Modeling impulsivity and risk aversion in the subthalamic nucleus with deep brain stimulation.

Acknowledgements: This work is supported by the STI 2030—Major Projects (grant 2021ZD0200407 to V.V.); the Medical Research Council Senior Clinical Fellowship (MR/W020408/1 to V.V.), the National Natural Science Foundation of China (T2250710686 to V.V. and 81971294 to D.L.), the Young Scientists Fund of the National Natural Science Foundation of China (grant 82201670 to Y.-J.Z.), the Science and Technology Commission of Shanghai Municipality (grant 20410712000 to D.L.) and the Sailing Program of the Science and Technology Commission of Shanghai Municipality (grant 22YF1403200 to Y.-J.Z.). ; Risk evaluation is ubiquitous in decisions. Deep brain stimulation of the subthalamic nucleus is effective for Parkinson's disease and obsessive-compulsive disorder, and can be associated with impulsivity and hypomania. Subthalamic stimulation has seemingly contrasting effects on impulsivity enhancing conflict-induced impulsivity but decreasing risk taking. Here, using a card gambling task paired with intracranial recordings (n = 25) and within-subject case control acute stimulation (n = 15) of the right subthalamic nucleus, we dissociated objective risk and uncertainty and subjective physiological markers of risk. Acute stimulation decreased risk taking (P = 0.010, Cohen's d = 0.72) and increased subthalamic theta activity (P < 0.001, Cohen's d = 0.72). Critically, stimulation negatively shifted the relationship between subthalamic physiology and a measure of evidence accumulation similar to observations with stimulation-induced conflict processing. This highlights the phenotypic and physiological heterogeneity of impulsivity, yet linking mechanisms underlying stimulation-induced conflict and risk. Finally, stimulation-induced risk seeking implicates the ventral subthalamic nucleus and dissociating anatomical and functional connectivity with the mesial prefrontal cortex. Our findings have implications for conceptualizations of impulsivity, and clinical relevance for neuropsychiatric disorders.