Using intracranial recording, stimulation, and computational modeling to map role of the subthalamic nucleus in human decision making

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be effective in ameliorating many of the motor symptoms in patients with Parkinson Disease (PD). In contrast to its positive motor effects, many studies have uncovered cognitive side effects of STN DBS. This is not surprising as the STN is known to be involved in cognitive as well as motor neural circuits. But despite this, DBS of the cognitive portions of the STN has only resulted in modest effects on treatment of cognitive disorders such as obsessive- compulsive disorder (OCD). These contrasting observations relate to two deficiencies in knowledge: 1) how neural activity in the STN relates to both normal and abnormal cognitive function, and 2) how DBS of the STN alters the relationship between cognitive function and neural activity to cause dysfunction. To examine these relationships, in this proposal, electrophysiological methods will be combined with decision-making models from mathematical psychology to study behavior and decision-making in a variety of two-choice decision (TCD) tasks. The cognitive processes active in TCD tasks have been well modeled and studied using Ratcliff’s diffusion decision model (DDM). The DDM allows the use a model-based approach to relate neural activity to cognitive processes to allow powerful inferences. The DDM requires data collected from large number of trials to generate accurate estimates of decision process fits to distributions of reaction times for correct and incorrect decisions. However, invasive recordings in humans are only obtained from intraoperative or perioperative situations which limit the amount of data and number of experimental manipulations that could be performed in any one subject. Recently, the FDA approved the Percept implantable pulse generator (IPG) that is capable of recording neural activity from implanted DBS electrodes on or off stimulation. In this proposal, patients with PD who have had this IPG implanted and connected to a STN DBS electrode will be recruited and asked to participate in behavioral experiments while their neural activity is monitored to achieve two aims. The first aim is to use the DDM to understand how neural signals from the STN relate to decision processes in three scenarios: when choices involve conflict, when choosing does not involve conflict, and when choosing requires inhibition of action. The proposal explores how these relationships change in response to instructions emphasizing response accuracy over speed. The first experiments will identify the cognitive processes that are related to STN activity. In the second aim, the proposal explores how these relationships are changed when DBS of the STN is turned on. In those experiments, the DDM is used to understand how the relationship between decision processes and neural activity is altered differentially between TCD tasks that involve conflict than those that don’t and whether these relationships are altered only in situations that demand tradeoff of accuracy over speed. This will help inform clinician how to best apply DBS to improve cognitive function in mental health disease and avoid its cognitive side effects when DBS is used in treating movement disorders.