Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold

James F Cavanagh, Thomas V Wiecki, Michael X Cohen, Christina M Figueroa, Johan Samanta, Scott J Sherman, Michael J Frank
2011 Nature Neuroscience  
nature neurOSCIenCe a r t I C l e S It is widely believed that the prefrontal cortex (PFC) facilitates deliberative control over behavior 1,2 , but many of the mechanistic details of this influence remain to be defined. Here we describe how a PFC-basal ganglia system implements slower, more controlled decisions during difficult choices. The mPFC has been proposed to instantiate control over behavior based on an evaluation of endogenous or exogenous conflict 3,4 . When control is needed, the
more » ... communicates with the STN of the basal ganglia, which acts as a brake on the cortico-striatal system to facilitate a more deliberative response process 5,6 . The STN receives direct projections from the mPFC, forming a 'hyperdirect' pathway that can rapidly modulate cortico-striatal processing 6-9 . This architecture makes the STN ideally suited to receive input from, and ultimately influence, processing of action selection in mPFC. Theories of cortico-basal ganglia functioning predict an interaction between mPFC and the STN in the online regulation of behavior, particularly when habitual responses are overridden to make planned and controlled responses. Although the mPFC is involved in both the facilitation and inhibition of candidate motor actions, the STN is thought to primarily inhibit the prepotent action 10,11 . According to this framework, mPFC-STN communication serves to exert control in conditions in which cortico-striatal signaling would induce impulsive responding. Although evidence supports this idea of a hyperdirect pathway, much of it remains correlational (functional magnetic resonance imaging, white matter tractography and nonhuman primate electrophysiology) 7,10-13 . Disrupting STN function through high-frequency deep brain stimulation (DBS) is an increasingly common treatment for Parkinson's disease, providing an opportunity to manipulate the STN area while monitoring control over decisions and actions. As might be expected, DBS can induce impulsivity in affected individuals' dayto-day lives 14 , and this effect can be captured in the laboratory. A previous study reported that STN-DBS disrupted the tendency to adaptively slow down when faced with difficult decisions 15 . On the basis of computational modeling of basal ganglia function in decision making, it was proposed that the mPFC influences processing in STN to modulate the decision threshold during response conflict 5 , and that DBS interferes with this function, thereby leading to impulsivity. Crucially, this abstract measure of decision threshold can be inferred from computational modeling of response time distributions 16 . This model-based approach helps to parse variance between multiple latent processes that have been suggested to be reflected in accuracy and response time. As yet, however, there are no empirical data that demonstrate such mPFC-STN interactions during conflict. Electroencephalograpy (EEG) is commonly used to assess mPFC activities during conflict and control 3,4 . Specifically, theta-band power over the mPFC increases following punishment, error or conflict, and the degree of theta power increase predicts subsequent response time slowing, suggesting a direct role in adaptive control [17] [18] [19] . Thus, this EEG feature is a promising candidate for measuring the influence of mPFC on conflict-related threshold adjustment while manipulating the effective functioning of the STN area via DBS (see Fig. 1a ). Here we present evidence from two separate studies in which we manipulated or directly measured activity in the STN area. Healthy participants and individuals with Parkinson's disease performed a reinforcement learning and choice conflict task while concurrent EEG was recorded. Affected individuals were tested twice, alternating It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying time until the right decision can be made. Using the drift diffusion model of decision making, we found that trial-to-trial increases in mPFC activity (EEG theta power, 4-8 Hz) were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson's disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity (2.5-5 Hz) during these same high-conflict decisions. Activity in these slow frequency bands may reflect a neural substrate for cortico-basal ganglia communication regulating decision processes.
doi:10.1038/nn.2925 pmid:21946325 pmcid:PMC3394226 fatcat:l7g7k7m5hndubjjla5acflcgrm