Molecular and neurochemical underpinnings of altered intrinsic neural timescales in Parkinson's disease: a multimodal imaging and transcriptomics study.

Parkinson's disease (PD) is characterized by widespread motor and non-motor impairments; however, the temporal dynamics underlying these functional disruptions remain unclear. The intrinsic neural timescale (INT), a novel neuroimaging metric that reflects the capacity of brain regions to integrate information over time, provides new insights into cortical hierarchy and dysfunction. In this study, we examined voxel-wise and network-level alterations in INT among PD patients using resting-state fMRI and integrated their molecular correlates with transcriptomic data from the Allen Human Brain Atlas and PET-derived neurotransmitter receptor maps. Our analysis revealed localized reductions in INT in the left insula, Rolandic operculum, and middle temporal gyrus in PD, while large-scale network hierarchies remained preserved. Partial least squares regression analysis indicated that changes in INT were significantly associated with spatial gene expression gradients, particularly those involving immune-metabolic stress and synaptic maintenance. Furthermore, cell-type enrichment analysis identified excitatory and inhibitory neurons as key cellular contributors. Notably, INT alterations correlated with cortical GABAA receptor density, suggesting a role for inhibitory neurotransmission in temporal integration deficits. These findings highlight a multiscale pathophysiological framework linking functional brain dynamics, molecular architecture, and neurochemical modulation in PD.