Anterior insular network disconnection and cognitive impairment in parkinson’s disease

Abstract 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 sub-regions 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 (adjusted R2=0.37, p In controls, cognitive performance was positively related to FC of the dAI with the FPN only (adjusted R2= 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 (rs=-0.33, p=0.014 and rs=-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.