Task- and resting-state fMRI studies in multiple sclerosis: From regions to systems and time-varying analysis. Current status and future perspective

Rocca, Maria; Schoonheim, Menno M.; Valsasina, Paola; Geurts, Jeroen J. G.; Filippi, Massimo

doi:10.1016/j.nicl.2022.103076

Cited by 38 publications

(37 citation statements)

References 223 publications

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“…29 Therefore, the increased connectivity seen in patients not using natalizumab may represent a failed attempt to compensate for brain lesions due to neuroinflammation and be the result of suboptimal treatment. However, on the other hand, it should also be considered that recent reviews described that several studies have found increased connectivity to be related with cognitive impairment, whereas other studies have found decreased connectivity to be related with cognitive impairment in MS. 14,30 Additionally, other studies found both increased and decreased connectivity in different brain regions to be related to poor cognitive and motor performances. 14,30 In the review by Jandric et al, 30 there was no clear relation between increased connectivity and earliest stages of the disease, as a compensatory phenomenon, and reduced connectivity in the late phases of the disease, as a result of structural damage progression, 30 as previously thought.…”

Section: Discussionmentioning

confidence: 99%

“…Also, both increased and decreased connectivity in the default mode network has been related to cognitive impairment, indicating that hyper-and hypo-connected networks lead to an inefficient cognition. 14 To date, however, no studies have evaluated the effects of natalizumab on brain connectivity of patients with MS, without progressive multifocal leukoencephalopathy. Therefore, the aim of this study is to analyze resting-state functional connectivity in MS patients treated with natalizumab in comparison to patients not treated with natalizumab and control subjects.…”

Section: Introductionmentioning

confidence: 99%

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Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

Corrêa

Duinkerken

Farinhas

et al. 2023

J Cent Nerv Syst Dis

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Background Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. Objectives To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Design Single-center retrospective cross-sectional study. Methods Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-β and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3 Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. Results In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls. Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl’s gyrus and in the right superior frontal gyrus in the ventral attention network. Conclusion Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

Corrêa

Duinkerken

Farinhas

et al. 2023

J Cent Nerv Syst Dis

View full text Add to dashboard Cite

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“…Another point worth mentioning is that although the sample size was not predetermined by a sample size calculation, the study rests on a large to very large sample when compared to existing studies (i.e., larger than 88% of all MS fMRI studies employing cognitive tasks reported by Rocca et al [2022] when only PwMS are considered, larger than 97% when also HP are considered).…”

Section: Discussionmentioning

confidence: 99%

Neural stress processing, glucocorticoid functioning, and body mass in lean to obese persons with multiple sclerosis

Meyer-Arndt

Brasanac

Gamradt

et al. 2022

Preprint

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Background and Objectives: Obesity aggravates disease severity in multiple sclerosis (MS). Altered neural processing of food motivation and cognitive control, and the sensitivity of these processes to stress have been recognized as key obesity mechanisms but never been investigated in MS. Methods: In this cross-sectional observational study, we evaluated the link between body mass and neural, endocrine and immunological stress parameters in persons with MS (PwMS). We conducted an Arterial-Spin-Labeling MRI task comprising a rest and stress stage (mental arithmetic plus evaluative feedback) in 57 PwMS (37 female, 46.4 +/- 10.6 years) covering the full spectrum of the Body Mass Index (BMI (kg/m2); 6 obese, 19 over-, 28 normal-, 4 underweight). We tested whether BMI in MS links to (i) functional connectivity (FC) between stress-reactive brain regions (showing activity differences for stress vs. rest) computed separately for the task's rest and stress stage, (ii) T cell glucocorticoid sensitivity and (iii) salivary cortisol secretion. Results: BMI correlated positively with MS relapse rate (t = 3.23, p = 0.003 = pFamily-Wise-Error (FWE)-corrected = 0.012, and f2 = 0.22) and rest stage FC between right anterior insula and supramarginal gyrus (t = 4.02, p = 2.5 x 10-4 = pFWE = 0.034, f2 = 0.51) and negatively with stress stage FC between right superior parietal lobule and cerebellum exterior (t = -3.67, p = 3.3 x 10-4 = pFWE = 0.045, f2 = 0.30). Further, BMI was negatively associated with the expression of the co-chaperone FKBP4 on CD8+ T cells (t = -2.96, p = 0.003 = pFWE = 0.024, f2 = 0.13) and positively with that of FKBP5 (t = 1.83, p = 0.003 = pFWE = 0.024, f2 = 0.38). Conclusion: Our study shows that higher BMI in MS is linked to increased FC between key food motivation and stimulus salience regions and to reduced FC between regions critically involved in cognitive control and generation of stressful states. We further report on correlations between BMI and co-chaperones modulating immune system stress responsivity. Taken together, these results demonstrate that BMI in MS is tied to stress processing across different biological systems.

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Task- and resting-state fMRI studies in multiple sclerosis: From regions to systems and time-varying analysis. Current status and future perspective

Cited by 38 publications

References 223 publications

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

Similar neural pathways link psychological stress and brain health in health and multiple sclerosis

Neural stress processing, glucocorticoid functioning, and body mass in lean to obese persons with multiple sclerosis

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