Christian L. Nicholas

Nature's clocks and human mood: the circadian system modulates reward motivation

Existing literature on reward motivation pays scant attention to the fact that reward potential of the environment varies dramatically with the light/dark cycle. Evolution, by contrast, treats this fact very seriously: In all species, the circadian system is adapted to optimize the daily rhythm of environmental engagement. We used 3 standard protocols to demonstrate that human reward motivation, as measured in the dynamics of positive affect (PA), is modulated endogenously by the circadian clock. Under naturalistic conditions, 13.0% of PA variance was explained by a 24-hr sinusoid. In a constant routine protocol, 25.0% of PA variance was explained by the unmasked circadian rhythm in core body temperature (CBT). A forced desynchrony study showed PA to align with CBT in exhibiting circadian periodicity independent of a 28-hr sleep/wake cycle. It is concluded that the circadian system modulates reward activation, and implications for models of normal and abnormal mood are discussed.

Pilot study of a mindfulness‐based, multi‐component, in‐school group sleep intervention in adolescent girls

Existing literature links poor sleep and anxiety symptoms in adolescents. This pilot study aimed to develop a practical method through which a program to improve sleep could reach adolescents in need and to examine the feasibility of a mindfulness‐based, multi‐component group sleep intervention using sleep and anxiety as outcome measures.

Recruitment and rate-coding strategies of the human genioglossus muscle

Single motor unit (SMU) analysis provides a means to examine the motor control of a muscle. SMUs in the genioglossus show considerable complexity, with several different firing patterns. Two of the primary stimuli that contribute to genioglossal activation are carbon dioxide (CO(2)) and negative pressure, which act through chemoreceptor and mechanoreceptor activation, respectively. We sought to determine how these stimuli affect the behavior of genioglossus SMUs. We quantified genioglossus SMU discharge activity during periods of quiet breathing, elevated CO(2) (facilitation), and continuous positive airway pressure (CPAP) administration (inhibition). CPAP was applied in 2-cmH(2)O increments until 10 cmH(2)O during hypercapnia. Five hundred ninety-one periods (each ∼ 3 breaths) of genioglossus SMU data were recorded using wire electrodes(n = 96 units) from 15 awake, supine subjects. Overall hypercapnic stimulation increased the discharge rate of genioglossus units (20.9 ± 1.0 vs. 22.7 ± 0.9 Hz). Inspiratory units were activated ∼ 13% earlier in the inspiratory cycle, and the units fired for a longer duration (80.6 ± 5.1 vs. 105.3 ± 4.2% inspiratory time; P < 0.05). Compared with baseline, an additional 32% of distinguishable SMUs within the selective electrode recording area were recruited with hypercapnia. CPAP led to progressive SMU inhibition; at ∼ 6 cmH(2)O, there were similar numbers of SMUs active compared with baseline, with peak frequencies of inspiratory units close to baseline, despite elevated CO(2) levels. At 10 cmH(2)O, the number of units was 36% less than baseline. Genioglossus inspiratory phasic SMUs respond to hypercapnic stimulation with changes in recruitment and rate coding. The SMUs respond to CPAP with derecruitment as a homogeneous population, and inspiratory phasic units show slower discharge rates. Understanding upper airway muscle recruitment/derecruitment may yield therapeutic targets for maintenance of pharyngeal patency.

Perceived poor sleep quality in the absence of polysomnographic sleep disturbance in women with severe premenstrual syndrome

Women with severe premenstrual syndrome report sleep‐related complaints in the late‐luteal phase, but few studies have characterized sleep disturbances prospectively. This study evaluated sleep quality subjectively and objectively using polysomnographic and quantitative electroencephalographic measures in women with severe premenstrual syndrome. Eighteen women with severe premenstrual syndrome (30.5 ± 7.6 years) and 18 women with minimal symptoms (controls, 29.2 ± 7.3 years) had polysomnographic recordings on one night in each of the follicular and late‐luteal phases of the menstrual cycle. Women with premenstrual syndrome reported poorer subjective sleep quality when symptomatic in the late‐luteal phase compared with the follicular phase (P < 0.05). However, there were no corresponding changes in objective sleep quality. Women with premenstrual syndrome had more slow‐wave sleep and slow‐wave activity than controls at both menstrual phases (P < 0.05). They also had higher trait‐anxiety, depression, fatigue and perceived stress levels than controls at both phases (P < 0.05) and mood worsened in the late‐luteal phase. Both groups showed similar menstrual‐phase effects on sleep, with increased spindle frequency activity and shorter rapid eye movement sleep episodes in the late‐luteal phase. In women with premenstrual syndrome, a poorer subjective sleep quality correlated with higher anxiety (r = −0.64, P = 0.005) and more perceived nighttime awakenings (r = −0.50, P = 0.03). Our findings show that women with premenstrual syndrome perceive their sleep quality to be poorer in the absence of polysomnographically defined poor sleep. Anxiety has a strong impact on sleep quality ratings, suggesting that better control of mood symptoms in women with severe premenstrual syndrome may lead to better subjective sleep quality.

Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan

Aging is associated with many changes in sleep, with one of the most prominent being a reduction in slow wave sleep. Traditional measures of this phenomenon rely on spontaneous activity and typically confound the incidence and amplitude of delta waves. The measurement of evoked K-complexes during sleep, enable separate assessment of incidence and amplitude taken from the averaged K-complex waveform. The present study describes data from 70 normal healthy men and women aged between 19 and 78 years. K-Complexes were evoked using short auditory tones and recorded from a midline array of scalp sites. Significant reductions with age were seen in the amplitude of the N550 component of the averaged waveform, which represents the amplitude of the K-complex, with linear regression analysis indicating approximately 50% of the variance was due to age. Smaller, yet still significant reductions were seen in the ability to elicit K-complexes. The data highlight the utility of evoked K-complexes as a sensitive marker of brain aging in men and women.

Actigraphy-assessed sleep during school and vacation periods: a naturalistic study of restricted and extended sleep opportunities in adolescents

School‐related sleep restriction in adolescents has been identified by studies comparing weekday and weekend sleep. This study compared weekday and vacation sleep to assess restricted and extended sleep opportunities. One‐hundred and forty‐six adolescents (47.3% male) aged 16.2 ± 1.0 years (M ± SD) from the general community wore an actigraph continuously for 4 weeks: the last week of a school term (Time‐E), the following 2‐week vacation, and the first week of the next term. Self‐reported sleep was assessed for each of the three time intervals, and chronotype was assessed using the Morningness–Eveningness Questionnaire at Time‐E. Daily actigraphy bedtime, rise‐time, time‐in‐bed, total sleep time, sleep onset latency, sleep efficiency, and % wake after sleep onset were analysed using latent growth curve modelling. The removal of school‐related sleep restriction was associated with an abrupt delay in sleep timing and increase in sleep duration. Subsequently, bedtime and rise‐time showed further linear delays throughout the vacation, while changes in time‐in‐bed were non‐significant. Sleep onset latency increased linearly, peaking in the middle of the second vacation week. Across the first vacation week, total sleep time and sleep efficiency linearly decreased, while % wake after sleep onset increased. These changes stabilized during the second vacation week. Older age and eveningness were associated with later bedtime and rise‐time, whilst females had longer time‐in‐bed, total sleep time and sleep onset latency. Compared with school days, sleep during the vacation was characterized by later timing, longer duration, lower quality and greater variability. Recovery from school‐related sleep restriction appeared to be completed within the 2 weeks of naturalistic extended sleep.

The Impact of Alcoholism on Sleep Evoked Δ Frequency Responses

BACKGROUND K-complexes (KCs) are evoked delta frequency electroencephalogram (EEG) responses during sleep that occur when large numbers of healthy cortical cells burst fire in a synchronized manner. The KC amplitude and incidence are sensitive measures of normal healthy brain aging. Given the known neurodegenerative consequences of alcohol abuse it was hypothesized that alcoholism would be associated with further KC amplitude and incidence reductions. METHODS Eighty-four subjects (42 alcoholics) screened for medical, psychiatric, and sleep problems participated. The protocol involved the presentation of auditory stimuli during stage 2 sleep throughout a night in the laboratory. The KCs were identified and averaged, to enable measurement of the P2, N550, and P900 peaks. RESULTS Compared with control subjects, alcoholic men and women had lower KC incidence (p < .001) and P2 (p < .001), N550 (p < .05), and P900 (p < .05) amplitudes. There was a significant diagnosis x site interaction (p < .001), indicating the group difference was largest at frontal sites. Longer sobriety correlated with increased N550 amplitude (p < .01). CONCLUSIONS The KC incidence and amplitude were negatively impacted in alcoholic men and women with exacerbation of the normal aging effects, particularly over frontal scalp regions. The observed relationship between improvements in KC measures and increased time of abstinence suggests that these measures might provide a useful marker of brain recovery with continued abstinence from alcohol.

The effects of alcoholism on auditory evoked potentials during sleep

Normal aging is associated with a reduction in the probability that an auditory stimulus will evoke a K‐complex during sleep. Additional concomitants of aging are a reduction in the amplitude of the K‐complex‐related N550, an augmentation of the P2 component and the appearance of a long‐lasting positivity (LLP) in the auditory evoked potential. Normal aging is also associated with a dramatic reduction in slow wave sleep (SWS) and a reduction in the volume of cortical gray matter, particularly in the frontal and prefrontal regions of the brain. As in aging, alcoholism is associated with reductions in both cortical gray matter and SWS. It can, therefore, be hypothesized that alcoholics would show similar evoked potential changes to those seen in aging. To test this hypothesis, we studied seven middle‐aged abstinent long‐term alcoholics and eight age‐matched normal controls. Each subject spent one night in the laboratory. Electroencephalogram (EEG) was recorded from six midline scalp sites and auditory stimuli were presented during stage 2 non‐rapid eye movement sleep. N550 amplitude in the K‐complex average was lower in the alcoholics as compared with controls as was the likelihood of K‐complex production. No differences were noted in either amplitude or latency of the P2 or N350 components, and both groups displayed a prominent LLP potential. The pattern of reduced K‐complex production and N550 amplitude in alcoholics as compared with age‐matched controls is consistent with an hypothesized association between atrophy of the frontal lobes and reductions in SWS and K‐complexes. The finding also suggests that the evoked K‐complex may be a relatively simple measure of the effect of alcoholism on EEG during sleep.

The Acute Effects of Alcohol on Sleep Architecture in Late Adolescence

BACKGROUND Alcohol consumption is prevalent in late adolescence; however, little is known about its effect on sleep in this group. In mature adults, alcohol decreases sleep onset latency (SOL) and sleep efficiency (SE) and increases wake after sleep onset (WASO). It also increases slow wave sleep (SWS) and decreases rapid eye movement (REM) sleep in the first half of the night, with the inverse occurring in the second half. Alcohols effect on sleep during late adolescence is of interest given that this age group shows both dramatic increases in alcohol consumption and significant developmental changes in the central nervous system. This study examined the effect of alcohol on sleep architecture in women and men aged 18 to 21 years and whether previously reported sleep architecture effects may have been as an artificial result of changes to sleep cycle length. METHODS Twenty-four (12 women) healthy 18- to 21-year-old light social drinkers (19.1 ± 1.0 years) underwent 2 conditions: presleep alcohol (target breath alcohol concentration [BAC] 0.10%) and placebo-administered under controlled conditions, followed by standard polysomnography. RESULTS In the alcohol condition, mean BAC at lights out was 0.084 ± 0.016%. Time in bed, total sleep time, and SOL (all p > 0.05) did not differ between conditions. However, there was less REM (p = 0.011) and more stage-2 sleep (p = 0.035) in the alcohol condition. Further, alcohol increased SWS (p = 0.02) and decreased REM sleep (p < 0.001) in the first half of the night and disrupted sleep in the second half, with increased WASO (interaction: p = 0.034), and decreased SE (p = 0.04) and SWS (p = 0.01) and no REM sleep rebound in the second half of the night (p = 0.262). Additionally, alcohol had no effect on sleep cycle length (p = 0.598). CONCLUSIONS The results were broadly consistent with the adult literature with the novel extension that half night sleep architecture effects could not be attributed to changes in sleep cycle length. However, alcohol did not reduce SOL, or result in a REM rebound following reduced REM in the first half of the night. The results suggest that the effects of alcohol on sleep are modified by sleeps prevailing developmental stage.

Autonomic regulation across phases of the menstrual cycle and sleep stages in women with premenstrual syndrome and healthy controls

To investigate the influence of menstrual cycle phase and the presence of severe premenstrual symptoms on cardiac autonomic control during sleep, we performed heart rate variability (HRV) analysis during stable non-rapid eye movement (NREM) and REM sleep in 12 women with severe premenstrual syndrome and 14 controls in the mid-follicular, mid-luteal, and late-luteal phases of the menstrual cycle. Heart rate was higher, along with lower high frequency (HF) power, reflecting reduced vagal activity, and a higher ratio of low frequency (LF) to high frequency power, reflecting a shift to sympathetic dominance, in REM sleep compared with NREM sleep in both groups of women. Both groups of women had higher heart rate during NREM and REM sleep in the luteal phase recordings compared with the mid-follicular phase. HF power in REM sleep was lowest in the mid-luteal phase, when progesterone was highest, in both groups of women. The mid-luteal phase reduction in HF power was also evident in NREM sleep in control women but not in women with PMS, suggesting some impact of premenstrual syndrome on autonomic responses to the hormone environment of the mid-luteal phase. In addition, mid-luteal phase progesterone levels correlated positively with HF power and negatively with LF/HF ratio in control women in NREM sleep and with the LF/HF ratio during REM sleep in both groups of women. Our findings suggest the involvement of female reproductive steroids in cardiac autonomic control during sleep in women with and without premenstrual syndrome.