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Lifespan Human Connectome Project: Children and Adolescents

NAMHC Concept Clearance

Presenter

Stacia Friedman-Hill, Ph.D.
Division of Developmental Translational Research

Goal

The goal of this initiative is to extend the experimental protocols developed through the Human Connectome Project (HCP) to children and adolescents to investigate the structural and functional changes that occur in the brain during typical development. Expansion of the HCP to include a broad range of subjects has the potential to significantly enhance the clinical relevance of the data and provide developmental benchmarks for understanding pathological processes in the etiology of human brain disorders.

Rationale

Over the course of the last decade, there has been an explosion of interest in the patterns of connectivity underlying structural and functional brain networks. Whereas older theories of brain disorders focused on single brain regions, the recent shift to studying connectivity and networks is revolutionizing how we understand neurological, mental, and developmental disorders, as well as age-related disorders and substance abuse. The NIH Blueprint for Neuroscience Research is currently funding the Human Connectome Project (HCP), a cooperative agreement to collect and share structural and functional connectivity data from a large sample of healthy adults, age 22-35. To date, HCP teams have developed and optimized non-invasive imaging technologies to acquire high resolution structural and functional in vivo data about axonal projections and neural connections from brains of hundreds of healthy adults. Demographic, sensory, motor, cognitive, emotional, and social function data have also been collected for each participant. The data and experimental protocols have been made available to the research community, and are now being used widely.

While the HCP launched the field of human connectomics and is providing the first well-characterized, quantitative datasets of human connectivity linked to genetic and behavioral data, the HCP is limited to the young adult brain—a very small portion of the overall human lifespan. Enormous structural and functional changes occur in the brain during typical development and aging. A complementary extension of the HCP to capture trajectories of maturation of structural and functional connectivity would greatly enhance the utility of this dataset and provide valuable reference data to support research examining the role of neurodevelopment in a variety of brain-based disorders.

The initiative will aim to:

  1. Maximize compatibility with existing HCP experimental imaging, behavioral, and genetic protocols, and justify changes due to limits of instrument sensitivity or special technical challenges in children and adolescents. Lifespan connectome projects will include high resolution structural MRI, multi-band diffusion spectrum imaging and high angular resolution diffusion imaging (HARDI), and resting state functional magnetic resonance imaging (rs-fMRI). Behavioral measurements may include those currently employed in the HCP, although these may be substituted or adapted with age-appropriate, developmentally normed measures.
  2. Study a large sample of children and adolescents, age 5-21. The initiative may include participants younger than 5, given appropriate sampling strategies for infants and toddlers, and bearing in mind tradeoffs between HCP compatibility vs. age-appropriate optimization and alterations of HCP protocols (e.g. scanning during awake vs. sleep state, shorted scan duration, data processing routines for segregation of white and gray matter, need for customized head coils).
  3. Ensure sufficient power for cross-sectional comparisons of age and sex. The initiative would encourage longitudinal measures for at least a subset of study participants.
  4. Be informed by data from lifespan pilot studies at the Washington University and Massachusetts General Hospital sites.
  5. Aggregate and store data in the Connectome Coordinating Facility. Consistent with HCP data release standards, NIMH anticipates that lifespan HCP data will be released on a regular basis during the course of the award.
  6. Consist of two-phase awards.
    • Phase 1 (1 year) will be a ramp-up period to begin recruitment, pilot imaging, behavioral, and genetic protocols, and establish schedules for data collection and deposit with the Connectome Coordinating Facility. Pilot studies are intended to augment the publicly available lifespan pilot studies and may include optimization of neuroimaging acquisition and processing protocols, adaptation of hardware for young participants, and modification of behavioral paradigms.
    • Phase 2 (3 years), depending on successful achievement of Phase 1 milestones, will focus on the acquisition and deposit of developmental data into the Connectome Coordinating Facility.

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