Cortico-basal ganglia circuitry: a review of key research and implications for functional connectivity studies of mood and anxiety disorders

There is considerable evidence that dysfunction of the cortico-basal ganglia circuits may be associated with several mood and anxiety disorders. However, it is unclear whether circuit abnormalities contribute directly either to the neurobiology of these conditions or to the manifestation of symptoms. Understanding the role of these pathways in psychiatric illness has been limited by an incomplete characterization of normal function. In recent years, studies using animal models and human functional imaging have greatly expanded the literature describing normal cortico-basal ganglia circuit function. In this paper, recent key studies of circuit function using human and animal models are reviewed and integrated with findings from other studies conducted over the previous decades. The literature suggests several hypotheses of cortico-basal ganglia circuitry function in mood and anxiety disorders that warrant further exploration. Hypotheses are proposed herein based upon the cortico-basal ganglia mechanisms of: (1) feedforward and feedback control, (2) circuit integration and (3) emotional control. These are presented as models of circuit function, which may be particularly relevant to future investigations using neuroimaging and functional connectivity analyses.