John R. Harsh

Bright Light Effects on Body-Temperature, Alertness, EEG and Behavior

The immediate psychophysiological and behavioral effects of photic stimulation on humans [bright light (BL) of 5K lux or dim light (DL) of 50 lux] were assessed in male subjects (N = 43) under four different conditions. For one condition the same subjects (N = 16) received alternating 90-min blocks of BL and DL during the nighttime h (2300-0800 h) under sustained wakefulness conditions. A second condition was similar to the first except that subjects (N = 8) received photic stimulation during the daytime hours. For the third and fourth conditions different subjects received either continuous BL (N = 10) or continuous DL (N = 9) during the nighttime hours. For the nighttime alternating condition body temperature decreased under DL but either increased or maintained under BL. For the continuous light condition, body temperature dropped sharply across the night under DL but dropped only slightly under BL. Sleepiness was considerably greater under DL than under BL, and the difference became larger as the night progressed. Similarly, alertness, measured by EEG beta activity, was greater under BL, and nighttime performance on behavioral tasks was also generally better. There were no differential effects between BL and DL on any measure during the daytime. These data indicate that light exerts a powerful, immediate effect on physiology and behavior in addition to its powerful influence on circadian organization.

The Relationship Between Reported Sleep Quality and Sleep Hygiene in Italian and American Adolescents

Objective. The purpose of the study was to examine the relationship between self-reported sleep quality and sleep hygiene in Italian and American adolescents and to assess whether sleep-hygiene practices mediate the relationship between culture and sleep quality. Methods. Two nonprobability samples were collected from public schools in Rome, Italy, and Hattiesburg, Mississippi. Students completed the following self-report measures: Adolescent Sleep-Wake Scale, Adolescent Sleep Hygiene Scale, Pubertal Developmental Scale, and Morningness/Eveningness Scale. Results. The final sample included 776 Italian and 572 American adolescents 12 to 17 years old. Italian adolescents reported much better sleep hygiene and substantially better sleep quality than American adolescents. A moderate-to-strong linear relationship was found between sleep hygiene and sleep quality in both samples. Separate hierarchical multiple regression analyses were performed on both samples. Demographic and individual characteristics explained a significant proportion of the variance in sleep quality (Italians: 18%; Americans: 25%), and the addition of sleep-hygiene domains explained significantly more variance in sleep quality (Italians: 17%; Americans: 16%). A final hierarchical multiple regression analysis with both samples combined showed that culture (Italy versus United States) only explained 0.8% of the variance in sleep quality after controlling for sleep hygiene and all other variables. Conclusions. Cross-cultural differences in sleep quality, for the most part, were due to differences in sleep-hygiene practices. Sleep hygiene is an important predictor of sleep quality in Italian and American adolescents, thus supporting the implementation and evaluation of educational programs on good sleep-hygiene practices.

The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy.

ABSTRACT Objective: This study assessed the efficacy and safety of armodafinil, the longer half-life enantiomer of modafinil, for the treatment of excessive sleepiness in patients with narcolepsy. Research design and methods: This was a multicenter double-blind study with 196 patients (aged 18–65 years) randomized to receive armodafinil 150 mg (n = 65), armodafinil 250 mg (n = 67), or placebo (n = 64) once daily for 12 weeks. Main outcome measures: Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) (six 20‐min subtests across the day), the Clinical Global Impression of Change (CGI-C), subjective measures of sleepiness (Epworth Sleepiness Scale), patient diaries, and evaluations of cognitive performance (Cognitive Drug Research) and fatigue (Brief Fatigue Inventory). Results: Armodafinil significantly increased MWT mean sleep latency (at 0900–1500) compared with placebo. The mean change from baseline at final visit for armodafinil was an increase of 1.3, 2.6, and 1.9 min in the 150‐mg, 250‐mg, and combined groups, respectively, compared with a decrease of 1.9 min for placebo ( p < 0.01 for all three comparisons). Mean late-day MWT latency (1500–1900) was also significantly improved (difference of armodafinil combined group relative to placebo at final visit: 2.8 min, p = 0.0358). The proportions of patients who showed at least minimal improvement in the CGI-C rating from baseline to final visit in the armodafinil 150‐mg, 250‐mg, and combined groups were 69%, 73%, and 71%, respectively, compared with 33% for placebo ( p < 0.0001). Both doses were associated with statistically significant improvements in memory, attention, and fatigue ( p < 0.05). The most common adverse events in patients receiving armodafinil were headache, nausea, and dizziness. Conclusions: Armodafinil significantly improved ability to sustain wakefulness throughout the day in patients with narcolepsy. Armodafinil also significantly improved overall clinical condition, memory, attention, and fatigue when compared with placebo.

Responsiveness to olfactory stimuli presented in sleep.

Whether humans react to olfactory stimuli presented in sleep was assessed. Responses of ten participants (mean age = 22.8 years) were recorded to repeated three-minute periods of either air alone or to a peppermint odor (0.26 mg/liter) during stage 2 sleep. These responses included behavioral (awakening, microswitch closure), autonomic (heart rate, EMG, respiration), and central (EEG) components. An odor delivery system is described comprised of an aquarium pump, Teflon and TYGON tubing, oxygen mask, filtering, and air flow valves. The data indicate that humans react behaviorally, autonomically and centrally to olfactory stimuli presented while sleeping. Although the percentage of overall responsivity to olfactory stimuli was low, significant differences (ANOVA) in responsivity to odor periods vs. nonodor periods were found for microswitch closures, EEG, EMG, and heart rate. For these measures eight or more of the ten participants showed this pattern of differential responsivity during odor and nonodor periods (Sign test = p less than 0.05). A time-of-night effect was also observed in that responsivity tended to be greatest early in the night. The effect on responsivity of other durations, concentrations, and odors requires additional research.

Psychometric properties of the Adolescent Sleep Hygiene Scale

This study evaluated the psychometric properties of the Adolescent Sleep Hygiene Scale (ASHS), a self‐report measure assessing sleep practices theoretically important for optimal sleep. Data were collected on a community sample of 514 adolescents (16–19; 17.7 ± 0.4 years; 50% female) participating in the late adolescent examination of a longitudinal study on sleep and health. Sleep hygiene and daytime sleepiness were obtained from adolescent reports, behavior from caretaker reports, and sleep‐wake estimation on weekdays from wrist actigraphy. Confirmatory factor analysis indicated the empirical and conceptually based factor structure were similar for six of the eight proposed sleep hygiene domains. Internal consistency of the revised scale (ASHSr) was α = 0.84; subscale alphas were: physiological: α = 0.60; behavioural arousal: α = 0.62; cognitive/emotional: α = 0.81; sleep environment: α = 0.61; sleep stability: α = 0.68; daytime sleep: α = 0.78. Sleep hygiene scores were associated positively with sleep duration (r = 0.16) and sleep efficiency (r = 0.12) and negatively with daytime sleepiness (r = −0.26). Results of extreme‐groups analyses comparing ASHSr scores in the lowest and highest quintile provided further evidence for concurrent validity. Correlations between sleep hygiene scores and caretaker reports of school competence, internalizing and externalizing behaviours provided support for convergent validity. These findings indicate that the ASHSr has satisfactory psychometric properties for a research instrument and is a useful research tool for assessing sleep hygiene in adolescents.

Modafinil facilitates performance on a delayed nonmatching to position swim task in rats.

Modafinil is a wake-promoting drug approved by the FDA for the treatment of narcolepsy. Recent evidence suggests that modafinil may improve learning and memory processes. To further evaluate possible cognitive properties associated with modafinil, male Sprague-Dawley rats were tested in a delayed nonmatching to position (DNMTP) task. A modified water maze allowed animals to make one of two choices for the location of the escape platform. Each trial consisted of two swims. On the information swim (IS), only one choice was open to the animal for escape. One minute later, a choice swim (CS) presented the animal with two choices with the escape platform in the opposite position. There were 10 trials per day for 10 days. Rats received 0, 30, 55, or 100 mg/kg ip of modafinil 30 min prior to testing. Locomotor activity was also assessed. Animals that received 55 and 100 mg/kg made significantly more correct choices, indicating that higher doses of modafinil learned the task faster than did controls. While animals that received 100 mg/kg did exhibit an enhancement of locomotor activity, this effect did not result in more efficient goal-directed behavior. The evidence is consistent with previous research showing that modafinil facilitates cognitive processes.

The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of acute nighttime sleep restriction, wake time, and daytime napping.

The cortisol awakening response (CAR) is presumed critically important for healthy adaptation. The current literature, however, is hampered by systematic measurement difficulties relative to awakening, especially with young children. While reports suggest the CAR is smaller in children than adults, well-controlled research in early childhood is scarce. We examined whether robust CARs exist in 2- to 4-year-old children and if sleep restriction, wake timing, and napping influence the CAR (n = 7). During a 25-day in-home protocol, researchers collected four salivary cortisol samples (0, 15, 30, 45 min post-wake) following five polysomnographic sleep recordings on nonconsecutive days after 4 hr (morning nap), 7 hr (afternoon nap), 10 hr (evening nap), 13 hr (baseline night), and 16 hr (sleep restriction night) of wakefulness (20 samples/child). The CAR was robust after nighttime sleep, diminished after sleep restriction, and smaller but distinct after morning and afternoon (not evening) naps. Cortisol remained elevated 45 min after morning and afternoon naps. .

Effect of sleep deprivation on NREM sleep ERPs and related activity at sleep onset.

This research assessed the impact of one night of sleep deprivation on the amplitudes of NREM-sleep event-related potentials (NREM ERPs) and on the frequency of occurrence of related electroencephalogram activity including sleep spindles, arousals, K-complexes, and vertex sharp waves (VSWs). The NREM ERPs identified included P220, N350, P450, N550 and P900. During a pre-deprivation night, ten subjects took two 20-min naps separated by a 20-min break at their normal bedtime. Brief tones were presented at three intensity levels (60, 75 and 90 dB) with a 5-s interstimulus interval. Following these naps, subjects were kept awake until their normal bedtime the following day. At that time, they repeated the two-nap procedure. The ERPs obtained for each tone and wake/sleep state for pre- and post-deprivation conditions were analyzed using repeated measures statistical procedures. As anticipated, NREM ERP amplitudes recorded both pre- and post-deprivation increased with tone intensity and with approaching sleep. Also, sleep deprivation was associated with more rapid sleep onset, reduced arousability, and greater spindle production. While sleep deprivation had no effect on the amplitude of P220. Post-deprivation amplitudes of N350, N550 and P900 were greater, especially following the 90-dB tone. There was a corresponding increase in VSWs and K-complexes. These findings are inconsistent with the view that NREM ERPs reflect arousal. The underlying mechanism(s) may facilitate initiation and maintenance of sleep.

Information processing and coping style during the wake/sleep transition

Information processing of meaningful events (subjects own name, neutral name and tones) was studied during the transition from wakefulness to sleep in two groups of subjects with opposing information processing styles, Monitors and Blunters. In two experimental sets, subjects were instructed to execute a fingerlift response to a predetermined stimulus type. Subjects own name produced the greatest number of K‐complexes and arousals relative to other name and tones. A task relevance effect was found for arousals but not for K‐complexes. The overall P3 amplitude was larger for Monitors than for Blunters, whereas Blunters showed a larger N350 to target stimuli than Monitors. The findings suggest that higher level processing continues during light sleep and that N350 may reflect a process related to sleep maintenance.

A Double-Blind, Placebo-Controlled Study of Armodafinil for Excessive Sleepiness in Patients With Treated Obstructive Sleep Apnea and Comorbid Depression

OBJECTIVE Treatment of excessive sleepiness in the context of obstructive sleep apnea (OSA) may be particularly difficult in those with depression because depression and/or antidepressant medications may cause sleepiness and fatigue in addition to that due to the OSA. This study evaluating armodafinil, a nonamphetamine wakefulness-promoting medication, is the first trial for treatment of excessive sleepiness in patients with treated OSA and comorbid depression. METHOD Men and women with OSA diagnosed using International Classification of Sleep Disorders criteria being treated with continuous positive airway pressure and comorbid major depressive disorder or dysthymic disorder according to DSM-IV-TR criteria were enrolled into a 12-week, randomized, double-blind, parallel-group study between September 2007 and March 2009 at 60 outpatient sites. Patients maintained on stable monotherapy with a serotonergic antidepressant and with a 17-item Hamilton Depression Rating Scale score < 17 received placebo or armodafinil (target dose: 200 mg once daily). Coprimary outcomes were the proportion of patients with at least minimal improvement on the Clinical Global Impression of Change (CGI-C) as related to excessive sleepiness and mean change from baseline in Maintenance of Wakefulness Test mean sleep latency at final visit; the key secondary outcome was mean change in the Epworth Sleepiness Scale score. RESULTS 249 patients were enrolled: 125 in the armodafinil group and 124 in the placebo group. The proportion of patients with at least minimal improvement on the CGI-C was statistically significantly greater in the armodafinil group (69%) compared with the placebo group (53%, P = .012). Mean (SD) increase in Maintenance of Wakefulness Test sleep latency was numerically but not significantly greater following armodafinil (2.6 [7.1] min) versus placebo (1.1 [7.6] min, P = .30) treatment. Mean decrease in Epworth Sleepiness Scale score was greater in the armodafinil group (-6.3 [4.8]) than in the placebo group (-4.8 [4.9], nominal P = .003). Headache, dry mouth, and insomnia were the most common adverse events occurring with armodafinil treatment. There was no clinically significant effect on depression in either group as measured by the Quick Inventory of Depressive Symptomatology-Self-Report 16. CONCLUSIONS Armodafinil significantly improved overall clinical condition related to excessive sleepiness as rated by the CGI-C and was well tolerated in patients with treated OSA and comorbid depression. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00518986.