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.