Cardiac autonomic regulation during sleep in idiopathic REM sleep behavior disorder

OBJECTIVE: To assess cardiac autonomic and respiratory changes from stage 2 non-rapid eye movement sleep (NREM) to rapid eye movement (REM) sleep in subjects with idiopathic REM sleep behavior disorder (RBD) and controls. We tested the hypothesis that REM-related cardiorespiratory activation is altered in subjects with RBD. DESIGN: Retrospective case-control study. SETTING: University hospital-based sleep research laboratory. PATIENTS: Ten subjects with idiopathic RBD (2 women, mean age 63.4 +/- 6.2 years) and 10 sex- and age-matched controls (mean age 63.9 +/- 6.3 years). INTERVENTION: One-night polysomnography was used to assess R-R variability during NREM and REM sleep. MEASUREMENTS AND RESULTS: Spectral analysis of R-R interval and respiration were performed. Mean R-R interval, low-frequency (LF) and high-frequency (HF) components in both absolute and normalized units (LFnu and HFnu), and the LF/HF ratio were obtained from 5-minute electrocardiogram segments selected during NREM and REM sleep under stable conditions (stable breathing pattern, no microarousals or leg movements). Respiratory frequency was also assessed. Values obtained were then averaged for each stage and analyzed by 2 x 2 analysis of variance with group (RBD subjects and controls) as factor and state (NREM and REM) as repeated measures. RR interval, HF, and HFnu components decreased from NREM to REM in controls but did not change in RBD subjects (Interaction P < 0.05). LFnu (interaction P < 0. 001), LF/HF (interaction P < 0. 001), and respiratory frequency (interaction P < 0. 05) increased from NREM to REM sleep in controls but remained stable in RBD subjects. CONCLUSION: REM-related cardiac and respiratory responses are absent in subjects with idiopathic RBD.     

Electrical activity of the cat amygdala during sexual behavior

Recordings from inplanted electrodes in the amygdala of male and female cats were taken during coitus and the female postcoital after reaction. In the female there was a marked increase in the amplitude and duration of the 30–40 Hz activity during coitus and after-reaction. In the male there was no observable change.     

Playback of female rat ultrasonic vocalizations during sexual behavior

Both male and female rats emit ultrasonic vocalizations during mating. In an earlier study, female vocalizations were shown to be associated with female darting: when the female was devocalized, she increased her rate of darting. In a preliminary playback study, tape-recorded female ultrasounds were presented to devocalized females paired with intact males. Darting was reduced towards presurgical control levels. In this study, the playback experiment was replicated using a refined procedure to present female ultrasounds to the mating rats. Taped vocalizations were obtained from females, and were presented in a manner which more closely approximated the patterning of ultrasound production seen in the intact female. Each rat pair was tested three times: once prior to the devocalization of the female, and twice afterwards. In one postsurgical test, taped ultrasounds were presented during mating; in the other, tape hiss was presented. Several patterns of behavior increased in frequency when the female was devocalized relative to the control condition, but decreased when tape recorded ultrasounds were presented. These patterns included female darting and approaches towards the partner by both males and females. The darting results confirm and extend the findings of our earlier paper. Changes in approach behavior were not observed previously because the male was confined in the earlier study. This study contains the first direct evidence that female vocalizations affect the socio-sexual behavior of the male.     

Time structure analysis of leg movements during sleep in REM sleep behavior disorder

STUDY OBJECTIVES: To compare the time structure of leg movements (LM) during sleep of patients with rapid eye movement (REM) sleep behavior disorder (RBD) with that of patients with restless legs syndrome (RLS) or control subjects. DESIGN: The polysomnographically recorded tibialis anterior activity during sleep was analyzed by means of a new approach able to consider duration, intermovement interval, sleep stage and time of night distribution, and periodicity. PATIENTS AND PARTICIPANTS: Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. MEASUREMENTS AND RESULTS: Most patients with RBD (85%) presented periodic leg movements during sleep (PLMS). PLMS occurred more frequently during non-REM sleep in patients with RLS and during REM sleep in patients with RBD. PLMS were shorter in duration, less often bilateral, and with a higher intermovement interval in patients with RBD compared to those with RLS. The number of PLMS decreased across the night in patients with RBD and in those with RLS, but not in control subjects. In all subjects, LM periodicity clearly depended on sleep state, with higher values during non-REM than during REM sleep. Patients with RBD showed a lower LM periodicity, compared with patients with RLS, in each of the sleep states. CONCLUSIONS: Significant differences, together with some similarities in LM time structure, were observed between patients with RBD and those with RLS; for this reason, our approach seems to indicate that their phenotype might be dependent on 2 factors: disease and sleep stage.     

REM sleep deprivation facilitates the estrogen effect on heterotypical sexual behavior in male rats

Gonadectomized male rats were submitted to REM sleep deprivation (REMd) for 120 hr and their hetero and homotypical sexual response to estradiol benzoate (EB) was tested. Subjects (Ss) receiving 20 micrograms EB showed lordosis quotients (LQ) twice as high as those receiving 10 micrograms EB and at the same time the LQs in these groups were higher than in the non-REMd groups. Gonadectomized-adrenalectomized control Ss showed the highest levels of lordosis throughout the experiment. REMd by itself does not produce lordosis response. The results indicate that the brain structures underlying this behavior in males are probably similar to those in females, since REMd increases lordosis in both cases. The lack of homotypical sexual behavior normally observed in gonadectomized male rats does not seem to be affected by this treatment. The issue of adequate controls for REMd experiments is discussed.     

Quantification of electromyographic activity during REM sleep in multiple muscles in REM sleep behavior disorder

STUDY OBJECTIVES: The aim of our study was to determine which muscle or combination of muscles (either axial or limb muscles, lower or upper limb muscles, or proximal or distal limb muscles) provides the highest rates of rapid eye movement (REM) sleep phasic electromyographic (EMG) activity seen in patients with REM sleep behavior disorder (RBD). SETTING: Two university hospital sleep disorders centers. PARTICIPANTS: Seventeen patients with idiopathic RBD (n = 8) and RBD secondary to Parkinson disease (n = 9). INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Patients underwent polysomnography, including EMG recording of 13 different muscles. Phasic EMG activity in REM sleep was quantified for each muscle separately. A mean of 1459.6 +/- 613.8 three-second REM sleep mini-epochs were scored per patient. Mean percentages of phasic EMG activity were mentalis (42 +/- 19), flexor digitorum superficialis (29 +/- 13), extensor digitorum brevis (23 +/- 12), abductor pollicis brevis (22 +/- 11), sternocleidomastoid (22 +/- 12), deltoid (19 +/- 11), biceps brachii (19 +/- 11), gastrocnemius (18 +/- 9), tibialis anterior (right, 17 +/- 12; left, 16 +/- 10), rectus femoris (left, 11 +/- 6; right, 9 +/- 6), and thoraco-lumbar paraspinal muscles (6 +/- 5). The mentalis muscle provided significantly higher rates of excessive phasic EMG activity than all other muscles but only detected 55% of all the mini-epochs with phasic EMG activity. Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles detected 82% of all mini-epochs containing phasic EMG activity. This combination provided higher rates of EMG activity than any other 3-muscle combination. Excessive phasic EMG activity was more frequent in distal than in proximal muscles, both in upper and lower limbs. CONCLUSION: Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD.     

Pituitary-gonadal function during sleep in men with hypoactive sexual desire and in normal controls

There is virtually no information on the psychobiology of hypoactive sexual desire (HSD) in men. This study compares pituitary and gonadal hormones and nocturnal penile tumescence (NPT) during sleep in 17 physically healthy men with HSD and 17 age-matched, nondysfunctional volunteers. There were six HSD men with problems of sexual arousal and 11 with secondary erectile impotence. The subjects, aged 27-55, were studied in a sleep laboratory for 4 nights with the last night devoted to sequential blood sampling every 20 min. The total group of HSD men had significantly lower plasma testosterone, measured hourly through the night, than controls, and there was a positive relation between testosterone and frequency of sexual behavior. There were no differences in free testosterone, prolactin, luteinizing hormone (LH), and estradiol between the HSD and control groups. The NPT parameters of HSD men with secondary impotence were consistently and significantly lower than the nondysfunctional men. These data are discussed with respect to the role of gonadal hormones in male sexual function, the significance of NPT as a window to central biologic events, and to possible heterogeneity of men with hypoactive sexual desire.     

EMG variance during polysomnography as an assessment for REM sleep behavior disorder

STUDY OBJECTIVES: In a previous study, we validated a polysomnographic assessment for REM sleep behavior disorder (RBD). The method proved to be reliable but required slow, labor-intensive visual scoring of surface electromyogram (EMG) activity. We therefore developed a computerized metric to assess EMG variance and compared the results to those previously published for visual scoring, bed partner-rated RBD symptom scores, and clinical assessments by sleep medicine specialists. DESIGN: Retrospective validation of new computer algorithm. SETTING: Sleep research laboratory PARTICIPANTS: Twenty-three subjects: 17 with neurodegenerative disorders (9 with probable or possible RBD), and 6 controls. INTERVENTIONS: N/A METHODS: We visually scored 2 consecutive nocturnal polysomnograms for each subject. A computer algorithm calculated the variance of the chin EMG during all 3-second mini-epochs, and compared variances during REM sleep to a threshold defined by variances during quiet NREM sleep. The percentage of all REM mini-epochs with variance above this threshold created a metric, which we refer to as the supra-threshold REM EMG activity metric (STREAM) for each subject. RESULTS: The STREAM correlated highly with the visually-derived score for RBD severity (Spearman rho = 0.87, P < 0.0001). A clinical impression of probable or possible RBD was associated to a similar extent with both STREAM (Wilcoxon rank sum test, P = 0.009) and the visually-derived score (P = 0.018). An optimal STREAM cutoff identified probable or possible RBD with 100% sensitivity and 71% specificity. The RBD symptom score correlated with both STREAM (rho = 0.42, P = 0.046) and the visual score (rho = 0.42, P = 0.048). CONCLUSIONS: These results suggest that a new, automated assessment for RBD may provide as much utility as a more time-consuming manual approach.     

Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients

OBJECTIVE: To evaluate the effectiveness of a clinician-delivered intervention, implemented during routine clinical care, in reducing unprotected sexual behavior of HIV-infected patients. DESIGN: A prospective clinical trial comparing the impact of a clinician-delivered intervention arm vs. a standard-of-care control arm on unprotected sexual behavior of HIV-infected patients. SETTING: The 2 largest HIV clinics in Connecticut. PARTICIPANTS: A total of 497 HIV-infected patients, aged > or =18 years, receiving HIV clinical care. INTERVENTION: HIV clinical care providers conducted brief client-centered interventions at each clinical encounter that were designed to help HIV-infected patients reduce unprotected sexual behavior. MAIN OUTCOME MEASURES: Unprotected insertive and receptive vaginal and anal intercourse and unprotected insertive oral sex; unprotected insertive and receptive vaginal and anal intercourse only. RESULTS: HIV-infected patients who received the clinician-delivered intervention showed significantly reduced unprotected insertive and receptive vaginal and anal intercourse and insertive oral sex over a follow-up interval of 18 months (P < 0.05). These behaviors increased across the study interval for patients in the standard-of-care control arm (P < 0.01). For the measure of unprotected insertive and receptive vaginal and anal sex only, there was a trend toward a reduction in unprotected sex among intervention arm participants over time (P < 0.09), and a significant increase in unprotected sex in the standard-of-care control arm (P < 0.01). CONCLUSIONS: A clinician-delivered HIV prevention intervention targeting HIV-infected patients resulted in reductions in unprotected sex. Interventions of this kind should be integrated into routine HIV clinical care.     

Sleep tendency during extended wakefulness: insights into adolescent sleep regulation and behavior

Sleep tendency (latency to sleep onset) was examined during extended waking in prepubertal and mature adolescents to determine whether sleep pressure is lower near bedtime in the latter group. Participants were nine prepubertal (pubertal stage Tanner 1, mean age 11.1 years, SD+/-1.3 years, five males) and 11 pubertally mature adolescents (Tanner 5, 13.9+/-1.2 years, three males). They spent 10 nights at home on an identical fixed 10-h sleep schedule followed by a 36-h constant routine with sleep latency tests at 2-h intervals using standard polysomnography. Saliva was collected to assess dim-light melatonin onset (DLMO) phase. DLMO was earlier in the Tanner 1 (mean clock time=20:33 hours, SD=49 min) than Tanner 5 group (21:29 hours+/-42 min). Sleep latency compared at a 'critical period' spanning 12.5 (20:30 hours clock time) to 18.5 h (02:30 hours) after waking did not differ at 20:30 hours, but was shorter for the Tanner 1 group at 22:30 hours (Tanner 1=9.2+/-6.3 min; Tanner 5=15.7+/-5.8 min), 00:30 hours (Tanner 1=3.6+/-1.7 min; Tanner 5=9.0+/-6.4 min), and 02:30 hours (Tanner 1=2.0+/-1.7 min; Tanner 5=4.3+/-3.2 min; trend). These differences were apparent controlling for circadian phase by partial correlation. Sleep tendency after 14.5, 16.5, and 18.5 h awake was lower in mature versus prepubertal adolescents, supporting our hypothesis that a developmental change of intrinsic sleep-wake regulation may provide physiologically mediated 'permission' for later bedtimes in older adolescents.     

Activation of POMC neurons during general arousal but not sexual behavior in male rats

Exogenous opioids influence male rat sexual behavior, suggesting that endogenous opioid peptides are released during mating. Supporting this hypothesis, the authors recently showed that mating induced activation of mu opioid receptors. However, it is unknown which ligand(s) is acting on these receptors during mating. The current set of experiments tested the hypothesis that beta-endorphin-producing neurons, that is, proopiomelanocortin (POMC) neurons, are activated during sexual behavior. Mating-induced activation of POMC neurons was investigated during either the dark phase or the light phase, following different components of male rat sexual behavior or following control manipulations that resulted in general arousal. Results show activation of POMC neurons in the mediobasal hypothalamus following general arousal but not specifically related to sexual behavior per se. In addition, mating did not activate the subpopulation of POMC neurons that project to the medial preoptic nucleus. These results suggest that it is unlikely that POMC neurons contribute to the action of endogenous opioids in the brain area during sexual behavior but instead may contribute to the change in arousal state essential for the expression of sexual behavior.     

Activity of peptidergic neurons in the amygdala during sexual behavior in the male rat

The medial amygdaloid nucleus (AME) occupies a central position in the circuitry that organizes sexual behavior in the male rat. It receives a projection from olfactory structures that are activated by pheromonal cues indicating receptivity in the female and projects in turn to limbic and hypothalamic structures that are thought to organize aspects of coitus. Electrical stimulation of the AME elicits a behavioral state that is indistinguishable by several measures from the post-ejaculatory interval. We used chronic single-unit recording techniques to determine the behavioral conditions in which the AME is normally active. We found that the cells indeed fired selectively during the presence of a receptive female, but that the discharge considerably anticipated copulation in time. We propose that sexual behavior in the male rat is a reaction chain of fixed action patterns, each one acting as a releaser for the next. The AME mediates an early event in the reaction chain, namely recognition of the receptive female, but electrical activation of the AME causes the reaction chain to proceed to its culminating behavior, the post-ejaculatory interval.     

Sex hormones and sexual behavior.

In certain animals the effects of gonadal steroids on sexual behavior are mediated directly by the central nervous system: however, in humans the degree to which sexual identity or sexual role behavior is directly determined by endocrine function is unclear. Furthermore, the relative importance of hormonal versus psychiatric, social, and cultural factors as determinents of sexual identify is in dispute. The findings of Imperato-McGinley and her associates, published in this issue, tend to support the theory that hormonal factors are of primary importance in determining male sexual identity. Patients with a deficiency of steroid 5alpha-reductase have decreased digydrotestosterone production during fetal development, and are thus born with female-like external genital organs. Generally they are raised as females but during childhood and puberty normal testerone activity takes place; therefore, at puberty the majority of these individuals assume a male identity. This identity change was attributed to androgen activity. Studies of this nature contribute to our understanding of the role of hormones; however, it must be kept in mind that the study provides only circumstantial evidence and that the findings do not rule out the possible influence of psychological, social, or cultural factors on sexual role behavior. For example, male pseudohermaphradites are frequently born with clitoromegaly, and during childhood this may introduce feelings of uncertainty as to sexual identity. Nor is it clear that the change to male identity is the result of the direct effect of testosterone on the central nervous system; the enlargement of accessory male organs at puberty may itself influence sexual role behavior.     

REM sleep characteristics in narcolepsy and REM sleep behavior disorder

STUDY OBJECTIVES: To assess the presence of polysomnographic characteristics of REM sleep behavior disorder (RBD) in narcolepsy; and to quantify REM sleep parameters in patients with narcolepsy, in patients with "idiopathic" RBD, and in normal controls. DESIGN: Sleep laboratory study PARTICIPANTS: Sixteen patients with narcolepsy and cataplexy matched for age and sex with 16 patients with "idiopathic" RBD and with 16 normal controls were studied. MEASUREMENTS AND RESULTS: Higher percentages of REM sleep without atonia, phasic electromyographic (EMG) activity, and REM density were found in patients with narcolepsy than normal controls. In contrast, RBD patients had a higher percentage of REM sleep without atonia but a lower REM density than patients with narcolepsy and normal controls. Based on a threshold of 80% for percentage of REM sleep with atonia, 50% of narcoleptics and 87.5% of RBD patients had abnormal REM sleep muscle activity. No significant behavioral manifestation in REM sleep was noted in either narcoleptics or controls. We also found a higher frequency of periodic leg movements during wake (PLMW) and during sleep (PLMS) in narcoleptic patients compared to controls. CONCLUSIONS: The present study demonstrates abnormalities in REM sleep motor regulation with an increased frequency of REM sleep without atonia, phasic EMG events and PLMS in narcoleptic patients when compared to controls. These abnormalities were seen more prominently in patients with RBD than in narcoleptics, with the exception of the PLMS index. We proposed that dysfunctions in hypocretin/dopaminergic system may lead to motor dyscontrol in REM sleep that results in dissociated sleep/wake states.     

Idiopathic central sleep apnea during REM sleep

Idiopathic central sleep apnea during rapid eye movement (REM) sleep is an extremely rare condition and only two cases have been reported so far. We present the case of a male patient who presented with chronic insomnia. Blood gas analysis during wakefulness suggested the presence of hypocapnia. Polysomnographic examination revealed central sleep apnea occurring predominantly during REM sleep. The patient responded well to continuous positive airway pressure (CPAP) at a pressure of 6 cmH₂O as well as to acetazolamide therapy.     

Dissociative experiences during sexual behavior among a sample of adults living with HIV infection and a history of childhood sexual abuse

Little attention has been given to the occurrence of dissociative symptoms during sexual behavior in adults who have experienced childhood sexual abuse (CSA). For this study, 57 adults living with HIV infection who had experienced CSA and were entering a treatment study for traumatic stress completed study assessments and clinical interviews, including a 15-item scale of dissociative experiences during sexual behavior. Predictor variables included Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnoses of posttraumatic stress disorder (PTSD) and dissociative disorders, rape by an intimate partner, duration of CSA, number of perpetrators of CSA, and current sexual satisfaction. A multiple regression analysis was conducted to identify significant associations between predictors and dissociation during sex. Mean differences by clinical diagnosis were also examined. Results indicated that PTSD, dissociative disorders, rape by an intimate partner, duration of CSA, and number of perpetrators of CSA were associated with increased dissociation during sexual behavior. Dissociation during sex likely increases vulnerability to sexual revictimization and risky sexual behavior. Standard behavioral prevention interventions may be ineffective for sexual situations when dissociation occurs, and prevention efforts should be integrated with mental health care for those who have experienced CSA.     

Adult sexual behavior deficits and altered hormone levels in male hamsters given steroids during development

Masculine sexual behavior and adult gonadotrophin and steroid hormone levels were assested in intact male hamsters (approximately 100 days old) which had received exogenous steroids on days 2–10 of postnatal life. Estradiol benzoate (EB), testosterone propionate (TP) or testosterone caused deficits in sexual behavior including elimination or decreases in ejaculatory capacity and intromission frequency. Androstenedione or progesterone had no effect on male sexual behavior. EB treatment caused increases in serum LH and FSH levels, normal serum androgen levels and reduced testis weight. TP neonatally administered resulted in decreased serum androgens and decreased testis weight but normal gonadotropin levels. Progesterone did not affect hormone levels or testis weight. Adult castration and TP replacement therapy in males treated neonatally with TP did not reinstate normal levels of ejaculation.     

Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder.

The clinical polysomnographic (PSG) reports of 2,650 consecutive adults studied during 41 months were reviewed retrospectively to identify all patients treated with fluoxetine or tricyclic antidepressants. The PSG reports of four other adult groups were also reviewed: periodic limb movement (PLM) disorder (n = 28); sleep terror/sleepwalking (ST/SW) (n = 54); rapid eye movement (REM) sleep behavior disorder (RBD) (n = 70); patients with clinically unremarkable sleep during two consecutive PSG studies (n = 30). Standard PSG recording and scoring methods were employed. A total of 1.5% (n = 41) and 2.0% (n = 52) of patients were receiving fluoxetine or tricyclics (amitriptyline or nortriptyline, n = 31; imipramine or desipramine, n = 16; protriptyline or trimipramine, n = 5). A selective association between fluoxetine and extensive, prominent eye movements in nonrapid eye movement (NREM) sleep was detected, utilizing Fisher's exact one-tailed statistic (p less than 0.00001 for each comparison). The detection rates were fluoxetine, 48.8% (20/41); tricyclics, 5.8% (3/52); RBD, 4.3% (3/70); objectively normal sleepers, 3.3% (1/30); PLM, ST/SW, 0% (0/82). These groups had similar mean ages (31.5-45.4 years) and gender distributions (50.0-60.7% male), apart from RBD. The effect of fluoxetine, a potent and specific serotonin reuptake inhibitor, on NREM eye movements is postulated to derive from potentiation of serotonergic neurons that inhibit brainstem "omnipause neurons", which, in turn, inhibit saccadic eye movements, thus resulting in disinhibited release of saccades. In addition, a 31-year-old man with obsessive-compulsive disorder developed RBD soon after starting fluoxetine therapy, which persisted at PSG study 19 months after fluoxetine discontinuation.