Human cerebral blood flow activity with diurnal variation differentially correlated with the suprachiasmatic nucleus

The human circadian rhythm is controlled by central and peripheral clocks, primarily by the central clock in the suprachiasmatic nucleus (SCN). We investigated the diurnal variation of basic metabolism in the human cerebrum by measuring human baseline cerebral activity at rest contrasted with the SCN baseline activity. To this end, we utilized magnetic resonance imaging perfusion data of cerebral blood flow (CBF) (N = 27, including both sexes), where each participant was scanned four times a day at six-hour intervals (18:00, 24:00, 6:00, and 12:00 local time). Similarly to the SCN exhibiting higher CBF activity at noon, we observed a consistent temporal activity pattern in the brain regions, including the limbic (cingulate, insular, and temporopolar) and sensorimotor (visual and somatosensory/motor) areas. In contrast, the hippocampus showed higher activity at midnight and lower activity at noon. To examine the functional interaction between the SCN and the cerebral regions showing diurnal variation, we calculated the resting-state functional connectivity using the database of the Human Connectome Project (N = 164, including both sexes). Notably, the hippocampus demonstrated greater functional connectivity with the SCN than the other regions. These results suggest that cerebral regions exhibit differential patterns of diurnal variation associated with their functional connectivity with the SCN.<b>Significance Statement</b> The human circadian rhythm is regulated primarily by the suprachiasmatic nucleus (SCN) and peripheral clocks. This study examined diurnal variations in human cerebral activity by measuring baseline cerebral blood flow at rest using magnetic resonance imaging. Participants were scanned four times a day (18:00, 24:00, 6:00, and 12:00). Similar to the SCN, cerebral regions in the limbic and sensorimotor areas showed higher activity at noon. However, the hippocampus exhibited peak activity at midnight and lower activity at noon. Functional connectivity analysis revealed stronger SCN-hippocampus connectivity than the other cerebral regions. These findings suggest that brain areas (i.e., the hippocampus and the limbic and sensorimotor areas) show distinct diurnal activity patterns linked to their functional connectivity with the SCN.