• Yasmine Y Fathy, Dagmar H Hepp, Frank J de Jong, GeurtsJeroen J GJJGDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: J.Geurts@amsterdamumc.nl., FonckeElisabeth M JEMJDepartment of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: e.foncke@amsterdamumc.nl., Henk W Berendse, Wilma D J van de Berg, and Menno M Schoonheim.
• Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Neurology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: y.fathy@amsterdamumc.nl.
• Neuroimage Clin. 2020 Jan 1; 28: 102364.

BackgroundThe 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.MethodsWhole-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.ResultsCognitive 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 R2 = 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 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).ConclusionsThese 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.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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