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 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, Excitabilit

Translation of functional domain abnormalities from human to mouse motor system

Multiple sclerosis (MS) is characterized by frequent impairment of motor skills, with the most prominent manifestations being spasticity, gait impairment, fatigue, or disabling tremor, all highly important determinants of physical disability. The optimization of the reverse translation from humans to mice of relevant readouts of abnormal motor function could definitively improve actual models of neuroinflammation to better match human functional outcomes in MS patients. The aim of this chapter is to provide a descriptive methodological framework to approach human motor function abnormalities that could ground a translational pathway from patients to mice

Dynamics of the human brain network revealed by time-frequency effective connectivity in fNIRS

International audienc

Correction: Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy.

[This corrects the article DOI: 10.1371/journal.pone.0168652.]

Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy.

Benign Essential Blepharospasm (BEB) and hemifacial spasm (HFS) are the most common hyperkinetic movement disorders of facial muscles. Although similar in clinical presentation different pathophysiological mechanisms are assumed. Botulinum Neurotoxin (BoNT) is a standard evidence-based treatment for both conditions. In this study we aimed to assess grey matter microstructural differences between these two groups of patients and compared them with healthy controls. In patients we furthermore tracked the longitudinal morphometric changes associated with BoNT therapy. We hypothesized microstructural differences between the groups at the time point of maximum symptoms representation and distinct longitudinal grey matter dynamics with symptom improvement.Cross-sectional and longitudinal analyses of 3T 3D-T1 MRI images from BEB, HFS patients prior to and one month after BoNT therapy and from a group of age and sex matched healthy controls. Cortical thickness as extracted from Freesurfer was assessed as parameter of microstructural integrity.BoNT therapy markedly improved motor symptoms in patients with BEB and HFS. Significant differences of grey matter integrity have been found between the two patients groups. The BEB group showed lower cortical thickness at baseline in the frontal-rostral, supramarginal and temporal regions compared to patients with HFS. In this group BoNT treatment was associated with a cortical thinning in the primary motor cortex and the pre-supplementary motor area (pre-SMA). Contrary patients with HFS showed no longitudinal CT changes. A decreased cortical thickness was attested bilaterally in the temporal poles and in the right superior frontal region in BEB patients in comparison to HC. Patients in the HFS group presented a decreased CT in the left lingual gyrus and temporal pole.Although patients with BEB and HFS present clinically with involuntary movements of facial muscles, they exhibited differences in cortical thickness. While BoNT therapy was equally effective in both groups, widespread changes of cortical morphology occurred only in BEB patients. We demonstrated specific disease- and therapy-dependent structural changes induced by BoNT in the studied hyperkinetic conditions

Demographic description of groups.

<p>Demographic description of groups.</p