Neural Basis of Effortful Decision Making

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PROJECT SUMMARY Current treatments for addiction remain limited by a gap in the fundamental knowledge of how different regions of prefrontal cortex interact in decision-making. Here, we examine the direct neural correlates in prefrontal cortex of the control and costs of effortful decision making in humans at high spatiotemporal resolution, laying the groundwork for the development of new treatments to improve decision making in addiction. This K23 Career Development Award aims to provide me with the necessary training to become an independent investigator translating intracranial studies of decision making into non-invasive biomarkers and targets for neuromodulation in addiction. Toward this end, I propose the following training objectives: (1) Develop advanced skills in neural decoding from intracranial electrophysiology data; (2) gain expertise in designing neuroeconomic and computational psychiatry experiments; and (3) gain expertise in utilizing brain stimulation in human behavioral experiments. The overall research objective of the proposed project is to resolve the roles played by prefrontal regions during effortful decision making by combining a neural decoding with functional connectivity analysis and with cortical stimulation to perturb network function. The central hypothesis is that anterior cingulate cortex (ACC) allocates cognitive resources for control, based on the cost of control assessed in orbitofrontal cortex (OFC), in turn determined by the efficiency evidence accumulation in dorsolateral prefrontal cortex (DLPFC). The specific aims of this research are to (1) Dissociate the roles of three prefrontal regions in the regulation of cognitive control. (2) Map the prefrontal network allocating cognitive effort, and (3) Causally dissect the cognitive effort network. Innovation: (1) Method: Use of neural decoding, information theory with intracranial electrophysiology and stimulation to characterize prefrontal networks in humans; (2) Design: Integration of experimental paradigms from neuroeconomics with computational models of neural processing and neurophysiology; (3) Concept: Measuring and modulating cognitive effort through simultaneous recording and stimulation of prefrontal regions during effortful decision-making. The proposed research is significant because it resolves a controversy over the functional roles of key regions of prefrontal cortex in effortful decision making that are putative targets for neuromodulation in addiction. The new fundamental knowledge generated by this proposal will lay the foundation for the development of novel biomarkers and targets for improving cognitive control and decision making in addiction with mechanism-based computationally guided neuromodulation.