2016 — 2019 |
Saletin, Jared Meyer |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
The Interaction of Brain Structure and Sleep Neurophysiology in Regulating the Neural Substrates of Inattention Symptoms in Pediatric Adhd @ Emma Pendleton Bradley Hospital
PROJECT SUMMARY Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurobehavioral disorders present during childhood and adolescence. ADHD associated with profound interpersonal and societal burden, yet the cause of ADHD is unknown. Sleep is an intimate regulator of cognition and behavior and sleep deprivation leads to inattention-like symptoms. One in three children with ADHD have sleep problems, yet the role of sleep in regulating inattention in ADHD is under-investigated. I propose to examine whether sleep contributes to the cause of inattention characteristic to pediatric ADHD. If so, sleep loss may provide a novel yet manageable risk factor in multiple conditions where sleep loss and inattention co-occur (e.g., ADHD, anxiety disorder, bipolar disorder, autism, obsessive compulsive disorder). In this K01 application I propose to address this concern with training in developmental psychopathology and neurobehavioral disorders (e.g., assessment, diagnosis, patient contact), multi-modal neuroimaging in children with such disorders, advanced statistical and analytical techniques (e.g., causal inference modeling), child and adolescent sleep (e.g., sleep disorders co-morbid in ADHD), and child/pubertal development. I propose a research plan that fully capitalizes on this inter- disciplinary training. I will characterize a sample of 68 youngsters (10-13 yo) across a dimension of symptom- level inattention, ranging from asymptomatic to severe attention deficits. Each child will enter a spend three nights in the laboratory: a sleep-rested night of laboratory sleep, a night with sleep restricted to 4 hours, and a full night of recovery sleep. I predict that increasing severity of attention will be associated with structural brain deficits in attention-regulating neuroanatomy that will lead to atypical sleep, and as a result increased vulnerability to sleep loss and decreased sensitivity to the benefits of sleep. If successful this project will greatly expand our knowledge of the role of sleep in ADHD.
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0.925 |
2021 |
Saletin, Jared Meyer |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Brain-Behavior Vulnerability to Sleep Loss in Children: a Dimensional Study of Attention and Impulsivity @ Emma Pendleton Bradley Hospital
Project Summary Children and adolescents increasingly experience insufficient or poorly timed sleep as early school start times collide with maturational changes in sleep regulation. However, we lack a deep understanding of both the brain-behavior consequences of this sleep loss and the factors that distinguish which children may be increasingly vulnerable and which are comparatively resilient to its effects. This is particularly salient for the brain-behavior mechanisms underlying attention and impulsivity: two cognitive domains which are acutely impacted by sleep loss, are critical for academic success, and are core aspects of neurodevelopmental disorders such as attention-deficit/hyperactivity-disorder (ADHD). Attempts to address these issues are hindered by limited mechanistic studies, overreliance on data from adults, and the use of neurotypical samples only. Thus, this R01 project tackles these challenges with a within-subject at-home sleep restriction experiment with combined methods of fMRI, neurocognitive testing, EEG, and circadian physiology to bear on this important problem. We aim to enroll (over five years) 150, 10-13-year-old children across levels of inattention and impulsivity. We will compare a sleep optimized baseline to 5 nights of sleep restriction. Each child is characterized on several attention and impulsivity metrics to compile baseline risk scores for each domain. Resting neural arousal (waking frontal EEG theta power) and circadian timing (melatonin onset phase angle) index sleep-relevant physiology as candidate mechanisms altering a child?s resilience to sleep loss. Repeated functional magnetic resonance imaging using task-based and resting paradigms, with complex modeling of behavior variability characterizes sleep loss?s impact on attention and impulsivity. A performance battery indexes neurocognitive impairments relevant for academic achievement. Finally, machine learning is used to determine examine distinct phenotypes of baseline risk factors and sleep-loss vulnerability in our sample. In sum, this project will advance both NICHD and NIMH?s goal to understand mechanisms of complex behavior; here, consequences and mediators of sleep loss for children.
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0.925 |
2021 |
Saletin, Jared Meyer |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Sleep and Circadian Timing: Mechanisms of Daytime Sleepiness and Impaired Cognition in Adhd @ Emma Pendleton Bradley Hospital
PROJECT ABSTRACT/SUMMARY Attention-deficit-hyperactivity-disorder (ADHD) affects nearly one in ten school-aged children. Although poor sleep is reported in this condition and has been related to waking behavioral struggles of children with ADHD, little is known about whether and how waking physiological sleepiness per se contributes to these behavioral profiles. Indeed, other than sleep-related breathing disorders, mechanisms underlying poor sleep and consequent physiological sleepiness are unknown. We propose two mechanistic targets within the sleep regulatory domain to tie together daytime sleepiness and learning outcomes in ADHD. Thus, this COBRE project uses an innovative laboratory study of operationally defined sleepiness, mechanisms of sleep regulation and circadian timing, and working memory (critical for learning success in the classroom) in children with and without ADHD. Our central hypothesis is that children with ADHD have underlying differences in Process S, sleep homeostasis, and Process C, circadian timing. Our methodology will be to enroll n=100, 9-11 year-old children (IQ ? 80), 50 with confirmable ADHD and 50 typically developing controls (TDCs) into a laboratory study. Following 2-weeks at home on a sleep schedule conforming to current recommendations (9 hours in bed) each child will come to the laboratory for three consecutive nights and days. All sleep in the lab will be monitored by polysomnography. Across a set of aims we will examine mechanisms of sleep and circadian regulatory processes, the level and pattern of physiological sleepiness per se, and the cognitive consequences of sleepiness, i.e., working memory. Together, these aims will serve to increase knowledge about the association of sleep homeostasis and circadian timing with ADHD symptoms, identify the role of physiological sleepiness in waking performance of children with ADHD, and determine whether sleep homeostasis regulation and/or circadian timing influence these outcomes. Our project will potentially inform innovative interventions that may target sleepiness in children with ADHD while preparing the project leader for an independent career at the intersection of sleep and clinical neurodevelopmental science.
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0.925 |