A Modulatory Brain Circuit Involved in the Cognitive Control of Choice and Decision-Making and Its Disorders

Abstract Background The cognitive control of action reflects our ability to extract and encode causal relationships between environmental events and to use that information to guide decision-making and, ultimately, our choice between different courses of action. Dysfunction in this capacity accompanies many major psychiatric conditions and neurodegenerative disorders. It is also powerfully affected by exposure to various drugs in a manner that precipitates the poor decision-making associated with addiction. Aims & Objectives To understand this process at both a psychological and a neural level we have adopted a model of cognitive control in animals in which the influence of predictive learning on action selection is assessed in an instrumental choice situation: the Pavlovian-instrumental transfer paradigm. We have been systematically investigating the core neural systems and cellular circuits that mediate this effect, and, in this presentation, I will describe recent evidence for a key modulatory neural circuit in the brain involved in this process. Method To investigate this circuit we used circuit-specific tools, including DREADDs, ontogenetic and ex-vivo electrophysiology to characterise specific connectivity and its functional role in choice and decision-making. Results Using these methods we established that this modulatory circuit links key structures involved in predictive learning with those that select and implement specific actions including infra limbic cortex, the ventral striatum, ventral palladium, mediodorsal thalamus and lateral orbitofrontal cortex in a cortico-striato-pallidal-thalamo-cortical feedback loop. Increasing and decreasing activity in this loop respectively caused an increase and decrease in the capacity for predictive learning to influence choice. Discussion & Conclusions We believe that this loop constitutes an essential component of the interface between cognition and emotion and that dysfunction, specifically in the modulatory function of this loop, underlies deficits in decision-making in a number of conditions, most notably obsessive compulsive disorder, addiction and psychosis.