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Clinical Trial
. 2013;8(2):e56578.
doi: 10.1371/journal.pone.0056578. Epub 2013 Feb 13.

Sleep Debt Elicits Negative Emotional Reaction Through Diminished Amygdala-Anterior Cingulate Functional Connectivity

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Free PMC article
Clinical Trial

Sleep Debt Elicits Negative Emotional Reaction Through Diminished Amygdala-Anterior Cingulate Functional Connectivity

Yuki Motomura et al. PLoS One. .
Free PMC article

Abstract

Objectives: Sleep debt reportedly increases emotional instability, such as anxiety and confusion, in addition to sleepiness and psychomotor impairment. However, the neural basis of emotional instability due to sleep debt has yet to be elucidated. This study investigated changes in emotional responses that are elicited by the simulation of short-term sleep loss and the brain regions responsible for these changes.

Subjects and methods: Fourteen healthy adult men aged 24.1±3.3 years (range, 20-32 years) participated in a within-subject crossover study consisting of 5-day sessions of both sleep debt (4 h for time in bed) and sleep control (8 h for time in bed). On the last day of each session, participants underwent polysomnography and completed the State-Trait Anxiety Inventory and Profile of Mood States questionnaires. In addition, functional magnetic resonance imaging was conducted while performing an emotional face viewing task.

Results: Restricted sleep over the 5-day period increased the activity of the left amygdala in response to the facial expression of fear, whereas a happy facial expression did not change the activity. Restricted sleep also resulted in a significant decrease in the functional connectivity between the amygdala and the ventral anterior cingulate cortex (vACC) in proportion to the degree of sleep debt (as indicated by the percentage of slow wave sleep and δ wave power). This decrease was significantly correlated with activation of the left amygdala and deterioration of subjective mood state.

Conclusion: The results of this study suggest that continuous and accumulating sleep debt that can be experienced in everyday life can downregulate the functional suppression of the amygdala by the vACC and consequently enhance the response of the amygdala to negative emotional stimuli. Such functional alteration in emotional control may, in part, be attributed to the neural basis of emotional instability during sleep debt.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Experimental protocol.
The study was conducted in a randomized crossover design, involving a sleep control (SC) and sleep debt (SD) session (for 5 days in each session) with a 2-week interval between the sessions. In the observational session before the experiment, participants visited the laboratory for a briefing session and gave their informed consent. One week later, participants came to the lab for PSG screening. One week after the PSG screening, the experimental sessions were started, with the order of the sessions counter-balanced across participants (i.e., SC-SD or SD-SC). Participants stayed at home on days 1–3 within each SC and SD session, according to the restrictive sleep-wake schedule that had been already instructed in the briefing (i.e., sleep time of 8 h for SC and 4 h for SD). Participants came to the lab on night 3 of the SC and SC sessions and spent the rest of the sessions (i.e., 2 days per session) in the sleep-lab with their sleep time controlled as instructed. On nights 3 and 4 in each session, participants underwent PSG measurement in the lab. On day 5, they completed questionnaires to check their mood state and sleepiness followed by fMRI scanning with an emotional task. SC, sleep control; SD, sleep debt; PSG, polysomnography; SSS, Stanford Sleepiness Scale; STAI, State-Trait Anxiety Inventory; POMS, Profile of Mood States.
Figure 2
Figure 2. Design of emotional facial presentations.
Facial pictures depicting fear or happy (i.e., emotional) or neutral expressions were used as the stimuli and were presented either non-consciously or consciously. In a non-conscious trial, an emotional image (either fear, happy, or neutral) was implicitly presented for 26 ms, followed by an explicit presentation for 174 ms of a neutral ‘masking’ face of the same identity as the preceding implicit emotional face (when the implicit face was neutral, the following explicit mask was of a different person of the same sex). Participants were required to press a button in response to each ‘target’ stimulus to keep themselves awake during the scanning.
Figure 3
Figure 3. Difference in amygdala activation between the sleep control (SC) and sleep debt (SD) sessions.
The map shows significantly greater activation in response to fearful face stimuli in the SD than SC session. Significant differences were seen in the left amygdala, peak MNI coordinate (x, y, z) = (−14, 4, −18) mm, T(13) = 5.60, p = .0001, k = 8 contiguous voxels. A similar trend was also observed in the right amygdala, (x, y, z) = (18, 2, −18) mm, T(13) = 3.41, p = .0005, k = 7. Significant clusters are rendered on a T1 anatomical referential image displayed in neurological convention, with the left side corresponding to the left hemisphere. The clusters shown are thresholded with a lenient alpha level (p<0.01, k>5) for visualization purposes. MNI, Montreal Neurological Institute template.
Figure 4
Figure 4. Difference in functional connectivity between sleep control (SC) and sleep debt (SD) sessions.
The map shows greater functional connectivity between the left amygdala and other voxels in the brain in SC than SD session. Significant differences were found in the vACC, peak MNI coordinate (x, y, z) = (14, 32, −4) mm, T(13) = 4.77, p = .0001, k = 9 contiguous voxels. The significant cluster with a stronger connection with the left amygdala is rendered on a T1 anatomical referential image displayed in neurological convention, with the left side corresponding to the left hemisphere. The clusters shown are thresholded with a lenient alpha level (p<0.01, k>5) for visualization purposes. MNI, Montreal Neurological Institute template; vACC, ventral anterior cingulate cortex.
Figure 5
Figure 5. Correlation between amygdala activation and amygdala–vACC functional connectivity.
Amygdala activation in response to fearful facial stimuli was negatively correlated with amygdala-vACC functional connectivity, r(13) = .64, p = .0001. The selected seed region within the amygdala was a cluster that showed greater functional connectivity with vACC in the SC than SD condition (p<0.001, uncorrected). Data from the SC and SD sessions were combined and plotted in one graph but differently colored; SD data in squares, SC in triangles. vACC, ventral anterior cingulate cortex; SC, sleep control condition; SD, sleep debt condition.
Figure 6
Figure 6. Correlation between the inter-session differences of amygdala–vACC functional connectivity and the inter-session differences STAI-state score.
Inter-session differences between sleep control and sleep debt sessions of amygdala-vACC functional connectivity in response to fearful facial stimuli correlated negatively with inter-session differences of STAI-state score, r(13) = .82, p = .0001. Δvalue, inter-session difference between sleep control and sleep debt sessions for each value; vACC, ventral anterior cingulate cortex; SC, sleep control condition; SD, sleep debt condition; FCamg-vACC, functional connectivity between amygdala and ventral ACC; STAI, State-Trait Anxiety Inventory.

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Grant support

This study was supported in part by a Grant-in-Aid for the Strategic Research Program for Brain Sciences (Understanding of molecular and environmental bases for brain health) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (URL: http://brainprogram.mext.go.jp/), an Intramural Research Grant (23-3) for Neurological and Psychiatric Disorders from NCNP(URL:http://www.ncnp.go.jp/), and KAKENHI (21390335)(URL:http://www.jsps.go.jp/j-grantsinaid/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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