Background:The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important. Objective: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients. Methods: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression. Results: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume (p < 0.01), decreased FA of the uncinate fasciculus (p < 0.05), and lower FC between the amygdala and frontal regions (p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found. Conclusion: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

Abstract Post-mortem in situ MRI has been used as an intermediate between brain histo(patho)logy and in vivo imaging. However, it is not known how comparable post-mortem in situ is to ante-mortem imaging. We report the unique situation of a patient with familial early-onset Alzheimer’s disease due to a PSEN1 mutation, who underwent ante-mortem brain MRI and post-mortem in situ imaging only 4 days apart. T1-weighted and diffusion MRI was performed at 3-Tesla at both time points. Visual atrophy rating scales, brain volume, cortical thickness and diffusion measures were derived from both scans and compared. Post-mortem visual atrophy scores decreased 0.5–1 point compared with ante-mortem, indicating an increase in brain volume. This was confirmed by quantitative analysis; showing a 27% decrease of ventricular and 7% increase of whole-brain volume. This increase was more pronounced in the cerebellum and supratentorial white matter than in grey matter. Furthermore, axial and radial diffusivity decreased up to 60% post-mortem whereas average fractional anisotropy of white matter increased approximately 10%. This unique case study shows that the process of dying affects several imaging markers. These changes need to be taken into account when interpreting post-mortem MRI to make inferences on the in vivo situation.

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