Cerebellar stimulation modulates working memory performance and anterior cerebellum-thalamic-cortical network connectivity in a subgroup of individuals with early course psychosis

Psychosis onset and clinical course are predicted by abnormalities in both cerebellar connectivity and verbal working memory that contribute to functional impairment. Transcranial direct current stimulation (tDCS) of the cerebellum may provide a viable treatment option to address verbal working memory deficits in psychosis. In this double-blind, randomized, crossover-controlled trial, twenty-seven individuals with an early course psychosis (ECP) diagnosis received anodal cerebellar stimulation or sham tDCS before a verbal working memory f MRI task then returned a week later for a counterbalanced session of sham or stimulation. An additional healthy control comparison group ( n = 36) received only sham. The tDCS intervention was well-tolerated (90% retention). In the sham stimulation condition, the ECP showed a verbal working memory deficit ( p = 0.006). During stimulation, verbal working memory improved ( d = 0 .016), though not significantly more than their own sham performance ( p = 0.66). Among the ECP group there was a clear “responder” subgroup ( n = 14) defined by a significant within-group verbal working memory improvement between conditions ( d = 0 .586), and between-group difference ( d = −0.580) compared to non-responders ( n = 11; p < 0.00001), excluding stable ceiling performance ( n = 2). Groups showed distinct sham-day biotypes of intrinsic and extrinsic cerebellar connectivity in an anterior cerebello-thalamo-cortical network. Responders showed lower sham-day verbal working memory performance ( d = −0.45, p = 0.001), had greater intrinsic anterior cerebellar network activity, and a distinct cerebellar tDCS response (stimulation>sham)- greater extrinsic connectivity in an anterior cerebello-thalamo-cortical network. These preliminary results suggest cerebellar tDCS may be a treatment option for a specific subgroup to address verbal working memory deficits and underscores the value of precision medicine.