Interoception as a neurocognitive mechanism underlying fatigue in multiple sclerosis

SALAMONE, PAULA; GONZALEZ CAMPO, CECILIA; PAGANI, FÁTIMA; SINAY, VLAMIDIR; BRUNO, DIANA; IBÁÑEZ, AGUSTÍN; GARCÍA, ADOLFO M.; SEDEÑO, LUCAS

Conferencia; 2018 ECTRIMS Conference, European Committee for Treatment and Research in Multiple Sclerosis; 2018

ECTRIMS

Background: Fatigue is one of the most common and disabling symptoms undermining the life quality of patients with multiple sclerosis (MS). Although the pathophysiology of MS-related fatigue is poorly understood, abundant evidence points to a key role of altered interoceptive mechanisms ?those implicated in monitoring of autonomic bodily information. Yet, no previous study has empirically evaluated the neurocognitive relationship between interoception and fatigue symptoms in MS. Goal: To conduct a systematic and multidimensional assessment of the relationship between interoception and fatigue in MS, integrating behavioral and neuroimaging evidence. Methods: The study comprised 29 patients with relapsing-remitting MS. Sixteen of them surpassed the cut-off of the Fatigue Severity Scale (FSS > 37) and were classified as fatigued MS (F-MS) patients, while 13 presented normal FSS values (< 37) and were classified as non-Fatigued MS (nF-MS) patients. A control group was formed with 28 sociodemographically matched healthy subjects presenting no fatigue symptoms (FSS < 37). Interoceptive accuracy (i.e., precision in tracking cardiac body-signals) was evaluated through a heartbeat detection task. Participants underwent a neuroimaging protocol (MRI and resting-state fMRI) to evaluate the link between fatigue levels and anatomical and functional connectivity (FC) properties of key interoceptive regions.Results: F-MS patients presented significant decreased interoceptive accuracy compared to controls (Tukey?s HSD test P< 0.05) and nF-MS (Tukey?s HSD test P< 0.05), while no differences were found between the latter two groups (Tukey?s HSD test P> 0.05). Only F-MS patients showed decreased gray matter volume and FC alterations in key interoceptive areas (cingulate cortex and the insula, uncorrected p-value < .001, extent threshold = 50 voxels). Fatigue scores in F-MS patients were negatively correlated with grey matter volume and FC in those areas (uncorrected p-value < .001, extent threshold = 50 voxels).Conclusion: This study offers unprecedented evidence that fatigue symptoms in MS are linked to behavioral, structural, and FC dysfunctions in the interoceptive domain. Our findings indicate that disruptions in neural regions and networks subserving interoception, alongside their outward manifestations, may constitute a neurocognitive signature of fatigue in MS patients. Disclosures : Partially supported by grants from CONICET, CONICYT/FONDECYT Regular (1170010), FONDAP 15150012, INECO Foundation, and by the Inter-American Development Bank.