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

• Published in: Communications biology Vol. 8; no. 1; p. 1320
• Main Authors: Derosiere, Gerard, Vassiliadis, Pierre, Dricot, Laurence, Dessain, Quentin, Delinte, Nicolas, Zénon, Alexandre, Duque, Julie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2025; Nature Publishing Group
• Subjects: 59/57; 631/378/1662; 631/378/2632/1663; 631/477/2811; 9/10; Apathy; Basal ganglia; Biomedical and Life Sciences; Cortex (motor); Decision making; Emotional behavior; Life Sciences; Magnetic fields; Motivation; Neural networks; Neuromodulation; Neuropsychology; Neurosciences; Prefrontal cortex; Reinforcement; Supplementary motor area; Transcranial magnetic stimulation; Valuation; γ-Aminobutyric acid
• ISSN: 2399-3642
• DOI: 10.1038/s42003-025-08780-8

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. Multimodal quantification of structural and effective connectivity in fronto–motor circuits reveals distinct neural substrates of apathy, effort and reward valuation in humans, highlighting potential neuromodulation targets for motivational deficits.