Differential value processing in the rostral and causal subthalamic nucleus during flexible and habitual decision-making in primates: Implications for cognitive dysfunction in Parkinson's disease

Abstract

The subthalamic nucleus (STN) is a major target region of deep brain stimulation (DBS) for Parkinson's disease (PD), effectively alleviating motor symptoms. However, STN-DBS can also induce cognitive impairments, suggesting that the STN contributes to cognitive functions beyond simple motor control. Furthermore, anatomical organization supports functional segregation of cognitive processes, as basal ganglia subregions encoding flexible and stable values topographically project to distinct STN subregions. Yet, whether the STN contributes to cognitive functions and, if so, how subregions of the STN differentially process cognitive flexibility and habitual stability remains unknown. Here, we reveal a rostral-caudal functional organization of the STN that differentially supports flexible value updating and long-term value memory, enabling adaptive and habitual decision-making, respectively. Neurons in the rostral STN (rSTN) preferentially encode flexibly updated values, whereas neurons in the caudal STN (cSTN) preferentially encode stable long-term value memories. Notably, inactivation of the STN along the rostral-caudal axis produced dissociable behavioral deficits: rSTN inactivation selectively impaired goal-directed behavior requiring flexible value updating, whereas cSTN inactivation selectively disrupted habitual behavior guided by long-term value memories. Together, these results reveal a rostral-caudal functional segregation of the STN, with the rSTN supporting goal-directed behavior and the cSTN supporting habitual behavior. These findings further provide a framework for understanding how STN dysfunction or STN-DBS in Parkinson's disease may differentially affect cognitive processes beyond motor control.