The role of SMA-M1 and vmPFC-M1 circuits in behavioral apathy

Apathy shows a large prevalence in various brain disorders but is also common in the general population, which can lead to substantial societal and personal costs. The behavioral component of apathy is characterized by a reduced propensity to initiate effortful, goal-directed actions. Yet the brain circuits underlying behavioral apathy are still unclear. We tested the hypothesis that behavioral apathy is associated with a reduction of effective connectivity in cortico-subcortico-cortical circuits connecting the supplementary motor area (SMA) and the ventromedial prefrontal cortex (vmPFC) to the primary motor cortex (M1). We exploited a dual-site paired-pulse transcranial magnetic stimulation protocol on 11 healthy subjects with different levels of behavioral apathy. These subjects performed an effort-based decision-making task and completed a questionnaire. The results showed that reduced connectivity in cortico-subcortico-cortical circuits connecting the vmPFC and M1 might contribute to a reduced propensity to engage in physical effort. Unexpectedly, findings showed a moderate facilitatory effect of the SMA/vmPFC over M1 with an inter-stimulation interval of 7 ms in the low apathy group, and no effect in the high apathy group. Consistently, we found a negative correlation between behavioral apathy scores and motor evoked potential ratios, suggesting that the alteration of effective connectivity in behavioral apathy is not specific to cortico-subcortico-cortical circuits.