Primary disruption of the default mode network subsystems in drug-naïve Parkinson's disease with mild cognitive impairments

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is related to the disrupted connectivity in networks involved in cognition, primarily in the default mode network (DMN). The DMN contains a midline core and two distinct subsystems (dorsal medial prefrontal cortex (DMPFC) and medial temporal lobe (MTL) subsystems). The strength of functional connectivity (FCS) in intra- and inter-subsystems of DMN and the regional FCS were compared between any two groups from 28 drug-naïve PD patients with MCI (PD-MCI), 19 drug-naïve PD patients with cognitive unimpaired (PD-CU), and 28 age- and sex-matched healthy controls (HCs) by using the nonparametric permutation method (10,000 permutations) with age, sex, and education as covariates and False Discovery Rate (FDR) correction. For intra-subsystems, the decreased FCS was only detected in the DMPFC subsystem of PD-MCI patients compared with HCs. For inter-subsystems, PD-MCI patients displayed decreased FCS between the posterior cingulate cortex (PCC) and DMPFC subsystem compared with HCs. Furthermore, the temporal parietal junction (TPJ) in the DMPFC subsystem showed decreased regional FCS in the PD-MCI subgroup relative to the HC group. No significant change of FCS was found between PD-MCI and PD-CU patients, and between PD-CU patients and HCs. The sum of FCS values within the DMPFC subsystem and FCS values between the PCC and DMPFC subsystem had a significant power to distinguish PD-MCI patients from PD-CU patients (area under curve (AUC) = 0.703). The DMPFC subsystem was predominantly disrupted in the PD-MCI subgroup and may have the potential to discriminate PD with MCI.