UC San Diego

Decisions are not made in isolation. Rather, they rely on internal states, contextual, temporal, and historical information. This subjective experience is a powerful driver of behavior and the associated neural mechanisms. However, most neurobiological investigations of decision-making ignore the impact of subjective experience and instead focus on constraining tasks (cues, trials) to isolate specific variables (choice, accuracy). By ignoring subjective experience and averaging across subjects and decisions, we may be left with an incomplete or inaccurate picture of the brain-behavior relationship. In this dissertation, I took a dual-pronged approach using relatively unconstrained tasks to investigate how subjective experience affects both behavior and the brain, with a focus on rodent premotor cortex (M2), as prior work has suggested that M2 is poised to be sensitive to this information. Chapter 1 explored how individual variation during learning affected decisions about when to explore versus exploit. Results suggested that individual experience with a rule strengthened exploitation of that rule, with projections from orbital frontal cortex to M2 necessary for this experience-based exploitation. Chapter 2 investigated what aspects of subjective experience were used to guide a self-paced, self-generated behavior. Mice used diverse sources of information beyond just prior actions and reward, including the passage of time and information-checking to guide decision-making. M2 integrated these information sources to bias strategy-level decision-making, while its projections into dorsal medial striatum (M2-DMS) were specifically necessary to implement a recent experience-based strategy. Chapter 3 explored how premotor function and sensitivity to subjective experience were affected by psychiatric disease. Prior chronic alcohol impaired behavioral flexibility, and this was causally linked to the induction of hyperactivity of M2-DMS neurons, suggesting human premotor regions as novel therapeutic targets for alcohol use disorder. These studies show that diverse aspects of subjective experience powerfully drive behavior and its neural representation. They implicate premotor circuits in integrating subjective experience to drive flexible behavior, a role which may be disrupted in psychiatric disease. This suggests that attempts to ignore or factor out subjective experience may be misguided; whether we take account of it or not, it likely will affect the brain and behavior.