Fronto-motor circuits linked to subclinical apathy

Abstract

Apathy is a syndrome characterized by a disruption in effort-reward decision-making, accompanied by structural and functional changes in a related fronto-basal ganglia (BG) network. While activity changes in the primary motor cortex (M1) during effort and reward valuation have been repeatedly observed, previous work on apathy has largely overlooked the connections between the fronto-BG network and M1, potentially missing key circuits in the apathy network. This study addresses this gap by investigating structural and effective connectivity in fronto-M1, fronto-BG-M1, and intra-M1 circuits in relation to apathy in 45 healthy subjects. Behavior was assessed using a battery of apathy-related questionnaires and computational modeling of effort and reward valuation in a decision-making task. Fronto-motor circuits were examined through a combination of MRI-derived tractography and paired-pulse transcranial magnetic stimulation, which probed structural and effective connectivity, respectively. The data reveal that apathy scores are associated with both structural and effective connectivity in fronto-M1 and fronto-BG-M1 circuits. Circuits originating from the supplementary motor area primarily index effort valuation, while connectivity in intra-M1 GABAergic circuits correlates exclusively with reward valuation. These findings suggest that distinct fronto-motor circuits are linked to different dimensions of motivated behavior and may constitute specific neuromodulation targets for patients suffering from apathy.