Research Research Digest Research Digest 16/04/21 Welcome to the 67th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study Authors: Manca R, Khan K, Mitolo M, De Marco M, Grieveson L, Varley R, Wilkinson ID, Venneri A (University of Sheffield, UK)Publication: Journal of the Neurological SciencesLink: https://www.sciencedirect.com/science/article/abs/pii/S0022510X21000198 Previous imaging studies measuring resting-state functional connectivity (FC) have shown that ME/CFS patients exhibit abnormal FC in several regions of the brain compared to the brains of healthy individuals, though results are inconsistent between studies, and it is still unclear how these neuro-abnormalities influence ME/CFS symptoms. The aim of this pilot study was to investigate FC changes that are associated with cognitive exertion in ME/CFS patients experiencing post-exertional malaise (PEM). 6 women diagnosed with ME/CFS (according to the International Consensus Criteria) and 10 healthy women were recruited for this study. All participants underwent both clinical and MRI assessment before and after completing cognitive tasks designed to elicit PEM. The authors show that at baseline, patients with ME/CFS had stronger functional connectivity between the main hubs of the salience network (SN) and areas in the left temporal lobe and the medulla, compared to healthy controls. When patients were in PEM, significant changes in FC were observed between the insula, involved in interoception, and frontal, temporal and subcortical nuclei, involved in reward processing and executive control. At baseline, ME/CFS patients reported significantly higher pain and non-significantly higher fatigue than healthy controls. Both pain and fatigue increased following cognitive exertion in patients, but not healthy controls. Changes in pain and fatigue levels were associated with changes observed in FC. No significant differences were observed between the two groups on any of the cognitive tasks. Cognitive performance did not reduce significantly in ME/CFS following exertion. Whist the authors acknowledge that their findings are limited by their small sample size, they believe that a larger investigation may clarify whether the SN plays a role in PEM symptoms experienced by the majority of patients with ME/CFS. Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myaglic Encephalomyelitis/Chronic Fatigue Syndrome Authors: Bond J, Nielsen T, Hodges L (Massey University, New Zealand)Publication: International Journal of Environmental Research and Public HealthLink: https://pubmed.ncbi.nlm.nih.gov/33671082/ Several studies have reported that ME/CFS patients exhibit various cardiovascular abnormalities such as impaired blood pressure and heart rate regulation, autonomic dysfunction, and irregular heart conduction. There is some evidence that chronic oxidative stress may be contributing to the observed vascular abnormalities. These authors hypothesised that ME/CFS patients may exhibit impaired arterial function due to oxidative stress and inflammation. The aim of this study was to examine the impact of physical activity on vascular function in ME/CFS. 11 ME/CFS patients (diagnosed with the International Consensus Criteria) and 11 age- and gender-matched controls were randomly assigned to either a 48-hour (7 patients and controls) or 72-hour protocol (4 patients and controls). Brachial blood pressure, augmentation index (AIx75, a measure of systemic arterial stiffness), and carotid-radial pulse wave velocity (crPWV, a measure of local arterial stiffness) were measured at baseline and either 48 or 72 hours following a maximal incremental cycle exercise test (which aimed to induce PEM in the ME/CFS patients). No differences in any of the 3 measures were observed at baseline between ME/CFS and control groups. At 48hrs, the mean AIx75 remained unchanged from baseline in the ME/CFS group but was significantly reduced in the control group. At 72hrs, both the ME/CFS & control groups had a non-significant increase in mean AIx75 from baseline (1.4% and 3.5% respectively). Neither group exhibited a significant difference in crPWV at the 48hr and 72hr timepoints compared to baseline. The authors conclude that ME/CFS patients may not exhibit normal exercise-induced vasodilation, and this may contribute to the onset of post-exertional malaise (PEM). They acknowledge the limitation of their small sample size, but suggest that their results add to the growing body of evidence that patients with ME/CFS suffer from impaired vascular function, and that further study of the impact of oxidative stress and inflammation on vascular function in ME/CFS is warranted. Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts Authors: Missailidis D, Sanislav O, Allan CY, Smith PK, Annesley SJ, Fisher PR (La Trobe University, Australia)Publication: International Journal of Molecular SciencesLink: https://www.mdpi.com/1422-0067/22/4/2046 The authors of this study have previously reported inefficient ATP synthesis by Complex V in the mitochondria of ME/CFS patient-derived lymphoblasts. Based on these findings, along with the findings of others, the authors hypothesise that there is dysregulation of the pathways providing mitochondria with the oxidisable substrates required for normal ATP synthesis. 34 ME/CFS (diagnosed based on the Canadian Consensus Criteria) and 31 healthy control lymphoblast cell lines were analysed using a combination of whole-cell transcriptomics, proteomics and energy stress signalling activity measures. The study found that, compared to healthy controls, ME/CFS lymphoblasts express unchanged levels of glycolytic enzymes but elevated levels of enzymes involved in the TCA cycle and pentose phosphate pathway, as well as protein, amino acid and fatty acid degradation. Taken together, the authors conclude that there is indeed a dysregulation of energy metabolism, and that in an attempt to compensate for the ATP inefficiency caused by Complex V, ME/CFS lymphoblasts are forced to rely on alternative sources of oxidisable substrates in order to function. A Conversation about Myalgic Encephalomyelitis Authors: Institute of Musculoskeletal Health and Arthritis and ICanCME Research NetworkLink: https://www.youtube.com/watch?v=ilcben3ssQY Canada’s Institute of Musculoskeletal Health and Arthritis hosted a webinar on ME/CFS in March as part of its ongoing webinar series. The speaker was Dr Nina Muirhead - a surgeon, researcher, medical educator, and member of ICanCME’s Working Group on Trainee Development and Medical Education. The webinar was co-hosted by Dr Karim Khan, Scientific Director at IMHA and Sabrina Poirier, Chair of ICanCME’s Working Group on Trainee Development and Medical Education.The webinar covered diagnosis and management of ME/CFS, connection between ME/CFS and long-COVID, and current and upcoming research. The webinar ran for approximately one hour and is free to view on the ICanCME Research Network’s YouTube channel.