Personalized functional imaging-guided rTMS on the superior frontal gyrus for post-stroke aphasia: A randomized sham-controlled trial.

BACKGROUND: Aphasia affects approximately one-third of stroke patients and yet its rehabilitation outcomes are often unsatisfactory. More effective strategies are needed to promote recovery. OBJECTIVE: We aimed to examine the efficacy and safety of the theta-burst stimulation (TBS) on the language area in the superior frontal gyrus (SFG) localized by personalized functional imaging, in facilitating post-stroke aphasia recovery. METHODS: This randomized sham-controlled trial uses a parallel design (intermittent TBS [iTBS] in ipsilesional hemisphere vs. continuous TBS [cTBS] in contralesional hemisphere vs. sham group). Participants had aphasia symptoms resulting from their first stroke in the left hemisphere at least one month prior. Participants received three-week speech-language therapy coupled with either active or sham stimulation applied to the left or right SFG. The primary outcome was the change in Western Aphasia Battery-Revised (WAB-R) aphasia quotient after the three-week treatment. The secondary outcome was WAB-R aphasia quotient improvement after one week of treatment. RESULTS: Ninety-seven patients were screened between January 2021 and January 2022, 45 of whom were randomized and 44 received intervention (15 in each active group, 14 in sham). Both iTBS (estimated difference = 14.75, p < 0.001) and cTBS (estimated difference = 13.43, p < 0.001) groups showed significantly greater improvement than sham stimulation after the 3-week intervention and immediately after one week of treatment (p's < 0.001). The adverse events observed were similar across groups. A seizure was recorded three days after the termination of the treatment in the iTBS group. CONCLUSION: The stimulation showed high efficacy and SFG is a promising stimulation target for post-stroke language recovery.

A precise language network revealed by the independent component-based lesion mapping in post-stroke aphasia.

Brain lesion mapping studies have provided the strongest evidence regarding the neural basis of cognition. However, it remained a problem to identify symptom-specific brain networks accounting for observed clinical and neuroanatomical heterogeneity. Independent component analysis (ICA) is a statistical method that decomposes mixed signals into multiple independent components. We aimed to solve this issue by proposing an independent component-based lesion mapping (ICLM) method to identify the language network in patients with moderate to severe post-stroke aphasia. Lesions were first extracted from 49 patients with post-stroke aphasia as masks applied to fMRI data in a cohort of healthy participants to calculate the functional connectivity (FC) within the masks and non-mask brain voxels. ICA was further performed on a reformatted FC matrix to extract multiple independent networks. Specifically, we found that one of the lesion-related independent components (ICs) highly resembled classical language networks. Moreover, the damaged level within the language-related lesioned network is strongly associated with language deficits, including aphasia quotient, naming, and auditory comprehension scores. In comparison, none of the other two traditional lesion mapping methods found any regions responsible for language dysfunction. The language-related lesioned network extracted with the ICLM method showed high specificity in detecting aphasia symptoms compared with the performance of resting ICs and classical language networks. In total, we detected a precise language network in patients with aphasia and proved its efficiency in the relationship with language symptoms. In general, our ICLM could successfully identify multiple lesion-related networks from complicated brain diseases, and be used as an effective tool to study brain-behavior relationships and provide potential biomarkers of particular clinical behavioral deficits.