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Original Investigation
April 8, 2021

Association of Sinonasal Inflammation With Functional Brain Connectivity

Author Affiliations
  • 1Division of Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology–Head and Neck Surgery, University of Washington, Seattle
  • 2Department of Otolaryngology–Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts
  • 3Department of Otolaryngology–Head and Neck Surgery, Massachusetts Eye and Ear, Boston
  • 4Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of California San Diego Medical Center, La Jolla
  • 5Department of Neurology, Massachusetts General Hospital, Boston
JAMA Otolaryngol Head Neck Surg. 2021;147(6):534-543. doi:10.1001/jamaoto.2021.0204
Key Points

Question  Is sinonasal inflammation associated with functional brain connectivity?

Findings  In this case-control study of 22 patients with chronic rhinosinusitis and 22 healthy controls, participants with sinonasal inflammation showed decreased brain connectivity within the frontoparietal network, a major functional hub. This region also showed increased connectivity to areas that activate during introspective processing and decreased connectivity to areas that are involved in detection and response to stimuli.

Meaning  This study provides initial evidence for alterations in functional brain connectivity as a potential basis for cognitive dysfunction seen in patients with chronic rhinosinusitis.


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.

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    4 Comments for this article
    Relation to tinnitus?
    Thomas Hunt Jr |
    I developed this shortly after my tinnitus kicked in, about 26 years ago. Has there or is there any evidence that the two might be related? In my case, I have 24/7 ringing (loud) in both ears and my right nasal cavity can't breathe/take in air. Can breathe out though. Been getting migraines since I was 12. Currently dealing with what seems like an unending migraine. Going on 3 months now. 43 years old.
    Spot-on description af chronic sinus infextion.
    Jana le Roux, BEng Computer Enineering | University of Pretoria (2004)
    Got this article in from my Goggle news feed. The effect described in the study is EXACLTY what my family and I live with every day. MAJOR impact on our quality of life.
    What are the next steps?
    Sheila Clift, Master's Educational Lead | Interested reader
    Aside from the age of the research participants, the medical and mental health symptoms could have been plucked directly from my health records!
    What are the implications of the findings on future (current?) treatment options? Are physicians utilizing the information obtained to generate sustainable symptom relief? Or possible elimination of the root causes? Where do I sign up to participate in future programs and projects related to these exciting findings?
    Pre-Frontal Cortex
    David Sparkman |
    Borreliosis Burgdoferi has an affinity for the Pre-Frontal Cortex, greatly decreasing activity there, and causes inflammation of all sinuses. But, it's difficult to detect and identify. It's not difficult to see what's really going on here. Chronic Lyme.