Venlafaxine modulates white matter integrity in dorsal and ventral language pathways after subcortical stroke: a longitudinal TBSS study

BACKGROUND: Subcortical aphasia results from disrupted cortico-subcortical language networks after left-hemispheric infarction. Venlafaxine, an SNRI, may accelerate language recovery, but its effects on white matter plasticity remain unclear. We used diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to assess early venlafaxine effects on dorsal and ventral language pathways in subacute stroke. METHODS: Thirty-two patients with first-ever left subcortical infarction and mild-to-moderate aphasia were randomized to venlafaxine (n=16; 75 mg/day, day 7-week 4) or control (n=16). DTI was acquired at 30±7 and 90±7 days post-stroke. TBSS compared fractional anisotropy (FA) in language-related tracts using permutation testing with TFCE (corrected p<0.05). . RESULTS: At Visit 2, venlafaxine recipients had higher FA in right superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), bilateral inferior fronto-occipital fasciculi (IFOF), and left inferior longitudinal fasciculus (ILF), but lower FA in left SLF and uncinate fasciculus (UF). At Visit 3, FA increases extended to SLF/AF and UF, yielding bilateral dorsal and ventral enhancement; only right ILF FA decreased. FA changes positively correlated with aphasia quotient, spontaneous language fluency, and picture-naming improvements. . CONCLUSION: Early venlafaxine induces biphasic white matter remodeling: initial contralesional and bilateral ventral enhancement, followed by bilateral integration, suggesting optimized language network reorganization.