Project Grant R01MH134966

INDIVIDUALIZED MECHANISMS OF NEURAL PLASTICITY AND RESPONSE TO INTERVENTIONS IN NEONATES - PSYCHIATRIC DISORDERS AFFECT UP TO 30% OF ALL YOUTH PRIOR TO AGE 18, CAN BE HIGHLY IMPAIRING, AND UP TO 50% OF AFFECTED CHILDREN REMAIN SYMPTOMATIC DESPITE THE BEST AVAILABLE TREATMENTS. PART OF THE CHALLENGE IS THAT THE ALTERED BRAIN DEVELOPMENT ASSOCIATED WITH DEVELOPING A PSYCHIATRIC DISORDER MAY BEGIN AT BIRTH OR EARLIER. THUS, INTERVENTIONS MAY NEED TO BE IMPLEMENTED EARLY IN INFANCY, AT A TIME WHEN THE BRAIN IS MOST PLASTIC (SUSCEPTIBLE TO EXTERNAL MANIPULATIONS). ONE PREVENTATIVE STRATEGY WOULD BE TO TARGET INTERVENTIONS TO SPECIFIC BRAIN NETWORKS WHEN THEY ARE MOST PLASTIC IN HIGH-RISK INDIVIDUALS. BEFORE WE CAN ENACT THIS VISION, HOWEVER, WE NEED TO LEARN SUBSTANTIALLY MORE ABOUT MECHANISMS OF PLASTICITY IN NEONATES. THE NEONATAL PERIOD IS A TIME OF RAPID DEVELOPMENT, WITH WEEK-TO-WEEK BRAIN CHANGES, AND INDIVIDUAL NEONATES VARY IN THEIR BRAIN ORGANIZATION AND IN THEIR SPECIFIC STAGE OF DEVELOPMENT. THUS, EXAMINATION OF MECHANISMS OF PLASTICITY IN NEONATES WILL REQUIRE MEASUREMENT OF WEEK-TO-WEEK CHANGES AND PERSONALIZED MEASURES OF PLASTICITY AND BRAIN ORGANIZATION. THIS PROPOSAL TESTS THE HYPOTHESIS THAT HIGH REGIONAL SPONTANEOUS ACTIVITY IN INDIVIDUAL NEONATES REFLECTS THEIR PERSONALIZED BRAIN REGIONS THAT CURRENTLY HAVE HIGH PLASTICITY AND THUS ARE MOST RESPONSIVE TO INTERVENTIONS. THIS HYPOTHESIS IS EVALUATED BY TESTING WHETHER SPONTANEOUS ACTIVITY IS HIGHEST IN THE PERSONALIZED BRAIN NETWORKS KNOWN TO BE RAPIDLY DEVELOPING DURING THE NEONATAL PERIOD, PREDICTS WHICH BRAIN REGIONS WILL HAVE THE MOST WEEK-TO-WEEK DEVELOPMENTAL CHANGES IN THEIR CONNECTIONS, AND PREDICTS WHICH BRAIN REGIONS WILL HAVE THE MOST CHANGE IN RESPONSE TO AN INTERVENTION DIRECTED AT SENSORY NETWORKS (MASSAGE) IN INDIVIDUAL NEONATES. WE TEST THESE HYPOTHESES USING PRECISION FUNCTIONAL MAPPING (PFM) IN 80 NEONATES AT TWO TIMEPOINTS ONE WEEK APART. BETWEEN TIMEPOINTS, HALF UNDERGO 45 MINUTES OF DAILY MASSAGE, AN ESTABLISHED NEONATAL INTERVENTION. MASSAGE IS USED AS A PROOF-OF-CONCEPT TO STUDY IMPACT ON SENSORY SYSTEMS WHEN THEY ARE HIGHLY PLASTIC. PFM COLLECTS 1+ HOURS OF MAGNETIC RESONANCE IMAGING (MRI) OVER 2 DAYS TO DERIVE RELIABLE MEASURES PERMITTING HIGHLY POWERED WITHIN-SUBJECT ANALYSES. PFM ALSO PERMITS BRAIN ACTIVITY AND BRAIN CONNECTIONS TO BE MEASURED WITHIN PERSONALIZED NETWORKS, WHICH IS REQUIRED FOR NEONATES BECAUSE OF HIGH VARIABILITY IN THE SPECIFIC STAGE OF DEVELOPMENT. RESULTS ARE EXPECTED TO CHARACTERIZE MECHANISMS OF PLASTICITY AND PROVIDE A MODEL FOR HOW TO TARGET SPECIFIC INTERVENTIONS TO SPECIFIC BRAIN NETWORKS WHEN THEY ARE MOST PLASTIC, OPTIMIZING NEURODEVELOPMENTAL TRAJECTORIES AND REDUCING PSYCHIATRIC RISK. WHILE THIS PROPOSAL USES MASSAGE AS A MODEL TO INFLUENCE SENSORY NETWORKS WHEN MOST PLASTIC, THIS BLUEPRINT CAN BE EXTENDED TO OTHER BRAIN NETWORKS AND INTERVENTIONS, REDUCING RISK FOR PSYCHIATRIC ILLNESS. RESULTS COULD ULTIMATELY HAVE HIGH PUBLIC HEALTH IMPACT BY HIGHLIGHTING A GUIDE TO OPTIMALLY TIME AND TARGET INTERVENTIONS TO PREVENT PSYCHIATRIC ILLNESSES IN HIGH-RISK INFANTS.