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Background: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. Objective: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. Methods: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. Results: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. Conclusion: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects.

Background: Using diffusion tensor imaging (DTI), it was previously found that demyelinated gray matter (GM) lesions have increased fractional anisotropy (FA) when compared to normal-appearing gray matter (NAGM) in multiple sclerosis (MS). The biological substrate underlying this FA change is so far unclear; both neurodegenerative changes and microglial activation have been proposed as causal contributors. Objective: To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions. Methods: We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry. Results: Overall, there were few activated microglia/macrophages, and no difference between GM lesions and NAGM was observed. However, cell density was increased in GM lesions compared to NAGM (309.67 ± standard deviation (SD) 124.44 vs 249.95 ± SD 56.75, p = 0.002). Conclusion: FA increase was not due to lesional and non-lesional differences in microglia activation and/or proliferation. We found an increase in general cellular density without a notable difference in cellular size, that is, tissue compaction, as a possible alternative explanation.

Background Digital therapeutics such as cognitive–emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive–emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement. Methods Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing. Results Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement. Discussion These findings provide initial evidence that cognitive–emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder. Conclusion Our findings pave the way for the principled design of large clinical and neuroimaging studies.