Computational model of striosomal circuit in normal and disordered decision-making

The striosomal and matrix compartments of the striatum and the regions to which they project are critical in decision-making, including irrational choices, a transdiagnostic symptom across psychiatric disorders. We propose a biologically-realistic computational model that suggests a mechanism for interaction between the striosomes-matrix, direct-indirect pathways, and dopamine-lateral habenula regions during decision-making. Our three-layered model validates experimental results obtained from: circuit recordings during decision-making, physiological recordings from brain slices, and decision-making phenotypes measured on animals and humans. It makes experimentally-testable predictions regarding shifts of circuit balances that create transdiagnostic symptoms across psychiatric disorders including post-traumatic stress disorder and substance abuse. It also explains the distinct role of each circuit component in producing decisions in disordered and non-disordered decision-making states, such as the role of the striosomal circuit in mediating decision-making accuracy and time-to-decision. This theory of mechanistic neural circuit interactions advances understanding of psychiatric disorders and the development of bioinformed treatments.