Neurocomputational mechanisms of learning and decision-making and their disruption in addiction

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Cognitive functions related to learning and decision-making are critical for adaptive behavior. For instance, the sense of smell has a strong influence on motivated behavior, in part, because of the ease with which we form and maintain associations between odors and important events. The basic neurocomputational mechanisms underlying these cognitive functions in humans and how they are disrupted in neuropsychiatric conditions are not well understood. This project studies these questions directly in humans, by investigating cognitive functions related to learning, behavior, and olfaction. To achieve our goals, we design behavioral tasks that isolate specific cognitive functions. We then determine the neural processes and representations that support them by utilizing non-invasive neural recording techniques such as high-resolution functional magnetic resonance imaging. In addition, to probe the causal contribution of brain areas and networks to these functions, we utilize non-invasive neuromodulation techniques such as transcranial magnetic stimulation. In addition, we perform studies in patient populations to examine whether and how these behavioral and neural processes are altered in neuropsychiatric disorders. In the last year, we published two review articles and two collaborative research manuscripts describing the results of experiments on neural representations underlying odor-reward associations and olfactory navigation. The first collaborative study trained rats to learn odor-reward associations either while recording single-unit activity or while imaging calcium flux in the lateral orbitofrontal cortex (OFC). Replicating previous work, single-unit activity contained information about both the sensory properties of odor cues and the rewards they predict, whereas the calcium signal provided only a degraded estimate of the information available in the single-unit spiking, reflecting primarily reward value. The second collaborative study used olfactometry, virtual reality software, and fMRI to investigate whether humans can navigate a virtual olfactory landscape by learning the spatial relationships among discrete odor cues and integrating this knowledge into a spatial map encoded in the entorhinal cortex. Over the course of training, participants improved their performance on the odor navigation task by taking more direct paths toward targets and completing trials faster. fMRI data revealed the emergence of grid-like responses in entorhinal and piriform cortices that were attuned to the same grid orientation, suggesting the presence of a brain network dedicated to olfactory navigation.