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

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.刺激-反应关联规则的切换能力，依赖于包含背内侧前额叶皮层（dorsomedial prefrontal cortex, dmPFC）与丘脑底核（subthalamic nucleus, STN）的神经环路。然而，该切换行为的确切神经运作机制仍不明晰。为解决这一问题，本研究在行为切换任务期间，对神经精神疾病患者的丘脑底核及背内侧前额叶皮层的局部场电位（local field potentials）进行了记录。漂移扩散建模（drift-diffusion modeling）分析显示，切换行为与证据累积过程的起始点偏移存在关联。在成功完成切换的试次中，背内侧前额叶皮层与丘脑底核的θ频段活动（theta activity）均显著增强；而时间延迟且强度过高的θ活动则会引发过早的切换错误。这种在成功与失败切换场景中，θ活动增强所呈现出的看似对立的影响，可通过θ活动与证据累积起始点之间的负相关关系得到解释。综上，本研究结果为刺激-反应关联快速重构背后的神经机制提供了全新视角，并揭示了θ活动对切换行为的金发姑娘效应（Goldilocks’ effect），即既不过强也不过弱的最优水平效应。