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

Abstract

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.

Abnormal cortical atrophy and functional connectivity are associated with depression in Parkinson’s disease

“…In addition, the RMFG is critical for higher-order executive functions, such as attention, working memory, planning, executive cognition, and emotion regulation ( Koenigs and Grafman, 2009 ), and its thickness has been directly associated with depression ( Michalski et al, 2017 ). The insula is also related to various emotional and cognitive functions in the human brain, and its dysfunction has been associated with depression in PD patients ( Christopher et al, 2014 ; Huang et al, 2020 ; Jonkman et al, 2021 ). Another study correlated abnormal insular-frontal hypoconnectivity with persistent depressive symptoms or antidepressant effects ( Morgan et al, 2018 ), and Lewy body pathology can extend to the anterior insular cingulate region and intermediate cortex, supporting the idea that insular dysfunction is an important cause of depressed PD ( Braak et al, 2003 ).…”

Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

“…In addition, lower structural and functional connectivity between the insula and ACC [ 170 , 171 ] and lower functional connectivity between the caudate and ACC was reported in MCI [ 126 ]. Reduced connectivity of the ACC to the dorsolateral prefrontal cortex could be ameliorated by an eight-week cognitive training [ 172 ].…”

The pathobiological basis of depression in Parkinson disease: challenges and outlooks

“…Dysfunction in extensive brain areas was involved in DPD, in particular disturbed connectivity between right middle frontal gyrus, anterior cingulate cortices and cerebellum was found in DPD (Wang et al 2018 ), while others reported microstructural alterations in the anterior insula with lower fractional anisotrophy between dorsal and anterior insular cortex subregions that are associated with cognitive and affective impairment in PD (Jonkman et al 2021 ). Furthermore, impaired interhemispheric synchrony with decreased connectivity was seen in the bilateral putamen, middle occipital and postcentral gyrus, paracentral lobule and cerebellum in DPD (Zhu et al 2016b ).…”

“…Resting state bidirectional connectivity alterations were observed between emotional and motor networks in DPD in the pathway from bilateral anterior insula and posterior orbital cortices to right basal ganglia(Liang et al 2016 ), while others confirmed the involvement of basal ganglia, default mode and left frontoparietal networks and SN in DPD (Wei et al 2018 ). There was evidence for clinically relevant microstructural alterations of the anterior insula with loss of interconnecting anterior insular-anterior cingulate cortex in DPD (Jonkman et al 2021 ). Brain network analysis revealed a significant hyperconnectivity among the default mode network (left lateral-parietal region), the medial prefrontal and left prefrontal cortex (part of the central executive network), suggesting how the functional connectivity pattern may signal a neural pathway for depression in PD (Alfano et al 2022 ).…”