Symptoms of fatigue and depression is reflected in altered default mode network connectivity in multiple sclerosis

Abstract

Background: Fatigue and depression are frequent and often co-occurring symptoms in multiple sclerosis (MS). Resting-state functional magnetic resonance imaging (rs-fMRI) represents a promising tool for disentangling differential associations between depression and fatigue and brain network function and connectivity. In this study we tested for associations between symptoms of fatigue and depression and DMN connectivity in patients with MS. Materials and methods: Seventy-four MS patients were included on average 14 months after diagnosis. They underwent MRI scanning of the brain including rs-fMRI, and symptoms of fatigue and depression were assessed with Fatigue Severity Scale (FSS) and Beck Depression Inventory II (BDI). A principal component analysis (PCA) on FSS and BDI scores was performed, and the component scores were analysed using linear regression models to test for associations with default mode network (DMN) connectivity. Results: We observed higher DMN connectivity with higher scores on the primary principal component reflecting common symptom burden for fatigue and depression (Cohen's f2=0.075, t=2.17, p=0.03). The secondary principal component reflecting a pattern of low fatigue scores with high scores of depression was associated with lower DMN connectivity (Cohen's f2=0.067, t=-2.1, p=0.04). Using continuous mean scores of FSS we also observed higher DMN connectivity with higher symptom burden (t=3.1, p=0.003), but no significant associations between continuous sum scores of BDI and DMN connectivity (t=0.8, p=0.4). Conclusion: Multivariate decomposition of FSS and BDI data supported both overlapping and unique manifestation of fatigue and depression in MS patients. Rs-fMRI analyses showed that symptoms of fatigue and depression was reflected in altered DMN connectivity, and that higher DMN activity was seen in MS patients with fatigue even with low depression scores.

Altered large-scale brain network interactions associated with HIV infection and error processing

“…Reduced RAI among PLWH. The bilaterally reduced RAIs observed among PLWH are similar to those previously observed across substance use and neuropsychiatric disorders (Alexopoulos et al, 2012;Bartova et al, 2015;Bednarski et al, 2011;Bonavita et al, 2017;Chang et al, 2014;Gauffin et al, 2013;Høgestøl et al, 2019;Lee et al, 2017;Liu et al, 2018;Oyegbile et al, 2019;Peterson BS et al, 2009;Schilbach et al, 2016;Sutherland et al, 2012;Verfaillie et al, 2018;Wang et al, 2019;Wang et al, 2013;Whitfield-Gabrieli & Ford, 2012;Wu et al, 2011;Yin et al, 2016;Zhang & Volkow, 2019;Zhou et al, 2016). Nicotine and other drug dependent individuals have displayed reduced RAIs during acute withdrawal (Lerman et al, 2014;.…”

“…In line with the triple network model (Menon, 2019;Menon, 2011), accumulating neuroimaging evidence links neuropsychiatric conditions not only with altered network-level rsFC (Alexopoulos et al, 2012;Bartova et al, 2015;Bednarski et al, 2011;Bonavita et al, 2017;Chang et al, 2014;Gauffin et al, 2013;Høgestøl et al, 2019;Lee et al, 2017;Liu et al, 2018;Oyegbile et al, 2019;Peterson BS et al, 2009;Schilbach et al, 2016;Sutherland et al, 2012;Verfaillie et al, 2018;Wang et al, 2019;Wang et al, 2013;Whitfield-Gabrieli & Ford, 2012;Wu et al, 2011;Yin et al, 2016;Zhang & Volkow, 2019;Zhou et al, 2016), but also with altered task-based network activity (Bartova et al, 2015;Bednarski et al, 2011;E.B. Liddle et al, 2011;.…”

Fatigue in brain tumor patients, towards a neuronal biomarker

“… Bisecco et al (2018) concluded that fatigue was mainly driven by connectivity changes in the DMN, after studying resting-state functional connectivity of the DMN and sensorimotor network in relapsing remitting multiple sclerosis patients with and without fatigue using independent component analysis. A study by Hogestol et al (2019) indicated that symptoms of fatigue were reflected in altered DMN connectivity. Higher DMN connectivity was seen in MS patients with fatigue even with low depression scores in patients with MS. Higher connectivity is generally interpreted to represent stronger connection between regions of a network.…”

“…In brain tumor patients, this damage could be the result of brain displacement due to a growing tumor. More recently, resting state studies in multiple sclerosis patients suggested a possible involvement of the DMN in fatigue, as fatigue was associated with increased DMN connectivity, ( Bisecco et al, 2018 , Hogestol et al, 2019 ).…”

Dissecting the cognitive phenotype of post-stroke fatigue using drift diffusion modeling of sustained attention

“…Still, the findings may pave the way for future clinical or experimental studies examining possible causal mechanisms, and subsequent interventions targeting a specific component of the extended cognitive phenotype of PSF. Further, fatigue is a complex and multifactorial syndrome that often co-occur with depression (Høgestøl et al, 2018), which represents a challenge for all research aiming to target unique and specific characteristics of fatigue.…”