Zack Shan

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating illness with an unknown pathogenesis. Although post-infectious (PI-ME/CFS) and gradual onset ME/CFS (GO-ME/CFS) manifest similar symptoms, it has long been suspected that different disease processes underlie them. However, the lack of biological evidence has left this question unanswered. In this study, we recruited PI-ME/CFS and GO-ME/CFS patients based on consensus diagnoses made by two experienced clinicians and compared their diffusion MRI features with those of rigorously matched healthy controls (HCs) with sedentary lifestyles. PI-ME/CFS patients showed significantly higher axial diffusivities (ADs) in several association and projection fibres compared to HCs. Higher AD values in PI-ME/CFS were significantly related to worse physical summary scores. In contrast, GO-ME/CFS patients exhibited significantly decreased ADs in the corpus callosum. Lower AD values in GO- ME/CFS patients were significantly associated with lower mental summary scores in commissural and projection fibres. Distinct patterns of AD alterations in PI-ME/CFS and GO- ME/CFS provide neurophysiological evidence of different disease processes and highlight the heterogeneities of ME/CFS. These results also help explain inconsistent findings in previous ME/CFS studies and guide future intervention design.

Background ‘Brain fingerprinting’ research posits that individual uniqueness can be identified by structural and functional features that may also be linked to mental health outcomes. Global structural features of the brain can be succinctly and directly captured from magnetic resonance imaging (MRI) via the eigenmodes of the cortical surface - known as geometric eigenmodes. This research investigates how the uniqueness of geometric eigenmodes changes across adolescence and their longitudinal relation to mental health and wellbeing.

Methods The current study utilised n=613 MRI, self-report and demographic datasets from N=116 community-recruited adolescents enrolled in the Longitudinal Adolescent Brain Study (LABS), between the ages of 12-17 years. MPRAGE scans at each participant’s visit were used to derive 225 left-hemisphere geometric eigenmodes. Eigenmodes were clustered into 14 eigengroups and developmental trajectories of their uniqueness and longitudinal associations with mental wellbeing and psychological distress were examined.

Results All eigengroups become significantly more unique longitudinally, and higher mode (shorter wavelength) eigengroups were more unique than lower mode groups in adolescence. Less uniqueness in ‘eigengroup 6’ was significantly associated with higher psychological distress and lower mental wellbeing at concurrent and future timepoints.

Conclusion Geometric eigengroup brain fingerprinting offers a novel way to examine neurodevelopment. This study provides evidence that eigengroups have distinct trajectories from adolescence to adulthood, consistent with other imaging studies demonstrating increasing uniqueness in this period. Importantly, they are associated with mental health state and thus may represent neurobiological markers for mental illness onset, building on previous LABS research demonstrating that the functional uniqueness of the ‘cognitive control network’ predicts psychological distress four months later.

Background. The Stroop task was used to investigate differences in cognitive function between Long COVID (LC), Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and healthy control subjects.

Methods. Subjects viewed four color words or neutral (XXXX) stimuli with the same (congruent) or different color ink (incongruent). Cognitive conflict was inferred from response times for pairings of prestimuli and subsequent stimuli. Overall effects were assessed by univariate analysis with time courses determined for binned response times.

Results. LC and ME/CFS had significantly longer response times than controls indicating cognitive dysfunction. Initial response times were ranked LC>ME>HC, and decreased according to power functions. At the end of the task (900s), times were ranked LC=ME>HC. Response times were significantly slower for stimuli following an incongruent prestimulus. Time series for Stroop effect, facilitation, interference, surprise index and practice power law parameters were generally similar in LC, ME/CFS and HC suggesting comparable patterns for recruitment of cognitive resources. The prestimulus data were analyzed and generated positive Stroop and interference effects that were distinct from stimulus effects.

Conclusion. LC and ME/CFS have global slowing of response times that cannot be overcome by practice suggesting slower neurotransmission or white matter conduction between network nodes during problem solving. Analysis of matched prestimulus – stimulus effects adds a new dimension for understanding cognitive conflict.

Brief Summary. Cognitive dysfunction in Long COVID and ME/CFS was demonstrated using the Stroop task which found global slowing of response times and limitations of practice effects.

Background: Adolescence is an important period for developing one’s sense of self. Social connectedness has been linked to a sense of self which in turn has links to resilience in mental disorders. Adolescence is also a period of increased risk of chronic sleep deprivation during a time of ongoing white matter (WM) maturation. The complex relationship between these variables and their relationship with the onset on mental disorders during adolescence remains largely unexplored.

Methods: N = 64 participants aged 12 years (M = 12.6) completed the Pittsburgh Sleep Quality Index (PSQI), Social connectedness scale (SCS) and a diffusion weighted Magnetic Resonance Imaging (MRI) scan to investigate the relationship of these variables to predict psychological distress via the Kessler psychological distress scale (K10) in early adolescents. Multiple regression analysis was used with K10 entered as the dependent variable and SCS, PSQI, and values of white matter integrity as the predictor variables.

Results: Results showed that while all four variables collectively accounted for a significant proportion of the variance in K10 (41.1%), SCS and PSQI were the only predictors that accounted for a significant proportion of variance uniquely.

Conclusions: These findings suggest interventions aimed at increasing levels of social connectedness and sleep quality during adolescence may reduce psychological distress. Future longitudinal reporting of this combination of variables is suggested.