- 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, Excitability…
