Neural representation of perceptual decisions, confidence, and actions in human basal ganglia and thalamus

Project Summary In planning and carrying our actions we have remarkable flexibility. We can change from sprinting to carefully stepping when we encounter an icy path, and we can immediately turn around based on ongoing thoughts, such as remembering that we forgot our keys. This constant interplay between our thoughts and our actions breaks down in neurologic and psychiatric disorders. For example, patients with Parkinson’s disease can often quickly walk in a straight line but are unable to turn around at will. However, the glue that binds cognitive and motor processes is unknown, and treatments for neuropsychiatric disorders target movement or cognition separately. In this proposal, we take a different approach – we focus on how brain structures essential for movement bind our thoughts and actions. This proposal seeks to record and stimulate the basal ganglia output nodes and motor thalamus, a group of interconnected deep brain nuclei thought to gate movement initiation. We perform our experiments in awake human subjects undergoing implantation of deep brain stimulation (DBS) electrodes. Subjects perform a decision-making task in which they judge the identity or expression of faces, reporting their choice and confidence about the choice with a reaching movement. In Aim 1, we show that the neural responses in the output nodes of basal ganglia and motor thalamus are not limited to encoding movement initiation. We will test the diversity of neural responses, especially co- encoding of movement kinematics with the confidence, outcome, and reward prediction errors associated with the movement. In Aim 2, we show that subjects adapt their decision strategy based on the history of past actions, confidence, and outcomes. We will test whether these factors are integrated by the neural responses across trials, and whether neural responses in the output nodes of basal ganglia and motor thalamus mediate adjustments of decisions strategy. In Aim 3, we will causally test the contribution of the neural responses in these regions to behavioral adjustments by disrupting the neural activity during precisely-times behavioral periods in this task. Our experiments will determine how the link between ongoing actions and thoughts influences future behavior and how this can be modified. The goal is to use the insights from this research to ultimately develop brain stimulation strategies that treat movement and cognitive deficits in neuropsychiatric disorders as two sides of the same coin.