Multimodal data fusion reveals functional and neurochemical correlates of Parkinson's disease

Neurobiol Dis. 2024 May 11:197:106527. doi: 10.1016/j.nbd.2024.106527. Online ahead of print.

Abstract

Background: Neurotransmitter deficits and spatial associations among neurotransmitter distribution, brain activity, and clinical features in Parkinson's disease (PD) remain unclear. Better understanding of neurotransmitter impairments in PD may provide potential therapeutic targets. Therefore, we aimed to investigate the spatial relationship between PD-related patterns and neurotransmitter deficits.

Methods: We included 59 patients with PD and 41 age- and sex-matched healthy controls (HCs). The voxel-wise mean amplitude of the low-frequency fluctuation (mALFF) was calculated and compared between the two groups. The JuSpace toolbox was used to test whether spatial patterns of mALFF alterations in patients with PD were associated with specific neurotransmitter receptor/transporter densities.

Results: Compared to HCs, patients with PD showed reduced mALFF in the sensorimotor- and visual-related regions. In addition, mALFF alteration patterns were significantly associated with the spatial distribution of the serotonergic, dopaminergic, noradrenergic, glutamatergic, cannabinoid, and acetylcholinergic neurotransmitter systems (p < 0.05, false discovery rate-corrected).

Conclusions: Our results revealed abnormal brain activity patterns and specific neurotransmitter deficits in patients with PD, which may provide new insights into the mechanisms and potential targets for pharmacotherapy.

Keywords: Amplitude of low-frequency fluctuation; Magnetic resonance imaging; Neuropharmacology; Neurotransmitters; Parkinson's disease; Positron emission tomography.