Time of day is associated with paradoxical reductions in global signal fluctuation and functional connectivity

• Published in: PLoS biology 2020-02, Vol.18 (2), p.e3000602-e3000602
• Main Authors: Orban, Csaba, Kong, Ru, Li, Jingwei, Chee, Michael W L, Yeo, B T Thomas
• Format: Article
• Language: English
• Subjects: Analysis; Arousal; Arousal - physiology; Biology and Life Sciences; Brain; Brain - diagnostic imaging; Brain - physiology; Brain Mapping; Brain research; Circadian Rhythm - physiology; Circadian rhythms; Cognition & reasoning; Computer and Information Sciences; Computer engineering; Diurnal variations; Engineering and Technology; Functional magnetic resonance imaging; Gene expression; Humans; Intelligence; Magnetic Resonance Imaging; Medicine; Medicine and Health Sciences; Memory; Nervous system; Neural networks; Neurosciences; Physical Sciences; Physiological aspects; Physiology; Research and Analysis Methods; Rest - physiology; Social Sciences; Software; Standard deviation; Time; Time of use
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000602

The brain exhibits substantial diurnal variation in physiology and function, but neuroscience studies rarely report or consider the effects of time of day. Here, we examined variation in resting-state functional MRI (fMRI) in around 900 individuals scanned between 8 AM and 10 PM on two different days. Multiple studies across animals and humans have demonstrated that the brain's global signal (GS) amplitude (henceforth referred to as "fluctuation") increases with decreased arousal. Thus, in accord with known circadian variation in arousal, we hypothesised that GS fluctuation would be lowest in the morning, increase in the midafternoon, and dip in the early evening. Instead, we observed a cumulative decrease in GS fluctuation as the day progressed. Although respiratory variation also decreased with time of day, control analyses suggested that this did not account for the reduction in GS fluctuation. Finally, time of day was associated with marked decreases in resting-state functional connectivity across the whole brain. The magnitude of decrease was significantly stronger than associations between functional connectivity and behaviour (e.g., fluid intelligence). These findings reveal time of day effects on global brain activity that are not easily explained by expected arousal state or physiological artefacts. We conclude by discussing potential mechanisms for the observed diurnal variation in resting brain activity and the importance of accounting for time of day in future studies.