Network alterations underlying anxiety symptoms in early multiple sclerosis

  • Background: Anxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially afects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients sufering from MS. Methods: Using 3-T MRI, anxiety-related atrophy maps were generated by correlating longitudinal cortical thinning with the severity of anxiety symptoms in MS patients. To determine brain regions functionally connected to these maps, we applied a technique termed “atrophy network mapping”. Thereby, the anxiety-related atrophy maps were projected onto a large normative connectome (n=1000) performing seed‐based functional connectivity. Finally, an instructed threat paradigm was conducted with regard to neural excitability and efective connectivity, using transcranial magnetic stimulation combined with high-density electroencephalography. Results: Thinning of the left dorsal prefrontal cortex was theBackground: Anxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially afects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients sufering from MS. Methods: Using 3-T MRI, anxiety-related atrophy maps were generated by correlating longitudinal cortical thinning with the severity of anxiety symptoms in MS patients. To determine brain regions functionally connected to these maps, we applied a technique termed “atrophy network mapping”. Thereby, the anxiety-related atrophy maps were projected onto a large normative connectome (n=1000) performing seed‐based functional connectivity. Finally, an instructed threat paradigm was conducted with regard to neural excitability and efective connectivity, using transcranial magnetic stimulation combined with high-density electroencephalography. Results: Thinning of the left dorsal prefrontal cortex was the only region that was associated with higher anxiety levels. Atrophy network mapping identifed functional involvement of bilateral prefrontal cortex as well as amygdala and hippocampus. Structural equation modeling confrmed that the volumes of these brain regions were signifcant determinants that infuence anxiety symptoms in MS. We additionally identifed reduced information fow between the prefrontal cortex and the amygdala at rest, and pathologically increased excitability in the prefrontal cortex in MS patients as compared to controls. Conclusion: Anxiety-related prefrontal cortical atrophy in MS leads to a specifc network alteration involving structures that resemble known neurobiological anxiety circuits. These fndings elucidate the emergence of anxiety as part of the disease pathology and might ultimately enable targeted treatment approaches modulating brain networks in MS. Keywords: Multiple sclerosis, Anxiety, Atrophy, Functional connectivity, Excitabilityshow moreshow less

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Metadaten
Author:Erik Ellwardt, Muthuraman MuthuramanORCiDGND, Gabriel Gonzalez-Escamilla, Venkata Chaitanya Chirumamilla, Felix Luessi, Stefan Bittner, Frauke Zipp, Sergiu Groppa, Vinzenz Fleischer
URN:urn:nbn:de:bvb:384-opus4-1109549
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/110954
ISSN:1742-2094OPAC
Parent Title (English):Journal of Neuroinflammation
Publisher:Springer Science and Business Media LLC
Place of publication:Berlin
Type:Article
Language:English
Year of first Publication:2022
Publishing Institution:Universität Augsburg
Release Date:2024/01/22
Tag:Cellular and Molecular Neuroscience; Neurology; Immunology; General Neuroscience
Volume:19
Issue:1
First Page:119
DOI:https://doi.org/10.1186/s12974-022-02476-0
Institutes:Fakultät für Angewandte Informatik
Fakultät für Angewandte Informatik / Institut für Informatik
Fakultät für Angewandte Informatik / Institut für Informatik / Professur für Informatik in der Medizintechnik
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)