Nearly 75 percent of mental illness in adults originates prior to age 24 years, and numerous links have been identified between the presence of childhood psychiatric problems and the later onset of adult illness. As such, the developmental origins of most psychiatric illnesses are increasingly being appreciated. Whether considering disorders affecting children, adolescents, adults or the elderly, early detection of disease risk and/or onset is the critical first step in prevention and treatment, respectively. In this regard, the imaging community is increasingly hopeful that normative assessments of brain development, maturation and aging can be obtained. We anticipate that these normative trajectories will facilitate the identification of markers of pathologic development capable of one day informing multiple aspects of clinical assessment and decision-making—ranging from determinations of risk, diagnosis, and prognosis, to the selection and timing of interventions, as well as treatment response monitoring.
Unfortunately, the imaging community remains without a large-scale dataset sampling lifespan—despite it being a crucial first step towards attaining normative assessments of human brain function and structure. The NKI-RS study is taking a key step forward in addressing this gap, through the employment of a cross-sectional lifespan design-sampling individuals between the ages of 6 and 85 years old in the same sample. As will be discussed in the following sections, a unique aspect of the NKI-RS study design that has made this possible is the careful attention given to imaging and phenotypic measures that can be used with individuals of any age.
Brain imaging studies tend to be opportunistic in their recruitment without regard for geographic, socioeconomic, ethnic, and racial representation of the community from which the sample is derived. Although understandable, such strategies increase the risk of artifactual recruitment biases. In response to this concern, the enhanced NKI-Rockland Sample will follow the model of epidemiologic studies and imaging efforts such as the NIH Study of Normal Brain Development by carefully controlling recruitment and enrollment in order to maximize the community representativeness of the sample and minimize biases inherent to opportunistic recruiting. Specifically, we will ensure that the population of each zip-code in Rockland County is proportionately represented in the sample. As demonstrated by the 2009 U.S. census, Rockland County is strikingly representative of the U.S. population in key demographic measures. Recruitment efforts will ensure maximal visibility throughout Rockland County by the distribution of flyers to approximately 100,000 households, as well as the use of social networking and free media.
Imaging the Brain at Unprecedented Speeds
Typically functional MRI allows researchers to measure patterns of brain activity throughout the full brain at a rate of one image every 3 seconds; diffusion imaging, which is commonly used to measure structural connectivity in the brain, can take upwards of 30-60 minutes to obtain high quality images. The Center for Magnetic Resonance Research (CMRR), University of Minnesota, recently developed a novel approach to acquiring functional MRI that has reduced sampling rates down to one image every 400-600 milliseconds for functional MRI studies of brain activity. When applied to diffusion imaging, this technology is now allowing researchers to capture structural connectivity throughout the brain, with great detail, in as little as 7 minutes. Initially developed for the Washington University-University of Minnesota (WU-Minn) consortium of the Human Connectome Project, these sequences have been provided to the NKI-RS effort to ensure the best quality data is obtained in the shortest time possible, given that pediatric and geriatric populations are participating in the study.
The NKI-RS captures a broad range of behavioral and cognitive phenomenology relevant to psychiatric health and illness, with great detail (i.e., deeply). The validity and value of assessments were evaluated by consulting leaders in the field of psychiatric phenotyping. To maximize scientific overlap, assessment selection was guided through consultation with and review of other phenotypic data collection and sharing initiatives, such as Brain Genomics Superstruct, the Human Connectome Project adn the Brain Behavior Laboratory at the University of Pennsylvania. Preference was given to measures that are available in forms suitable for individuals across the targeted age range and with age-normed data, though exceptions were made when deemed justified by consensus. The protocol strives to attain both breadth and depth in terms of psychiatrically relevant phenotypic variables.
Following review of the initial plan for the NKI-RS phenotypic protocol and study design, the Child Mind Institute’s Scientific Research Council recommended that the protocol’s administration schedule be decompressed from one to two days (scheduled within 2 weeks of each other) to minimize participant fatigue and burden—thereby protecting the integrity of data collection. In response to these recommendations, the Child Mind Institute has provided the NKI-RS with the funding necessary to decompress the design from a one- to two-day protocol. Additional funding and manpower was also provided to minimize the burden on the NKI-RS staff as well. Minimization of both participant and experimenter burden is essential to the success of scientific endeavors.
State of the Art Neuroinformatics Infrastructure
Given the substantial increase in phentoyping, as well as the time-consuming and error-prone nature of collecting and managing data from paper and pencil assessments, the Child Mind Institute has provided the NKI-RS with a state of the art data capture and management system developed by the Mind Research Network. Named the COllaborative Informatics and Neuroimaging Suite (COINS), this system enables web-based management and administration of all phenotypic assessments (e.g., participant questionnaires), as well as the automatic integration of phenotypic and neuroimaging data in an easily searchable platform. Pilot testing of the COINS with participants from the NKI-RS pilot effort indicated increased participant satisfaction and decreased data management error.
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