Regional homogeneity alterations differentiate between tremor dominant and postural instability gait difficulty subtypes of Parkinson's disease

Parkinson's disease (PD) can be classified into the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype, which present with different clinical courses and prognoses. However, the symptom-specific intrinsic neural mechanisms underlying the subtypes of PD still remain elusive. In the current study, we utilized resting-state fMRI (rs-fMRI) combined with the regional homogeneity (ReHo) method to investigate the modulations of neural activity in 13 patients with predominantly PIGD (p-PIGD) and 15 patients with predominantly TD (p-TD) in the resting state. Compared with healthy controls, the p-PIGD and the p-TD groups both displayed ReHo changes in the default mode network (DMN). By contrast, the p-TD group exhibited more ReHo alterations in the cerebellum involved in the cerebellothalamo-cortical (CTC) loops, whilst the p-PIGD group in extensive cortical and sub-cortical areas, including the frontal, parietal, occipital, temporal, limbic lobes, basal ganglia and thalamus, which are involved in the striatalthalamo-cortical (STC) loops. Direct comparison between the two groups showed significant ReHo alterations in the primary visual cortex. Our findings underscore the differential involvement of the STC and CTC circuits underlying the two subtypes of PD. Moreover, relatively widespread neural activity abnormality, especially in the motor-related regions as well as the visual network, is apparently a characteristic feature of PIGD symptoms. This study could shed light on the underlying pathophysiology and clinical heterogeneity of PD presentation.