R01MH129855

Statistical Approaches to Improving Functional Connectivity Estimates with an Application to Autism - Abstract

Functional magnetic resonance imaging (fMRI) is used to estimate the correlations between brain regions. Despite the many insights into brain function provided by fMRI, the field is currently experiencing a reproducibility crisis. For instance, Autism Spectrum Disorder (ASD) is thought to be the result of disordered brain connections, but the ASD literature contains conflicting reports of both hypo- and hyper-connectivity.

Participant head motion is a crucial factor, and the exclusion of high-motion participants can reduce the impacts of motion. However, motion quality control removes more than 50% of data in pediatric fMRI studies. In ASD, the most severely impaired children tend to be removed, resulting in a characterization of only a limited part of the autism spectrum.

In addition, methodological development and empirical studies have focused on functional connectivity measured at rest. Children move less during some tasks, such as watching a movie. Dynamic connectivity during a task may offer crucial insights into diseases of brain connectivity with larger effect sizes, but popular methods do not utilize task information during model fitting.

The overall objective of this grant is to develop statistical methods that decrease bias and improve efficiency in functional connectivity studies. Our proposal is motivated by a resting-state fMRI study on ASD with hundreds of children from the Kennedy Krieger Institute and Johns Hopkins University. We will assess external validity in an independent test dataset that will be collected at the Marcus Autism Center and Emory University, where we will also conduct a study of engagement during a movie with social interactions.

To achieve our objective, we propose the following:

1) Develop a missing data method for deconfounding to reveal functional connectivity signatures of ASD. This aim addresses sampling biases due to motion quality control.

2) Develop a causal mediation framework for signal decomposition of functional connectivity and motion. This aim will be used to disentangle neural versus motion contributions to function connectivity in ASD.

3) Develop a novel covariance regression model for dynamic functional connectivity during a task. This aim will test the scientific hypothesis that the neural underpinnings of engagement differ in children with ASD compared to typically developing children.

We will develop software so that the proposed methods can be broadly applied to neuroimaging studies, including neurological disorders and mental health. Completing these aims will 1) provide tools that will improve reproducibility in functional connectivity studies and 2) reveal the neural underpinnings of ASD. This can aid in the development of treatments and educational strategies.

Emory University

THE MISSION OF THE NATIONAL INSTITUTE OF MENTAL HEALTH (NIMH) IS TO TRANSFORM THE UNDERSTANDING AND TREATMENT OF MENTAL ILLNESSES THROUGH BASIC AND CLINICAL RESEARCH, PAVING THE WAY FOR PREVENTION, RECOVERY, AND CURE. WE FULFILL THIS MISSION BY SUPPORTING AND CONDUCTING RESEARCH ON MENTAL ILLNESSES, HEALTH SERVICES, AND THE UNDERLYING BASIC SCIENCE OF THE BRAIN AND BEHAVIOR; SUPPORTING THE TRAINING OF SCIENTISTS TO CARRY OUT BASIC AND CLINICAL MENTAL HEALTH RESEARCH; AND COMMUNICATING WITH SCIENTISTS, PATIENTS, PROVIDERS, AND THE PUBLIC ABOUT MENTAL HEALTH RESEARCH ADVANCES AND PRIORITIES. IN MAY 2024, NIMH RELEASED ITS STRATEGIC PLAN FOR RESEARCH. THE STRATEGIC PLAN BUILDS ON THE SUCCESSES OF PREVIOUS NIMH STRATEGIC PLANS BY PROVIDING A FRAMEWORK FOR SCIENTIFIC RESEARCH AND EXPLORATION, AND ADDRESSING NEW CHALLENGES IN MENTAL HEALTH.THE NEW STRATEGIC PLAN OUTLINES FOUR HIGH-LEVEL GOALS: GOAL 1: DEFINE THE BRAIN MECHANISMS UNDERLYING COMPLEX BEHAVIORS GOAL 2: EXAMINE MENTAL ILLNESS TRAJECTORIES ACROSS THE LIFESPAN GOAL 3: STRIVE FOR PREVENTION AND CURES GOAL 4: STRENGTHEN THE PUBLIC HEALTH IMPACT OF NIMH-SUPPORTED RESEARCH THESE FOUR GOALS FORM A BROAD ROADMAP FOR THE INSTITUTES RESEARCH PRIORITIES OVER THE NEXT FIVE YEARS, BEGINNING WITH THE FUNDAMENTAL SCIENCE OF THE BRAIN AND BEHAVIOR, AND EXTENDING THROUGH EVIDENCE-BASED SERVICES THAT IMPROVE PUBLIC HEALTH OUTCOMES.

93.242 - Mental Health Research Grants

National Institute of Mental Health (NIMH) [HHS - NIH]

Atlanta, Georgia 30322 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 402% from $702,158 to $3,523,863.