Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated neurological disorder, and up to 50% of patients experience depression. We investigated how white matter network disruption is related to depression in MS. METHODS: Using electronic health records, 380 participants with MS were identified. Depressed individuals (MS+Depression group; n = 232) included persons who had an ICD-10 depression diagnosis, had a prescription for antidepressant medication, or screened positive via Patient Health Questionnaire (PHQ)-2 or PHQ-9. Age- and sex-matched nondepressed individuals with MS (MS-Depression group; n = 148) included persons who had no prior depression diagnosis, had no psychiatric medication prescriptions, and were asymptomatic on PHQ-2 or PHQ-9. Research-quality 3T structural magnetic resonance imaging was obtained as part of routine care. We first evaluated whether lesions were preferentially located within the depression network compared with other brain regions. Next, we examined if MS+Depression patients had greater lesion burden and if this was driven by lesions in the depression network. Primary outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. RESULTS: MS lesions preferentially affected fascicles within versus outside the depression network (ß = 0.09, 95% CI = 0.08 to 0.10, p < .001). MS+Depression patients had more lesion burden (ß = 0.06, 95% CI = 0.01 to 0.10, p = .015); this was driven by lesions within the depression network (ß = 0.02, 95% CI = 0.003 to 0.040, p = .020). CONCLUSIONS: We demonstrated that lesion location and burden may contribute to depression comorbidity in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression patients had more disease than MS-Depression patients, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Mapping the relationship of white matter lesions to depression in multiple sclerosis.

Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. Objective: To investigate how white matter network disruption is related to depression in MS. Design: Retrospective case-control study of participants who received research-quality 3-tesla neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from May 1 to September 30, 2022. Setting: Single-center academic medical specialty MS clinic. Participants: Participants with MS were identified via the electronic health record (EHR). All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 783 were included. Inclusion in the depression group (MS+Depression) required either: 1) ICD-10 depression diagnosis (F32-F34.*); 2) prescription of antidepressant medication; or 3) screening positive via Patient Health Questionnaire-2 (PHQ-2) or -9 (PHQ-9). Age- and sex-matched nondepressed comparators (MS-Depression) included persons with no depression diagnosis, no psychiatric medications, and were asymptomatic on PHQ-2/9. Exposure: Depression diagnosis. Main Outcomes and Measures: We first evaluated if lesions were preferentially located within the depression network compared to other brain regions. Next, we examined if MS+Depression patients had greater lesion burden, and if this was driven by lesions specifically in the depression network. Outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. Secondary measures included between-diagnosis lesion burden, stratified by brain network. Linear mixed-effects models were employed. Results: Three hundred-eighty participants met inclusion criteria, (232 MS+Depression: age[SD]=49[12], %females=86; 148 MS-Depression: age[SD]=47[13], %females=79). MS lesions preferentially affected fascicles within versus outside the depression network (ß=0.09, 95% CI=0.08-0.10, P<0.001). MS+Depression had more white matter lesion burden (ß=0.06, 95% CI=0.01-0.10, P=0.015); this was driven by lesions within the depression network (ß=0.02, 95% CI 0.003-0.040, P=0.020). Conclusions and Relevance: We provide new evidence supporting a relationship between white matter lesions and depression in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression had more disease than MS-Depression, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

T1 /T2 ratio from 3T MRI improves multiple sclerosis cortical lesion contrast.

BACKGROUND AND PURPOSE: Cortical demyelinated lesions are prevalent in multiple sclerosis (MS), associated with disability, and have recently been incorporated into MS diagnostic criteria. Presently, advanced and ultrahigh-field MRIs-not routinely available in clinical practice-are the most sensitive methods for detection of cortical lesions. Approaches utilizing MRI sequences obtainable in routine clinical practice remain an unmet need. We plan to assess the sensitivity of the ratio of T1 -weighted and T2 -weighted (T1 /T2 ) signal intensity for focal cortical lesions in comparison to other high-field imaging methods. METHODS: 3-Tesla and 7-Tesla MRI collected from 10 adults with MS were included in the study. T1 /T2 images were calculated by dividing 3T T1 -weighted (T1 w) images by 3T T2 -weighted (T2 w) fluid-attenuated inversion recovery images for each participant. A total of 614 cortical lesions were identified using 7T T2 *w and T1 w images and corresponding voxels were assessed on registered 3T images. Signal intensities were compared across 3T imaging sequences, including T1 /T2 , T1 w, T2 w, and inversion recovery susceptibility-weighted imaging with enhanced T2 weighting (IR-SWIET) images. RESULTS: T1 /T2 images demonstrated a larger contrast between median lesional and nonlesional cortical signal intensity (median ratio = 1.29, range: 1.19-1.38) when compared to T1 w (1.01, 0.97-1.10, p < .002), T2 w (1.17, 1.07-1.26, p < .002), and IR-SWIET (1.21, 1.01-1.29, p < .03). CONCLUSION: T1 /T2 images are sensitive to cortical lesions. Approaches incorporating T1 /T2 could improve the accessibility of cortical lesion detection in research settings and clinical practice.

Susceptibility to unconscious influences is unaffected by a challenging inhibitory task or mental exhaustion.

Unconscious influences have been demonstrated in a variety of behavioural contexts, however, a key question remains - to what extent do such influences vary with our changing mental states? We examine whether a prior inhibitory challenge increases susceptibility to subliminal priming in a stem completion task employing neutral (Experiment 1) and reward salient terms (Experiment 2). Results show stem completions to be significantly influenced by unconscious priming, and the challenging inhibitory task (the Stroop) to be significantly more mentally exhausting than the control task. However, neither the degree of inhibitory challenge, trait self-control, nor task-related mental exhaustion significantly influenced unconscious priming. Bayesian analysis provides strong evidence that prior inhibitory challenge does not affect susceptibility to unconscious priming. The study supports the conclusion that unconscious processing can be independent of consciously experienced mental states and provides reassurance that inhibitory impairment, common to mood disorders, should not increase susceptibility to unconscious influences.