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)

Abstract

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.

Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence

“…In terms of the results, the therapeutic potential of ipsilesional iTBS in ameliorating chronic non-fluent aphasia has been supported by Chou et al [ 26 ]. Two studies [ 24 , 25 ] reported naming and semantic fluency improved immediately after iTBS treatment and persisted for at least 3 months, and the longer course of iTBS treatment had a more pronounced effect. Zheng et al creatively employed cTBS to suppress the right STG (the homologous area to Wernicke's area) and found that the improvement in both auditory comprehension and repetition was accompanied by a significant decrease in activity in the right pars triangularis (rPTr) (the homologous area to Broca's area) and a marked increase in spontaneous neural activity in the left prefrontal cortex [ 23 ].…”

Prolonged intermittent theta burst stimulation for post-stroke aphasia: protocol of a randomized, double-blinded, sham-controlled trial

“…And it has shown to be promising in modulating cortical excitability and inducing neuroplastic changes in specific brain regions involved in language processing ( 17 ). Previous studies have consistently shown that iTBS is a valuable treatment modality for enhancing language function and inducing cortical plasticity in human brain networks over the short- and intermediate-term ( 15 , 18 ). However, it is important to note that the degree of improvement in language scores has been relatively modest, and certain clinical trials have reported improvement limited to specific aspects, such as comprehension ( 19 ).…”

“…Most iTBS studies have used 600 pulses ( 18 , 20 ), but study showed that increasing iTBS stimulation dose resulted in dose-dependent effects at the local level (cortical excitability) ( 21 ). The effect of three consecutive 600 pulses iTBS, named prolonged iTBS (piTBS), on cortical excitability was the most significant ( 21 ).…”

“…Another important factor affecting efficacy is the stimulation target. Classical language centers include Broca’s and Wernicke’s areas and their homologs in the right hemisphere continue to dominate the selection of target locations for TMS treatment of aphasia ( 18 , 19 , 24 ). Therapeutic efficacy based on these target targets remains limited.…”

Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study

“…However, research is lacking on whether cTBS of the contralesional pSTG improves language outcomes in patients with PSA, and the underlying mechanisms are still unknown. Resting-state fMRI (rs-fMRI) has proven to be a feasible tool for the exploration of networkwide lesion effects with the potential to provide insight into network reconfiguration following stroke and is increasingly being utilized to investigate PSA ( Ilkhani et al, 2018 ; Allendorfer et al, 2021a , b ). Therefore, the present study was conducted to determine whether inhibitory cTBS over the right pSTG (coupled with SLT) benefits patients with subacute aphasia and to explore the remodeling mechanism of neural plasticity.…”