Abstract Recent estimates indicate that, conservatively, up to 5% of children in the United States have sufficient behavioral and cognitive effects due to prenatal alcohol exposure that they qualify for a fetal alcohol spectrum disorder (FASD). Children with an FASD experience a range of effects, including deficits in sensory, motor, and executive functions, which are in turn related to poor long-term outcomes. However, few evidence-based interventions are available for children with an FASD and, of these, only two target academic or cognitive skills. Music training (MT) targets a complex array of skills including auditory and visual perception, multisensory integration, attention, and working memory. These MT targets align well with the deficits experienced by children with FASD and, therefore, MT may be well-suited for improving outcomes for these children. In this project, we hypothesize that MT improves brain function and targeted skills via improvement in predictive coding. The predictive coding framework posits that a primary role of the brain is to predict the environment and optimize outcomes through identifying and correcting prediction errors. MT provides direct practice of predictive coding when participants regularly produce sounds (environment) and adjust their behavior to correct any errors (fix incorrect notes/timing). We further posit that this bottom-up training will help optimize sensory, motor, and cognitive function relative to top-down strategies, leading to better outcomes. Our pilot MT intervention in children with an FASD provided exciting evidence for acceptance of MT by children and parents and for the occurrence of pre-/post-MT changes at the neural and behavioral level in children with MT vs. those without MT. In the R61 phase, we will conduct a randomized cross-over study of a 12-week MT intervention relative to a music listening (ML) control period in a larger sample to examine neurophysiological changes in predictive coding and behavioral effects due to MT in FASD in children 8-16 years of age. We will assess changes in 1) brain function using magnetoencephalography and electroencephalography, 2) brain structure using structural magnetic resonance imaging and diffusion tensor imaging, and 3) cognition and behavior using neuropsychological assessment and questionnaires at three time points (pre-trial (week 1), cross-over (week 13), and post-trial (week 28)). In the R33 phase, we will again implement a randomized cross-over design in 8-16 year-olds with an FASD to: a) compare MT effects relative to a cognitive training (CT) control and b) evaluate dose effects by comparing 12- vs. 24-weeks of intervention. We hypothesize that the bottom-up approach of MT, which improves sensory (auditory) and motor functioning, will lead to changes in brain connectivity, which in turn will improve cognitive functioning relative to the top- down approach of CT. We have assembled a strong multidisciplinary team to implement a music training intervention and assess the outcomes using objective neuroimaging, cognitive, and behavioral measures. Future studies will explore how MT can contribute to a strengths-based intervention approach for FASD.

Narrative This innovative project will use objective neuroimaging and neuropsychological measures to examine the efficacy of music training to alleviate the effects of prenatal alcohol exposure in children with a fetal alcohol spectrum disorder (FASD). We hypothesize that music training will benefit children with an FASD by improving sensory and motor function in combination with improving brain connectivity more broadly, leading to improved cognitive and behavioral functioning. This study addresses the needs of children with an FASD, their families, and the NIAAA Strategic Plan which calls for new intervention approaches to improve the quality of life of individuals impacted by prenatal alcohol exposure.