rTMS with motor training modulates cortico-basal ganglia-thalamocortical circuits in stroke patients

Abstract

Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke.

Methods: Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed.

Results: Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p < 0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group.

Conclusion: According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits.

Fig. 1

Randomization Process of Subjects by CONSORT diagram

Fig. 2

Experimental design. A. rTMS and motor training. B. Sequential finger training task.

Fig. 3

Behavioral results. Left: Changes in Motor Performance during fMRI before and after rTMS. Upper: The real rTMS group showed significant improvement in movement accuracy with interaction effect between time and intervention. Lower: No significant changes in movement time were observed in either group. Right: Results of the Jebsen hand function test before, after, and 1 month after rTMS. The real rTMS group showed significant improvement in performance time for the simulated feeding task (D) with a significant interaction effect between time (pre-rTMS vs. post-rTMS vs. I month later) and type of intervention (real vs. sham stimulation). * p < 0.05; comparison with before rTMS sessions. Error bars indicate the standard deviation.

Fig. 4

A-B. fMRI results for performance of the sequential finger motor task in the sham (A) and rTMS (B) groups. C. The ipsilesional sensorimotor cortex, ipsilesional thalamus, and contralesional caudate nucleus were defined as areas of significant interaction between the real and sham groups after rTMS intervention. AH, Affected hemisphere; UH, Unaffected hemisphere; SMC, Sensorimotor cortex; MFC, Medial frontal cortex; PPC, Posterior parietal cortex; Cbll, Cerebellum; BG, Basal ganglia; Cd, Caudate nucleus; Th, Thalamus