Striatal stimulation enhances cognitive control and evidence processing in rodents and humans.

Reimer, Adriano E.; Dastin-van Rijn, Evan M.; Kim, Jaejoong; Mensinger, Megan E.; Sachse, Elizabeth M.; Wald, Aaron; Hoskins, Eric; Singh, Kartikeya; Alpers, Abigail; Cooper, Dawson; Lo, Meng-Chen; de Oliveira, Amanda Ribeiro; Simandl, Gregory; Stephenson, Nathaniel; Widge, Alik S.

Brain disorders, in particular mental disorders, might be effectively treated by direct electrical brain stimulation, but clinical progress requires understanding of therapeutic mechanisms. Animal models have not helped, because there are no direct animal models of mental illness. Here, we propose a potential path past this roadblock, by leveraging a common ingredient of most mental disorders: impaired cognitive control. We previously showed that deep brain stimulation (DBS) improves cognitive control in humans. We now reverse translate that result using a set-shifting task in rats. DBS-like stimulation of the midstriatum improved reaction times without affecting accuracy, mirroring our human findings. Impulsivity, motivation, locomotor, and learning effects were ruled out through companion tasks and model-based analyses. To identify the specific cognitive processes affected, we applied reinforcement learning drift-diffusion modeling. This approach revealed that DBS-like stimulation enhanced evidence accumulation rates and lowered decision thresholds, improving domain-general cognitive control. Reanalysis of prior human data showed that the same mechanism applies in humans. This reverse/forward translational model could have near-term implications for clinical DBS practice and future trial design. Editor's summary: Because of the complexity of cognitive processes involved in mental disorders, it has proven difficult to test therapeutic strategies in animal models. Here, Reimer et al. used a reverse translational approach to understand how deep brain stimulation (DBS) improves cognitive control, a process impaired in many mental disorders. A combination of learning tasks and computational models showed that striatal stimulation improved information processing needed for decision making in rats. Complementary computational models applied to previously collected clinical data indicate that similar mechanisms were at play in humans. These results suggest that cognitive control could be used as a readout for the preclinical testing of DBS interventions. —Daniela Neuhofer

DEEP brain stimulation; CONTROL (Psychology); COGNITIVE ability; BRAIN stimulation; ELECTRIC stimulation

Science Translational Medicine, 2024, Vol 16, Issue 778, p1

1946-6234

Academic Journal

10.1126/scitranslmed.adp1723