Association between sleep slow-wave activity and in-vivo estimates of myelin in healthy young men.

Sleep has been suggested to contribute to myelinogenesis and associated structural changes in the brain. As a principal hallmark of sleep, slow-wave activity (SWA) is homeostatically regulated but also differs between individuals. Besides its homeostatic function, SWA topography is suggested to reflect processes of brain maturation. Here, we assessed whether interindividual differences in sleep SWA and its homeostatic response to sleep manipulations are associated with in-vivo myelin estimates in a sample of healthy young men. Two hundred twenty-six participants (18-31 y.) underwent an in-lab protocol in which SWA was assessed at baseline (BAS), after sleep deprivation (high homeostatic sleep pressure, HSP) and after sleep saturation (low homeostatic sleep pressure, LSP). Early-night frontal SWA, the frontal-occipital SWA ratio, as well as the overnight exponential SWA decay were computed over sleep conditions. Semi-quantitative magnetization transfer saturation maps (MTsat), providing markers for myelin content, were acquired during a separate laboratory visit. Early-night frontal SWA was negatively associated with regional myelin estimates in the temporal portion of the inferior longitudinal fasciculus. By contrast, neither the responsiveness of SWA to sleep saturation or deprivation, its overnight dynamics, nor the frontal/occipital SWA ratio were associated with brain structural indices. Our results indicate that frontal SWA generation tracks inter-individual differences in continued structural brain re-organization during early adulthood. This stage of life is not only characterized by ongoing region-specific changes in myelin content, but also by a sharp decrease and a shift towards frontal predominance in SWA generation.

Exploring scoring methods for research studies: Accuracy and variability of visual and automated sleep scoring.

Sleep studies face new challenges in terms of data, objectives and metrics. This requires reappraising the adequacy of existing analysis methods, including scoring methods. Visual and automatic sleep scoring of healthy individuals were compared in terms of reliability (i.e., accuracy and stability) to find a scoring method capable of giving access to the actual data variability without adding exogenous variability. A first dataset (DS1, four recordings) scored by six experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to explore intra-expert variability. Percentage agreements and Conger's kappa were derived from epoch-by-epoch comparisons on pairwise and consensus scorings. On DS1 the number of epochs of agreement decreased when the number of experts increased, ranging from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 the hypothesis of intra-expert variability was supported by a systematic decrease in kappa scores between autoscoring used as reference and each single expert between datasets (.75-.70). Although visual scoring induces inter- and intra-expert variability, autoscoring methods can cope with intra-scorer variability, making them a sensible option to reduce exogenous variability and give access to the endogenous variability in the data.

Seasonality in human cognitive brain responses.

Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations.

Photic memory for executive brain responses.

Light is a powerful stimulant for human alertness and cognition, presumably acting through a photoreception system that heavily relies on the photopigment melanopsin. In humans, evidence for melanopsin involvement in light-driven cognitive stimulation remains indirect, due to the difficulty to selectively isolate its contribution. Therefore, a role for melanopsin in human cognitive regulation remains to be established. Here, sixteen participants underwent consecutive and identical functional MRI recordings, during which they performed a simple auditory detection task and a more difficult auditory working memory task, while continuously exposed to the same test light (515 nm). We show that the impact of test light on executive brain responses depends on the wavelength of the light to which individuals were exposed prior to each recording. Test-light impact on executive responses in widespread prefrontal areas and in the pulvinar increased when the participants had been exposed to longer (589 nm), but not shorter (461 nm), wavelength light, more than 1 h before. This wavelength-dependent impact of prior light exposure is consistent with recent theories of the light-driven melanopsin dual states. Our results emphasize the critical role of light for cognitive brain responses and are, to date, the strongest evidence in favor of a cognitive role for melanopsin, which may confer a form of "photic memory" to human cognitive brain function.

In vivo marker of brainstem myelin is associated to quantitative sleep parameters in healthy young men.

The regional integrity of brain subcortical structures has been implicated in sleep-wake regulation, however, their associations with sleep parameters remain largely unexplored. Here, we assessed association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem and the variability in the sleep electrophysiology in a large sample of 18-to-31 years healthy young men (N = 321; ~ 22 years). Separate Generalized Additive Model for Location, Scale and Shape (GAMLSS) revealed that sleep onset latency and slow wave energy were significantly associated with MTsat estimates in the brainstem (pcorrected ≤ 0.03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction-pcorrected ≤ 0.03), with higher MTsat value linked to better values in the two sleep metrics in the younger individuals of our sample aged ~ 18 to 20 years. Similar associations were detected across different parts of the brainstem (pcorrected ≤ 0.03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the brainstem nuclei essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.

Characterization of periodic upper limb movement disorder in a patient with restless arms syndrome.

BACKGROUND: Restless legs syndrome (RLS) and the frequently associated periodic limb movements (PLM) are common neurological disorders whose pathophysiology remains elusive. We report on the case of a 40-year-old patient presenting with severe restlessness in the upper limbs, a poorly known variant of RLS. CASE REPORT: Video-polysomnography was performed because of the associated poor sleep quality and daytime sleepiness evocative of PLM. An electromyogram of the extensor carpi radialis muscle was added. Remarkably, our patient had movements of repeated extension of the small finger that contrasted with the extension of the hallux, characteristic for PLM. Pramipexol was an effective treatment relieving the patient's upper limbs of discomfort and ameliorating her restless sleep. CONCLUSIONS: Involvement of the upper limbs in RLS is relatively common, but restlessness may be located on the upper limbs solely. One should be aware of the upper limb variant, and that treatment by dopaminergic agonists proves to be very efficient.

Alzheimer's disease genetic risk and sleep phenotypes in healthy young men: association with more slow waves and daytime sleepiness.

STUDY OBJECTIVES: Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer's disease (AD). Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset. METHODS: We computed whole-genome PRS for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation, and extended sleep opportunity, in a carefully selected homogenous sample of 363 healthy young men (22.1 years ± 2.7) devoid of sleep and cognitive disorders. RESULTS: AD PRS was associated with more slow-wave energy, that is, the cumulated power in the 0.5-4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with larger slow-wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness. CONCLUSIONS: These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and support the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.

Age-related decrease in cortical excitability circadian variations during sleep loss and its links with cognition.

Cortical excitability depends on sleep-wake regulation, is central to cognition, and has been implicated in age-related cognitive decline. The dynamics of cortical excitability during prolonged wakefulness in aging are unknown, however. Here, we repeatedly probed cortical excitability of the frontal cortex using transcranial magnetic stimulation and electroencephalography in 13 young and 12 older healthy participants during sleep deprivation. Although overall cortical excitability did not differ between age groups, the magnitude of cortical excitability variations during prolonged wakefulness was dampened in older individuals. This age-related dampening was associated with mitigated neurobehavioral consequences of sleep loss on executive functions. Furthermore, higher cortical excitability was potentially associated with better and lower executive performance, respectively, in older and younger adults. The dampening of cortical excitability dynamics found in older participants likely arises from a reduced impact of sleep homeostasis and circadian processes. It may reflect reduced brain adaptability underlying reduced cognitive flexibility in aging. Future research should confirm preliminary associations between cortical excitability and behavior and address whether maintaining cortical excitability dynamics can counteract age-related cognitive decline.

Automatic artifacts and arousals detection in whole-night sleep EEG recordings.

BACKGROUND: In sleep electroencephalographic (EEG) signals, artifacts and arousals marking are usually part of the processing. This visual inspection by a human expert has two main drawbacks: it is very time consuming and subjective. NEW METHOD: To detect artifacts and arousals in a reliable, systematic and reproducible automatic way, we developed an automatic detection based on time and frequency analysis with adapted thresholds derived from data themselves. RESULTS: The automatic detection performance is assessed using 5 statistic parameters, on 60 whole night sleep recordings coming from 35 healthy volunteers (male and female) aged between 19 and 26. The proposed approach proves its robustness against inter- and intra-, subjects and raters' scorings, variability. The agreement with human raters is rated overall from substantial to excellent and provides a significantly more reliable method than between human raters. COMPARISON: Existing methods detect only specific artifacts or only arousals, and/or these methods are validated on short episodes of sleep recordings, making it difficult to compare with our whole night results. CONCLUSION: The method works on a whole night recording and is fully automatic, reproducible, and reliable. Furthermore the implementation of the method will be made available online as open source code.

Local modulation of human brain responses by circadian rhythmicity and sleep debt.

Human performance is modulated by circadian rhythmicity and homeostatic sleep pressure. Whether and how this interaction is represented at the regional brain level has not been established. We quantified changes in brain responses to a sustained-attention task during 13 functional magnetic resonance imaging sessions scheduled across the circadian cycle, during 42 hours of wakefulness and after recovery sleep, in 33 healthy participants. Cortical responses showed significant circadian rhythmicity, the phase of which varied across brain regions. Cortical responses also significantly decreased with accrued sleep debt. Subcortical areas exhibited primarily a circadian modulation that closely followed the melatonin profile. These findings expand our understanding of the mechanisms involved in maintaining cognition during the day and its deterioration during sleep deprivation and circadian misalignment.

Modulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition.

INTRODUCTION: Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. METHODS: In an event-related functional magnetic resonance imaging (fMRI) study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control (Braver et al., 2007), the Stroop task has been built to induce proactive or reactive control processes according to the task context. RESULTS: Behavioral results did not show any significant group differences for reaction times but Val allele carriers individuals are less accurate in the processing of incongruent items. fMRI results revealed that proactive control is specifically associated with increased activity in the anterior cingulate cortex (ACC) in carriers of the Met allele, while increased activity is observed in the middle frontal gyrus (MFG) in carriers of the Val allele. CONCLUSION: These observations, in keeping with a higher cortical dopamine level in MM individuals, support the hypothesis of a COMT Val(158)Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al.

Influence of noise correction on intra- and inter-subject variability of quantitative metrics in diffusion kurtosis imaging.

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing number of studies, DKI has a potential to establish itself as a valuable tool in brain diagnostics. However, to become a routine procedure, DKI still needs to be improved in terms of robustness, reliability, and reproducibility. As it requires acquisitions at higher diffusion weightings, results are more affected by noise than in diffusion tensor imaging. The lack of standard procedures for post-processing, especially for noise correction, might become a significant obstacle for the use of DKI in clinical routine limiting its application. We considered two noise correction schemes accounting for the noise properties of multichannel phased-array coils, in order to improve the data quality at signal-to-noise ratio (SNR) typical for DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise correction approaches in Monte Carlo simulations and in in vivo human studies. The intra-subject reproducibility is investigated in a single subject study by varying the SNR level and SNR spatial distribution. Then the impact of the noise correction on inter-subject variability is evaluated in a homogeneous sample of 25 healthy volunteers. Results show a strong impact of noise correction on the MK estimate, while the estimation of FA and MD was affected to a lesser extent. Both intra- and inter-subject SNR-related variability of the MK estimate is considerably reduced after correction for the noise bias, providing more accurate and reproducible measures. In this work, we have proposed a straightforward method that improves accuracy of DKI metrics. This should contribute to standardization of DKI applications in clinical studies making valuable inferences in group analysis and longitudinal studies.