Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis

Pardini, Matteo; Bonzano, Laura; Bergamino, Maurizio; Bommarito, Giulia; Feraco, Paola; Murugavel, Abitha; Bove, Marco; Brichetto, Giampaolo; Uccelli, Antonio; Mancardi, Gianluigi; Roccatagliata, Luca

doi:10.1177/1352458514546791

Cited by 38 publications

(50 citation statements)

References 37 publications

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“…A significant inverse correlation between FA and RD and limited changes in the AD values in patients with NMOSD compared to HCs suggest that the WM damage in NMOSD is related more to demyelination than to axonal degeneration. This is consistent with previous TBSS DTI studies, which showed widespread DTI metric changes and found that the lower FA was driven by higher RD in NMOSD .…”

Section: Discussionsupporting

confidence: 93%

Diffusion tensor imaging of normal‐appearing white matter in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

Kim

Kwak

Hyun

et al. 2017

Euro J of Neurology

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Section: Discussionsupporting

confidence: 93%

Diffusion tensor imaging of normal‐appearing white matter in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

Kim

Kwak

Hyun

et al. 2017

Euro J of Neurology

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“…Several lines of evidence suggest that atrophy as well as functional changes in the ACC are related to fatigue in MS patients ( 6 , 8 , 10 , 108 , 109 ). Multiple structural imaging studies found an association between increased white and gray matter atrophy in the ACC and subjective fatigue in MS patients ( 6 , 8 , 108 ). Furthermore, functional imaging studies found that MS patients with fatigue have a larger and more significant activation of the ACC during the execution of simple motor tasks than patients without fatigue ( 10 , 109 ).…”

Section: Studies On the Involvement Of The Insula The Anterior Cingumentioning

confidence: 99%

The Representation of Inflammatory Signals in the Brain â€“ A Model for Subjective Fatigue in Multiple Sclerosis

2014

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In multiple sclerosis (MS) patients, fatigue is rated as one of the most common and disabling symptoms. However, the pathophysiology underlying this fatigue is not yet clear. Several lines of evidence suggest that immunological factors, such as elevated levels of pro-inflammatory cytokines, may contribute to subjective fatigue in MS patients. Pro-inflammatory cytokines represent primary mediators of immune-to-brain-communication, modulating changes in the neurophysiology of the central nervous system. Recently, we proposed a model arguing that fatigue in MS patients is a subjective feeling, which is related to inflammation. Moreover, it implies that fatigue can be measured behaviorally only by applying specific cognitive tasks related to alertness and vigilance. In the present review, we focus on the subjective feeling of MS-related fatigue. We examine the hypothesis that the subjective feeling of MS-related fatigue may be a variant of inflammation-induced sickness behavior, resulting from cytokine-mediated activity changes within brain areas involved in interoception and homeostasis including the insula, the anterior cingulate, and the hypothalamus. We first present studies demonstrating a relationship between pro-inflammatory cytokines and subjective fatigue in healthy individuals, in people with inflammatory disorders, and particularly in MS patients. Subsequently, we discuss studies analyzing the impact of anti-inflammatory treatment on fatigue. In the next part of this review, we present studies on the transmission and neural representation of inflammatory signals, with a special focus on possible neural concomitants of inflammation-induced fatigue. We also present two of our studies on the relationship between local gray and white matter atrophy and fatigue in MS patients. Finally, we discuss some implications of our findings and future perspectives.

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“…Despite the absence of a systematic pattern of cortical damage in MS (Kluckow, Rehbein, Schwab, Witte, & Bublak, 2016), significant atrophy has been repeatedly observed in interoceptive regions, such as the insula and the ACC (Lansley, Mataix-Cols, Grau, Radua, & Sastre-Garriga, 2013). Moreover, the heterogeneous patterns of white matter lesions in this condition include alterations in pathways of interoceptive areas, such as the ACC white matter bundle within the left cingulate fasciculus (Pardini et al, 2015). In the same vein, MS involves functional connectivity alterations across several regions (Faivre et al, 2012;Rocca et al, 2012Rocca et al, , 2015Roosendaal et al, 2010), crucially including both hypo-connectivity in the ACC (Rocca et al, 2015) and the insula (He et al, 2009), and hyper-connectivity in networks including these areas and the somatosensory cortex (SSC) (Faivre et al, 2012;Rocca et al, 2012;Roosendaal et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…b): Links indicate interregional connectivity. Indeed, the heterogeneous patterns of functional connectivity alterations in MS include abnormalities between interoceptive areas, such as the ACC and the insula(Faivre et al, 2012;Rocca et al, 2015;Roosendaal et al, 2010), alongside disruptions in relevant anatomical pathwaysfor example, the ACC white matter bundle within the left cingulate fasciculus (CruzGomez, Ventura Campos, Belenguer, Avila, & Forn, 2013;Pardini et al, 2015). Colors indicate statistically significant differences (p < .05; green = interoception > mind wandering; red = MS patients > controls; black = no significant differences).…”

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confidence: 99%

Altered neural signatures of interoception in multiple sclerosis

Salamone

Esteves

Sinay

et al. 2018

Human Brain Mapping

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Multiple sclerosis (MS) patients present several alterations related to sensing of bodily signals. However, no specific neurocognitive impairment has yet been proposed as a core deficit underlying such symptoms. We aimed to determine whether MS patients present changes in interoception-that is, the monitoring of autonomic bodily information-a process that might be related to various bodily dysfunctions. We performed two studies in 34 relapsing-remitting, early-stage MS patients and 46 controls matched for gender, age, and education. In Study 1, we evaluated the heartbeat-evoked potential (HEP), a cortical signature of interoception, via a 128-channel EEG system during a heartbeat detection task including an exteroceptive and an interoceptive condition. Then, we obtained whole-brain MRI recordings. In Study 2, participants underwent fMRI recordings during two resting-state conditions: mind wandering and interoception. In Study 1, controls exhibited greater HEP modulation during the interoceptive condition than the exteroceptive one, but no systematic differences between conditions emerged in MS patients. Patients presented atrophy in the left insula, the posterior part of the right insula, and the right anterior cingulate cortex, with abnormal associations between neurophysiological and neuroanatomical patterns. In Study 2, controls showed higher functional connectivity and degree for the interoceptive state compared with mind wandering; however, this pattern was absent in patients, who nonetheless presented greater connectivity and degree than controls during mind wandering. MS patients were characterized by atypical multimodal brain signatures of interoception. This finding opens a new agenda to examine the role of inner-signal monitoring in the body symptomatology of MS.

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Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis

Abstract: Our data point to the cingulum bundle and its projections as the key network involved in subjective fatigue perception in MS. More generally, these results suggest the potential of the connectionist framework to generate coherent models of the neural basis of complex symptomatology in MS.

Cited by 38 publications

References 37 publications

Diffusion tensor imaging of normal‐appearing white matter in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

Diffusion tensor imaging of normal‐appearing white matter in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

The Representation of Inflammatory Signals in the Brain â€“ A Model for Subjective Fatigue in Multiple Sclerosis

Altered neural signatures of interoception in multiple sclerosis

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