Gray matter-specific changes in brain bioenergetics after acute sleep deprivation: a 31P magnetic resonance spectroscopy study at 4 Tesla.

STUDY OBJECTIVES: A principal function of sleep may be restoration of brain energy metabolism caused by the energetic demands of wakefulness. Because energetic demands in the brain are greater in gray than white matter, this study used linear mixed-effects models to examine tissue-type specific changes in high-energy phosphates derived using 31P magnetic resonance spectroscopy (MRS) after sleep deprivation and recovery sleep. DESIGN: Experimental laboratory study. SETTING: Outpatient neuroimaging center at a private psychiatric hospital. PARTICIPANTS: A total of 32 MRS scans performed in eight healthy individuals (mean age 35 y; range 23-51 y). INTERVENTIONS: Phosphocreatine (PCr) and ß-nucleoside triphosphate (NTP) were measured using 31P MRS three dimensional-chemical shift imaging at high field (4 Tesla) after a baseline night of sleep, acute sleep deprivation (SD), and 2 nights of recovery sleep. Novel linear mixed-effects models were constructed using spectral and tissue segmentation data to examine changes in bioenergetics in gray and white matter. MEASUREMENTS AND RESULTS: PCr increased in gray matter after 2 nights of recovery sleep relative to SD with no significant changes in white matter. Exploratory analyses also demonstrated that increases in PCr were associated with increases in electroencephalographic slow wave activity during recovery sleep. No significant changes in ß-NTP were observed. CONCLUSIONS: These results demonstrate that sleep deprivation and subsequent recovery-induced changes in high-energy phosphates primarily occur in gray matter, and increases in PCr after recovery sleep may be related to sleep homeostasis.

Effects of sleep deprivation on brain bioenergetics, sleep, and cognitive performance in cocaine-dependent individuals.

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent ³¹P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, ³¹P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain ß-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: a [31]P MRS brain imaging study.

Insomnia afflicts many individuals, but particularly those in chronic methadone treatment. Studies examining sleep deprivation (SD) have begun to identify sleep restoration processes involving brain bioenergetics. The technique ([31])P magnetic resonance spectroscopy (MRS) can measure brain changes in the high-energy phosphates: alpha-, beta-, and gamma-nucleoside triphosphate (NTP). In the present study, 21 methadone-maintained (MM) and 16 control participants underwent baseline (BL), SD (40 wakeful hours), recovery1 (RE1), and recovery2 (RE2) study nights. Polysomnographic sleep was recorded each night and ([31])P MRS brain scanning conducted each morning using a 4T MR scanner (dual-tuned proton/phosphorus head-coil). Interestingly, increases in total sleep time (TST) and sleep efficiency index (SEI) commonly associated with RE sleep were not apparent in MM participants. Analysis of methadone treatment duration revealed that the lack of RE sleep increases in TST and SEI was primarily exhibited by short-term MM participants (methadone <12 months), while RE sleep in long-term MM (methadone >12 months) participants was more comparable to control participants. Slow wave sleep increased during RE1, but there was no difference between MM and control participants. Spectral power analysis revealed that compared to control participants; MM participants had greater delta, theta, and alpha spectral power during BL and RE sleep. ([31])P MRS revealed that elevations in brain beta-NTP (a direct measure of ATP) following RE sleep were greater in MM compared to control participants. Results suggest that differences in sleep and brain chemistry during RE in MM participants may be reflective of a disruption in homeostatic sleep function.

Effect of zolpidem on sleep in women with perimenopausal and postmenopausal insomnia: a 4-week, randomized, multicenter, double-blind, placebo-controlled study.

BACKGROUND: Although most adults in the United States obtain less sleep than they need, women report more sleep deprivation throughout their lifetime than do men. The prevalence of self-reported sleep difficulty increases as women make the transition from the premenopausal to the postmenopausal period. OBJECTIVE: The purpose of this study was to assess the clinical efficacy and safety of zolpidem as a treatment for insomnia in perimenopausal and postmenopausal women. METHODS: Women who were perimenopausal or postmenopausal for >or=6 months, who had developed insomnia in conjunction with menopausal symptoms, and who had difficulty maintaining sleep or had nonrestorative sleep for >or=6 months were eligible for this 4-week, multicenter study. Sleep maintenance difficulty had to occur an average of >or=3 nights per week and had to be accompanied by >or=2 nocturnal hot flashes, hot flushes, or night sweats. Patients were randomized in a double-blind fashion to 1 of 2 treatment groups--zolpidem 10 mg or placebo. Capsules were provided in weekly blister cards, and patients were instructed to take 1 capsule each night at bedtime. Patients recorded estimates of their sleep quality and quantity and daytime functioning on daily morning and evening questionnaires, and made weekly global assessments of sleep. RESULTS: The study included 141 women (mean age +/- SD, 50.8 +/- 4.5 years; age range, 39-60 years). Increases in reported total sleep time were significantly greater in the zolpidem group than in the placebo group (P < 0.01) for each treatment week. Wake time after sleep onset and number of awakenings decreased significantly in the zolpidem group compared with the placebo group (P < 0.05). Each week, approximately twice as many patients in the zolpidem group as in the placebo group reported improved sleep (P < 0.001 for each week). The improvement in sleep-related difficulty with daytime functioning was significantly greater in the zolpidem group than in the placebo group (P < 0.05). The effects of zolpidem did not diminish with the duration of treatment. CONCLUSIONS: Zolpidem 10 mg/d was effective and well tolerated in the treatment of menopause-related insomnia in perimenopausal and postmenopausal women.

Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group.

Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men.

STUDY OBJECTIVES: To investigate chemical changes in the brains of healthy adults after sleep deprivation and recovery sleep, using phosphorous magnetic resonance spectroscopy. DESIGN: Three consecutive nights (baseline, sleep deprivation, recovery) were spent in the laboratory. Objective sleep measures were assessed on the baseline and recovery nights using polysomnography. Phosphorous magnetic resonance spectroscopy scans took place beginning at 7 am to 8 am on the morning after each of the 3 nights. SETTING: Sleep laboratory in a private psychiatric teaching hospital. PARTICIPANTS: Eleven healthy young men. INTERVENTIONS: Following a baseline night of sleep, subjects underwent a night of total sleep deprivation, which involved supervision to ensure the absence of sleep but was not polysomnographically monitored. MEASUREMENTS AND RESULTS: No significant changes in any measure of brain chemistry were observed the morning after a night of total sleep deprivation. However, after the recovery night, significant increases in total and beta-nucleoside triphosphate and decreases in phospholipid catabolism, measured by an increase in the concentration of glycerylphosphorylcholine, were observed. Chemical changes paralleled some changes in objective sleep measures. CONCLUSIONS: Significant chemical changes in the brain were observed following recovery sleep after 1 night of total sleep deprivation. The specific process underlying these changes is unclear due to the large brain region sampled in this exploratory study, but changes may reflect sleep inertia or some aspect of the homeostatic sleep mechanism that underlies the depletion and restoration of sleep. Phosphorous magnetic resonance spectroscopy is a technique that may be of value in further exploration of such sleep-wake functions.