Showing papers on "Slow-wave sleep published in 2002"
TL;DR: Rats repeatedly ran through a sequence of spatial receptive fields of hippocampal CA1 place cells in a fixed temporal order, consistent with evidence that the hippocampus is crucial for spatial learning in rodents and the formation of long-term memories of events in time in humans.
1,149 citations
TL;DR: Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience, and spindle density was correlated to recall performance both before and after sleep.
Abstract: Declarative memory consolidation is enhanced by sleep. In the investigation of underlying mechanisms, mainly rapid eye movement (REM) sleep and slow-wave sleep have been considered. More recently, sleep stage 2 with sleep spindles as a most prominent feature has received increasing attention. Specifically, in rats hippocampal ripples were found to occur in temporal proximity to cortical sleep spindles, indicating an information transfer between the hippocampus and neocortex, which is supposed to underlie the consolidation of declarative memories during sleep. This study in humans looks at the changes in EEG activity during nocturnal sleep after extensive training on a declarative learning task, as compared with a nonlearning control task of equal visual stimulation and subjectively rated cognitive strain. Time spent in each sleep stage, spindle density, and EEG power spectra for 28 electrode locations were determined. During sleep after training, the density of sleep spindles was significantly higher after the learning task as compared with the nonlearning control task. This effect was largest during the first 90 min of sleep ( p < 0.01). Additionally, spindle density was correlated to recall performance both before and after sleep ( r = 0.56; p < 0.05). Power spectra and time spent in sleep stages did not differ between learning and nonlearning conditions. Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience.
772 citations
TL;DR: Data indicate that disruption of HA-synthesis causes permanent changes in the cortical-EEG and sleep–wake cycle and that, at moments when high vigilance is required, mice lacking brain HA are unable to remain awake, a prerequisite condition for responding to behavioral and cognitive challenges.
Abstract: The hypothesis that histaminergic neurons are involved in brain arousal is supported by many studies However, the effects of the selective long-term abolition of histaminergic neurons on the sleep–wake cycle, indispensable in determining their functions, remain unknown We have compared brain histamine(HA)-immunoreactivity and the cortical-EEG and sleep–wake cycle under baseline conditions or after behavioral or pharmacological stimuli in wild-type (WT) and knock-out mice lacking the histidine decarboxylase gene (HDC−/−) HDC−/−mice showed an increase in paradoxical sleep, a decrease in cortical EEG power in θ-rhythm during waking (W), and a decreased EEG slow wave sleep/W power ratio Although no major difference was noted in the daily amount of spontaneous W, HDC−/−mice showed a deficit of W at lights-off and signs of somnolence, as demonstrated by a decreased sleep latencies after various behavioral stimuli, eg, WT-mice placed in a new environment remained highly awake for 2–3 hr, whereas HDC−/−mice fell asleep after a few minutes These effects are likely to be attributable to lack of HDC and thus of HA In WT mice, indeed, intraperitoneal injection of α-fluoromethylhistidine (HDC-inhibitor) caused a decrease in W, whereas injection of ciproxifan (HA-H3 receptor antagonist) elicited W Both injections had no effect in HDC−/−mice Moreover, PCR and immunohistochemistry confirmed the absence of the HDC gene and brain HA-immunoreactive neurons in the HDC−/−mice These data indicate that disruption of HA-synthesis causes permanent changes in the cortical-EEG and sleep–wake cycle and that, at moments when high vigilance is required (lights off, environmental change… ), mice lacking brain HA are unable to remain awake, a prerequisite condition for responding to behavioral and cognitive challenges We suggest that histaminergic neurons also play a key role in maintaining the brain in an awake state faced with behavioral challenges
468 citations
TL;DR: The results of a series of studies on total and selective sleep deprivation in the rat are integrated and several changes suggested that sleep may be necessary for effective thermoregulation.
Abstract: The results of a series of studies on total and selective sleep deprivation in the rat are integrated and discussed. These studies showed that total sleep deprivation, paradoxical sleep deprivation, and disruption and/or deprivation of non-rapid eye movement (NREM) sleep produced a reliable syndrome that included death, debilitated appearance, skin lesions, increased food intake, weight loss, increased energy expenditure, decreased body temperature during the late stages of deprivation, increased plasma norepinephrine, and decreased plasma thyroxine. The significance of this syndrome for the function of sleep is not entirely clear, but several changes suggested that sleep may be necessary for effective thermoregulation.
442 citations
TL;DR: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.
Abstract: Objective: To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome (RLS). Methods: Patients with RLS (22 idiopathic, 2 secondary to iron deficiency) were randomized and treated for 6 weeks with either gabapentin or placebo. After a 1-week washout they crossed over to the alternative treatment for 6 weeks. Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. At the end of each treatment period, all-night polysomnography was performed. Results: Compared to placebo, gabapentin was associated with reduced symptoms on all rating scales. In addition, sleep studies showed a significantly reduced periodic leg movements during sleep (PLMS) index and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin. The mean effective dosage at the end of the 6-week treatment period was 1,855 mg, although therapeutic effects were already observed at the end of week 4 (1,391 mg). Conclusions: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.
375 citations
TL;DR: Findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
344 citations
TL;DR: NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep.
Abstract: Design: We compared EEG frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective insomnia sufferers (those with relatively long total sleep time and relative underestimation of sleep time compared with PSG), and objective insomnia sufferers (those with relatively short PSG total sleep time) with EEG frequency spectra in normals. We also studied the correlation between these indices and the degree of underestimation of sleep. Further, we determined the degree to which sleep EEG indexes related to sleep complaints. Setting: Duke University Medical Center Sleep Laboratory. Participants: Normal (N=20), subjective insomnia (N=12), and objective insomnia (N=18) subjects. Interventions: N/A Measurements and Results: Lower delta and greater alpha, sigma, and beta NREM EEG activity were found in the patients with subjective insomnia but not those with objective insomnia, compared with the normal subjects. These results were robust to changes in the subtyping criteria. No effects were found for REM spectral indexes. Less delta non- REM EEG activity predicted greater deviation between subjective and PSG estimates of sleep time across all subjects. For the subjective insomnia subjects, diminished low-frequency and elevated higher frequency non- REM EEG activity was associated with their sleep complaints. Conclusions: NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep.
306 citations
TL;DR: Current opinion is that partial sleep deprivation in the second half of the night is equally effective as TSD, and new data cast doubt on the time-honoured conviction that REM sleep deprivation is more effective than non-REM SD.
272 citations
TL;DR: The negative transmodal BOLD response which is most pronounced during NREM sleep stages 1 and 2 reflects a deactivation predominantly in the visual cortex suggesting that this decrease in neuronal activity protects the brain from the arousing effects of external stimulation during sleep not only in the primary targeted sensory cortex but also in other brain regions.
182 citations
TL;DR: The findings suggest that the nonlinear properties of the heartbeat dynamics are more pronounced during REM sleep, which is useful in distinguishing between the sleep stages.
Abstract: We study correlation properties of the magnitude and the sign of the increments in the time intervals between successive heartbeats during light sleep, deep sleep, and rapid eye movement ~REM! sleep using the detrended fluctuation analysis method. We find short-range anticorrelations in the sign time series, which are strong during deep sleep, weaker during light sleep, and even weaker during REM sleep. In contrast, we find long-range positive correlations in the magnitude time series, which are strong during REM sleep and weaker during light sleep. We observe uncorrelated behavior for the magnitude during deep sleep. Since the magnitude series relates to the nonlinear properties of the original time series, while the sign series relates to the linear properties, our findings suggest that the nonlinear properties of the heartbeat dynamics are more pronounced during REM sleep. Thus, the sign and the magnitude series provide information which is useful in distinguishing between the sleep stages.
174 citations
TL;DR: The purpose was to study the effect of gabapentin (GBP) on sleep and the effects of the newer AEDs on sleep are unknown.
Abstract: Summary: Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep.
Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test.
Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects.
Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption.
TL;DR: The role of sleep and sleep deprivation in the EEG evaluation of epilepsy is discussed and seizures appear to have a very close relationship with sleep in certain epilepsy syndromes.
Abstract: There is an extremely intimate relationship between sleep and epilepsy. In this manuscript I will review the influence that sleep has on epilepsy. Sleep is a potent activator of interictal epileptiform discharges. Sharp waves are infrequent during wakefulness in benign focal epilepsy of childhood, but may occur in runs of several discharges per page in sleep. The interictal discharges become almost continuous in non-REM sleep in the syndrome of encephalopathy with electrical status epilepticus during slow wave sleep. In some patients with West syndrome a hypsarrhythmia pattern may only appear in sleep whereas in others there may be an increase in discharges in a semiperiodic fashion resulting in a burst-suppression like pattern. Seizures appear to have a very close relationship with sleep in certain epilepsy syndromes. In benign focal epilepsy of childhood the seizures occur almost exclusively in sleep, while supplementary sensorimototor area seizures tend to occur in clusters during sleep. Juvenile myoclonic epilepsy has a close relationship with the sleep-wake cycle with seizures tending to occur predominantly on awakening. I also discuss the role of sleep and sleep deprivation in the EEG evaluation of epilepsy.
TL;DR: While deeper stages of NREM sleep activate IEDs, lighter stages ofNREM sleep promote seizures, at least for single seizures occurring in 1 night.
Abstract: Study objectives Interictal epileptiform discharges (IEDs) are facilitated by NREM stages 3 and 4 sleep and as sleep is deepening. To determine whether sleep influences seizures in a similar way to IEDs, we examined seizure rates in various stages of sleep in epilepsy patients undergoing overnight video-EEG-polysomnography (VPSG). Design Cross-sectional study. Setting Neurology Department. PATIENTS, MEASUREMENTS, AND INTERVENTIONS: We reviewed VPSGs from our Sleep and Epilepsy Laboratories to identify patients with recorded seizures during sleep. A total of 55 patients having 117 seizures were identified. Results Ninety-five percent of seizures occurred in NREM sleep (61% in stage 2, 20% in stage 1, 14% in stages 3 and 4 combined), and 5% in REM sleep. Adjusting for time spent in each stage of sleep, patients had 0.34 seizures per hour in stage 1, 0.38 seizures per hour in stage 2, 0.29 seizures/hr in stage 3 and 4 combined, and 0.09 seizures per hour in REM sleep. Seizures/hour was higher in NREM sleep (0.35 for NREM and 0.09 for REM; p=0.0001). For single seizures occurring in 1 night, seizure rate was significantly higher in NREM stages 1 and 2 as compared to NREM stages 3 and 4 sleep. A significant increase in log delta power, an automated measure of sleep depth, was observed in the 10 minutes prior to seizures. Conclusions Both seizures and IEDs are facilitated by NREM sleep. While deeper stages of NREM sleep activate IEDs, lighter stages of NREM sleep promote seizures, at least for single seizures occurring in 1 night.
TL;DR: Indicating a priming-like enhancement of emotional reactivity after periods rich in REM sleep, results do not confirm a cathartic function of REM sleep or sleep in general.
Abstract: OBJECTIVE Since Freud's "Interpretation of Dreams," sleep has been related to emotional functions, where dreams were assumed to play a cathartic role. In psychophysiological research, this role was attributed mainly to rapid eye movement (REM) sleep. The present study compared processing pictures with negative emotional impact over intervals covering either early sleep dominated by slow-wave sleep (SWS) or late REM sleep-dominated sleep. METHOD Emotional reactions were assessed by a nonverbal rating procedure along the two emotional dimensions valence (positive vs. negative) and arousal (low vs. high). Two groups of healthy men were tested across 3-hour periods of early and late nocturnal sleep (sleep group) or corresponding intervals filled with wakefulness (wake group). After the intervals, subjects rated new pictures together with old pictures already presented before the interval. Sleep was recorded polysomnographically. RESULTS As expected, the amount of REM sleep was about three times greater during late than early nocturnal sleep, whereas a reversed distribution was observed for SWS (p<.001). Valence ratings indicated a shift toward enhanced negative ratings after late sleep (p<.05), contrasting with a trend toward more positive ratings after early sleep (p<.10). Arousal habituated slightly to repeated presentation of the same stimuli, but sleep generally enhanced subsequent arousal ratings (p<.05). Effects of sleep did not depend on whether pictures had low or high emotional impact. CONCLUSIONS Indicating a priming-like enhancement of emotional reactivity after periods rich in REM sleep, results do not confirm a cathartic function of REM sleep or sleep in general.
TL;DR: It is concluded that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not, and the methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.
TL;DR: The increase in K-complex frequency together with the decrease seen in stimulus-related alpha activity supports the view that they reflect a sleep maintenance, rather than an arousal, response.
Abstract: Study objectives To determine whether K-complex production is better interpreted as being an arousal response or reflective of a sleep protective micro-state. Design A 3-night study--night 1 as a baseline night, night 2 as a sleep fragmentation night, followed immediately by night 3 as a recovery night. On nights 1 and 3, approximately 400 auditory stimuli were presented during nonREM sleep in the first two sleep cycles, using stimulus parameters previously found to be optimal for K-complex production. Setting The sleep research laboratory at the University of Melbourne. Participants Six young healthy subjects (3 female). Interventions One night of sleep fragmentation. Ten-second auditory tones of up to 110 dB were presented throughout the entire night at approximately 1-minute intervals. Measurements and results Sleep drive was increased on the recovery night, as indicated by increased amounts of slow wave sleep, increased sleep efficiency, and a reduction in stimulus-related alpha activity. The incidence of both evoked and spontaneous K-complexes increased significantly on the recovery night. When K-complex trials were averaged, neither N550 (Fz) amplitude nor latency differed between the 2 nights. When vertex sharp waves were averaged, N350 (Cz) amplitude was increased significantly on the recovery night. Conclusions The increase in K-complex frequency together with the decrease seen in stimulus-related alpha activity supports the view that they reflect a sleep maintenance, rather than an arousal, response.
TL;DR: Sleep-disordered breathing during NREM sleep, but not REM sleep, is associated with increased risk of daytime sleepiness, according to the multiple sleep latency test.
Abstract: SLEEP-DISORDERED BREATHING IS CHARACTERIZEDBY REPETITIVE EPISODES OF PARTIAL OR COMPLETECOLLAPSE OF THE UPPER AIRWAY DURING SLEEP. Theresulting decrease or cessation in airflow is often associated withoxyhemoglobin desaturation and/or an arousal from sleep. Inpatients with sleep-disordered breathing, respiratory events mayoccur throughout non-rapid eye movement (NREM) and rapideye movement (REM) sleep. The typical finding is that respira-tory events during REM sleep are longer and are associated witha greater degree of hypoxemia than events that occur duringNREM sleep. These characteristics may be related to the markeddifferences in arousal responses to respiratory stimuli (i.e.,hypoxemia and hypercapnia) between REM and NREM sleep.In general, greater stimulus intensities are required to elicit anarousal from REM than NREM sleep.
TL;DR: It is demonstrated that depression induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg of trazodone, thus suggesting a key-lock principle in the treatment of depression.
Abstract: Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (five females, six males) aged 35-75 years (mean age 54.1 +/- 11.4) suffering from nonorganic insomnia (F 51.0) related to a depressive episode (F 32) or recurrent depressive disorder (F 33). as compared with 11 age- and sex-matched normal controls (five females, six males) aged 36-75 years (mean age 53.0 +/- 13.5). PSG demonstrated decreased sleep efficiency, total sleep time (TST), total sleep period (TSP) and sleep stage S2, as well as increased wakefulness during TSP, early morning awakening, sleep latency to S1, S2, S3 and sleep stage S1 in depressed patients. Subjective sleep quality and the total score of the Self-Assessment of Sleep and Awakening Quality Scale (SSA) were deteriorated as were morning and evening well being, drive, mood and fine motor activity right. Evening and morning blood pressure, the O2 desaturation index and periodic leg movement (PLM) index were increased. In a subsequent acute, placebo-controlled cross-over design study, the acute effects of 100 mg of trazodone, a serotonin reuptake inhibitor with a sedative action due to 5-HT2 and alpha1 receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in sleep efficiency (primary target variable), TST, TSP and SWS (S3 + S4), as well as a decrease in wakefulness during the TSP, early morning awakening and S2. There was no change in rapid eye movement (REM) sleep with the exception of an increase in the REM duration in minutes. Trazodone also caused an improvement in subjective sleep quality, affectivity, numerical memory and somatic complaints. All respiratory variables remained within normal limits. Critical flicker frequency and moming diastolic blood pressure were decreased. The present study demonstrated that depression induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg of trazodone, thus suggesting a key-lock principle in the treatment of depression.
TL;DR: The findings suggest that mirtazapine has considerable effects on slow wave sleep, and further studies are recommended to investigate the efficiency of antidepressants, in respect to the effects of 5-HT2 blockade onSlow wave sleep.
Abstract: Study objectives Mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant. This study aims at objectively investigating the effects of single-dose mirtazapine on sleep of healthy volunteers. Design and setting We studied the effect of acute administration of mirtazapine (30 mg) on the sleep polysomnogram, using a double-blind, placebo-controlled design. Subjects spent 3 consecutive nights in the laboratory. First night allowed for adaptation to the laboratory and application of electroencephalogram electrodes, while the second and third nights were reserved for recording baseline sleep and studying the effects of drug treatment, respectively. Participants Young healthy volunteers (n=20), with a mean age of 24 years, were randomly separated into two groups: placebo (n=10) and mirtazapine (n=10). Interventions On the third night, subjects received either placebo or mirtazapine. Comparisons were made between sleep variables from baseline values in both groups. Independent samples t-test was utilized to evaluate the differences between the two groups. Measurement and results Mirtazapine improved the variables related to sleep continuity when compared with placebo. It increased the sleep efficiency index, while decreasing the number of awakenings and their duration. The slow wave sleep time was increased, while the stage 1 sleep time was decreased significantly. There was no significant effect on rapid eye movement sleep variables. Conclusion Our findings suggest that mirtazapine has considerable effects on slow wave sleep. Further studies are recommended to investigate the efficiency of antidepressants, in respect to the effects of 5-HT2 blockade on slow wave sleep.
TL;DR: The most likely explanation for the altered sleep architecture noted to occur in women who are fully breastfeeding their infants is an increase in circulating PRL, which occurs in lactating women.
Abstract: Major physiological changes occur following parturition and the onset of lactation, including the withdrawal of oestrogen and progesterone, with a consequent increase in circulating prolactin (PRL). Changes in other circulating hormones are well known to alter sleep architecture in other circumstances. We therefore aimed to assess whether sleep architecture is altered in fully lactating women as a result of hormonal changes associated with lactation. A descriptive comparison study was undertaken on 12 fully breastfeeding women (B/F), 12 age-matched control women (CTRL), and seven postnatal women who had chosen to bottle-feed their infants (BOTTLE). Maternal age, infant age and body mass index (BMI) were similar between all three groups. We performed overnight polysomnography utilizing the Portable Compumedics P-series. The total sleep time (TST) and rapid eye movement (REM) sleep time were similar in the three groups of women. However, B/F women demonstrated a marked increase in slow wave sleep (SWS), 182 +/- 41 min compared with CTRL (86 +/- 22 min, P < 0.001 compared with B/F) and BOTTLE subjects (63 +/- 29 min, P < 0.001 compared with B/F). There was a compensatory reduction in light non-rapid eye movement (NREM) sleep in B/F when compared with CTRL and BOTTLE. The most likely explanation for the altered sleep architecture noted to occur in women who are fully breastfeeding their infants is an increase in circulating PRL, which occurs in lactating women. Enhanced SWS may be another important factor to support breastfeeding in the postnatal period.
TL;DR: Sleep-disordered breathing seems to be frequently associated with parasomnias during slow wave sleep, emphasizing the utility of performing esophageal pressure monitoring in cases of sleep walking or night terrors.
Abstract: STUDY OBJECTIVES: The aim of the study was to determine the role of respiratory events, assessed by means of esophageal pressure monitoring, during arousals from slow wave sleep in adult patients with parasomnias. DESIGN: N/A. SETTING: N/A. PATIENTS: Ten patients with parasomnias (sleepwalking, night terrors, or both) and 10 control subjects matched for gender and age underwent 3 consecutive nights of polysomnography. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: By increasing sleep fragmentation, esophageal pressure monitoring has a deleterious effect on sleep architecture in patients with parasomnias and in control subjects. Respiratory events occur more frequently in parasomniacs than in controls. Respiratory effort seems to be responsible for the occurrence of a great number of arousal reactions in parasomniacs and is involved in triggering the parasomnia episodes. CONCLUSION: Sleep-disordered breathing seems to be frequently associated with parasomnias during slow wave sleep, emphasizing the utility of performing esophageal pressure monitoring in cases of sleep walking or night terrors.
TL;DR: The data support the idea that unihemispheric sleep allows Cetaceans to monitor the environment and the state of both eyelids during sleep and wakefulness in a sub-adult male white whale over a 4-day-period.
TL;DR: This study reconfirms the previously described paradoxical stimulation-correlated negative BOLD signal change in the rostro-medial occipital cortex, expanding this response mode to an age spectrum ranging from the newborn to the adult.
TL;DR: Arousals show only one side of the multi-faceted activation complexes, whereas the three subtypes of CAP provide a graded picture of arousal features from the strongest A3 subtypes, showing a prevalence of EEG desynchrony, to the weakest A1 phases, which are dominated by EEG synchrony and represent the prevalent components of CAP.
TL;DR: Although it is suggested that geldanamycin is acting by upregulating or otherwise modulating molecular chaperone activity, the drug may also be modulating other pathways regulated by Hsp90, these studies have revealed a drug that can fully protect against the toxicity of α-synuclein to dopaminergic neurons in Drosophila.
Abstract: globally activate the stress response (data not shown), although the Lewy body–like inclusions immunolabel for Hsp70 (ref. 5). As 3 μg/ml prevents dopaminergic cell loss due to α-synuclein toxicity, it is possible that only a modest change in or redistribution of molecular chaperones is sufficient for neuroprotection. Current anti-PD agents, including levodopa, dopamine receptor agonists (such as bromocriptine), and monoamine oxidase B inhibitors (such as deprenyl), are designed to relieve the symptoms of PD by restoring dopamine levels in the basal ganglia. Our studies define a potential drug class that promotes the survival of dopaminergic neurons. Although we suggest that geldanamycin is acting by upregulating or otherwise modulating molecular chaperone activity, the drug may also be modulating other pathways regulated by Hsp90. Regardless, these studies have revealed a drug that can fully protect against the toxicity of α-synuclein to dopaminergic neurons in Drosophila. Geldanamycin and its derivatives warrant further exploration as cytoprotective agents for the treatment of neurodegenerative diseases involving α-synuclein toxicity, including PD.
TL;DR: The topography of the occipital activation during stage‐1 sleep supports a hypothesis of this state being a state of imagery, and the rCBF decreases in premotor cortex, thalamus and cerebellum could be indicative of a general decline in preparedness for goal directed action during stage-1 sleep.
Abstract: This is the first report on the distribution of regional cerebral blood flow (rCBF) changes during stage-1 sleep or somnolence. Two hypotheses were tested: (A) that rCBF differed between the awake relaxed state and stage-1 sleep, (B) that hypnagogic hallucinations frequently experienced at sleep onset would be accompanied by measurable changes in rCBF using positron emission tomography (PET). Eight subjects were PET-scanned with (15)O-labeled water injection in three conditions: awake, stage-1 sleep with reportable experiences and stage-1 sleep without reportable experiences. Electroencephalography (EEG) was performed continuously during the experiment. Sleep interviews were performed after each scan. The EEG was scored blindly to determine sleep stage. The sleep interviews revealed a substantial increase in how unrealistic and how leaping the thoughts were during stage-1 sleep. During sleep there was a relative flow increase in the occipital lobes and a relative flow decrease in the bilateral cerebellum, the bilateral posterior parietal cortex, the right premotor cortex and the left thalamus. Hypnagogic experiences seemed not to be associated with any relative flow changes. The topography of the occipital activation during stage-1 sleep supports a hypothesis of this state being a state of imagery. The rCBF decreases in premotor cortex, thalamus and cerebellum could be indicative of a general decline in preparedness for goal directed action during stage-1 sleep. Stage-1 sleep seems more similar to other forms of altered awareness, for example, relaxation meditation than to deeper sleep stages. We are of the opinion that stage-1 sleep represents the dreaming state of wakefulness, while rapid eye movement (REM) sleep reflects the dreaming state of the unaware, sleeping brain.
TL;DR: The preservation of light sleep in the face of severe loss of deep sleep in AE argues that 3 rather than the usually considered two (non REM and REM) independent states of sleep exist.
TL;DR: Preliminary results suggest that primary insomnia may be associated with abnormal central nervous system activity during NREM sleep that is particularly linked to basal ganglia dysfunction.
Abstract: Study Objectives: The objectives of this study were to: 1) demonstrate the feasibility of combining polysomnography and SPECT neuroimaging to study NREM sleep in primary insomnia and 2) evaluate possible functional CNS abnormalities associated with insomnia. Design: Patients with insomnia and good sleeper controls were studied polysomnographically for three nights with a whole brain SPECT Scan of NREM sleep on Night 3. Groups were screened for medical/psychiatric history, substance use, and matched on age, body mass index, and education. Setting: Sleep Research Laboratory and Nuclear Medicine Center Participants: Nine females, 5 patients with chronic psychophysiologic insomnia and 4 healthy good sleepers (mean age 36 years, SD 12, range 27-55). Interventions: N/A Measurements and Results: Tomographs of regional cerebral blood flow during the 1st NREM sleep cycle were successfully obtained. Contrary to our expectations, patients with insomnia showed a consistent pattern of hypoperfusion across all 8 pre-selected regions of interest, with particular deactivation in the basal ganglia (p=.006). The frontal medial, occipital, and parietal cortices also showed significant decreases in blood flow compared to good sleepers (p<.05). Subjects with insomnia had decreased activity in the basal ganglia relative to the frontal lateral cortex, frontal medial cortex, thalamus, occipital and parietal cortices (p<.05). Conclusions: This study demonstrated the feasibility of combining neuroimaging and polysomnography to study cerebral activity in chronic insomnia. These preliminary results suggest that primary insomnia may be associated with abnormal central nervous system activity during NREM sleep that is particularly linked to basal ganglia dysfunction.
TL;DR: This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge in idiopathic generalised epilepsy (IGE) patients and offers a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy.
Abstract: This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge (SWD) in idiopathic generalised epilepsy (IGE) patients. Numerous converging observations showed that full REM-sleep and alert wakefulness exert strong inhibition. A critical zone of vigilance which is a transitional state between waking and non-REM (NREM) sleep, and NREM sleep and REM sleep, has a promoting effect on the absence type spike wave discharge. Spike wave discharges are associated with phasic arousals without awakening and are attached to oscillation son the microstructural level of sleep, perpetuated by cyclic arousal events known as 'cyclic alternating pattern' (CAP), especially within the critical zone, but also along the whole sleep process. More specifically SWD seems to be attached to the 'A-phase' of CAP which is a reactive one and reflects synchronised NREM sleep EEG elements, like K-complexes, spindles and delta groups. The more slow wave elements are found in phase A--like in subtype A1--the more the coincidence with SWD occurs, and the more it is characterised by fast rhythms--as in subtype A2 and A3--the less the association with SWD could be observed. Since subtype A1 is associated with the first sleep cycle and with the descending branches of cycles, it is concluded that SWD appear in those dynamic moments of vigilance level oscillations which were characterised by strong sleep-like answers to arousal influences in high sleep pressure periods of sleep cyclicity. These data harmonize with another line of evidence suggesting that SWD represent the epileptic variant of the complex thalamocortical system function which is the substrate of NREM sleep EEG phenomena. In idiopathic generalised epilepsy there is a growing body of evidence that--as it was assumed by Gloor--spindles transform to SWD pattern. These data explain why those dynamic changes which evoke sleep responses are promoting for the occurrence of SWD. Adapting these data we offer a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy. We assume that it is mainly due to the forced vigilance level oscillations, especially in morning, when elevated sleep pressure and circadian wake promoting forces, representing opposite tendencies, increase the amount of oscillations.
TL;DR: Evidence is provided that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.
Abstract: Animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. Sleep‐wake states have been shown to differentially modulate the generation of epileptiform EEG spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. Using these statedependent mechanisms to assist us in identifying neuronal correlates of human epilepsy, we recorded interictal neuronal activity from mesial temporal lobe (MTL) areas in epileptic patients implanted with depth electrodes required for medical diagnosis during polysomnographically defined sleep‐wake states. Results show that single neurons recorded ipsilateral to seizure-initiating MTL (“epileptic”) areas had significantly higher firing rates ( p 0.01) and burst propensity ( p 0.01) and greater synchrony of discharges ( p 0.003) compared with neurons recorded from contralateral non-seizure-generating MTL (“non-epileptic”) areas. In particular, during episodes of slow wave sleep (SWS) and rapid eye movement (REM) sleep, epileptic hippocampal neurons had significantly higher burst rates compared with non-epileptic hippocampal neurons (both p 0.01). In contrast, during episodes of wakefulness (Aw), no difference in burst firing between epileptic and non-epileptic hippocampal neurons was observed. Furthermore, synchronous firing was significantly higher between epileptic MTL neurons compared with non-epileptic MTL neurons during SWS ( p 0.04) and REM sleep ( p 0.02), but no difference in neuronal synchrony was found between epileptic and nonepileptic neurons during Aw. These results provide evidence that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and confirm that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.