Estimating duration depends on the sequential integration (accumulation) of temporal information in working memory. Using fMRI, we directly compared the accumulation of information in temporal versus spatial domains. Participants estimated either the duration or distance of the dynamic trajectory of a moving dot or, in a control condition, a static line stimulus. Comparing the duration versus distance of static lines activated an extensive cortico-striatal network. By contrast, comparing the duration versus distance of dynamic trajectories, both of which required sequential integration of information, activated SMA alone. Indeed, activity in SMA, as well as right inferior occipital cortex, increased parametrically as a function of stimulus duration and also correlated with individual differences in the propensity to overestimate stimulus duration. By contrast, activity in primary visual cortex increased parametrically as a function of stimulus distance. Crucially, a direct comparison of the parametric responses to duration versus distance revealed that activity in SMA increased incrementally as a function of stimulus duration but not as a function of stimulus distance. Collectively, our results indicate that SMA responds to the active accumulation of information selectively in the temporal domain.

Purpose Using optimized fast volumic echo planar spectroscopic imaging (3D-EPSI), we aimed to detect local metabolic abnormalities over the complete human brain in multiple sclerosis patients. Materials and methods Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins) and creatine+phosphocreatine (tCr). After spatial normalisation, maps from 19 patients suffering from relapsing-remitting multiple sclerosis were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and grey matter (GM) atrophy maps were also generated. Results Two-group ANOVA (SPM8, p<0.005, FDR corrected p<0.05 at the cluster level with age and sex as confounding covariates) comparing Patients and controls matched for age and sex showed clusters of abnormal metabolite levels with i) decreased NAA (around −15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction, ii) increased m-Ins (around +20%) inside WM T2 lesions and in the normal appearing WM of temporal-occipital lobes suggesting glial activation. Conclusion We demonstrated the ability to map non-invasively over the complete brain - from vertex to cerebellum – with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact.

Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.

Background: Cortical lesions are common in multiple sclerosis (MS). T 2 *weighted (T 2 *w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B 0 ) fluctuations. Purpose: The aim of this study was to determine whether motion and B 0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T 2 *w magnetic resonance imaging. Materials and Methods: In this prospective study, a gradient-recalled echo sequence incorporating a navigator allowing for motion and B 0 field correction was applied to collect T 2 *w images at 7 T from adults with MS between August 2019 and March 2020. T 2 *-weighted images were acquired in 1 to 3 partially overlapping scans per individual and were reconstructed using global average B 0 correction ("uncorrected") or motion correction and spatially linear B 0 correction ("corrected"). Image quality rating and manual segmentation of cortical lesions were performed on uncorrected and corrected images. Lesions seen on a single scan were retrospectively evaluated on the complementary scan. The association of cortical lesions with clinical disability was assessed. Mixed models were used to determine the effect of correction on lesion detection as well as on the relationship between disability and lesion count. Results: A total of 22 T 2 *w scans were performed on 11 adults with MS (mean [SD] age, 49 [11] years; 8 women). Quality improved for 20 of 22 scans (91%) after correction. A total of 69 cortical lesions were identified on uncorrected images (median per scan, 2; range, 0-11) versus 148 on corrected images (median per scan, 4.5; range, 0-25; rate ratio [RR], 2.1; P < 0.0001). For low-quality uncorrected scans with moderate to severe motion artifact (18/22, 82%), there was an improvement in cortical lesion detection with correction (RR, 2.5; P < 0.0001), whereas there was no significant change in cortical lesion detection for high-quality scans (RR, 1.3; P = 0.43). Conclusions: Navigator-guided motion and B 0 correction substantially improves the overall image quality of T 2 *w magnetic resonance imaging at 7 T and increases its sensitivity for cortical lesions.

Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechanisms leading to brain damage. This study aimed to characterize cortical lesions in marmosets with EAE using ultrahigh-field (7 T) MRI and histological analysis. Tissue preparation was optimized to enable the acquisition of high-spatial resolution (50-μm isotropic) T2*-weighted images. A total of 14 animals were scanned in this study, and 70% of the diseased animals presented at least one cortical lesion on postmortem imaging. Cortical lesions identified on MRI were verified with myelin proteolipid protein immunostaining. An optimized T2*-weighted sequence was developed for in vivo imaging and shown to capture 65% of cortical lesions detected postmortem. Immunostaining confirmed extensive demyelination with preserved neuronal somata in several cortical areas of EAE animals. Overall, this study demonstrates the relevance and feasibility of the marmoset EAE model to study cortical lesions, among the most important yet least understood features of MS.

Background: The “central vein sign” (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. Objective: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. Methods: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. Results: CVS+ lesions were larger compared to CVS− lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). Conclusion: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

For the first time, using high resolution 2D-PRESS semi-LASER (1)H-MRSI acquired at 7 T, we demonstrated that the neurochemical profiles were different between thalamic nuclei, and that these profiles were dependent on the brain hemisphere.

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