Time-of-day matters - pronounced regional morning-to-evening effects in structural brain metrics

In recent decades magnetic resonance imaging (MRI) has established itself as the golden standard for studying human brain structure in health and disease. As a result, it has become increasingly more important to identify factors that may influence study outcomes and contribute to misleading conclusions. With the regional time-of-day (TOD) differences in structural brain metrics utterly neglected and several studies reporting inconsistent TOD changes on the global brain level, this work set out to investigate this phenomenon with voxel-based (VBM) and surface-based morphometry (SBM) using the largest longitudinal dataset to date (N = 77). VBM revealed ubiquitous and often bilaterally symmetric differences in local grey and white matter volume across multiple cortical and subcortical brain regions. The impact of TOD on regional SBM indices was less pronounced than for VBM, and no significant effects were observed for the global volume- and surface-based anatomical metrics. Our findings likely reflect a combination of experience- and circadian-related processes, with the former possibly linked to memory formation. By showing that TOD has a prevalent effect on local anatomical brain metrics, our study underlines the need for this factor to be strictly controlled at the stage of experimental planning and data analysis. Highlights ### Competing Interest Statement The authors have declared no competing interest.