Diminished ascending drive in transdiagnostic anhedonia shifts the cortico-subcortical hierarchy away from bottom-up dominance

Abstract

Anhedonia, the diminished capacity to experience or pursue pleasure, is a core feature of mood and psychotic disorders, yet the large-scale brain dynamics underlying it remain uncharacterized. Dominant accounts posit striatal hypofunction with compensatory prefrontal over-recruitment, but they rest on activation magnitudes and symmetric correlations, which cannot resolve the direction of influence. Here, in 210 adults from the Transdiagnostic Connectome Project, we defined symptom-derived low- and high-anhedonia subgroups and estimated each participant's directed effective connectivity using a whole-brain generative model fitted to resting-state fMRI. In high anhedonia, the cortex shifted upstream relative to the subcortex, flattening the cortico-subcortical hierarchy. Correspondingly, the net balance of direct cortico-subcortical flow shifted from bottom-up to balanced. This shift recurred within the frontostriatal reward circuit and replicated across independent halves of each participant's data. Flow asymmetry also increased with subject-level severity. Decomposing flow into ascending and descending arms showed that both weakened in high anhedonia, but ascending subcortex-to-cortex and striatum-to-prefrontal drive fell more than the descending drive. These findings identify a reorganization of cortico-subcortical hierarchy in anhedonia and suggest that the previously reported prefrontal over-recruitment reflects diminished ascending drive rather than stronger cortical output.