Association of Sinonasal Inflammation With Functional Brain Connectivity

Abstract

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed.

Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes.

Design, setting, and participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020.

Main outcomes and measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery.

Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing.

Conclusions and relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.

Figure 1.. Spatial Representation of Selected Networks and Regions of Interest

A, Anatomical nodes used for internetwork connectivity analysis predefined within CONN toolbox corresponding to the networks of interest are overlaid over the 3-dimensional standard Montreal Neurologic Institute (MNI) brain template for default mode (blue spheres), salience (green spheres), dorsal-attention (yellow spheres), and frontoparietal (red spheres) networks. B, Functionally connected networks extracted by independent component analysis for intranetwork connectivity analysis are overlaid over axial slices of the standard MNI brain template. Colors represent correlations threshold at t > 3.5. ACC indicates anterior cingulate cortex; FEF, frontal eye field; INS, insular sulcus; IPS, intraparietal sulcus; LP, lateral parietal; LPFC, lateral prefrontal cortex; MPFC, medial prefrontal cortex; PCC, precuneus cortex; PPC, posterior parietal cortex; RPFC, rostral prefrontal cortex; SMG, supramarginal gyrus.

Figure 2.. Differences Between Participants With Inflammation vs Healthy Controls Within the Frontoparietal Network

Color scale represents t value over an inflated Montreal Neurologic Institute (MNI) brain template. Table includes cluster size in mm³, MNI coordinates of the peak intensity voxel, family-wise error–corrected peak P and t-score values.

Figure 3.. Connectivity Between the Frontoparietal Seed and Nodes of High-Order Cognitive Networks

A, Participants with severe inflammation showed significant increased connectivity (red lines) with default mode nodes (blue spheres) and decreased connectivity (blue lines) with nodes of the salience network (green spheres) at a family-wise error–corrected P < .05. B, Histogram shows a dose-dependent association between connectivity strength showed and degree of inflammation. ACC indicates anterior cingulate cortex; AI, anterior insula; FEF, frontal eye field; IPS, intraparietal sulcus; L, left; LP, lateral parietal; LPFC, lateral prefrontal cortex; MPFC, medial prefrontal cortex; PCC, precuneus cortex; PPC, posterior parietal cortex; R, right; RPFC, rostral prefrontal cortex; SMG, supramarginal gyrus. ^aFamily-wise error–corrected P < .05.