Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

Figure 1. Experimental protocol. Subjects were enrolled in a 14-day and 13-night study, with 8 h of sleep on the first 2 days, 12 h of sleep for the next 9 days, a night of total sleep deprivation, and a night of recovery sleep. MRI was performed at 9 h after the midpoint of sleep on day 1 (BL1), sleep on day 6 (ES4), sleep on day 11 (ES9), and the TSD period on day 12. Subjects underwent overnight PSG measurements throughout the study period. Black bars, sleep time; HS, habitual sleep at home; BL1, baseline day 1; ES4, extended sleep day 4; ES9, extended sleep day 9; TSD, total sleep deprivation; RS, recovery sleep.

Figure 2. Comparison of the subjective sleepiness and mood state scores among different sleep conditions. KSS (A), PANAS-NA (B), and STAI-S (C) were analyzed based on the following two research questions (RQs): (RQ1) Comparison between BL1 and ES9 to investigate the effect of extended sleep (t test for KSS and STAI-S and Wilcoxon signed-rank test for PANAS-NA); (RQ2) Comparison between BL1 and TSD to determine whether the TSD would erase the effect of sleep extension and whether the subjective indices after TSD would be comparable to those at the baseline level. ***p < 0.001, *p < 0.05, †p < 0.1; p values were adjusted for multiple comparison. RQ, research question; KSS, Karolinska Sleepiness Scale; PANAS-NA, Positive And Negative Affect Schedule, Negative Affect; STAI-S, State-Trait Anxiety Inventory-State Anxiety scale; BL1, baseline Day 1; ES4, extended sleep Day 4; ES9, extended sleep Day 9; TSD, total sleep deprivation.

Figure 3. Comparison of the amygdala ROI and rCBF among different sleep conditions. (A) Amygdala ROI. Left amygdala: center MNI coordinates (x, y, z) = (−20, −4, −16) mm, 179 contiguous voxels; right amygdala, (x, y, z) = (24, −4, −16) mm, 178 contiguous voxels; clusters are rendered on a T1 anatomical reference image displayed in neurological convention, with the left side corresponding to the left hemisphere. MNI, Montreal Neurological Institute template. (B) Amygdala rCBF for the four sleep conditions. *p < 0.05, †p < 0.1; p values were adjusted for multiple comparison. Data were analyzed based on the following two research questions: (RQ1) Comparison between BL1 and ES9 to investigate the effect of extended sleep (t test for KSS and STAI-S and Wilcoxon signed-rank test for PANAS-NA); (RQ2) Comparison between BL1 and TSD to determine whether the TSD would erase the effect of sleep extension and whether the subjective indices after TSD would be comparable to those at the baseline level. RQ, research question; rCBF, regional cerebral blood flow; BL1, baseline Day 1; ES4, extended sleep Day 4; ES9, extended sleep Day 9; TSD, total sleep deprivation.

Figure 4. Medial prefrontal cortex (MPFC) ROI and functional connectivity between the amygdala and MPFC. (A) MPFC ROI: peak MNI coordinate (x, y, z) = (8, 44, 0) mm, 34 contiguous voxels; clusters are rendered on a T1 anatomical reference image displayed in neurological convention, with the left side corresponding to the left hemisphere. MNI, Montreal Neurological Institute template. (B) Functional connectivity between the amygdala and MPFC for the four sleep conditions. *p < 0.05, †p < 0.1; p values were adjusted for multiple comparison. Data were analyzed based on the following two research questions: (RQ1) Comparison between BL1 and ES9 to investigate the effect of extended sleep (t test for KSS and STAI-S and Wilcoxon signed-rank test for PANAS-NA); (RQ2) Comparison between BL1 and TSD to determine whether the TSD would erase the effect of sleep extension and whether the subjective indices after TSD would be comparable to those at the baseline level. RQ, research question; FCamg–MPFC, functional connectivity between the amygdala and medial prefrontal cortex; BL1, baseline Day 1; ES4, extended sleep Day 4; ES9, extended sleep Day 9; TSD, total sleep deprivation.

Figure 5. Structural equation modeling of psychological and neuroimaging variables. The functional connectivity between the amygdala and MPFC predicted the amygdala rCBF, which further predicted the PANAS-NA and STAI-S scores. The model included the data of the four sleep conditions (n = 58). β, standardized coefficient; R2, square of multiple correlation coefficient; r, correlation coefficient; R1–3, residual of each endogenous variable; FCamg–MPFC, functional connectivity between the amygdala and medial prefrontal cortex; rCBF, regional cerebral blood flow; PANAS-NA, Positive And Negative Affect Schedule-Negative Affect score; STAI, State-Trait Anxiety Inventory-State Anxiety score. †p < 0.1, *p < 0.05, **p < 0.01.