Project Grant F30AA033608

MUSIC TRAINING'S EFFECT ON BRAIN FUNCTIONAL CONNECTIVITY IN CHILDREN WITH FETAL ALCOHOL SPECTRUM DISORDER - PROJECT SUMMARY FETAL ALCOHOL SPECTRUM DISORDER (FASD) AFFECTS AN ESTIMATED 1 IN 20 U.S. CHILDREN, YET MOST GO UNDIAGNOSED. CHILDREN WITH FASD DISPLAY A WIDE RANGE OF COGNITIVE AND BEHAVIORAL CHALLENGES, INCLUDING SENSORY, LEARNING, ATTENTION, AND SOCIAL DEFICITS. DESPITE THIS SIGNIFICANT PUBLIC HEALTH NEED, FEW EVIDENCE-BASED INTERVENTIONS EXIST, AND THE NEURAL MECHANISM UNDERLYING EXISTING INTERVENTIONS IS ALSO UNCLEAR. PREVIOUS WORK HAS SHOWN ATYPICAL RESTING STATE FUNCTIONAL CONNECTIVITY (RSFC) PATTERNS IN CHILDREN WITH FASD. MUSIC TRAINING (MT) HAS BEEN SHOWN TO ALTER RSFC AND IMPROVE OUTCOMES IN CHILDREN WITH AUTISM SPECTRUM DISORDER, SUGGESTING IT MAY BE A POTENTIAL INTERVENTION FOR FASD. HOWEVER, THERE IS A LIMITED UNDERSTANDING OF IF AND HOW MT WOULD AFFECT RSFC IN CHILDREN WITH FASD. THUS, THE OBJECTIVE OF THIS PROPOSAL IS TO USE MAGNETOENCEPHALOGRAPHY (MEG) TO INVESTIGATE RSFC IN A LONGITUDINAL RANDOMIZED CONTROLLED TRIAL COMPARING THE EFFECTS OF MT AND COGNITIVE TRAINING (CT, ACTIVE CONTROL) FOR CHILDREN WITH FASD. MY CENTRAL HYPOTHESIS IS THAT MT WILL INDUCE SIGNIFICANT AND MORE ROBUST CHANGES IN RSFC THAN CT, POTENTIALLY DRIVEN BY TRAINING-INDUCED NEUROPLASTICITY WITH MT. MT ALSO HAS A POTENTIAL ADVANTAGE OF SELF-MOTIVATION FROM LEARNING HOW TO PLAY MUSIC, WHICH IS AN IMPORTANT INCENTIVE FOR THIS PEDIATRIC POPULATION. THE LONG-TERM GOAL IS TO GAIN A MECHANISTIC UNDERSTANDING OF THE INTERVENTION EFFECTS ON BRAIN CONNECTIVITY IN CHILDREN WITH FASD. I WILL PURSUE THE FOLLOWING 3 AIMS: (S.A.1) TO EVALUATE HOW MT AND CT AFFECT WHOLE-BRAIN STATIC RSFC: USING PHASE LOCKING VALUE (PLV) ANALYSIS, I WILL ASSESS MT/CT- INDUCED CHANGES ON THE OVERALL CONNECTIVITY OVER TIME AND IDENTIFY THE LARGE-SCALE NETWORKS MODIFIED BY EACH INTERVENTION. (S.A.2) TO EVALUATE HOW MT AND CT AFFECT WHOLE-BRAIN DYNAMIC RSFC: USING HIDDEN MARKOV MODELING (HMM), I WILL ASSESS MT/CT-INDUCED CHANGES ON THE MICRO-TEMPORAL PATTERNS OF CONNECTIVITY UNABLE TO BE CAPTURED BY SUMMATIVE, STATIC CONNECTIVITY MEASURES. (S.A.3) TO EVALUATE RESTING STATE BRAIN-BEHAVIOR CONNECTION: I WILL ASSESS THE RELATIONSHIP BETWEEN RSFC MEASURES AND COGNITIVE AND BEHAVIORAL PERFORMANCE, EVALUATING FOR TRANSLATIONAL CORRELATES OF RSFC IN CHILDREN WITH FASD. OVERALL IMPACT: THE PROPOSED AIMS OFFER RIGOROUS TRAINING IN CONDUCTING PEDIATRIC INTERVENTION RESEARCH, COLLECTING HIGH-QUALITY NEUROIMAGING DATA, AND APPLYING ADVANCED ANALYTICAL METHODS, ALL OF WHICH WILL SUPPORT MY DEVELOPMENT AS A PHYSICIAN-SCIENTIST IN NEUROSCIENCE. SUCCESSFUL COMPLETION OF THESE AIMS WILL PROVIDE NOVEL INSIGHTS INTO HOW MT AND CT INFLUENCE RESTING-STATE NETWORKS IN CHILDREN WITH FASD AND COULD LAY THE GROUNDWORK FOR DEVELOPING FUTURE MECHANISM- BASED INTERVENTIONS.