Acute Effect of a Saffron Extract (Safr'InsideTM) and Its Main Volatile Compound on the Stress Response in Healthy Young Men: A Randomized, Double Blind, Placebo-Controlled, Crossover Study.

According to animal studies, saffron and its main volatile compound safranal may reduce biological and behavioral signs of acute stress. However, little is known about its impact in humans. This study investigated the acute effect of a saffron extract and safranal on the biological and psychological stress responses in healthy men experiencing a laboratory stress procedure. In this double-blind, placebo-controlled, randomized, cross-over study, 19 volunteers aged 18-25 received a single dose of 30 mg saffron extract (Safr'InsideTM), 0.06 mg synthetic safranal, or a placebo on three visits separated by a 28-day washout. Thirteen minutes after administration, participants were exposed to the Maastricht acute stress test (MAST). Salivary cortisol and cortisone were collected from 15 min before the MAST (and pre-dose), 3 min before the MAST, and then 15, 30, 45, 60, and 75 min after the MAST, and stress and anxiety were measured using visual analogic scales. Compared to the placebo, stress and anxiety were significantly toned down after Safranal and Safr'InsideTM administration and coupled with a delay in the times to peak salivary cortisol and cortisone concentrations (p < 0.05). Safr'InsideTM and its volatile compound seem to improve psychological stress response in healthy men after exposure to a lab-based stressor and may modulate the biological stress response.

Sleep deprivation therapy to reset the circadian pacemaker in a non-24-hour sleep-wake disorder: a case report.

NONE: Non-24-hour sleep-wake disorder is 1 of several chronic circadian rhythm sleep-wake disorders. It is defined as progressive daily shifts in sleep onset and wake times. It mainly affects patients who are sight-impaired, is relatively rare in sighted patients, and is difficult to treat, with no guidelines. This case report discusses non-24-hour sleep-wake disorder in a sighted young man who complained of alternating severe insomnia and excessive sleepiness, with a sleep agenda and actigraphic data showing a daily delay of approximately 2 hours. A novel therapy by total sleep deprivation followed by a combination of morning light therapy and nocturnal melatonin administration was efficient in stopping his free-running sleep-wake pattern both immediately and in the long term. The treatment combination for 6 months resulted in stable circadian entrainment to a 24-hour cycle. Compliance with chronotherapy was maintained over the course of follow-up.

Towards a Pragmatic Approach to a Psychophysiological Unit of Analysis for Mental and Brain Disorders: An EEG-Copeia for Neurofeedback.

This article proposes what we call an "EEG-Copeia" for neurofeedback, like the "Pharmacopeia" for psychopharmacology. This paper proposes to define an "EEG-Copeia" as an organized list of scientifically validated EEG markers, characterized by a specific association with an identified cognitive process, that define a psychophysiological unit of analysis useful for mental or brain disorder evaluation and treatment. A characteristic of EEG neurofeedback for mental and brain disorders is that it targets a EEG markers related to a supposed cognitive process, whereas conventional treatments target clinical manifestations. This could explain why EEG neurofeedback studies encounter difficulty in achieving reproducibility and validation. The present paper suggests that a first step to optimize EEG neurofeedback protocols and future research is to target a valid EEG marker. The specificity of the cognitive skills trained and learned during real time feedback of the EEG marker could be enhanced and both the reliability of neurofeedback training and the therapeutic impact optimized. However, several of the most well-known EEG markers have seldom been applied for neurofeedback. Moreover, we lack a reliable and valid EEG targets library for further RCT to evaluate the efficacy of neurofeedback in mental and brain disorders. With the present manuscript, our aim is to foster dialogues between cognitive neuroscience and EEG neurofeedback according to a psychophysiological perspective. The primary objective of this review was to identify the most robust EEG target. EEG markers linked with one or several clearly identified cognitive-related processes will be identified. The secondary objective was to organize these EEG markers and related cognitive process in a psychophysiological unit of analysis matrix inspired by the Research Domain Criteria (RDoC) project.

Development of a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination.

INTRODUCTION: A new approach to treat obstructive sleep apnea (OSA) is upper airway stimulation therapy (UAS). Electrical pulses applied to the hypoglossal nerve induce tongue protrusion, increase airway patency and decrease the frequency of apneic and hypopneic events. Thus, the main objective of this study was to design a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination. METHOD: This study has designed the Tongue Adverse Event and Satisfaction Questionnaire (TAESQ) and an endobuccal examinations divided into an endobuccal lesion examination (ELE) and an endobuccal risk factor examination (ERFE). Evaluations were conducted at month 6 post-implantation. RESULTS: The study population after implantation of UAS device consisted of ten Caucasian males with a mean age of 51.9 ± 11.8 years, and a mean BMI of 28.6 ± 3.3. The AHI of the ten participants ranged from 46.7 ± 12.2/h at baseline to 14.5 ± 8.9/h with the Inspire therapy at the 6-month follow-up. The TAESQ revealed pain (30%), followed by less tongue sensitivity (20%) and tongue weakness (10%). The ELE did not reveal any lesions. The ERFE revealed that some participants had tissue and dental risk factors but not associated to more adverse events. CONCLUSION: The TAESQ, ELE and ERFE have been designed and studied on a small number of participants. These evaluations could systematically be included in the care pathway of patients treated by UAS to better investigate tongue discomfort and tongue lesion for patients treated with this technology.

Sensory Gating Capacity and Attentional Function in Adults With ADHD: A Preliminary Neurophysiological and Neuropsychological Study.

Objective: The inability to filter sensory input correctly may impair higher cognitive function in ADHD. However, this relationship remains largely elusive. The objectives of the present study is to investigate the relationship between sensory input processing and cognitive function in adult patients with ADHD. Method: This study investigated the relationship between deficit in sensory gating capacity (P50 amplitude changes in a double-click conditioning-testing paradigm and perceptual abnormalities related to sensory gating deficit with the Sensory Gating Inventory [SGI]) and attentional and executive function (P300 amplitude in an oddball paradigm and attentional and executive performances with a neuropsychological test) in 24 adult patients with ADHD. Results: The lower the sensory gating capacity of the brain and the higher the distractibility related to sensory gating inability that the patients reported, the lower the P300 amplitude. Conclusion: The capacity of the brain to gate the response to irrelevant incoming sensory input may be a fundamental protective mechanism that prevents the flooding of higher brain structures with irrelevant information in adult patients with ADHD.

Hypoglossal nerve stimulation on sleep and level of alertness in OSA: A preliminary study.

OBJECTIVES: To quantify the effect of hypoglossal nerve stimulation (HNS), a novel therapy for patients with obstructive sleep apnea, on objective level of alertness (measured with Maintenance of Wakefulness Test [MWT] values) and nocturnal sleep architecture. METHODS: Ten male patients (mean age 52.0 ± 9.4 years; mean body mass index 28.8 ± 3.3 kg/m2) noncompliant to continuous positive airway pressure received HNS (Inspire therapy) and were prospectively evaluated at baseline and 6 months after HNS therapy. Polysomnographic parameters (sleep breathing and sleep architecture) and objective level of alertness (MWT) were measured. RESULTS: The mean preimplantation apnea-hypopnea index of 46.7/h ± 12.2/h was reduced to 14.5/h ± 8.9/h at 6 months postimplantation (p < 0.001). The mean MWT latency improved from 25.0 ± 12.8 minutes at baseline to 36.8 ± 7.0 minutes after 6 months of treatment (p = 0.004). A reduction of N1% (11.8 ± 10.6 vs 4.2 ± 1.9, p = 0.04) was observed. The reduction in the duration of wake after sleep onset (WASO) was 71.4 ± 32.4 minutes vs 53.4 ± 13.5 minutes (p = 0.06) but was not significant. MWT latencies at 6 months were negatively correlated with the intensity of stimulation (r = -0.63, p = 0.05). Intensity of stimulation was positively correlated with WASO (r = 0.76, p = 0.01). CONCLUSION: HNS improved the objective level of alertness and changed nocturnal sleep architecture. The level of neural stimulation determines the amount of nocturnal WASO and the level of objective level of alertness.

Using Recent BCI Literature to Deepen our Understanding of Clinical Neurofeedback: A Short Review.

In their recent paper, Alkoby et al. (2017) provide the readership with an extensive and very insightful review of the factors influencing NeuroFeedback (NF) performance. These factors are drawn from both the NF literature and the Brain-Computer Interface (BCI) literature. Our short review aims to complement Alkoby et al.'s review by reporting recent additions to the BCI literature. The object of this paper is to highlight this literature and discuss its potential relevance and usefulness to better understand the processes underlying NF and further improve the design of clinical trials assessing NF efficacy. Indeed, we are convinced that while NF and BCI are fundamentally different in many ways, both the BCI and NF communities could reach compelling achievements by building upon one another. By reviewing the recent BCI literature, we identified three types of factors that influence BCI performance: task-specific, cognitive/motivational and technology-acceptance-related factors. Since BCIs and NF share a common goal (i.e., learning to modulate specific neurophysiological patterns), similar cognitive and neurophysiological processes are likely to be involved during the training process. Thus, the literature on BCI training may help (1) to deepen our understanding of neurofeedback training processes and (2) to understand the variables that influence the clinical efficacy of NF. This may help to properly assess and/or control the influence of these variables during randomized controlled trials.

[Implantable nerve stimulation for obstructive sleep apnea hypopnea syndrome]. / Traitement du syndrome d'apnées et hypopnées obstructives du sommeil par stimulation nerveuse implantable.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disorder that has been identified as a contributor to cardiovascular disease making it a major public health problem. Continuous positive airway pressure is the standard treatment but compliance is suboptimal. Mandibular advancement devices and surgery have limited indications, inconstant efficiency and potential irreversible side effects. Stimulation of the hypoglossal nerve, that innervates the genioglossus, a protrusor muscle of the tongue, is now a new treatment option for moderate and severe cases of OSAHS. Two types of stimulation are currently available: stimulation synchronous with inspiration and continuous stimulation. The indication of each type of stimulation and long-term effects still need to be assessed but the implantable nerve stimulation is a promising treatment for patients without a therapy solution so far.

Sensory gating in adult with attention-deficit/hyperactivity disorder: Event-evoked potential and perceptual experience reports comparisons with schizophrenia.

BACKGROUND: In daily life, adults with attention-deficit/hyperactivity disorder (ADHD) report abnormal perceptual experiences that can be related to sensory gating deficit. This study investigated and compared P50 suppression (a neurophysiological measure of sensory gating) and perceptual abnormalities related to sensory gating deficit in ADHD and schizophrenias patients. METHODS: Three groups were compared: 24 adults with ADHD, 24 patients with schizophrenia and 24 healthy subjects. The Sensory Gating Inventory (SGI), a validated self-report questionnaire, was used to measure perceptual abnormalities related to sensory gating deficit. P50 suppression was measured by P50 amplitude changes in a dual-click conditioning-testing auditory event-related potential procedure. RESULTS: Adults with ADHD had significantly higher scores on the SGI and significantly lower P50 suppression than healthy subjects. These deficits were similar to those found in patients with schizophrenia. A correlation was found between both the SGI and P50 suppression data in adults with ADHD and patients with schizophrenia. DISCUSSION: The findings confirm previous results found in patients with schizophrenia. Moreover, adults with ADHD, similar to patients with schizophrenia, had abnormal P50 suppression and reported being flooded with sensory stimuli. Abnormal neurophysiologic responses to repetitive stimuli gave rise to clinically abnormal perceptions.

In-car nocturnal blue light exposure improves motorway driving: a randomized controlled trial.

UNLABELLED: Prolonged wakefulness greatly decreases nocturnal driving performance. The development of in-car countermeasures is a future challenge to prevent sleep-related accidents. The aim of this study is to determine whether continuous exposure to monochromatic light in the short wavelengths (blue light), placed on the dashboard, improves night-time driving performance. In this randomized, double-blind, placebo-controlled, cross-over study, 48 healthy male participants (aged 20-50 years) drove 400 km (250 miles) on motorway during night-time. They randomly and consecutively received either continuous blue light exposure (GOLite, Philips, 468 nm) during driving or 2*200 mg of caffeine or placebo of caffeine before and during the break. Treatments were separated by at least 1 week. The outcomes were number of inappropriate line crossings (ILC) and mean standard deviation of the lateral position (SDLP). Eight participants (17%) complained about dazzle during blue light exposure and were removed from the analysis. Results from the 40 remaining participants (mean age ± SD: 32.9±11.1) showed that countermeasures reduced the number of inappropriate line crossings (ILC) (F(2,91.11) = 6.64; p<0.05). Indeed, ILC were lower with coffee (12.51 [95% CI, 5.86 to 19.66], p = 0.001) and blue light (14.58 [CI, 8.75 to 22.58], p = 0.003) than with placebo (26.42 [CI, 19.90 to 33.71]). Similar results were found for SDLP. Treatments did not modify the quality, quantity and timing of 3 subsequent nocturnal sleep episodes. Despite a lesser tolerance, a non-inferior efficacy of continuous nocturnal blue light exposure compared with caffeine suggests that this in-car countermeasure, used occasionally, could be used to fight nocturnal sleepiness at the wheel in blue light-tolerant drivers, whatever their age. More studies are needed to determine the reproducibility of data and to verify if it can be generalized to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01070004.

In-car countermeasures open window and music revisited on the real road: popular but hardly effective against driver sleepiness.

This study investigated the effects of two very commonly used countermeasures against driver sleepiness, opening the window and listening to music, on subjective and physiological sleepiness measures during real road driving. In total, 24 individuals participated in the study. Sixteen participants received intermittent 10-min intervals of: (i) open window (2 cm opened); and (ii) listening to music, during both day and night driving on an open motorway. Both subjective sleepiness and physiological sleepiness (blink duration) was estimated to be significantly reduced when subjects listened to music, but the effect was only minor compared with the pronounced effects of night driving and driving duration. Open window had no attenuating effect on either sleepiness measure. No significant long-term effects beyond the actual countermeasure application intervals occurred, as shown by comparison to the control group (n = 8). Thus, despite their popularity, opening the window and listening to music cannot be recommended as sole countermeasures against driver sleepiness.

Inhibitory motor control in apneic and insomniac patients: a stop task study.

The aim of this study was to assess with a stop task the inhibitory motor control efficiency--a major component of executive control functions--in patients suffering from sleep disorders. Twenty-two patients with untreated obstructive sleep apnea syndrome (OSAS) (mean age 46 +/- 9 years; mean apnea-hypopnea index, AHI = 30 +/- 20) and 13 patients with psychophysiological insomnia (mean age 47 +/- 12 years) were compared with individually matched healthy controls. Sleep disturbances in the patient populations were clinically and polysomnographically diagnosed. The stop task has a frequent visual 'Go' stimulus to set up a response tendency and a less frequent auditory 'Stop' signal to withhold the planned or prepotent response. The stop signal reaction time (SSRT) reflects the time to internally suppress the ongoing response. SSRT was slower for the apneic patients than for their respective controls (248 +/- 107 versus 171 +/- 115 ms, anova, P < 0.05) but not for the insomniac patients compared with their controls (235 +/- 112 versus 194 +/- 109 ms, NS). Moreover, in apneic patients, slower SSRT was associated with lower nocturnal oxygen saturation (r = -0.477, P < 0.05). By contrast, neither apneics nor insomniacs differed from their matched controls for reaction times on Go trials. To conclude, unlike insomniacs, OSAS patients present an impaired inhibitory motor control, an executive function which is required in many common everyday life situations. Inhibitory motor control relies on the integrity of the inferior prefrontal cortex, which could be affected by nocturnal oxyhemoglobin desaturation in apneic patients.

Aging and nocturnal driving: better with coffee or a nap? A randomized study.

STUDY OBJECTIVE: To test the effects of coffee and napping on nocturnal driving in young and middle-aged participants. DESIGN: A cup of coffee (200 mg of caffeine), a placebo (decaffeinated coffee, 15 mg of caffeine), or a 30-minute nap were tested. Participants drove 125 highway miles between 18:00 and 19:30 and between 02:00 and 03:30 after coffee, placebo, or a nap. SETTING: Sleep laboratory and open French highway. PARTICIPANTS: Twelve young (range, 20-25 years) and 12 middle-aged participants (range, 40-50 years). MEASUREMENTS: Inappropriate line crossings, self-perceived fatigue and sleepiness, and polysomnographic recordings were analyzed. RESULTS: Compared to daytime, after placebo the number of inappropriate line crossings was significantly increased (2 versus 73 for young participants, P < 0.01 and 0 versus 76 for the middle-aged participants, P < 0.05). Both coffee and napping reduced the risk of inappropriate line crossings, compared with placebo, in young participants (respectively, by three-quarters, incidence rate ratios [IRR] = 0.26 95% confidence interval [CI], 0.09-0.74, P < 0.05 and by two thirds, IRR = 0.34 95% CI, 0.20-0.58, P < 0.001) and in middle-aged participants (respectively by nine tenths, IRR = 0.11 95% CI, 0.05-0.21, P < 0.001 and by one fifth, IRR = 0.77 95% CI, 0.63-0.95, P < 0.05). A significant interaction between age and condition (IRR = 2.27 95% CI, 1.28-4.16 P < 0.01) showed that napping led to fewer inappropriate line crossings in younger participants than in middle-aged participants. During napping, young participants slept more (P < 0.01) and had more delta sleep (P < 0.05) than middle-aged participants. Self-perceived sleepiness and fatigue did not differ in both age groups, but coffee improved sleepiness (P < 0.05), whereas napping did not. CONCLUSIONS: Coffee significantly improves performance in young and middle-aged participants. Napping is more efficient in younger than in older participants. Countermeasures to sleepiness should be adapted according to the age of drivers.

The effects of coffee and napping on nighttime highway driving: a randomized trial.

BACKGROUND: Sleep-related accidents often involve healthy young persons who are driving at night. Coffee and napping restore alertness, but no study has compared their effects on real nighttime driving performances. OBJECTIVE: To test the effects of 125 mL of coffee (half a cup) containing 200 mg of caffeine, placebo (decaffeinated coffee containing 15 mg of caffeine), or a 30-minute nap (at 1:00 a.m.) in a car on nighttime driving performance. DESIGN: Double-blind, randomized, crossover study. SETTING: Sleep laboratory and open highway. PARTICIPANTS: 12 young men (mean age, 21.3 years [SD, 1.8]). MEASUREMENTS: Self-rated fatigue and sleepiness, inappropriate line crossings from video recordings during highway driving, and polysomnographic recordings during the nap and subsequent sleep. INTERVENTION: Participants drove 200 km (125 miles) between 6:00 p.m. and 7:30 p.m. (daytime reference condition) or between 2:00 a.m. and 3:30 a.m. (coffee, decaffeinated coffee, or nap condition). After intervention, participants returned to the laboratory to sleep. RESULTS: Nighttime driving performance was similar to daytime performance (0 to 1 line crossing) for 75% of participants after coffee (0 or 1 line crossing), for 66% after the nap (P = 0.66 vs. coffee), and for only 13% after placebo (P = 0.041 vs. nap; P = 0.014 vs. coffee). The incidence rate ratios for having a line crossing after placebo were 3.7 (95% CI, 1.2 to 11.0; P = 0.001) compared with coffee and 2.9 (CI, 1.7 to 5.1; P = 0.021) compared with nap. A statistically significant interindividual variability was observed in response to sleep deprivation and countermeasures. Sleep latencies and efficiency during sleep after nighttime driving were similar in the 3 conditions. LIMITATIONS: Only 1 dose of coffee and 1 nap duration were tested. Effects may differ in other patient or age groups. CONCLUSIONS: Drinking coffee or napping at night statistically significantly reduces driving impairment without altering subsequent sleep.

The effect of CNS activation versus EEG arousal during sleep on heart rate response and daytime tests.

OBJECTIVE: To induce a heart rate change in normal subjects using auditory stimulation without inducing EEG arousals and to assess the effects on daytime functioning and compare results to auditory stimulation leading to short EEG arousals. METHODS: Six normal young men initially randomized into two groups (A and B) underwent 4 nights of nocturnal polysomnography (normal sleep on night 1, auditory stimulation without EEG arousal or normal sleep on nights 2 and 3 using Latin square design, and auditory stimulation with EEG arousal on night 4). MSLT and PVT were performed during days following nights 2-4. RESULTS: MSLT and PVT results showed significant differences after EEG arousal compared to stimulation without EEG arousal and to normal sleep; there were no significant differences after normal sleep compared to stimulation without EEG arousal. RR interval showed significant differences during undisturbed sleep compared to stimulation without EEG arousal and to stimulation with EEG arousal; RR interval without EEG arousal also differed significantly from RR interval with EEG arousal. CONCLUSION: Activation of the brain-stem can lead to autonomic nervous system (ANS) response without objective consequences the next day. SIGNIFICANCE: ANS responses induced by auditory stimulation during sleep without EEG arousal do not have the same effects on daytime sleepiness and performance as sleep fragmentation associated with EEG arousals.

Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: Correlations of fronto-parietal activation with performance.

Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep deprivation (SD) in 26 healthy young adults to examine the neural correlates of inter-individual differences in performance. The extent of performance decline was not significantly different between the two SD test periods although there was greater variability in performance at SD35. In both SD sessions, there was reduced task-related activation (relative to normal sleep) in both superior parietal regions and the left thalamus. Activation of the left parietal and left frontal regions after normal sleep was negatively correlated with performance accuracy decline from normal sleep to SD24 thus differentiating persons who maintained working memory performance following SD from those who were vulnerable to its effects.