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Sleep

Why sleep?

In the course of his or her life, the average person sleeps for more than 25 years. Despite major advances in understanding the circadian and homeostatic factors that regulate sleep, much remains unknown about its functions — that is, why we sleep. Sleep is believed to play important roles across a broad range of processes, including memory consolidation, neuroprotective actions, hormonal function, and interactions with the cardiovascular and immune systems. Nonetheless, in many ways 'sleep' currrently remains an umbrella term for a heterogeneous set of interacting processes that need to be better characterized and understood.

Individual differences in sleep

People vary considerably in their typical quality and quantity of sleep. On one level, brain activity as measured by the electroencephalogram (EEG) is a heritable 'fingerprint', aspects of which correlate with a range of clinical, demographic and cognitive variables. On another level, individuals suffering from disorders of sleep (including sleep apnea, insomnia, hypersomnia and narcolepsy) can exhibit markedly aberrant sleep patterns. The genetic basis of most of this clinically meaningful variability is largely unknown, however.

Sleep and health

Individual differences in sleep (especially lack of sleep) have been associated with a host of chronic medical conditions including obesity, diabetes, hypertension, heart disease, and ultimately shortened life expectancy. For some disorders (e.g. major depressive disorder and bipolar disorder) sleep problems are core clinical features. The direction of these associations is typically unclear. Do sleep problems lead to disease, or disease to abnormal sleep? Or does a third factor — such as a shared genetic basis — give rise to both sleep and health phenotypes? Delineating these types of causal networks will be important because it may provide a basis for identifying targets for intervention and patient stratification.

Current projects

This is a non-exhaustive list of recent and ongoing projects (primarily computational tool and methods development) and collaborations (applying these tools to existing or new data collections led by others):

Data, tools and methods

  • National Sleep Research Resource: working with founding-member Dr. Susan Redline, Dr. Purcell co-directs the NSRR, an NLBI-funded respository or sleep research data

  • Luna: we are devloping a growing library of tools designed to work with large numbers of sleep studies, with a current focus on the sleep EEG

  • Personalized sleep staging: Dr. Purcell is the PI of an NHLBI-funded R01 to support the development of methods to better capture between-individual variability in automated sleep staging, and to define new quantitative metrics, beyond traditional classification of sleep stages, to better capture individual differences in sleep

  • Dynamics: Dr. Purcell is the PI of an NHLBI-funded R21 to develop methods to better capture ultradian dynamics in sleep signals (patterns of change within a single night)

Sleep neurophysiology, psychiatric disease and genetics

  • MARS: Mood and Rhythms of Sleep: This project is a newly awarded, Wellcome Trust funded project to develop sleep-based objective biomarkers for bipolar disorder and major depression.

  • The role of cerebellar cortical and thalamocortical circuits in bipolar disorder: with Dr. Jen Pan (Broad Institute) and others, this new and highly multidiscplinary project funded by Breakthrough Discoveries for thriving with Bipolar Disorder (BD2) will investigate the role of gene-driven dysfunction within key brain structures to create a framework for validating targets identified in human genetic studies and potentially uncover specific therapeutic opportunities for carriers of those risk factors.

  • GRINS: the Global Research Initiative on the Neurophysiology of Schizophrenia is a collaboration with investigators at the Stanley Center, Broad Institute and Wuxi Mental Health Center (China), as well as other investigators at Mass General and McLean Hospitals. This project focuses on collecting high density sleep EEG and other measures in patients with schizophrenia and matched controls.

  • Animal models: in collaboration with Dr. Jen Pan at the Stanley Center for Psychiatric Research, Broad Institute, and others, we are studying the effects of human mutations associated with psychiatric disease, in vivo in the sleep EEG. Sleep EEG GWAS: leveraging genetically informative datasets in the NSRR, we aim to perform genome-wide association studies to link objective measures of sleep macro- and micro-architecture with genetic risk for psychiatric disease.

Sleep and cognitive aging

  • MESA/MrOS: working with collaborators from the MESA and MrOS studies, we have characterized multiple facets of sleep macro and micro archtiecture in almost 4,000 older adults, showing how they change with age and predict cognitive performance. Next, we will focus longitudinally to examine changes in sleep and cognition over multiple years.

  • Harvard Aging Brain Study: in a collaboration led by Jasmeer Chatwal and others, we will be investigating sleep neurophysiological metrics in relation to PET imaging markers of cognitive aging.

  • Contributions of sleep to preclinical and clinical AD: we will be collaborating on a new study led by Drs. Jayandra Himali and Matthew Pase, on the links between sleep, brain morphometry and other imaging measures.

Sleep and cognitive development

  • RASP and ESP studies: these ongoing projects aim to compile pediatric sleep studies, either using retrospective clinical studies, or prospectively collecting research studies, in order to evaluate the degree to which the development and maturation of sleep patterns relate to neurodevelopmental differences in young children. This is a multi-site collaboration with NIMH Intramural researchers and other sites (Boston Children's, Geisinger, New York University, Baylor College of Medicine).

  • NIMH toddlers study: we collaborate with NIMH intramural researchers Drs. Ashura Buckley and Audrey Thurm, looking at how the sleep EEG of very young children predicts cognitive development.

  • Sleep and cognitive development in children: we are characterizing developmental changes in the sleep EEG, with a focus on functional connectivity indexed by coherence analysis.

Sleep epidemiology and health

  • Sleep, race and health disparities: working with collaborators at Harvard School of Public Health, Dr. Purcell is PI of a NIMHD-funded R21 to better determine which aspects of sleep may contribute to racial and ethnic disparities in health outcomes

  • Normative studies for sleep biomarkers: if objective sleep metrics are ever to be used as clinically useful biomarkers, it will be important to first characterize baseline sources of variability in these measures, to identify unbiased and reliable measures. This involves studying sleep biomarkers in large and diverse datasets, following our work on sleep spindles, for example.