Autoren:	Ellwardt, Erik Muthuraman, Muthuraman Gonzalez-Escamilla, Gabriel Chirumamilla, Venkata Chaitanya Luessi, Felix Bittner, Stefan Zipp, Frauke Groppa, Sergiu Fleischer, Vinzenz
Titel:	Network alterations underlying anxiety symptoms in early multiple sclerosis
Online-Publikationsdatum:	10-Feb-2023
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Background Anxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially affects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients suffering 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 effective 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 identified functional involvement of bilateral prefrontal cortex as well as amygdala and hippocampus. Structural equation modeling confirmed that the volumes of these brain regions were significant determinants that influence anxiety symptoms in MS. We additionally identified reduced information flow 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 specific network alteration involving structures that resemble known neurobiological anxiety circuits. These findings elucidate the emergence of anxiety as part of the disease pathology and might ultimately enable targeted treatment approaches modulating brain networks in MS.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8793
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Journal of neuroinflammation 19
Seitenzahl oder Artikelnummer:	119
Verlag:	BioMed Central
Verlagsort:	London
Erscheinungsdatum:	2022
ISSN:	1742-2094
DOI der Originalveröffentlichung:	10.1186/s12974-022-02476-0
Enthalten in den Sammlungen:	DFG-491381577-G