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.