<b>Optimal level of human intracranial theta activity for</b><b>behavioral</b><b>switching in the subthalamo-medio-prefrontal circuit</b>

The ability to switch between rules associating stimuli and responses depend on a circuit including the dorsomedial prefrontal cortex (dmPFC) and the subthalamic nucleus (STN). However, the precise neural implementations of switching remain unclear. To address this issue, we recorded local field potentials from the STN and from the dmPFC of neuropsychiatric patients during behavioral switching. Drift-diffusion modeling revealed that switching was associated with a shift in the starting point of evidence accumulation. Theta activity increased in dmPFC and STN during successful switch trials, while temporally delayed and excessive levels of theta led to premature switch errors. This seemingly opposing impact of increased theta in successful and unsuccessful switching was explained by a negative correlation between theta activity and the starting point. Together, these results shed a new light on the neural mechanisms underlying the rapid reconfiguration of stimulus-response associations, revealing a Goldilocks’ effect of theta activity on switching behavior.