Diurnal variation of brain activity in the human suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, the SCN was localized, and its activity was investigated using perfusion imaging. We scanned each participant four times a day, every six hours, and higher activity was observed at noon while lower activity was recorded in the early morning. The SCN activity was then measured every thirty minutes for six hours from midnight to dawn and showed a decreasing trend and was comparable with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of mammals and is modulated by physical lights rather than the local time.

Methods
In this study, two experiments were conducted, wherein the first investigated the whole cycle of the diurnal activity of the SCN in humans. Participants were scanned four times within 24 hours (18:00, 24:00, 6:00, and 12:00 local time). In the second experiment, we investigated the human SCN activity in more detail during the night. Participants stayed in the scanner throughout the night, except for brief unavoidable interruptions, and were scanned every 30 min from 24:00 to 6:00. Perfusion images of pseudo-continuous arterial spin labeling (pCASL) in each participant were acquired. Twenty-seven and twenty right-handed participants without neurological/psychiatric illness or sleep disorders participated in the first and second experiments.

Whole brain perfusion images were acquired using pCASL imaging with multiband-EPI (number of measurements = 90, repetition time = 4.0 s, echo time = 25.2 ms, partial Fourier = 6/8, flip angle = 90°, labeling duration = 1.5 s, post labeling delay = 1.64 s, slice thickness = 1.82 mm, distance factor = 10%, number of slices = 72, slice acquisition order = ascending, in-plane field of view = 212 × 212 mm2, matrix size = 106 × 106, multiband acceleration factor = 6). Two M0 images, which were included in the pCASL sequence, were also acquired after the label/control images series. The perfusion images were corrected for motion and distortion. The cerebral blood flow (CBF) images in the standard MNI space were calculated using a command line interface of oxford_asl included in FSL software. Spatially minimal smoothing was applied to the CBF images (FWHM = 2.0 mm), and the absolute CBF values [ml/100mg/min] of the regions of interest were extracted and sent for statistical analyses.