Abnormal brain activities in multiple frequency bands in Parkinson's disease with apathy

Apathy is among the most prevalent and incapacitating non-motor symptoms of Parkinson's disease (PD). PD patients with apathy (PD-A) have been reported to have abnormal spontaneous brain activity mainly in 0.01-0.08 Hz. However, the frequency-dependence of brain activity in PD-A remains unclear. Therefore, this study aimed to examine whether abnormalities in PD-A are associated with specific frequency bands.

Overall, 28 patients with PD-A, 19 PD patients without apathy (PD-NA), and 32 gender-, age-matched healthy controls (HCs) were enrolled. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data, demographic information, and neuropsychological assessments, including apathy, depression, anxiety and cognitive function for every participant. The amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) were calculated in the conventional (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) frequency bands based on statistical parametric mapping (SPM12) and RESTplus V1.25. Two-sample t-tests were performed to compare the differences among the three groups.

PD-A reduced ALFF in the right anterior cingulate gyri in the slow-5 band and decreased fALFF in the right middle frontal gyrus in the conventional band, compared to patients with PD-NA. However, PerAF, ReHo, and DC could not distinguish PD-A from PD-NA in the three bands. PD-A had higher ALFF and fALFF in the left middle occipital gyrus and lower fALFF in the bilateral insula in the slow-5 band compared to the HCs. Furthermore, abnormal DC value in hippocampus and parahippocampus was observed separately in the conventional band and in the slow-4 band between PD-A and HCs. Moreover, PD-A and PD-NA showed lower ReHo in cerebellum in the three bands compared to the HCs.

Our study revealed that PD-A and PD-NA might have different neurophysiological mechanisms. Concurrently, the ALFF in the slow-5 band and fALFF in the conventional band were sensitive in differentiating PD-A from PD-NA. The influence of apathy on the disease can be considered in the future research on PD, with the effects of frequency band taken into account when analyzing spontaneous brain activities in PD-A.