Long-term effects of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Sleep-wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep-wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid-sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short-term study to take part in the current study on sleep-wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes. METHODS: A pre-post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep-wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist. RESULTS: One year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (ß = -25.40 min; confidence interval: -10.99, -39.82), and sleep onset time was delayed (ß = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found. CONCLUSIONS: We did not find a change in sleep-wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long-term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long-term effects of enhancing environmental light in ID settings is evident.

Light up: an intervention study of the effect of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Evidence-based interventions to improve the sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities (ID) are limited. Increasing light exposure has been shown to be effective in improving the sleep-wake rhythm, mood, and behaviour in other populations. The current study investigates the effect of installing environmental dynamic lighting in common living rooms of care facilities on sleep-wake rhythm, mood, and behaviour in older adults with ID. METHODS: A non-randomised, non-concurrent, multiple baseline study was performed from October 2017 to May 2018. Fifty-four participants [mean (SD) age of 63.42 (8.6) years, 65% female] in six care facilities were included. All participants had three baseline measurements (Weeks 1, 5 and 9). Dynamic lighting was installed in Week 10, after which three intervention measurements took place (Weeks 12, 17 and 24). Sleep characteristics and the sleep-wake rhythm were assessed using actigraphy (GENEActiv). Mood was measured with the Anxiety, Depression and Mood Scale (ADAMS) and behaviour with the Aberrant Behaviour Checklist (ABC). RESULTS: Mixed-effect regression analysis showed a worsening of the primary outcome interdaily stability (P = 0.001). This could be attributed to one care facility, whereas interdaily stability did not change in the other care facilities (P = 0.74). Dynamic lighting led to earlier mid-sleep (P = 0.003) and sleep onset (P < .0001) and improved mood as indicated by lower scores on the ADAMS depression (-0.64 SD, P < 0.001) and social avoidance (-0.47 SD, P = 0.004) subscales. The prevalence of screening above cut-off for depression decreased from 23 to 9.8% (OR = .16, P = 0.003). For behaviour, a decrease was seen in hyperactivity (-0.43 SD, P < 0.001), lethargy (-0.35 SD, P = 0.008) and irritability (-0.33 SD, P < .001) as measured with the ABC. No adverse effects were reported. CONCLUSION: Installing dynamic lighting in common living areas for older adults with ID improved the mood and behaviour of the residents up to 14 weeks after placement. Integrated dynamic lighting is a promising, undemanding and potentially effective addition to improve mood and behaviour in care organisations for people with ID, but does not seem to do so by improving sleep or sleep-wake rhythms.

Shedding light on light exposure in elderly with intellectual disabilities.

BACKGROUND: Light exposure affects mood and sleep regulation. Sleep problems and mood complaints are common in elderly with intellectual disabilities (ID) living in care facilities. Insufficient light exposure is hypothesised to contribute to the high prevalence of these problems. The current study is the first to describe the personal light exposure pattern during the waking day in elderly with ID. METHODS: The study sample consists of 82 elderly with ID (aged 62.3 ± 9.4 years) living in 16 residential homes of three care organisations in the Netherlands. Personal light exposure was measured continuously for 7-10 days using a HOBO data logger light sensor, measuring illuminance at chest height. Participants wore a wrist-worn accelerometer (Actiwatch or Geneactiv) to indicate the bedtimes to determine the waking day. RESULTS: The variation in illuminance is small during the waking day. Elderly with ID spend most of their waking day (mean duration = 14:32:43 h) in dim light (1-500 lux) environment and spend a median of 32 min in light > 1000 lux. Within participants, the threshold associated with better sleep (>50 min of light > 1000 lux) was reached for 34% of the days, and the threshold associated with less depressive symptoms (>30 min of light > 1000 lux) was reached in 46% of the days. Exposure > 1000 lux was lower during weekends than during weekdays. CONCLUSION: Elderly with ID spend most of their waking day in low light levels and did not meet the proposed values associated with better sleep and mood. Given the importance of adequate light exposure for regulation of sleep and mood, and the prevalence of sleep and mood problems in elderly with ID, the current study suggests that the lit environment for this already frail population should be given more attention.

The impact of maintenance therapy on sleep-wake rhythms and cancer-related fatigue in pediatric acute lymphoblastic leukemia.

PURPOSE: To assess the impact of maintenance therapy and the additional impact of dexamethasone treatment on cancer-related fatigue and sleep-wake rhythms in pediatric acute lymphoblastic leukemia (ALL) patients and to determine the association between these outcomes. METHODS: A national cohort of pediatric ALL patients (≥ 2 years) was included (± 1 year post-diagnosis). Patients receiving dexamethasone were assessed twice (assessment with and without dexamethasone). Actigraphy assessments were used to calculate sleep-wake outcomes with nonparametric methods. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Sleep-wake rhythms and cancer-related fatigue were compared between patients participating in the assessment without dexamethasone and healthy children (linear regression) and between assessments with and without dexamethasone (mixed models). Using linear regression, associations between sleep-wake outcomes and cancer-related fatigue were determined during assessments with and without dexamethasone. RESULTS: Responses were collected for 125 patients (113 assessments with and 81 without dexamethasone). The sleep-wake rhythm was less stable (p = 0.03) and less robust (p = 0.01), with lower physical activity levels (p < 0.001) and higher cancer-related fatigue levels (p < 0.001) in ALL patients compared to healthy children. Physical activity was lower (p = 0.001) and cancer-related fatigue more severe (p ≤ 0.001) during assessments with dexamethasone compared to without dexamethasone. Sleep-wake outcomes were significantly associated with cancer-related fatigue during periods without dexamethasone, but not during periods with dexamethasone. CONCLUSION: Sleep-wake rhythms are disturbed, physical activity levels lower, and cancer-related fatigue levels higher during maintenance therapy. Interventions aimed to enhance sleep-wake rhythms during maintenance therapy could improve cancer-related fatigue. Families should be supported in coping with the additional burden of dexamethasone treatment to improve well-being of ALL patients.

Restless legs syndrome in migraine patients: prevalence and severity.

BACKGROUND AND PURPOSE: Our aim was to study not only the prevalence but more importantly the severity and the correlation between sleep quality and restless legs syndrome (RLS) in a large population of well-defined migraine patients as poor sleep presumably triggers migraine attacks. METHODS: In a large cross-sectional and observational study, data on migraine and RLS were collected from 2385 migraine patients (according to the International Classification of Headache Disorders ICHD-IIIb) and 332 non-headache controls. RLS severity (International RLS Study Group severity scale) and sleep quality (Pittsburgh Sleep Quality Index) were assessed. Risk factors for RLS and RLS severity were calculated using multivariable-adjusted regression models. RESULTS: Restless legs syndrome prevalence in migraine was higher than in controls (16.9% vs. 8.7%; multivariable-adjusted odds ratio 1.83; 95% confidence interval 1.18-2.86; P = 0.008) and more severe (adjusted severity score 14.5 ± 0.5 vs. 12.0 ± 1.1; P = 0.036). Poor sleepers were overrepresented amongst migraineurs (50.1% vs. 25.6%; P < 0.001). Poorer sleep quality was independently associated with RLS occurrence (odds ratio 1.08; P < 0.001) and RLS severity (P < 0.001) in migraine patients. CONCLUSION: Restless legs syndrome is not only twice as prevalent but also more severe in migraine patients, and associated with decreased sleep quality.

Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. METHODS: This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. RESULTS: Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. CONCLUSIONS: White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo models.

Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic effects of the immunosuppressive drug cyclosporine A (CsA) upon 6 h of exposure of the mouse cytotoxic T cell line CTLL-2, the thymoma EL-4 and primary splenocytes and compared these to the effects in spleens of mice orally treated with CsA for 7 days. EL-4 and CTLL-2 cells showed the highest similarities in response. CsA affected many genes in primary splenocytes that were not affected in EL-4 or CTLL-2. Pathway analysis demonstrated that CsA upregulated the unfolded protein response, endoplasmic reticulum stress and NRF2 activation in EL-4 cells, CTLL-2 cells and primary mouse splenocytes but not in mouse spleen in vivo. As expected, CsA downregulated cell cycle and immune response in splenocytes in vitro, spleens in vivo as well as CTLL-2 in vitro. Genes up- and downregulated in human Jurkat, HepG2 and renal proximal tubular cells were similarly affected in CTLL-2, EL-4 and primary splenocytes in vitro. In conclusion, of the models tested in this study, the known mechanism of immunotoxicity of CsA is best represented in the mouse cytotoxic T cell line CTLL-2. This is likely due to the fact that this cell line is cultured in the presence of a T cell activation stimulant (IL-2) making it more suitable to detect inhibitory effects on T cell activation.

Guided Internet-delivered cognitive behavioural treatment for insomnia: a randomized trial.

BACKGROUND: Insomnia is a prevalent problem with a high burden of disease (e.g. reduced quality of life, reduced work capacity) and a high co-morbidity with other mental and somatic disorders. Cognitive behavioural therapy (CBT) is effective in the treatment of insomnia but is seldom offered. CBT delivered through the Internet might be a more accessible alternative. In this study we examined the effectiveness of a guided Internet-delivered CBT for adults with insomnia using a randomized controlled trial (RCT). METHOD: A total of 118 patients, recruited from the general population, were randomized to the 6-week guided Internet intervention (n = 59) or to a wait-list control group (n = 59). Patients filled out an online questionnaire and a 7-day sleep diary before (T0) and after (T1) the 6-week period. The intervention group received a follow-up questionnaire 3 months after baseline (T2). RESULTS: Almost three-quarters (72.9%) of the patients completed the whole intervention. Intention-to-treat (ITT) analysis showed that the treatment had statistically significant medium to large effects (p < 0.05; Cohen's d between 0.40 and 1.06), and resulted more often in clinically relevant changes, on all sleep and secondary outcomes with the exception of sleep onset latency (SOL) and number of awakenings (NA). There was a non-significant difference in the reduction in sleep medication between the intervention (a decrease of 6.8%) and control (an increase of 1.8%) groups (p = 0.20). Data on longer-term effects were inconclusive. CONCLUSIONS: This study adds to the growing body of literature that indicates that guided CBT for insomnia can be delivered through the Internet. Patients accept the format and their sleep improves.

Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. TRIAL REGISTRATION: Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

Do better nights lead to better days? Guided internet-based cognitive behavioral therapy for insomnia in people suffering from a range of mental health problems: Protocol of a pragmatic randomized clinical trial.

BACKGROUND: Insomnia is the transdiagnostically shared most common complaint in disorders of anxiety, stress and emotion regulation. Current cognitive behavioral therapies (CBT) for these disorders do not address sleep, while good sleep is essential for regulating emotions and learning new cognitions and behaviours: the core fundaments of CBT. This transdiagnostic randomized control trial (RCT) evaluates whether guided internet-delivered cognitive behavioral therapy for insomnia (iCBT-I) (1) improves sleep, (2) affects the progression of emotional distress and (3) enhances the effectiveness of regular treatment of people with clinically relevant symptoms of emotional disorders across all mental health care (MHC) echelons. METHODS: We aim for 576 completers with clinically relevant symptoms of insomnia as well as at least one of the dimensions of generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), posttraumatic stress disorder (PTSD) or borderline personality disorder (BPD). Participants are either pre-clinical, unattended, or referred to general- or specialized MHC. Using covariate-adaptive randomization, participants will be assigned to a 5 to 8-week iCBT-I (i-Sleep) or a control condition (sleep diary only) and assessed at baseline, and after two and eight months. The primary outcome is insomnia severity. Secondary outcomes address sleep, severity of mental health symptoms, daytime functioning, mental health protective lifestyles, well-being, and process evaluation measures. Analyses use linear mixed-effect regression models. DISCUSSION: This study can reveal for whom, and at which stage of disease progression, better nights could mean substantially better days. TRIAL REGISTRATION: International Clinical Trial Registry Platform (NL9776). Registered on 2021-10-07.

Guided internet-based cognitive behavioral therapy for insomnia in patients with borderline personality disorder: Study protocol for a randomized controlled trial.

Borderline personality disorder (BPD) is a highly disabling psychiatric disorder with emotion dysregulation at its core, resulting in affective instability, impulsivity and sometimes self-harming or suicidal behavior. Sleep is increasingly recognized to play a crucial role in emotion regulation. BPD patients often suffer from (severe) insomnia, potentially aggravating symptoms and preventing recovery from BPD. Yet, the effects of insomnia treatments have not been investigated in context of BPD. Guided internet-based cognitive behavioral therapy for insomnia (iCBT-I; i-Sleep) has been proven effective in improving both insomnia and affective symptoms. In this randomized controlled trial among 96 patients with a DSM-5 diagnosis of BPD (or other personality disorder with ≥4 BPD traits) and insomnia symptoms, we will test the effectiveness of iCBT-I before regular BPD treatment starts, during the waitlist period, on BPD symptoms. Patients in the control group monitor their sleep through a sleep diary during the waitlist period and also receive standard BPD treatment after that. Using linear mixed models we will test the hypothesis that the iCBT-I group improves more than the control group on BPD symptoms (primary outcome), insomnia severity, additional subjective and objective sleep variables, emotion regulation, comorbid anxiety and depression complaints, and quality of life. These effects are thought to arise from a direct effect of improved sleep on emotion regulation and a synergistic effect on the consolidation and internalization of the BPD treatment effect. To our knowledge, this is the first trial assessing effectiveness of CBT-I in patients with BPD (traits). The accessibility of the studied intervention greatly facilitates clinical implication in case of positive results.

Dynamics underlying spontaneous human alpha oscillations: a data-driven approach.

Although the cognitive and clinical correlates of spontaneous human alpha oscillations as recorded with electroencephalography (EEG) or magnetoencephalography (MEG) are well documented, the dynamics underlying these oscillations is still a matter of debate. This study proposes a data-driven method to reveal the dynamics of these oscillations. It demonstrates that spontaneous human alpha oscillations as recorded with MEG can be viewed as noise-perturbed damped harmonic oscillations. This provides evidence for the hypothesis that these oscillations reflect filtered noise and hence do not possess limit-cycle dynamics. To illustrate the use of the model, we apply it to two data-sets in which a decrease in alpha power can be observed across conditions. The associated differences in the estimated model parameters show that observed decreases in alpha power are associated with different kinds of changes in the dynamics. Thus, the model parameters are useful dynamical biomarkers for spontaneous human alpha oscillations.

Chronic insomnia: clinical and research challenges--an agenda.

Chronic insomnia afflicts up to 10% of the population in Western industrialized countries. It is characterized by delayed sleep onset, problems in maintaining sleep, early morning awakening or the feeling of non-restorative sleep coupled with significant daytime impairments on an emotional, social or professional level. It can occur as a co-morbid condition in any other medical or mental disorder, but also as a primary condition. Within the last decade new diagnostic and differential diagnostic approaches have been suggested that enhance diagnostic precision. Epidemiological data and data relating to the health care and cost situation of chronic insomnia suggest a huge burden for society. Chronic insomnia leads to a clear-cut increased risk for psychopathology (i. e., affective disorders) and probably also for cardiovascular and metabolic dysfunction. The pathophysiology of the condition is still poorly understood and will profit from integrating modern neuroscientific approaches (animal studies, molecular biology, neuroimaging, neurophysiology, etc.). Current treatment strategies are mainly based on cognitive behavioural interventions (CBT-I) and hypnotic treatment with benzodiazepine receptor agonists and sedating antidepressants. Although the effectiveness of these treatments has been clearly demonstrated, a substantial proportion of patients proves to be treatment-resistant or profits only poorly. The question of long-term pharmaceutical treatment of chronic insomnia, at least in Europe, is unresolved and urgently needs answers. Novel rational treatment avenues require clues on causes and mechanisms from integrated neuroscientific approaches. The important issues concerning insomnia treatment in the future especially in Europe will be reviewed and discussed critically.

Discovery of key whole-brain transitions and dynamics during human wakefulness and non-REM sleep.

The modern understanding of sleep is based on the classification of sleep into stages defined by their electroencephalography (EEG) signatures, but the underlying brain dynamics remain unclear. Here we aimed to move significantly beyond the current state-of-the-art description of sleep, and in particular to characterise the spatiotemporal complexity of whole-brain networks and state transitions during sleep. In order to obtain the most unbiased estimate of how whole-brain network states evolve through the human sleep cycle, we used a Markovian data-driven analysis of continuous neuroimaging data from 57 healthy participants falling asleep during simultaneous functional magnetic resonance imaging (fMRI) and EEG. This Hidden Markov Model (HMM) facilitated discovery of the dynamic choreography between different whole-brain networks across the wake-non-REM sleep cycle. Notably, our results reveal key trajectories to switch within and between EEG-based sleep stages, while highlighting the heterogeneities of stage N1 sleep and wakefulness before and after sleep.

Manipulation of skin temperature improves nocturnal sleep in narcolepsy.

OBJECTIVE: Besides excessive daytime sleepiness, disturbed nocturnal sleep is a major complaint of patients with narcolepsy. Previously, alterations in skin temperature regulation in narcoleptic patients have been shown to be related to increased sleepiness. This study tests the hypothesis that direct control of nocturnal skin temperature might be applied to improve the disturbed sleep of narcoleptic patients. METHODS: Participants were eight patients (five males) diagnosed as having narcolepsy with cataplexy according to the ICSD-2 criteria, mean (SD) age 28.6 (6.4) years, range 18-35 years. During two nights, sleep was recorded polysomnographically while proximal and distal skin temperature were manipulated using a comfortable thermosuit that induced skin temperature to cycle slowly with an amplitude of only 0.4 degrees C within the comfortable range normally observed during sleep. Logistic regression was used to evaluate the effect of skin temperature manipulation on the probability of occurrence of different sleep stages and nocturnal wakefulness. RESULTS: Proximal skin warming significantly suppressed wakefulness and enhanced slow wave sleep (SWS). In contrast, distal skin warming enhanced wakefulness and stage 1 sleep at the cost of SWS and REM sleep. The optimal combination of proximal skin warming and distal skin cooling led to a 160% increase in SWS, a 50% increase in REM sleep and a 68% decrease in wakefulness, compared with the least beneficial combination of proximal skin cooling and distal skin warming. INTERPRETATION: Subtle skin temperature manipulations under controlled conditions significantly improved the typical nocturnal sleep problems in narcolepsy.

Observations on the cortical silent period in Parkinson's disease.

Transcranial magnetic stimulation is a tool in the neurosciences to study motor functions and nervous disorders, amongst others. Single pulses of TMS applied over the primary motor cortex lead to a so-called cortical silent period in the recording from the corresponding muscle, i.e. a period of approximately 100ms with no muscle activity. We here show that in Parkinson's disease (PD), this cortical silent period in some cases is interrupted by short bursts of EMG activity. We describe in detail these interruptions in two patients with PD. These interruptions may number up to 3 per cortical silent period and show a consistent frequency across trials and hemispheres within a given patient; the two patients described here do differ, however, in the time-delay of the interruptions and hence the induced frequency. For one patient, the frequency of the interruptions proved to be around 13 Hz, the other patient showed a frequency of around 17 Hz. The results corroborate earlier findings of cortical oscillations elicited by pulses of TMS and may be related to abnormal oscillatory activity found in the cortical-subcortical motor system in PD.

Shortened seasonal photoperiodic cycles accelerate aging of the diurnal and circadian locomotor activity rhythms in a primate.

The gray mouse lemur (Microcebus murinus), a prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Previous studies indicated that longevity can be altered by long-term acceleration of seasonal rhythms, providing a model for assessing various aspects of aging. To assess the effect of aging and accelerated aging on the circadian system of this primate, we compared the circadian rhythm of the locomotor activity in adult mouse lemurs (2-4.5 years, n = 9), aged mouse lemurs (5-9 years, n = 10), and adult mouse lemurs that had been exposed from birth to a shortened seasonal photoperiodic cycle (2-4.5 years, n = 7). Compared to adult animals, aged mouse lemurs showed a significant increase in intradaily variability and an advanced activity onset. Aging was characterized by a decrease in amplitude, with both a decrease in nocturnal activity and an increase in daytime activity. When maintained in constant dim red light, aged animals exhibited a shortening of the free-running period (22.8 +/- 0.1 h) compared to adult animals (23.5 +/- 0.1 h). A 3- to 5-year exposure to an accelerated seasonal photoperiodic rhythm ("annual" duration of 5 months) in accelerated mouse lemurs produced disturbances of the locomotor activity rhythm that resembled those of aged mouse lemurs, whether animals were studied in entrained or in free-running conditions. The present study demonstrated a weakened and fragmented locomotor activity rhythm during normal aging in this primate. Increasing the number of expressed seasonal cycles accelerated aging of parameters related to circadian rhythmicity in adult animals.

Environmental light and suprachiasmatic nucleus interact in the regulation of body temperature.

The mammalian biological clock, located in the suprachiasmatic nucleus (SCN), is crucial for circadian rhythms in physiology and behavior. However, equivocal findings have been reported on its role in the circadian regulation of body temperature. The goal of the present studies was to investigate the interaction between the SCN and environmental light in the regulation of body temperature. All recordings were performed by telemetry in free moving male Wistar rats. Firstly, we demonstrated an endogenous circadian rhythm in body temperature independent of locomotor activity. This rhythm was abolished by stereotactic lesioning of the SCN. Secondly, we demonstrated a circadian phase-dependent suppressive effect of light ('negative masking') on body temperature. Light suppressed body temperature more at the end of the subjective night (circadian time [CT] 22) than in the middle (CT 6) and at the end (CT 10) of the subjective day. This circadian-phase dependent suppression was not demonstrated in SCN-lesioned animals. Surprisingly, after half a year of recovery from lesioning of the SCN, light regained its suppressing action on body temperature, resulting in a daily body temperature rhythm only under light-dark conditions. In contrast to body temperature, light could not substantially mimic a daytime inhibitory SCN-output in the regulation of heart rate and locomotor activity. The present results suggest that, after lesioning of the SCN as main relay station for the immediate body temperature-inhibition by light, secondary relay nuclei can fully take over this function of the SCN. These findings provide a possible explanation for the controversy in literature over the question whether the SCN is required for the diurnal rhythm in body temperature. Furthermore, they show that light may have an acute effect on behavior and physiology of the organism via the SCN, which extends beyond the generally acknowledged effect on melatonin secretion.

Long-term fitness training improves the circadian rest-activity rhythm in healthy elderly males.

In old age, the circadian timing system loses optimal functioning. This process is even accelerated in Alzheimer's disease. Because pharmacological treatment of day-night rhythm disturbances usually is not very effective and may have considerable side effects, nonpharmacological treatments deserve attention. Bright light therapy has been shown to be effective. It is known from animal studies that increased activity, or an associated process, also strongly affects the circadian timing system, and the present study addresses the question of whether an increased level of physical activity may improve circadian rhythms in elderly. In the study, 10 healthy elderly males were admitted to a fitness training program for 3 months. The circadian rest-activity rhythm was assessed by means of actigraphy before and after the training period and again 1 year after discontinuation. As a control for possible seasonal effects, repeated actigraphic recordings were performed during the same times of the year as were the pre and post measurements in a control group of 8 healthy elderly males. Fitness training induced a significant reduction in the fragmentation of the rest-activity rhythm. Moreover, the fragmentation of the rhythm was negatively correlated with the level of fitness achieved after the training. No seasonal effect was found. Previous findings in human and animal studies are reviewed, and several possible mechanisms involved in the effect of fitness training on circadian rhythms are discussed. The results suggest that fitness training may be helpful in elderly people suffering from sleep problems related to circadian rhythm disturbances.