledgements

This study was partly supported by Grant-in-Aid for JSPS Fellows (25-5251), by Grant-in-Aid for Young Scientists (B) (26870321), by The Shimizu Foundation for Immunology and Neuroscience Grant for 2013 (203130600051), by Research Grant-in-Aid from the Magnetic Health Science Foundation (203130600054) (to S.K.), by Grant-in-Aid for Scientific Research (B) (24300192) and for Exploratory Research (24650226) (to T.M.) from the Japan Society for the Promotion of Science and by Grant-in-Aid for

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