Body temperature has been reported to influence human performance. Performance is be better when body high/near its circadian peak and worse low/near minimum. We assessed whether this relationship between performance reflects the regulation of both internal biological timekeeping system and/or on independent phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment while controlling for phase hours awake. Most neurobehavioral measures varied as function time...

As the ear has dual functions for audition and balance, eye a role in detecting light wide range of behavioral physiological separate from sight [1Czeisler C.A. Shanahan T.L. Klerman E.B. Martens H. Brotman D.J. Emens J.S. Klein T. Rizzo 3rd, J.F. Suppression melatonin secretion some blind patients by exposure to bright light.N. Engl. J. Med. 1995; 332: 6-11Crossref PubMed Scopus (532) Google Scholar, 2Ruberg F.L. Skene Hanifin J.P. Rollag M.D. English Arendt Brainard G.C. Melatonin...

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod–cone photoreceptors. To assess relative contribution of melanopsin and photoreceptors to in humans, we compared responses normally sighted individuals ( n = 24) with a blind individual lacking function. Here, show visual are required for normal continuous exposure at low irradiance levels, sustained constriction during...

Abstract Sleep—wake homeostatic and internal circadian timedependent brain processes interact to regulate human function so that alert wakefulness is promoted during the daytime consolidated sleep at nighttime. The consequence of chronically altering normal relationship between these for largely unknown. We tested cognitive vigilance performance while subjects lived in laboratory over a month. on either 24.0- or 24.6-hr day lengths. Half maintained sleep—wakefulness time (synchronized...

Abstract Light regulates multiple non-image-forming (or nonvisual) circadian, neuroendocrine, and neurobehavioral functions, via outputs from intrinsically photosensitive retinal ganglion cells (ipRGCs). Exposure to light directly enhances alertness performance, so is an important regulator of wakefulness cognition. The roles rods, cones, ipRGCs in the impact on cognitive brain functions remain unclear, however. A small percentage blind individuals retain photoreception offer a unique...

PurposeThe limitations of current US Food and Drug Administration (FDA)–approved medications for the treatment attention-deficit/hyperactivity disorder (ADHD) set need development novel, effective, tolerable to treat this disorder. The purpose study was evaluate whether with SPN-812 (viloxazine extended-release) significantly reduces symptoms ADHD in children.MethodsThis a randomized, double-blind, placebo-controlled 6-week trial assess efficacy safety once-daily 100- 200-mg male female...

Attention-deficit/hyperactivity disorder is a neurodevelopmental that typically begins in childhood and often persists into adulthood. Recent phase III trials have demonstrated the efficacy safety of viloxazine extended-release capsules (viloxazine ER; Qelbree®) pediatrics (6–17 years age). The aim this study was to evaluate ER adults with attention-deficit/hyperactivity disorder. This III, randomized, double-blind, placebo-controlled, two-arm trial (18–65 age) Eligible subjects were...

Significance Millions of individuals obtain insufficient sleep on a daily basis, which leads to impaired performance. Whether these decrements are caused by short duration or extended wakefulness is unknown. In this study, healthy volunteers were randomized into either chronically sleep-restricted control protocol while living 20-h “day,” thus enabling without wakefulness. We demonstrate that chronic sleep, even wakefulness, neurobehavioral performance at all times the day, when circadian...

Intraindividual night-to-night sleep duration is often insufficient and variable. Here we report the effects of such chronic variable deficiency on neurobehavioral performance ability state-of-the-art models to predict these changes. Eight healthy males (mean age ± SD: 23.9 2.4 years) studied at our inpatient intensive physiologic monitoring unit completed an 11-day protocol with a baseline 10-hour opportunity three cycles two 3-hour time-in-bed (TIB) one TIB opportunities. Participants...

Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light entrain the pacemaker, a small proportion retain photic entrainment, melatonin suppression, and other nonimage-forming responses light. It is thought that these persist because survival melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily pacemaker are functionally distinct from rod cone photoreceptors mediate vision. We...

This phase 3 clinical trial evaluated the efficacy and safety of viloxazine extended-release capsules (VLX-ER) as a monotherapy for attention-deficit/hyperactivity disorder (ADHD) in adolescents (12-17 years).

Sleep inertia, subjectively experienced as grogginess felt upon awakening, causes cognitive performance impairments that can require up to 1.5 hr dissipate. It is unknown, however, how chronic sleep restriction (CSR) influences the magnitude and duration of inertia–related deficits. Twenty-six healthy participants were enrolled in one two in-laboratory protocols (one 32 day randomized control 38 protocol) separated influence circadian effects on using different "day"-lengths (20 42.85...

Machine learning (ML) was used to determine whether early response can predict efficacy outcome in pediatric subjects with ADHD treated SPN-812. We data from four Phase 3 placebo-controlled trials of 100- 600-mg/day SPN-812 (N=1397; 6-17 years age). The treatment defined as having a ≥50% reduction change baseline (CFB) Rating Scale-5 (ADHD-RS-5) Total score at Week 6. variables were: ADHD-RS-5 score, age, body weight, and mass index baseline; CFB 1, cumulative 2, 3; Clinical Global...

Endogenous circadian rhythmicity and sleep-wake homeostasis are robust regulators of human alertness performance, yet few studies have examined how these regulatory processes affect motivation. Moreover, the influence motivation on independent phase hours awake, has not been studied. Healthy subjects, 12 males 3 females, ages 20 to 41, participated in a 2-week 28-h forced desynchrony protocol address issues. Subjects performed battery tests every 2 during scheduled wakefulness. Performance...

Weight gain and obesity have reached epidemic proportions in modern society. Insufficient sleep – which is also prevalent society eating at inappropriate circadian times been identified as risk factors for weight gain, yet the impact of chronic insufficient on timing subjective hunger physiologic metabolic outcomes are not well understood. We investigated how impacts fasting hormones a 32-day in-laboratory randomized single-blind control study, with healthy younger participants (range, 20-34...

Chronic circadian disruption (CCD), such as occurs during rotating shiftwork, and insufficient sleep are each independently associated with poor health outcomes, including obesity glucose intolerance. A potential mechanism for is increased energy intake (i.e., eating), particularly the night, when physiological response to altered. However, contributions of CCD subjective hunger, appetite, food preference, appetitive hormones not clear. To disentangle influences these factors, we studied...

Accurate determination of circadian phase is necessary for research and clinical purposes because the influence master pacemaker on multiple physiologic functions. Melatonin presently most accurate marker activity human pacemaker. Current methods analyzing plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based physiologically-based linear differential equations. To determine which method provides assessment phase, we compared ability to fit data...

Early response to viloxazine extended-release (viloxazine ER, Qelbree®) treatment predicted efficacy outcome in pediatric subjects with attention-deficit/hyperactivity disorder (ADHD). This study sought determine whether the machine learning lasso model used would predict ER an adult population based on early improvements ADHD symptoms. We data from a double-blind, placebo-controlled, flexible-dose (200-600 mg) of (N = 354; 18 60 years old). Area under Receiver Operating Characteristic Curve...

Purpose: The ADHD Rating Scale (ADHD-RS) assesses 18 symptoms of inattention and hyperactivity/impulsivity has been used in many clinical trials to evaluate the treatment effect drugs on ADHD. fifth edition this scale (ADHD-RS-5) also impact six domains functional impairment (FI): family relationships, peer completing/returning homework, academic performance at school, controlling behavior self-esteem. Here, we report viloxazine extended-release capsules (viloxazine ER), a novel nonstimulant...

Abstract The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding how light information is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to image formation such as circadian resetting and entrainment, pupil constriction, enhancement alertness, well modulation cognition. More recently, it was demonstrated that may also contribute basic visual functions. impact on function,...

Objectives: Clinical trials in psychiatry frequently report results from lengthy, comprehensive assessments to characterize a subject emotionally, cognitively, and behaviorally before after treatment. However, the potential treatment implications of these how they translate into clinical practice remain unclear. Conversely, Global Impressions (CGI) scales are quick, intuitive used assess functional impact clinically relevant terms. The objectives present analyses scores symptom severity...