Structural network topology and microstructural alterations of the anterior insula associate with cognitive and affective impairment in Parkinson's disease.

The aim of the current study was to assess the structural centrality and microstructural integrity of the cortical hubs of the salience network, the anterior insular cortex (AIC) subregions and anterior cingulate cortex (ACC), and their relationship to cognitive and affective impairment in PD. MRI of 53 PD patients and 15 age-matched controls included 3D-T1 for anatomical registration, and diffusion tensor imaging for probabilistic tractography. Network topological measures of eigenvector and betweenness centrality were calculated for ventral (vAI) and dorsal (dAI) AIC. Microstructural tract integrity between vAI, dAI and the ACC was quantified with fractional anisotrophy (FA) and mean diffusivity (MD). Structural integrity and connectivity were related to cognitive and affective scores. The dAI had significantly higher eigenvector centrality in PD than controls (p < 0.01), associated with higher depression scores (left dAI only, rs = 0.28, p < 0.05). Tracts between dAI and ACC showed lower FA and higher MD in PD (p < 0.05), and associated with lower semantic fluency, working memory and executive functioning, and higher anxiety scores (range 0.002 < p < 0.05). This study provides evidence for clinically relevant structural damage to the cortical hubs of the salience network in PD, possibly due to extensive local neuropathology and loss of interconnecting AIC-ACC tracts.

Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies.

AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls. The load and distribution of α-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups. RESULTS: A decreasing gradient of α-synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed α-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal α-synuclein inclusions or significant reduction in density in patient groups. CONCLUSIONS: Our study highlights the vulnerability of the anterior agranular insula to α-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.