A Pilot Randomized Controlled Trial of Intermittent Theta Burst Stimulation as Stand-Alone Treatment for Post-Stroke Aphasia: Effects on Language and Verbal Functional Magnetic Resonance Imaging (fMRI)

BACKGROUND: There is an ongoing need for facilitating language recovery in chronic post-stroke aphasia. The primary aim of this study (NCT01512264) was to examine if noninvasive intermittent theta burst stimulation (iTBS) applied to the injured left-hemispheric cortex promotes language improvements and fMRI changes in post-stroke aphasia. MATERIAL/METHODS: Participants were randomized to 3 weeks of sham (Tx0) or 1–3 weeks of iTBS (Tx123). We assessed participants who completed the first 2 functional MRI (fMRI) sessions (T1, T2) where they performed 2 overt language fMRI tasks, and examined longitudinal response after 3 months (T3). Language performance and fMRI activation changes, and relationships between these changes were assessed. RESULTS: From T1 to T2, both groups showed improvements on the Boston Naming Test (BNT). From T1 to T3, Tx123 improved on the Aphasia Quotient, post-scan word recognition on the verbal paired associates task (VPAT), and perceived communicative ability. Each group exhibited significant activation changes between T1 and T2 for both tasks. Only the Tx123 group exhibited fMRI activation changes between T2 to T3 on the verb-generation task and between T1 and T3 on VPAT. Delayed aphasia symptom improvement for Tx123 was associated with increased left ventral visual stream activation from T1 to T3 (rho=0.74, P=0.0058), and with decreased bilateral supplementary motor area activation related to VPAT encoding from T2 to T3 (rho=−0.80, P=0.0016). CONCLUSIONS: Observed iTBS-induced language improvements and associations between delayed fMRI changes and aphasia improvements support the therapeutic and neurorehabilitative potential of iTBS in post-stroke aphasia recovery.