Modulatory effects of fMRI acquisition time of day, week and year on adolescent functional connectomes across spatial scales: Implications for inference.

Metabolic, hormonal, autonomic and physiological rhythms may have a significant impact on cerebral hemodynamics and intrinsic brain synchronization measured with fMRI (the resting-state connectome). The impact of their characteristic time scales (hourly, circadian, seasonal), and consequently scan timing effects, on brain topology in inherently heterogeneous developing connectomes remains elusive. In a cohort of 4102 early adolescents with resting-state fMRI (median age = 120.0 months; 53.1 % females) from the Adolescent Brain Cognitive Development Study, this study investigated associations between scan time-of-day, time-of-week (school day vs weekend) and time-of-year (school year vs summer vacation) and topological properties of resting-state connectomes at multiple spatial scales. On average, participants were scanned around 2 pm, primarily during school days (60.9 %), and during the school year (74.6 %). Scan time-of-day was negatively correlated with multiple whole-brain, network-specific and regional topological properties (with the exception of a positive correlation with modularity), primarily of visual, dorsal attention, salience, frontoparietal control networks, and the basal ganglia. Being scanned during the weekend (vs a school day) was correlated with topological differences in the hippocampus and temporoparietal networks. Being scanned during the summer vacation (vs the school year) was consistently positively associated with multiple topological properties of bilateral visual, and to a lesser extent somatomotor, dorsal attention and temporoparietal networks. Time parameter interactions suggested that being scanned during the weekend and summer vacation enhanced the positive effects of being scanned in the morning. Time-of-day effects were overall small but spatially extensive, and time-of-week and time-of-year effects varied from small to large (Cohen's f ≤ 0.1, Cohen's d<0.82, p < 0.05). Together, these parameters were also positively correlated with temporal fMRI signal variability but only in the left hemisphere. Finally, confounding effects of scan time parameters on relationships between connectome properties and cognitive task performance were assessed using the ABCD neurocognitive battery. Although most relationships were unaffected by scan time parameters, their combined inclusion eliminated associations between properties of visual and somatomotor networks and performance in the Matrix Reasoning and Pattern Comparison Processing Speed tasks. Thus, scan time of day, week and year may impact measurements of adolescent brain's functional circuits, and should be accounted for in studies on their associations with cognitive performance, in order to reduce the probability of incorrect inference.