Network localization of functional and structural correlates of apathy in Parkinson’s disease

Background: Apathy is a prevalent and debilitating neuropsychiatric syndrome in Parkinson's disease (PD). While numerous functional and structural brain studies have investigated the neural correlates of PD with apathy (PD-A), their findings have often been inconsistent. Network neuroscience suggests that such a syndrome may be best understood as disruptions of distributed brain networks. Methods: We conducted a systematic review to identify whole-brain studies reporting functional or structural alterations in patients with PD-A compared to those without apathy (PD-NA), or studies correlating apathy severity. Significant peak coordinates (195 foci from 24 studies) were integrated using functional connectivity network mapping (FCNM), leveraging resting-state functional magnetic resonance imaging from 1,093 healthy Human Connectome Project (HCP) participants. We quantified spatial overlap between the PD-A-associated network and canonical brain networks. Results: The FCNM analysis revealed that the spatially diverse brain regions previously reported in the PD-A literature converged onto a common functional connectivity network. This network predominantly involved the bilateral inferior frontal gyrus, bilateral anterior insula, bilateral dorsolateral prefrontal cortex, bilateral caudate nucleus, and bilateral thalamus. The PD-A associated network showed the highest spatial overlap with the ventral attention network (VAN; 34.05%), subcortical network (28.47%), and frontoparietal network (FPN; 24.89%). Robustness analyses confirmed these findings. Conclusion: Brain functional and structural correlates of apathy in PD converge on distributed networks involving the VAN, FPN, and subcortical circuits. Our network localization approach offers a unifying neurobiological framework for apathy in PD, potentially reconciling previous inconsistencies and informing the development of network-targeted interventions.