Striatal stimulation enhances cognitive control and evidence processing in rodents and humans
Adriano E. Reimer, Evan M. Dastin-van Rijn, Jaejoong Kim, Megan E. Mensinger, Elizabeth M. Sachse, Aaron Wald, Eric Hoskins, Kartikeya Singh, Abigail Alpers, Dawson Cooper, Meng-Chen Lo, Amanda Ribeiro de Oliveira, Gregory Simandl, Nathaniel W. Stephenson, Alik S. Widge
Abstract
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.