Recovery Sleep Reverses Impaired Response Inhibition due to Sleep Restriction: Evidence from a Visual Event Related Potentials Study

Objective

To investigate response inhibition after total sleep deprivation (TSD) and the restorative effects of one night of recovery sleep (RS).

Methods

Fourteen healthy male participants performed a visual Go/NoGo task, and electroencephalogram recordings were conducted at five time points: (1) baseline, (2) after 12 h of TSD, (3) after 24 h of TSD, (4) after 36 h of TSD, and (5) following 8 h of RS. The dynamic changes in response inhibition during TSD and after 8 h of RS were investigated by examining the NoGo-N2 and NoGo-P3 event-related potential components.

Results

Compared with baseline, NoGo-P3 amplitudes were decreased, while the NoGo-N2 latency increased along with the awake time prolonged. NoGo anteriorization, which was minimized after 24 h of TSD, progressively decreased with increasing TSD. After 8 h of RS, recoveries of both the NoGo-P3 amplitude and NoGo-N2 latency in the prefrontal cortex were observed compared with the values after 36 h of TSD.

Conclusion

TSD induced a dose-dependent functional decline in the response inhibition of NoGo-N2 and NoGo-P3 on prefrontal cortex activation, and 8 h of RS resulted in recovery or maintenance of the response inhibition. However, it was not restored to baseline levels.

Limitations

Participants were chosen male college students only, thus the findings cannot be generalized to older people and women. Additionally, the sample size was small, and, thus, speculations on the meaning of the results of this study should be cautious. The EEG continuous recording should be employed to monitor the decline of alertness following TSD.     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

Total sleep deprivation alters cardiovascular reactivity to acute stressors in humans

Exaggerated cardiovascular reactivity to mental stress (MS) and cold pressor test (CPT) has been linked to increased risk of cardiovascular disease. Recent epidemiological studies identify sleep deprivation as an important risk factor for hypertension, yet the relations between sleep deprivation and cardiovascular reactivity remain equivocal. We hypothesized that 24-h total sleep deprivation (TSD) would augment cardiovascular reactivity to MS and CPT and blunt the MS-induced forearm vasodilation. Because the associations between TSD and hypertension appear to be stronger in women, a secondary aim was to probe for sex differences. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded during MS and CPT in 28 young, healthy subjects (14 men and 14 women) after normal sleep (NS) and 24-h TSD (randomized, crossover design). Forearm vascular conductance (FVC) was recorded during MS. MAP, FVC, and MSNA (n = 10) responses to MS were not different between NS and TSD (condition × time, P > 0.05). Likewise, MAP and MSNA (n = 6) responses to CPT were not different between NS and TSD (condition × time, P > 0.05). In contrast, increases in HR during both MS and CPT were augmented after TSD (condition × time, P ≤ 0.05), and these augmented HR responses persisted during both recoveries. When analyzed for sex differences, cardiovascular reactivity to MS and CPT was not different between sexes (condition × time × sex, P > 0.05). We conclude that TSD does not significantly alter MAP, MSNA, or forearm vascular responses to MS and CPT. The augmented tachycardia responses during and after both acute stressors provide new insight regarding the emerging links among sleep deprivation, stress, and cardiovascular risk.     

Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.     

完全睡眠剥夺对大脑注意网络冲突效应和脑电样本熵的影响*

目的: 本研究分析睡眠剥夺对个体选择性注意网络冲突效应和脑电样本熵的影响,探讨睡眠剥夺对大脑注意网络的影响。方法: 25名健康受试者参与36 h完全睡眠剥夺试验。试验于当天9:00开始,于次日21:00结束,试验采用自身前后对照设计。受试者在睡眠剥夺前后分别完成注意网络任务,同步采集受试者的脑电图。用脑电样本熵算法分析脑电图的delta、theta、alpha、beta和gamma频率段的脑电复杂度并对比各频段脑电样本熵在睡眠剥夺前、后的变化。结果: 同睡眠剥夺前比较,睡眠剥夺后与受试者的注意网络冲突效应密切相关的反应时显著下降(P＜0.01),正确率显著增加(P＜0.01)。脑电样本熵分析发现在beta频率段,与注意网络冲突控制相关的脑电样本熵值在睡眠剥夺后明显增大(P＜0.01)。其余脑电频率段脑电样本熵未发现显著差异。结论: 表明完全睡眠剥夺后大脑的注意网络冲突效应降低,表明睡眠剥夺后执行冲突控制能力的下降。     

Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men

Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations.We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I were decreased at D4 (P<0.001). One night of recovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r = 0.393 and r = 0.490 respectively), and negatively with circulating free IGF-I (r = ?0.494). In conclusion, 25h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.     

Restricted sleep regime in rhesus monkeys: differential effect of one night's sleep loss and selective REM deprivation.

The differential effect of either one night's total sleep deprivation (TSD) or of selective REM deprivation (REMD) was examined on post-deprivation daytime EEG patterns with respect to control, in the same group of rhesus monkeys. TSD resulted in significantly decreased wakefulness and increased amounts of NREM and REM on the first day following TSD. In contrast, highly significant REM elevation without alteration of other EEG states occurred for 3 days after REMD. Post-deprivation behavioural and photic-induced neural changes were minor. The results obtained after sleep deprivation in simians are comparable with similar findings in human subjects.     

36 h完全睡眠剥夺对客体工作记忆相关电位的影响*

目的:采用事件相关电位(ERP)技术探讨36 h完全睡眠剥夺对客体工作记忆的影响。方法:本研究采用自身前后对照设计,16名睡眠质量良好的健康大学生(平均年龄为23岁,年龄范围21～28岁)分别在清醒状态下及36 h完全睡眠剥夺后接受2-back客体工作记忆任务,同时采集脑电数据。选用重复测量方差分析的方法比较睡眠剥夺前后与客体工作记忆有关的P2、N2、P3成分的波幅和潜伏期的差异。结果:在36 h完全睡眠剥夺后,与客体工作记忆加工相关的N2波的潜伏期显著延长(P＜0.05),波幅减少但未见统计学差异(P＞0.05); P2波潜伏期显著延长(P＜0.05),波幅未见明显变化(P＞0.05)。P3波波幅、潜伏期未见统计学差异(P＞0.05)。结论:36 h的完全睡眠剥夺影响了客体工作记忆相关电位,损害了个体的客体工作记忆加工能力。     

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances.To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29 ± 3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P < 0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.     

Sustained attention performance during sleep deprivation: evidence of state instability

Nathaniel Kleitman was the first to observe that sleep deprivation in humans did not eliminate the ability to perform neurobehavioral functions, but it did make it difficult to maintain stable performance for more than a few minutes. To investigate variability in performance as a function of sleep deprivation, n = 13 subjects were tested every 2 hours on a 10-minute, sustained-attention, psychomotor vigilance task (PVT) throughout 88 hours of total sleep deprivation (TSD condition), and compared to a control group of n = 15 subjects who were permitted a 2-hour nap every 12 hours (NAP condition) throughout the 88-hour period. PVT reaction time means and standard deviations increased markedly among subjects and within each individual subject in the TSD condition relative to the NAP condition. TSD subjects also had increasingly greater performance variability as a function of time on task after 18 hours of wakefulness. During sleep deprivation, variability in PVT performance reflected a combination of normal timely responses, errors of omission (i.e., lapses), and errors of commission (i.e., responding when no stimulus was present). Errors of omission and errors of commission were highly intercorrelated across deprivation in the TSD condition (r = 0.85, p = 0.0001), suggesting that performance instability is more likely to include compensatory effort than a lack of motivation. The marked increases in PVT performance variability as sleep loss continued supports the "state instability" hypothesis, which posits that performance during sleep deprivation is increasingly variable due to the influence of sleep initiating mechanisms on the endogenous capacity to maintain attention and alertness, thereby creating an unstable state that fluctuates within seconds and that cannot be characterized as either fully awake or asleep.     

Electromyographic indices, orofacial myofunctional status and temporomandibular disorders severity: A correlation study

This study examined whether there is an association between surface electromyography (EMG) of masticatory muscles, orofacial myofunction status and temporomandibular disorder (TMD) severity scores. Forty-two women with TMD (mean 30 years, SD 8) and 18 healthy women (mean 26 years, SD 6) were examined. According to the Research Diagnostic Criteria for TMD (RDC/TMD), all patients had myogenous disorders plus disk displacements with reduction. Surface EMG of masseter and temporal muscles was performed during maximum teeth clenching either on cotton rolls or in intercuspal position. Standardized EMG indices were obtained. Validated protocols were used to determine the perception severity of TMD and to assess orofacial myofunctional status. TMD patients showed more asymmetry between right and left muscle pairs, and more unbalanced contractile activities of contralateral masseter and temporal muscles (p<0.05, t-test), worse orofacial myofunction status and higher TMD severity scores (p<0.05, Mann-Whitney test) than healthy subjects. Spearman coefficient revealed significant correlations between EMG indices, orofacial myofunctional status and TMD severity (p<0.05). In conclusion, these methods will provide useful information for TMD diagnosis and future therapeutic planning.     

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.     

Meta-Analysis of the Relationship Between Total Sleep Deprivation and Performance

Studies consistently show that total sleep deprivation (TSD) and measures of performance are negatively correlated. However, an accurate quantitative summary of the relationship between these variables has not yet been reported. After collection of the data from 27 relevant studies, meta-analytic techniques were used to test several hypotheses. The correlations were found to be highest for TSD of ≥45 h, speed rather than accuracy measures of performance, and work-paced rather than self-paced tasks. These findings are consistent with the “lapse hypothesis” that posits microsleeps during long hours of sleep deprivation.     

Meta-Analysis of the Relationship Between Total Sleep Deprivation and Performance

Studies consistently show that total sleep deprivation (TSD) and measures of performance are negatively correlated. However, an accurate quantitative summary of the relationship between these variables has not yet been reported. After collection of the data from 27 relevant studies, meta-analytic techniques were used to test several hypotheses. The correlations were found to be highest for TSD of ≥45 h, speed rather than accuracy measures of performance, and work-paced rather than self-paced tasks. These findings are consistent with the “lapse hypothesis” that posits microsleeps during long hours of sleep deprivation.     

Total sleep deprivation does not significantly degrade semantic encoding

ABSTRACT

Sleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding.     

Neurophysiological Effects of Sleep Deprivation in Healthy Adults,a Pilot Study

Total sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood changes, which are partly compensated by stress regulating brain systems, resulting in altered dopamine and cortisol levels in order to stay awake if needed. These systems, however, have never been studied in concert. At baseline, after a regular night of sleep, and the next morning after TSD, 12 healthy subjects performed a semantic affective classification functional magnetic resonance imaging (fMRI) task, followed by a [¹¹C]raclopride positron emission tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points during both days. Affective symptoms were measured using Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue scales. After TSD, perceived energy levels, concentration, and speed of thought decreased significantly, whereas mood did not. During fMRI, response speed decreased for neutral words and positive targets, and accuracy decreased trendwise for neutral words and for positive targets with a negative distracter. Following TSD, processing of positive words was associated with increased left dorsolateral prefrontal activation. Processing of emotional words in general was associated with increased insular activity, whereas contrasting positive vs. negative words showed subthreshold increased activation in the (para)hippocampal area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by-voxel [¹¹C]raclopride binding potential (BP_ND) was observed in left caudate. TSD induces widespread cognitive, neurophysiologic and endocrine changes in healthy adults, characterized by reduced cognitive functioning, despite increased regional brain activity. The blunted HPA-axis response together with altered [¹¹C]raclopride binding in the basal ganglia indicate that sustained wakefulness requires involvement of additional adaptive biological systems.     

Discrimination of muscle tension in chronic pain patients and healthy controls.

The purpose of this study was to assess the perception of muscle tension in chronic pain patients and healthy controls. Twenty chronic back pain patients, 20 patients who suffered from temporomandibular pain and dysfunction, and 20 healthy controls were instructed to produce eight different levels of muscle contraction in either the m. masseter or the m. erector spinae. Each level was produced three times; trials were presented in random order. Analyses of the accuracy and the sensitivity of discrimination of muscle tension levels revealed that the patients were less able to perceive muscle contraction levels correctly and that they underestimated their actual levels of muscle tension. Patients and controls did not differ in the extent to which they contracted muscles not involved in the task. Patients suffering from musculoskeletal disorders seem to display a genuine deficit in discrimination of muscle tension that is related to neither local physiological changes at the site of pain, lack of motivation, in-attention, nor fatigue.     

Masseter EMG activity during sleep and sleep bruxism

The masseter muscle is involved in the complex and coordinated oromotor behaviors such as mastication during wakefulness. The masseter electromyographic (EMG) activity decreases but does not disappear completely during sleep: the EMG activity is generally of low level and inhomogeneous for the duration, amplitude and intervals. The decreased excitability of the masseter motoneurons can be determined by neural substrates for NREM and REM sleep. The masseter EMG activity is increased in association with the level of arousal fluctuations within either sleep state. In addition, there are some motor events such as REM twitches, swallowing and rhythmic masticatory muscle activity (RMMA), whose generation might involve the additional activation of specific neural circuits. Sleep bruxism (SB) is characterized by exaggerated occurrence of RMMA. In SB, the rhythmic activation of the masseter muscle can reflect the rhythmic motor inputs to motoneurons through, at least in part, common neural circuits for generating masticatory rhythm under the facilitatory influences of transient arousals. However, it remains elusive as to which neural circuits determine the genesis of sleep bruxism. Based on the available knowledge on the masseter EMG activity during sleep, this review presents that the variety of the masseter EMG phenotypes during sleep can result from the combinations of the quantitative, spatial and temporal neural factors eventually sending net facilitatory inputs to trigeminal motoneurons under sleep regulatory systems.     

Altered Resting-State Amygdala Functional Connectivity after 36 Hours of Total Sleep Deprivation

Objectives

Recent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD). However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI) to investigate the functional connectivity changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the brain after 36 h of TSD.

Materials and Methods

Fourteen healthy adult men aged 25.9±2.3 years (range, 18–28 years) were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW) and after 36 h of TSD.

Results

TSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC) and right precentral gyrus.

Conclusion

These findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.     

Phase Advance Is an Actimetric Correlate of Antidepressant Response to Sleep Deprivation and Light Therapy in Bipolar Depression

The combination of total sleep deprivation (TSD) and light therapy (LT) in bipolar depression causes rapid antidepressant effects, and its mechanism of action has been hypothesized to involve the enhancement of all of the monoaminergic systems targeted by antidepressant drugs (serotonin, dopamine, norepinephrine). It is still unknown if the clinical effects are paralleled by changes in biological rhythms. In a before/after design of a study of biological correlates of response, 39 inpatients affected by Type I Bipolar Disorder whose current depressive episode was without psychotic features were treated for one week with repeated TSD combined with morning LT. Wrist actigraphy was recorded throughout the study. Two‐thirds of the patients responded to treatment (50% reduction in Hamilton Depression score). Responders showed an increase in daytime activity, phase‐advance of the activity‐rest rhythm of 57 min compared to the pre‐treatment baseline, and reduced nighttime sleep. Non‐responders did not show significant changes in the parameters of their activity‐rest rhythm. Phase advance of the activity‐rest rhythm is an actimetric correlate of the antidepressant response to TSD and LT in bipolar depression. Results are consistent with the known effects of sleep‐wake manipulations and neurotransmitter function on the suprachiasmatic nucleus.