Fatigue in multiple sclerosis is associated with multimodal interoceptive abnormalities
Open accessAbstract
Background: Fatigue ranks among the most common and disabling symptoms in multiple sclerosis (MS). Recent theoretical works have surmised that this trait might be related to alterations across interoceptive mechanisms. However, this hypothesis has not been empirically evaluated. Objectives: To determine whether fatigue in MS patients is associated with specific behavioral, structural, and functional disruptions of the interoceptive domain. Methods: Fatigue levels were established via the Modified Fatigue Impact Scale. Interoception was evaluated through a robust measure indexed by the heartbeat detection task. Structural and functional connectivity properties of key interoceptive hubs were tested by magnetic resonance imaging (MRI) and resting-state functional MRI. Machine learning analyses were employed to perform pairwise classifications. Results: Only patients with fatigue presented with decreased interoceptive accuracy alongside decreased gray matter volume and increased functional connectivity in core interoceptive regions, the insula, and the anterior cingulate cortex. Each of these alterations was positively associated with fatigue. Finally, machine-learning analysis with a combination of the above interoceptive indices (behavioral, structural, and functional) successfully discriminated (area under the curve > 90%) fatigued patients from both non-fatigued and healthy controls. Conclusion: This study offers unprecedented evidence suggesting that disruptions of neurocognitive markers subserving interoception may constitute a signature of fatigue in MS.
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The hybrid approach of using group-level statistical analysis for dimensionality reduction has been employed in previous studies.
“This hybrid approach has been employed in previous studies (Dottori et al., 2017; Fittipaldi et al., 2020; Gonzalez Campo et al., 2020; Kassraian-Fard et al., 2016; McMillan et al., 2012).”
From Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference (2023) · cites this paper as Gonzalez Campo et al., 2020
Interoception was assessed using a validated motor-tracking heartbeat detection task.
“Interoception was assessed using a validated motor-tracking heartbeat detection task with two, 2-min experimental conditions, where attention was directed to either external or internal cues (Garcı ´a-Cordero et al., 2017; Gonzalez Campo et al., 2020; Richter et al., 2021; Salamone et al., 2021) available online here: http://bit.ly/2EpfGrq.”
From Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease (2023) · cites this paper as Gonzalez Campo et al., 2020
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- Authors
- Gonzalez Campo, C., Salamone, P. C., Rodríguez-Arriagada, N., Richter, F., Herrera, E., Bruno, D., Pagani Cassara, F., Sinay, V., García, A. M., Ibáñez, A., & Sedeño, L.
- Affiliations
- Institute of Translational and Cognitive Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina/Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Translational and Cognitive Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina/National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Translational and Cognitive Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina
- University of Cologne (DE)
- Universidad Icesi (CO)
- Favaloro University (AR)
- Institute of Translational and Cognitive Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina/Instituto de Neurociencias de Fundación Favaloro, Buenos Aires, Argentina
- Corresponding author
- Sedeño, Lucas
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2019-11-28
- Volume
- 26
- Issue
- 14
- Pages
- 1845-1853
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- PMC
- PMC7253315
- OpenAlex
- W2990667840
- Cited by
- 70
- References
- 45
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 12 · 2020: 5
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- PubMed Central (acceptedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- consejo nacional de investigaciones científicas y técnicas
- comisión nacional de investigación científica y tecnológica
- INECO Foundation
- inter-american development bank
- PICT
- national institute on aging
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- multiple sclerosis, fatigue, interoception, interoceptive accuracy, insula, anterior cingulate cortex, gray matter volume, functional connectivity, resting-state fMRI, neuroimaging biomarkers, Modified Fatigue Impact Scale
- MeSH terms
- Cerebral Cortex, Fatigue, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Interoception
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