Enhanced amygdala–cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation

Fig. 1.. (A) Protocol of experiment 1. The first scanning session took place in the morning of day 2 after 9 h BS. Participants were then randomized to either a TSD or a control condition. In the TSD condition, participants with one night of TSD had the second scanning session in the morning of day 3. After two nights of RS, participants had the third scanning session in the morning of day 5. In the control condition, participants with ≥8 h CS every night had the second and third scanning sessions in the morning of days 3 and 5, respectively. All participants completed the POMS scale every 2 h during day 2 to 5. (B) POMS-negative mood score across the four consecutive days for the TSD group and the control group. Negative mood worsened significantly following one night of TSD compared to BS and improved significantly after one night of RS. The dashed lines represent the median values, and the dotted lines represent the quartiles. TIB: time in bed; BS: baseline sleep; TSD: total sleep deprivation; RS: recovery sleep; CS: control sleep; POMS: Profile of Mood States. ***P < 0.001.

Fig. 2.. (A) Increased FC of the amygdala with ACC following TSD relative to BS in the healthy TSD group. Paired t tests were performed to examine the differences in FC of amygdala with all other voxels in the brain between BS and TSD, with age, gender, and head motion as covariates. The threshold was set at whole-brain FWE-corrected P < 0.001 at a cluster level, with cluster size larger than 30 voxels. (B) FC between the amygdala and ACC increased significantly after TSD, while it decreased significantly after RS2 in the TSD group. There were no significant amygdala–ACC connectivity changes among corresponding days in the control group. The dashed lines represent the median values, and the dotted lines represent the quartiles. (C) The scatter plot shows a significant correlation between increased amygdala–ACC connectivity and reduced mood worsening from baseline to TSD while controlling for age, gender, head motion, and baseline negative mood (rho = −0.414, P < 0.01). FC: functional connectivity; ACC: anterior cingulate cortex; BS: baseline sleep; TSD: total sleep deprivation; RS: recovery sleep; CS: control sleep; FWE: family-wise error. ***P < 0.001.

Fig. 3.. (A) Location of bilateral DN seed (red), R.MFG and R.SFG (yellow) regions of interest. DN connectivity with (B) R.MFG and (C) R.SFG increased after TSD, while decreased following RS2 in the TSD group. There were no significant DN–R.MFG/SFG connectivity changes among corresponding days in the control group. The dashed lines represent the median values, and the dotted lines represent the quartiles. After TSD, neither (D) DN–R.MFG nor (E) DN–R.SFG connectivity increases correlated significantly with mood worsening while controlling for age, gender, head motion, and baseline negative mood (respective rho = 0.016 and −0.065, P > 0.05). DN: dorsal nexus; R.MFG: right middle frontal gyrus; R.SFG: right superior frontal gyrus; FC: functional connectivity; BS: baseline sleep; TSD: total sleep deprivation; RS: recovery sleep; CS: control sleep. *P < 0.05.

Fig. 4.. (A) Thirteen out of 30 depressed participants experienced mood improvement (i.e., decreases of HDRS score) after TSD compared to BS, and the remaining seventeen participants experienced mood nonimprovement (i.e., worsening or no change). (B) Comparison of amygdala–ACC FC between BS and TSD in improved mood group (pink) and unimproved mood group (blue). Amygdala–ACC FC increases after TSD were evident in patients with improved mood (P < 0.05), while the increases in patients with unimproved mood did not reach statistical significance. The dashed lines represent the median values, and the dotted lines represent the quartiles. (C) Scatter plot showing a significant correlation between increased amygdala–ACC FC and improved depressive mood from BS to TSD while controlling for age, gender, head motion, and baseline depressive mood (rho = −0.461, P < 0.05). (D) Twenty out of 29 patients experienced mood improvement after RS, rather than returning to depressed status. (E) Comparison of amygdala–ACC FC between TSD and RS in improved mood group (pink) and unimproved mood group (blue). Amygdala–ACC FC decreases after RS were evident in patients with unimproved mood (P < 0.01), while the…