Differential effect of conditioning sequences in coupling inhibitory/facilitatory repetitive transcranial magnetic stimulation for poststroke motor recovery

Abstract

Introduction: While neuromodulation through unihemispheric repetitive transcranial magnetic stimulation (rTMS) has shown promise for the motor recovery of stroke patients, the effectiveness of the coupling of different rTMS protocols remains unclear.

Aims: We aimed to test the long-term efficacy of this strategy with different applying sequences and to identify the electrophysiological correlates of motor improvements to the paretic hand.

Results: In our sham-controlled, double-blinded parallel study, 48 stroke patients (2-6 months poststroke) were randomly allocated to three groups. Group A underwent 20-session rTMS conditioning initiated with 10-session 1 Hz rTMS over the contralesional primary motor cortex (M1), followed by 10-session intermittent theta burst stimulation (iTBS) consequently over the ipsilesional M1; Group B underwent the same two paradigms but in reverse; and Group C received sham stimulation that was identical to Group A. We tested cortical excitability and motor assessments at the baseline, postpriming rTMS, postconsequent rTMS, and at 3-months follow-up. Group A manifested greater improvement than Group B in Fugl-Meyer Assessment (FMA), Wolf Motor Function testing (WMFT) score, and muscle strength (P = 0.001-0.02) post the priming rTMS. After the consequent rTMS, Group A continued to present a superior outcome than Group B in FMA (P = 0.015) and WMFT score (P = 0.008) with significant behavior-electrophysiological correlation.

Conclusions: Conditioning the contralesional M1 prior to ipsilesional iTBS was found to be optimal for enhancing hand function, and this effect persisted for at least 3 months. Early modulation within 6 months poststroke rebalances interhemispheric competition and appears to be a feasible time window for rTMS intervention.

Keywords: Coupling stimulation; Facilitatory repetitive transcranial magnetic stimulation; Inhibitory repetitive transcranial magnetic stimulation; Motor recovery; Stroke.

Figure 1

The flowchart illustrates recruitment, group allocation, allocation treatment, follow‐up and analysis.

Figure 2

Experimental design. The daily repetitive transcranial magnetic stimulation (rTMS) session comprised either 10 min of 1 Hz rTMS or 190 second of intermittent theta burst stimulation (iTBS) protocol. Group A received 10 sessions of 1 Hz rTMS initially then followed with 10 sessions of iTBS protocol, over a period of 4 weeks. Group B underwent the same paradigms but in reverse; and Group C received sham stimulation identical to Group A. Each subject received 1‐h physiotherapy immediately following rTMS. Evaluations were arranged prior to the intervention, after 10 sessions of rTMS (post 1), after 20 sessions (post 2), and 3 months after the intervention (post 3).

Figure 3

The effects of repetitive transcranial magnetic stimulation (rTMS). (A) Change in Fugl‐Meyer Assessment (FMA) along the visits. (B) Change in Wolf Motor Function test‐Functional Ability Scale (WMFT) along the visits. (C) Change of contralesional motor map area for each visit. Significance levels: ^a P < 0.05; ^b P < 0.01; ^c P < 0.001, in comparison with baseline level over sham Group C; ^dSignificance between Post 1 and Post 2 results; ^eSignificance between Group A (1 Hz rTMS‐iTBS) and Group B (iTBS‐1 Hz rTMS). Error bar = SD. iTBS, intermittent theta burst stimulation.

Figure 4

Linear relationships of Fugl‐Meyer Assessment (FMA) and UH motor map area. A better FMA outcome is associated with a smaller volume of excitable motor area (P = 0.035, r = −0.34) with closer relationship in Group A. UH, unaffected hemisphere.