Fronto-motor circuits linked to effort-based decision-making and apathy in healthy subjects.

Apathy is marked by disruptions in effort-based decision-making for rewards and alterations in fronto-basal ganglia (BG) circuits. While changes in primary motor cortex (M1) activity during effort and reward valuation have been reported, prior work on apathy and effort-based decision-making has overlooked the connections between fronto-BG structures and M1. Here, we addressed this gap by investigating structural and effective connectivity within fronto-M1, fronto-BG-M1, and intra-M1 circuits in 45 healthy participants using tractography and paired-pulse transcranial magnetic stimulation. These measures were related to apathy scores and computational parameters of effort and reward valuation modelled from decision-making behavior. Apathy scores were associated with both structural and effective connectivity in orbitofrontal cortex-originating circuits. Additionally, effort and reward valuation were preferentially linked to supplementary motor area-related circuits and intra-M1 GABAergic circuits, respectively. These findings reveal dissociable circuit-level contributions to different dimensions of motivated behavior and identify potential neuromodulation targets for treating apathy.