Anterior insular network disconnection and cognitive impairment in Parkinson's disease

Background: The insula is a central brain hub involved in cognition and affected in Parkinson's disease (PD). The aim of this study was to assess functional connectivity (FC) and betweenness centrality (BC) of insular subregions and their relationship with cognitive impairment in PD. Methods: Whole-brain 3D-T1, resting-state functional MRI and a battery of cognitive tests (CAMCOG) were included for 53 PD patients and 15 controls. The insular cortex was segmented into ventral (vAI) and dorsal (dAI) anterior and posterior sub-regions. Connectivity between insular sub-regions and resting-state networks was assessed and related to cognition; BC was used to further explore nodes associated with cognition. Results: Cognitive performance was significantly lower in PD patients compared to controls (p < 0.01) and was associated with FC of the dAI with default mode network (DMN) (adjusted R-2 = 0.37, p < 0.001). In controls, cognitive performance was positively related to FC of the dAI with the fronto-parietal network (FPN) only (adjusted R-2 = 0.5, p = 0.003). Regionally, FC of the dAI with the anterior cingulate cortex (ACC) was significantly reduced in PD (F(1,65) = 11, p = 0.002) and correlated with CAMCOG (r = 0.4, p = 0.001). DMN and FPN showed increased BC in PD which correlated with cognition and reduced connectivity of dAI with the ACC (r(s) = 0.33, p = 0.014 and r(s) = 0.44, p = 0.001 respectively). Conclusions: These results highlight the relevance of the insula in cognitive dysfunction in PD. Disconnection of the dAI with ACC was related to altered centrality in the DMN and FPN only in patients. Disturbance in this network triad appears to be particularly relevant for cognitive impairment in PD.