A5025236648- Sleep and Wakefulness Research
- Circadian rhythm and melatonin
- Sleep and related disorders
- Neural dynamics and brain function
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Diet and metabolism studies
- Photonic and Optical Devices
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Photoreceptor and optogenetics research
- Diet, Metabolism, and Disease
- Obesity, Physical Activity, Diet
- Health and Lifestyle Studies
- Bat Biology and Ecology Studies
- Diabetes Treatment and Management
- Growth Hormone and Insulin-like Growth Factors
- Spaceflight effects on biology
- EEG and Brain-Computer Interfaces
- Cystic Fibrosis Research Advances
- Regulation of Appetite and Obesity
- Liver Disease Diagnosis and Treatment
- Light effects on plants
- Neuroscience and Neuropharmacology Research
Colorado School of Mines
2016-2025
University of Colorado Anschutz Medical Campus
2016-2025
University of Colorado Denver
2018-2023
Children's Hospital Colorado
2018-2023
Gettysburg College
2011-2013
University of Michigan
2010-2011
Brigham and Women's Hospital
2007-2010
Beth Israel Deaconess Medical Center
2007-2010
Harvard University
2010
Boston University
2007
A workshop was held at the National Institute for Diabetes and Digestive Kidney Diseases with a focus on impact of sleep circadian disruption energy balance diabetes. The identified number key principles research in this area specific opportunities. Studies would be facilitated by active collaboration between investigators sleep/circadian metabolism/diabetes. There is need to translate elegant findings from basic into improving metabolic health American public. also studying humans move...
Abstract Context To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed timing of adolescence, which is an emerging link between health and insulin sensitivity (SI), decreased SI PCOS. Objective examine differences melatonin rhythm obese adolescent PCOS control subjects, evaluate relationships variables SI. Design Cross-sectional study. Participants Obese (n = 59) or without 33). Outcome Measures Estimated...
Narcolepsy with cataplexy is caused by a loss of orexin (hypocretin) signaling, but the physiologic mechanisms that result in poor maintenance wakefulness and fragmented sleep remain unknown. Conventional scoring cannot reveal much about process transitioning between states or variations within states. We developed an EEG spectral analysis technique to determine whether state instability mouse model narcolepsy reflects abnormal wake states, faster movements transitions analyzed recordings...
Recent work in experimental neurophysiology has identified distinct neuronal populations the rodent brain stem and hypothalamus that selectively promote wake sleep. Mutual inhibition between these cell groups suggested conceptual model of a sleep–wake switch controls transitions sleep while minimizing time spent intermediate states. By combining wake- sleep-active with governing different stages sleep, “sleep–wake network” may be defined. To better understand dynamics inherent this network,...
Abstract Light at night in adults suppresses melatonin a nonlinear intensity‐dependent manner. In children, bright light of single intensity before bedtime has robust suppressing effect. To our knowledge, whether evening different intensities is related to suppression young children unknown. Healthy, good‐sleeping (n = 36; 3.0–4.9 years; 39% male) maintained stable sleep schedule for 7 days followed by 29.5‐h in‐home dim‐light circadian assessment (~1.5 lux). On the final protocol, received...
Orexin-producing neurons are clearly essential for the regulation of wakefulness and sleep because loss these cells produces narcolepsy. However, little is understood about how dynamically interact with other wake- sleep-regulatory nuclei to control behavioral states. Using survival analysis wake bouts in wild-type orexin knockout mice, we found that orexins necessary maintenance long wakefulness, but deficiency has impact on <1 min. Since often begin firing several seconds before onset...
This study presents a novel mathematical modeling framework that is uniquely suited to investigating the structure and dynamics of sleep-wake regulatory network in brain stem hypothalamus. It based on population firing rate model formalism modified explicitly include concentration levels neurotransmitters released postsynaptic populations. Using this framework, interactions among primary hypothalamic neuronal nuclei involved rat regulation are modeled. The captures realistic polyphasic...
Narcolepsy is caused by loss of the orexin (also known as hypocretin) neurons. In addition to peptides, these neurons release additional neurotransmitters, which may produce complex effects on sleep/wake behavior. Currently, it remains unknown whether promote initiation well maintenance wakefulness, and influence or sleep. To determine dynamics behavior, we analyzed architecture in a novel mouse model acute neuron loss.We used survival analysis other statistical methods analyze orexin-tTA ;...
Abstract Study Objectives Disrupted nighttime sleep (DNS) is a core narcolepsy symptom of unconsolidated resulting from hypocretin neuron loss. In this study, we define DNS objective measure and evaluate its diagnostic utility for pediatric type 1 (NT1). Methods This was retrospective, multisite, cross-sectional study polysomnograms (PSGs) in 316 patients, ages 6–18 years (n = 150 NT1, n 22 2, 27 idiopathic hypersomnia, 117 subjectively sleepy subjects). We assessed continuity PSG measures...
We determine if young people with narcolepsy type 1 (NT1), 2 (NT2), and idiopathic hypersomnia (IH) have distinct nocturnal sleep stability phenotypes compared to subjectively sleepy controls.
During hibernation, animals cycle between torpor and arousal. These cycles involve dramatic but poorly understood mechanisms of dynamic physiological regulation at the level gene expression. Each cycle, Brown Adipose Tissue (BAT) drives periodic arousal from by generating essential heat. We applied digital transcriptome analysis to precisely timed samples identify molecular pathways that underlie intense activity hibernator BAT. A cohort transcripts increased during torpor, paradoxical...
Late sleep timing is prevalent in early childhood and a risk factor for poor behavioral health outcomes. Sleep influenced by the phase of circadian clock, with later linked to delayed onset young children. Light strongest zeitgeber and, adults, evening light produces delay an intensity-dependent manner. The phase-shifting response children, however, currently unknown. In present study, 33 healthy, good-sleeping children aged 3.0 4.9 years (M = 4.14 years, 39% male) completed 10-day...
Although the sensitivity of circadian system to characteristics light (e.g., biological timing, intensity, duration, spectrum) has been well studied in adults, data early childhood remain limited. Utilizing a crossover, within-subjects design, we examined differences response evening exposure at two different correlated color temperatures (CCT) preschool-aged children. Healthy, good sleeping children ( n = 10, 3.0-5.9 years) completed 10-day protocols. In each protocol, after maintaining...
Circadian rhythms, intrinsic 24-h cycles that drive rhythmic changes in behavior and physiology, are important for normal physiology health. Previous work adults has identified sex differences circadian rhythms of melatonin, temperature, the period human timing system. However, less is known about at other developmental stages. To address this gap, we considered a secondary analysis sleep data from two studies involving adolescent participants during academic year: ( n = 32, 15 females). We...
The dynamics of sleep and wake are strongly linked to the circadian clock. Many models have accurately predicted behaviour resulting from dynamic interactions between these two systems without specifying physiological substrates for interactions. By contrast, recent experimental work has identified much relevant physiology sleep–wake regulation, but interaction difficult study experimentally. To bridge approaches, we developed a neuronal population model dynamic, bidirectional,...
Growing evidence suggests that brain activity during sleep, as well sleep regulation, are tightly linked with synaptic function and network excitability at the local global levels. We previously reported a mutation in synaptobrevin 2 (Vamp2) restless (rlss) mice results marked increase of wakefulness suppression particular REM (REMS), increased consolidation wakefulness. In this study, using finer-scale vivo electrophysiology recordings, we report spontaneous cortical rlss NREM (NREMS) is...
ABSTRACT The pineal secretion of the hormone melatonin demonstrates a circadian (~24 h) rhythm with onset production at night and offset each morning under tight control for entrained individuals. Melatonin exerts both acute sleep‐promoting effects phase‐shifting on clock. Due to its hypnotic chronobiotic (phase shifting) effects, exogenous supplements are increasingly being used as treatment variety sleep diseases disorders. Phase shifting clock can also be accomplished through ocular...
Waking and sleep states are regulated by the coordinated activity of a number neuronal populations in brainstem hypothalamus whose synaptic interactions compose sleep-wake regulatory network. Physiologically based mathematical models network contain mechanisms operating on multiple time scales including relatively fast synaptic-based between populations, much slower homeostatic circadian processes that modulate temporal patterning. In this study, we exploit naturally arising slow scale drive...
The timing of human sleep is strongly modulated by the 24 h circadian rhythm, and desynchronization sleep-wake cycles from rhythm can negatively impact health. To investigate dynamics modulation patterns entrainment cycle with we developed a one-dimensional map for physiologically based, regulatory network model sleep. dictates phase at which onset occurs on day n+1 as function $n$. We numerically compute reduced, though still high-dimensional, version that incorporates recent measurements...
Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour >155 mg/dl, or monophasic pattern of excursion during an oral tolerance test (OGTT) reflect a worse cardiometabolic profile. Post-pubertal overweight/obese without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 0.5). All participants completed OGTT...
Orexin (also known as hypocretin) neurons play a key role in regulating sleep-wake behavior, but the links between orexin neuron electrophysiology and function have not been explored. are wake-active, spiking activity may anticipate transitions to wakefulness by several seconds. However, it is suggested that while system necessary maintain sustained wake bouts, has little effect on brief bouts. In vitro experiments investigating actions of dynorphin, colocalized neuropeptide, indicate...