Association of Synchronized Oscillations of Sleep with Brain Maturation and Neuropsychiatric Disorders
Open Access
- Author:
- Ricci, Anna
- Graduate Program:
- Anatomy (PHD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 25, 2022
- Committee Members:
- Jidong Fang, Major Field Member
Patricia Mclaughlin, Co-Chair of Committee
Loren Evey, Major Field Member
Daniel Waschbusch, Major Field Member
Paul Eslinger, Outside Unit & Field Member
Julio Fernandez-Mendoza, Co-Chair & Dissertation Advisor
Patricia Mclaughlin, Program Head/Chair - Keywords:
- Development
Sleep
Sleep spindles
Slow wave activity
Brain maturation
Attention-deficit/hyperactivity disorder
Learning disorders
Internalizing disorders - Abstract:
- The transition from childhood to adolescence is a critical developmental period during which the brain undergoes structural and functional changes. The high neural plasticity of the adolescent brain is a key feature that allows these neurodevelopmental changes to occur, but also makes the adolescent more susceptible to harmful stimuli. Altered neurodevelopment in this transitional period may contribute to an increased burden of mental health disorders, including attention-deficit/hyperactivity (ADHD), learning (LD), and internalizing (ID; e.g., mood/anxiety) disorders. Neural networks involved in sleep-wake regulation as well as the functional aspects of sleep overlap extensively with neural circuits involved in cognition, emotion and behavior. It is well known that poor sleep is a common complaint among youth with neurodevelopmental and psychiatric disorders. However, it is important to clarify the specific neural mechanisms and sleep microstructural events that contribute to sleep complaints, as it may provide insight on developmental interventions and potential treatment options. This dissertation examined EEG metrics of sleep intensity, integrity and depth as they relate to brain maturational processes and how developmental disruptions in these sleep EEG biomarkers may inform the pathophysiology of mental health disorders in childhood and adolescence. Slow wave activity (SWA) occurs in the delta-frequency range, is a trademark for visually scoring slow wave sleep and is a metric of sleep intensity, while sleep spindle activity (SSA) occurs in the sigma-frequency range, is a trademark for visually scoring stage 2 of non-rapid eye movement (NREM) sleep and is a metric of sleep integrity. The odds ratio product (ORP) is a continuous score ranging from 0 (deep sleep) to 2.5 (full wakefulness) and is a standardized metric of sleep depth. The work in this dissertation showed in 664 youth aged 6 to 21 1) A cubic decline in SWA with a peak at age 7 and a nadir at age 19; 2) A quadratic increase in SSA density that plateaued by age 15; 3) A linear increase in ORP from age 6 to 21; and 4) Sex and pubertal-related differences in the trajectories of SWA and SSA consistent with earlier brain and pubertal maturation in females. In addition, we showed evidence for 1) A 3-year maturational delay in peak central SWA during childhood and a 67% steeper slope of decline during adolescence in unmedicated youth with ADHD/LD; 2) ORP to capture decreased sleep depth in adolescents with unmedicated ADHD/LD; 3) Stimulants to normalize ORP levels and, thus, sleep depth in adolescents with ADHD/LD; 4) A lower longitudinal decline in frontal SWA in youth with chronic unmedicated IDs; and 5) Antidepressants and anxiolytics to increase central and frontal ORP and, thus, cortical arousability in adolescents with IDs. Our data replicated, in a population-based sample of youth, prior study findings supporting SWA as a biomarker of synaptic pruning and the local/synaptic control of sleep intensity, SSA of sleep integrity and local changes in thalamocortical circuits, and ORP of the global/state control of sleep depth. In addition, our novel data in youth with psychopathology and pharmacotherapy provided evidence for altered cortical development and decreased NREM sleep depth and intensity in unmedicated youth with ADHD/LD, while stimulants appeared to normalize sleep depth in these youth. We also showed that adolescents with chronic unmedicated IDs experienced less changes in frontal SWA, indicating potential alterations in neural networks in the frontal cortex. In contrast to stimulants, antidepressants and anxiolytics were associated with decreased sleep depth and increased cortical arousability in adolescents with IDs. Overall, we have contributed important replication data and novel data on EEG biomarkers of sleep intensity, integrity and depth that may inform the development, risk and treatment of neurodevelopmental and psychiatric disorders in children and adolescents.