Neurophysiology and Neuropharmacology of Decisions

Abstract

<p>Negotiating the complex decisions that we encounter daily requires coordinated neu- </p><p>ronal activity. The enormous variety of decisions we make, the intrinsic complexity </p><p>of the situations we encounter, and the extraordinary flexibility of our behaviors </p><p>suggest the existence of intricate neural mechanisms for negotiating contexts and </p><p>making choices. Further evidence for this prediction comes from the behavioral al- </p><p>terations observed in illness and after injury. Both clinical and scientific evidence </p><p>suggest that decision signals are carried by electrical neuronal activity and influenced </p><p>by neuromodulatory chemicals. This dissertation addresses the function of two puta- </p><p>tive contributors to decision-making: neuronal activity in posterior cingulate cortex </p><p>and modulatory effects of serotonin. I found that posterior cingulate neurons respond </p><p>phasically to salient events (informative cues; intentional saccades; and reward deliv- </p><p>ery) across multiple contexts. In addition, these neurons signal heuristically guided </p><p>choices across contexts in a gambling task. These observations suggest that posterior </p><p>cingulate neurons contribute to the detection and integration of salient information </p><p>necessary to transform event detection to expressed decisions. I also found that </p><p>lowering levels of the neuromodulator serotonin increased the probability of making </p><p>risky decisions in both monkeys and mice, suggesting that this neurotransmitter con- </p><p>tributes to preference formation across species. These results suggest that posterior </p><p>cingulate cortex and serotonin each contribute to decision formation. In addition, the </p><p>unique serotonergic pro jections to posterior cingulate cortex, as well as the frequent </p><p>implication of altered serotonergic and posterior cingulate function in psychiatric dis- </p><p>orders, suggest that the confluence of cingulate and serotonergic activity may offer </p><p>key insights into normal and pathological mechanisms of decision making.</p>