Abstract
BACKGROUND: The pre-supplementary motor area (preSMA) is a critical region within domain-general networks involved in speech production. However, the impact of post-stroke aphasia (PSA) on functional reorganization in this area remains unclear. OBJECTIVE: This study aimed to investigate alterations in functional connectivity (FC) of the preSMA in patients with PSA and their relationships with neurotransmitters and speech production recovery. METHODS: We conducted language assessments using the Western Aphasia Battery (WAB) on 31 patients with left hemisphere strokes at approximately 28 days and 3 months post-stroke. Functional magnetic resonance imaging (fMRI) was performed on all PSA patients and 22 normal controls (NCs) at baseline. We compared the FC of the bilateral preSMA between the two groups. RESULTS: Compared to NCs, PSA patients exhibited decreased FC between the ipsilesional preSMA and the prefrontal-cingulate cortex, insula, and caudate, as well as between the contralesional preSMA and the prefrontal cortex and caudate. These FC changes were significantly associated with various neurotransmitters, particularly metabotropic glutamate, kappa opioid receptor, and cannabinoid receptor. Moreover, FC between the preSMA and the prefrontal-cingulate cortex showed negative correlation trends with changes in WAB-AQ and WAB subtests (naming, auditory comprehension, and repetition) at the three-month assessment. These findings were partially validated in an independent dataset (patients: N = 17; controls: N = 22). CONCLUSION: Our results suggest that functional connections of the preSMA are disrupted in PSA patients, which may be associated with neurotransmitter activity.