Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study, by Riccardo Manca, Katija Khan, Micaela Mitolo, Matteo De Marco, Lynsey Grieveson, Rosemary Varley, Iain D Wilkinson, Annalena Venneri in Journal of the Neurological Sciences, January 2021 []



  • Cognitive effort can induce PEM and worsening of ME/CFS symptoms.
  • PEM is associated with changes in functional connectivity of the salience network.
  • Increased right insular FC with frontal areas is associated with symptom worsening.

Research abstract:


A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic system, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).


A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated


Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.


Cognitive exertion can induce worsening of ME/CFS-related symptoms.

These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

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