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Abstract Objective Cognitive and affective symptoms in multiple sclerosis (MS) can be independently impaired and have different pathways of progression. Cognitive alterations have been described since the earliest MS stages; by contrast, the social cognition (SC) domain has never been investigated in the first year from MS diagnosis. We aimed to evaluate SC and unravel its neural bases in newly diagnosed MS patients. Methods Seventy MS patients underwent at diagnosis a 3 T‐MRI and a neuropsychological/SC assessment (median time between diagnosis and MRI/cognitive evaluation = 0 months). We tested two matched reference samples: 31 relapsing–remitting MS patients with longer course (mean ± SD disease duration = 7.0 ± 4.5 years) and 38 healthy controls (HCs). Cortical thicknesses (CTh) and volumes of brain regions were calculated. Results Newly diagnosed MS patients performed significantly lower than HCs in facial emotion recognition (global: p

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Background. Fatigue is one of the most distressing symptoms among persons with multiple sclerosis (PwMS). The experience of fatigue is inherently interoceptive, yet no study to date has explicitly investigated the insular cortex (IC) as a primary goal in the experience of fatigue in PwMS. In addition, it is unknown how brain regions such as IC play a role in state or trait fatigue. Objective. Assess the involvement of the IC in trait fatigue and state fatigue in PwMS with and without clinical fatigue. Methods. Trait and state fatigue, cognitive status, and structural MRI were assessed in 27 PwMS. PwMS were stratified into nonclinical fatigue (nF-MS, FSS≤4.0) (n=10) and clinical fatigue (F-MS, FSS≥5.0) (n=10). Voxel-based morphometry analysis (VBM) for the whole sample (n=20) and for the two groups was performed. Anatomical covariance analysis (ACA) analysis was conducted by selecting different volumes included in the corticostriatal network (CoStN) and analyzing interhemispheric correlations between those volumes to explore the state of the CoStN in both groups. Results. In the VBM analysis, when considering the whole sample of PwMS, higher levels of trait fatigue were negatively associated with grey matter (GM) volume in the left dorsal anterior insula (dAI) (rho=−0.647; p=0.002; R2=0.369). When comparing nF-MS versus F-MS, significant differences were found in the left dAI, where the F-MS group showed less GM volume in the left dAI. In the ACA analysis, the F-MS group showed fewer significant interhemispheric correlations in comparison with the Low-FSS group. Conclusions. The present results provide support to the interoceptive component of self-reported fatigue and suggest that changes in the relationship between the different anatomical regions involved in the CoStN are present even in nonclinical trait fatigue. Those changes might be responsible for the experience of trait fatigue in PwMS. Future studies with larger samples and multimodal MRI acquisitions should be considered to fully understand the changes in the CoStN and the specific role of the IC in trait fatigue.