The Role of Continuous Theta Burst TMS in the Neurorehabilitation of Subacute Stroke Patients: A Placebo-Controlled Study

Abstract

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects. Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up. Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered. Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.

Keywords: brain oscillations; continuous theta burst stimulation; neurophysiology; neurorehabilitation; stroke; transcranial magnetic stimulation.

Figure 1

Experimental design and procedures. Group E (Experimental) includes patients who received real stimulation, while in group C (Control) are those patients who received sham stimulation. *Represents the stroke lesion site, which could be either left- or right-sided.

Figure 2

EEG tasks: eyes opening + closure (top), arm elevation (middle), thumb opposition (bottom).

Figure 3

Scores in the Wolf Motor Function Test log performance time (left chart) and functional ability scale (right chart), throughout the three time points. Error bars depict ±1 SE.

Figure 4

Non-significant changes in motor-evoked potentials of the affected (left chart) and unaffected (right chart) hemispheres. Error bars show ±1 SE.

Figure 5

Time-response plots of the mean beta power. A group average response of the ipsilesional motor area for an average of the channels of interest (FC3 or 4; FC1 or 2; C3 or 4; C1 or 2; Cz; CP3 or 4; CP1 or 2) is represented, for the experimental group, throughout the three assessment points. Pre-movement and preparation of the affected thumb opposition reveal changes induced by the protocol on beta power of the affected hemisphere (A). Significant differences (*p < 0.05) are also illustrated in the bars chart (B). Error bars represent ±1 SE.