Resting-state frontostriatal functional connectivity in Parkinson's disease-related apathy

Background: One of the most common neuropsychiatric symptoms in PD is apathy, affecting between 23 and 70% of patients and thought to be related to frontostriatal dopamine deficits. In the present study, we assessed functional resting-state frontostriatal connectivity and structural changes associated with the presence of apathy in a large sample of PD subjects and healthy controls, while controlling for the presence of comorbid depression and cognitive decline. Methods: Thirty-one healthy controls (HC) and 62 age, sex and education-matched PD patients underwent resting-state functional MRI. Apathy symptoms were evaluated with the Apathy Scale (AS). The 11 Beck Depression Inventory-II items that measure dysphoric mood symptoms as well as relevant neuropsychological scores were used as nuisance factors in connectivity analyses. Voxel-wise analyses of functional connectivity between frontal lobes (limbic, executive, rostral motor and caudal motor regions), striata (limbic, executive, sensorimotor regions) and thalami were performed. Subcortical volumetry/shape analysis and fronto-subcortical voxel-based morphometry were performed to assess structural changes. Results: Twenty-five PD patients were classified as apathetic (PD-A) (AS>13). PD-A patients showed functional connectivity reductions compared with HC and with non-apathetic patients (PD-NA), mainly in left-sided circuits, and predominantly involving limbic striatal and frontal territories. Similarly, severity of apathy negatively correlated with connectivity in these circuits. No significant effects were found in structural analyses. Conclusions: Our results indicate that the presence of apathy in PD is associated with functional connectivity reductions in frontostriatal circuits, predominating in the left hemisphere and mainly involving its limbic components.