Introduction
heterogenous, TRD, treatment-resistant depression, anhedonia, reward-related deficits
CORTEX
Ketamine is a rapidly acting antidepressant drug, with promising effects in patients with treatment-resistant depression (TRD). Ketamine is also effective in ameliorating anhedonia, which can otherwise be refractory to conventional antidepressant treatment [The ACC is heterogenous and is comprised of several subregions including the subgenual (sgACC), perigenual (pgACC), and dorsal (dACC) regions – each of which has different anatomical [It remains unclear which subregions are important in ketamine’s antidepressant effects. Rodent studies suggest that the rodent homolog of sgACC (specifically Brodmann Area [BA]25) – infralimbic cortex (IL) – is a critical site of action mediating ketamine’s acute antidepressant-like effects [Furthermore, whether certain subregions are more or less important in ketamine’s anti-anhedonic effects is uncertain. Preclinical work in marmosets – whose ACC is more homologous to human ACC – suggests that ketamine’s modulation of sgACC and a downstream reward-related network (including dACC, insula, and ventral striatum) is critical in ameliorating reward-related deficits induced by sgACC over-activity [In light of this growing body of preclinical and clinical work, circuit-based perspectives on ketamine’s action have emerged, with the ACC as a region of importance [The modulation of different ACC subregions by ketamine has not been compared in a single study. In the context of a double-blind, randomized placebo-controlled trial, we compared the modulation of sgACC, pgACC and dACC resting-state functional connectivity (rsFC) with the rest of the brain, following ketamine 