β Oscillation during Slow Wave Sleep and Rapid Eye Movement Sleep in the Electroencephalogram of a Transgenic Mouse Model of Huntington’s Disease

Study objectives

To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington’s disease (HD).

Design

In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease.

Measurements and results

Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9–11 weeks (presymptomatic period) through 6–7 months (symptomatic period). Recording data revealed a unique β rhythm (20–35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep.

Conclusions

In addition to providing a new in vivo biomarker and insight into Huntington''s disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep.     

Differential Associations of Early- and Late-Night Sleep with Functional Brain States Promoting Insight to Abstract Task Regularity

Background

Solving a task with insight has been associated with occipital and right-hemisphere activations. The present study tested the hypothesis if sleep-related alterations in functional activation states modulate the probability of insight into a hidden abstract regularity of a task.

Methodology

State-dependent functional activation was measured by beta and alpha electroencephalographic (EEG) activity and spatial synchronization. Task-dependent functional activation was assessed by slow cortical potentials (SPs). EEG parameters during the performance of the Number Reduction Task (NRT) were compared between before sleep and after sleep sessions. In two different groups, the relevant sleep occurred either in the first or in the second half of the night, dominated by slow wave sleep (SWS) or by rapid eye movement (REM) sleep.

Principal Findings

Changes in EEG parameters only occurred in the early-night group, not in the late-night group and indicated occipital and right-hemisphere functional alterations. These changes were associated with off-line consolidation of implicit task representations and with the amount of SWS but they did not predict subsequent insight. The gain of insight was, however, independently associated with changes of spectral beta and alpha measures only in those subjects from the two sleep groups who would subsequently comprehend the hidden regularity of the task. Insight-related enhancement of right frontal asymmetry after sleep did not depend on sleep stages.

Significance

It is concluded that off-line restructuring of implicit information during sleep is accompanied by alterations of functional activation states after sleep. This mechanism is promoted by SWS but not by REM sleep and may contribute to attaining insight after sleep. Original neurophysiologic evidence is provided for alterations of the functional activation brain states after sleep. These alterations are associated with a decrease in controlled processing within the visual system and with an increase in the functional connectivity of the right hemisphere, and are supported by SWS in the first half of the night.     

Quantitative Changes in the Sleep EEG at Moderate Altitude (1630 m and 2590 m)

Background

Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep.

Methods

Fourty-four healthy men (mean age 25.0±5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design.

Results

Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8–4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (∼4% at 1630 m and 15% at 2590 m), while theta activity (4.6–8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4–8 Hz and 13–14.4 Hz) and breathing variables (AHI, ODI; 0.8–4.6 Hz).

Conclusions

The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.     

Covert Reorganization of Implicit Task Representations by Slow Wave Sleep

Background

There is evidence that slow wave sleep (SWS) promotes the consolidation of memories that are subserved by mediotemporal- and hippocampo-cortical neural networks. In contrast to implicit memories, explicit memories are accompanied by conscious (attentive and controlled) processing. Awareness at pre-sleep encoding has been recognized as critical for the off-line memory consolidation. The present study elucidated the role of task-dependent cortical activation guided by attentional control at pre-sleep encoding for the consolidation of hippocampus-dependent memories during sleep.

Methodology

A task with a hidden regularity was used (Number Reduction Task, NRT), in which the responses that can be implicitly predicted by the hidden regularity activate hippocampo-cortical networks more strongly than responses that cannot be predicted. Task performance was evaluated before and after early-night sleep, rich in SWS, and late-night sleep, rich in rapid eye movement (REM) sleep. In implicit conditions, slow cortical potentials (SPs) were analyzed to reflect the amount of controlled processing and the localization of activated neural task representations.

Principal Findings

During implicit learning before sleep, the amount of controlled processing did not differ between unpredictable and predictable responses, nor between early- and late-night sleep groups. A topographic re-distribution of SPs indicating a spatial reorganization occurred only after early, not after late sleep, and only for predictable responses. These SP changes correlated with the amount of SWS and were covert because off-line RT decrease did not differentiate response types or sleep groups.

Conclusions

It is concluded that SWS promotes the neural reorganization of task representations that rely on the hippocampal system despite absence of conscious access to these representations.

Significance

Original neurophysiologic evidence is provided for the role of SWS in the consolidation of memories encoded with hippocampo-cortical interaction before sleep. It is demonstrated that this SWS-mediated mechanism does not depend critically on explicitness at learning nor on the amount of controlled executive processing during pre-sleep encoding.     

Odor fear conditioning modifies piriform cortex local field potentials both during conditioning and during post-conditioning sleep

Background

Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning.

Methodology/Principal Findings

We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day.

Conclusions/Significance

The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference.     

Chronic Upper Airway Obstruction Induces Abnormal Sleep/Wake Dynamics in Juvenile Rats

Objectives

Conventional scoring of sleep provides little information about the process of transitioning between vigilance-states. We used the state space technique to explore whether rats with chronic upper airway obstruction (UAO) have abnormal sleep/wake states, faster movements between states, or abnormal transitions between states.

Design

The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed to increase upper airway resistance with no evidence for frank obstructed apneas or hypopneas; 24-h electroencephalography of sleep/wake recordings of UAO and sham-control animals was analyzed using state space technique. This non-categorical approach allows quantitative and unbiased examination of vigilance-states and state transitions. Measurements were performed 2 weeks post-surgery at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep.

Measurements and Results

UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. State transitions from light SWS to wake and vice versa and microarousals were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake and light SWS, and increasing deep SWS in UAO.

Conclusions

State space technique enables visualization of vigilance-state transitions and velocities that were not evident by traditional scoring methods. This analysis provides new quantitative assessment of abnormal vigilance-state dynamics in UAO in the absence of frank obstructed apneas or hypopneas.     

Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice

Background

The sleep sequence: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the β4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-β4-deficient mutant (PLC-β4−/−) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-β4−/− mice, however.

Methodology/Principal Findings

Therefore, we analyzed 24-h sleep electroencephalogram in PLC-β4−/− mice. PLC-β4−/− mice exhibited normal non-REM sleep both during the day and nighttime. PLC-β4−/− mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-β4−/− mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22°C–4°C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca²⁺ mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-β4−/− mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-β4−/− mice.

Conclusions/Significance

These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-β4−/− mice.     

Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background

Sleep spindles are ∼1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phase-locked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators.

Methodology/Principal Findings

We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere.

Conclusions/Significance

The heterogeneity of MEG sources implies that multiple generators are active during human sleep spindles. If the source modeling is correct, then EEG spindles are generated by a different, diffusely synchronous system. Animal studies have identified two thalamo-cortical systems, core and matrix, that produce focal or diffuse activation and thus could underlie MEG and EEG spindles, respectively. Alternatively, EEG spindles could reflect overlap at the sensors of the same sources as are seen from the MEG. Although our results generally match human intracranial recordings, additional improvements are possible and simultaneous intra- and extra-cranial measures are needed to test their accuracy.     

Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives

1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design

Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting

Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients

Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions

Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes.

Measurements and Results

An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%).

Conclusions

The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.     

Upregulation of GPR109A in Parkinson’s Disease

Background

Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson’s disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin is also thought to be involved in the regulation of circadian rhythm. Here we evaluated the relationships among the receptor, niacin levels and EEG night-sleep in individuals with PD.

Methods and Findings

GPR109A expression (blood and brain), niacin index (NAD-NADP ratio) and cytokine markers (blood) were analyzed. Measures of night-sleep function (EEG) and perceived sleep quality (questionnaire) were assessed. We observed significant up-regulation of GPR109A expression in the blood as well as in the substantia nigra (SN) in the PD group compared to age-matched controls. Confocal microscopy demonstrated co-localization of GPR109A staining with microglia in PD SN. Pro and anti-inflammatory cytokines did not show significant differences between the groups; however IL1-β, IL-4 and IL-7 showed an upward trend in PD. Time to sleep (sleep latency), EEG REM and sleep efficiency were different between PD and age-matched controls. Niacin levels were lower in PD and were associated with increased frequency of experiencing body pain and decreased duration of deep sleep.

Conclusions

The findings of associations among the GPR109A receptor, niacin levels and night-sleep function in individuals with PD are novel. Further studies are needed to understand the pathophysiological mechanisms of action of niacin, GPR109A expression and their associations with night-sleep function. It would be also crucial to study GPR109A expression in neurons, astrocytes, and microglia in PD. A clinical trial to determine the symptomatic and/or neuroprotective effect of niacin supplementation is warranted.     

Sleep phenotyping in a mouse model of extreme trait anxiety

Background

There is accumulating evidence that anxiety impairs sleep. However, due to high sleep variability in anxiety disorders, it has been difficult to state particular changes in sleep parameters caused by anxiety. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology.

Methodology/Principal Findings

Sleep-wake behavior in mouse lines with high (HAB), low (LAB) and normal (NAB) anxiety-related behaviors was monitored for 24 h during baseline and recovery after 6 h sleep deprivation (SD). The amounts of each vigilance state, sleep architecture, and EEG spectral variations were compared between the mouse lines. In comparison to NAB mice, HAB mice slept more and exhibited consistently increased delta power during non-rapid eye movement (NREM) sleep. Their sleep patterns were characterized by heavy fragmentation, reduced maintenance of wakefulness, and frequent intrusions of rapid eye movement (REM) sleep. In contrast, LAB mice showed a robust sleep-wake rhythm with remarkably prolonged sleep latency and a long, persistent period of wakefulness. In addition, the accumulation of delta power after SD was impaired in the LAB line, as compared to HAB mice.

Conclusions/Significance

Sleep-wake patterns were significantly different between HAB and LAB mice, indicating that the genetic predisposition to extremes in trait anxiety leaves a biological scar on sleep quality. The enhanced sleep demand observed in HAB mice, with a strong drive toward REM sleep, may resemble a unique phenotype reflecting not only elevated anxiety but also a depression-like attribute.     

Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia

Background

Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.

Methodology/Principal Findings

Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (∼11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.

Conclusions/Significance

Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.     

Association between Poor Glycemic Control,Impaired Sleep Quality,and Increased Arterial Thickening in Type 2 Diabetic Patients

Objective

Poor sleep quality is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and objective sleep architecture and its influence on arteriosclerosis in patients with type-2 diabetes mellitus (DM). The present study examined the association of objective sleep architecture with both glycemic control and arteriosclerosis in type-2 DM patients.

Design

Cross-sectional study in vascular laboratory.

Methods

The subjects were 63 type-2 DM inpatients (M/F, 32/31; age, 57.5±13.1) without taking any sleeping promoting drug and chronic kidney disease. We examined objective sleep architecture by single-channel electroencephalography and arteriosclerosis by carotid-artery intima-media thickness (CA-IMT).

Results

HbA1c was associated significantly in a negative manner with REM sleep latency (interval between sleep-onset and the first REM period) (β=-0.280, p=0.033), but not with other measurements of sleep quality. REM sleep latency associated significantly in a positive manner with log delta power (the marker of deep sleep) during that period (β=0.544, p=0.001). In the model including variables univariately correlated with CA-IMT (REM sleep latency, age, DM duration, systolic blood pressure, and HbA1c) as independent variables, REM sleep latency (β=-0.232, p=0.038), but not HbA1c were significantly associated with CA-IMT. When log delta power was included in place of REM sleep latency, log delta power (β=-0.257, p=0.023) emerged as a significant factor associated with CA-IMT.

Conclusions

In type-2 DM patients, poor glycemic control was independently associated with poor quality of sleep as represented by decrease of REM sleep latency which might be responsible for increased CA-IMT, a relevant marker for arterial wall thickening.     

Delayed Onset of a Daytime Nap Facilitates Retention of Declarative Memory

Background

Learning followed by a period of sleep, even as little as a nap, promotes memory consolidation. It is now generally recognized that sleep facilitates the stabilization of information acquired prior to sleep. However, the temporal nature of the effect of sleep on retention of declarative memory is yet to be understood. We examined the impact of a delayed nap onset on the recognition of neutral pictorial stimuli with an added spatial component.

Methodology/Principal Findings

Participants completed an initial study session involving 150 neutral pictures of people, places, and objects. Immediately following the picture presentation, participants were asked to make recognition judgments on a subset of “old”, previously seen, pictures versus intermixed “new” pictures. Participants were then divided into one of four groups who either took a 90-minute nap immediately, 2 hours, or 4 hours after learning, or remained awake for the duration of the experiment. 6 hours after initial learning, participants were again tested on the remaining “old” pictures, with “new” pictures intermixed.

Conclusions/Significance

Interestingly, we found a stabilizing benefit of sleep on the memory trace reflected as a significant negative correlation between the average time elapsed before napping and decline in performance from test to retest (p = .001). We found a significant interaction between the groups and their performance from test to retest (p = .010), with the 4-hour delay group performing significantly better than both those who slept immediately and those who remained awake (p = .044, p = .010, respectively). Analysis of sleep data revealed a significant positive correlation between amount of slow wave sleep (SWS) achieved and length of the delay before sleep onset (p = .048). The findings add to the understanding of memory processing in humans, suggesting that factors such as waking processing and homeostatic increases in need for sleep over time modulate the importance of sleep to consolidation of neutral declarative memories.     

Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia

Background

Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep.

Methodology/Principal Findings

To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control.

Conclusions/Significance

These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD).     

Amygdala opioid receptors mediate the electroacupuncture-induced deterioration of sleep disruptions in epilepsy rats

Background

Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control. Effects of acupuncture of Feng-Chi (GB20) acupoints on epilepsy suppression and insomnia treatment have been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot). Therefore, this study was designed to investigate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi acupoints on sleep disruptions in rats with focal epilepsy.

Results

Our result indicates that administration of pilocarpine into the left central nucleus of amygdala (CeA) induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep. High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints, in which a 30-min EA stimulation was performed before the dark period of the light:dark cycle in three consecutive days, further deteriorated pilocarpine-induced sleep disruptions. The EA-induced exacerbation of sleep disruption was blocked by microinjection of naloxone, μ- (naloxonazine), κ- (nor-binaltorphimine) or δ-receptor antagonists (natrindole) into the CeA, suggesting the involvement of amygdaloid opioid receptors.

Conclusion

The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints exhibits no benefit in improving pilocarpine-induced sleep disruptions; in contrast, EA further deteriorated sleep disturbances. Opioid receptors in the CeA mediated EA-induced exacerbation of sleep disruptions in epileptic rats.     

Early Postnatal EEG Features of Perinatal Arterial Ischaemic Stroke with Seizures

Background

Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases.

Objective

To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS) seizures.

Design

Retrospective observational study.

Patients

Neonates >37 weeks born between 2003 and 2011 in two hospitals.

Method

Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized.

Results

Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction) when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1–2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%).

Conclusions

Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance.     

Evaluation of two minimally invasive techniques for electroencephalogram recording in wild or freely behaving animals

Insight into the function of sleep may be gained by studying animals in the ecological context in which sleep evolved. Until recently, technological constraints prevented electroencephalogram (EEG) studies of animals sleeping in the wild. However, the recent development of a small recorder (Neurologger 2) that animals can carry on their head permitted the first recordings of sleep in nature. To facilitate sleep studies in the field and to improve the welfare of experimental animals, herein, we test the feasibility of using minimally invasive surface and subcutaneous electrodes to record the EEG in barn owls. The EEG and behaviour of four adult owls in captivity and of four chicks in a nest box in the field were recorded. We scored a 24-h period for each adult bird for wakefulness, slow-wave sleep (SWS), and rapid-eye movement (REM) sleep using 4 s epochs. Although the quality and stability of the EEG signals recorded via subcutaneous electrodes were higher when compared to surface electrodes, the owls’ state was readily identifiable using either electrode type. On average, the four adult owls spent 13.28 h awake, 9.64 h in SWS, and 1.05 h in REM sleep. We demonstrate that minimally invasive methods can be used to measure EEG-defined wakefulness, SWS, and REM sleep in owls and probably other animals.     

The Relationship between Thermoregulation and REM Sleep Behaviour Disorder in Parkinson’s Disease

Background

This study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinson’s Disease.

Methods

The study group comprised 12 patients with Parkinson’s Disease and 11 healthy age-matched controls. We investigated markers of thermoregulation (core-body temperature profile), circadian rhythm (locomotor actigraphy) and sleep (polysomnography).

Results

The mesor (the mean value around which the core temperature rhythm oscillates) of the core-body temperature in patients with Parkinson’s Disease was significantly lower than that of controls. In addition, the nocturnal fall in CBT (the difference between the mesor and the nadir temperature) was also significantly reduced in PD patients relative to controls. Furthermore, in patients the reduction in the amplitude of their core-body temperature profile was strongly correlated with the severity of self-reported rapid eye movement sleep behaviour disorder symptom, reduction in the percentage of REM sleep and prolonged sleep latency. By contrast, these disturbances of thermoregulation and sleep architecture were not found in controls and were not related to other markers of circadian rhythm or times of sleep onset and offset.

Conclusions

These findings suggest that the brainstem pathology associated with disruption of thermoregulation in Parkinson’s disease may also contribute to rapid eye movement sleep behavioural disorder. It is possible that detailed analysis of the core-body temperature profile in at risk populations such as those patients with idiopathic rapid eye movement sleep behaviour disorder might help identify those who are at high risk of transitioning to Parkinson’s Disease.     

Factors Influencing Sleep Disturbances among Spouse Caregivers of Cancer Patients in Northeast China

Background

In China, spouse caregivers of cancer patients (SCCPs) are involved in all aspects of patient care and experience psychological distress which could result in sleep disturbance and fatigue. However, few studies have explored the differences between SCCPs and the general population, or what factors affect SCCPs'' sleep. This study aims to (1) Compare the differences in sleep disturbances and fatigue severity between SCCPs and the age- and gender-matched general population, and (2) Identify selected personal characteristics, including coping style that affect sleep disturbances in SCCPs.

Methodology/Principal Findings

The Stress and Coping Model was used to guide this study. Participants were recruited from the northeast part of China and included 600 people from the general population and 300 SCCPs. Participants completed a socio-demographic form, Fatigue Scale-14, trait Coping Style Questionnaire, and Symptom Checklist-90.

Results

The majority of the participants were middle age, most of whom (78.7%) spent more than 8 hours each day taking care of their spouses. Compared to the general population, the SCCPs experienced significant sleep disturbances with a mean of 7.30 (SD = 1.27), and fatigue severity with a mean of 8.11 (SD = 3.25). Among the selected SCCPs'' personal characteristics, current poor health status (β = 0.14, P<0.001), having a spouse under mixed treatment (β = 0.13, p<0.001), and financial burden (β = 0.14, P<0.001) are the significant predictors for sleep disturbances. Positive coping is the predictor for fewer sleep disturbances (β = 0.27, P<0.001). Those who reported sleep disturbances also experienced higher physical and mental fatigue severity (P<0.001).

Conclusion

Intervention to improve coping style in SCCPs is needed. Further research is also needed to explore the other mediators and moderators that regulate sleep disturbance and health outcomes in the SCCPs.