Understanding neurophysiological deficits in response inhibition in children with FASD

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Abstract Recognition of subtle signs of fetal alcohol spectrum disorder has increased the estimated prevalence rate to between 2-5% of school-aged children. While the neurocognitive profile of FASD has been characterized, the underlying mechanisms that lead to these neurocognitive deficits are still poorly understood. Poor inhibitory functioning is one of the executive function impairments identified in children with FASD and likely is related to many of the secondary deficits experienced by individuals with FASD including increased rates of addictions, incarceration and susceptibility to other neuropsychiatric disorders. Therefore, understanding the underlying brain mechanisms that lead to impaired inhibitory functioning in early elementary age children is important to guide development of intervention approaches. In other clinical populations altered functional network connectivity assessed with fMRI is associated with poor inhibitory functioning. Another large body of work originating largely from EEG indicates that neural oscillations play a key role in cognitive control and mediating inhibitory responses. By using MEG we will extend these prior EEG results to the FASD population through identifying the cortical source location and timing of evoked activity and examining resting network connectivity at the source level. Using the high temporal resolution of MEG, we will capture both resting neural oscillations, resting brain connectivity, and task evoked neural oscillations related to both successful and unsuccessful inhibition during a child-friendly Go/No-Go task. This project period will examine younger children in the 6-8 year age range and focus on neural oscillations using MEG and functional network connectivity using both MEG and fMRI. Aim 1 will use MEG to examine event-related responses, including averaged evoked response and task-evoked neural oscillations during the Go/No-Go task. This aim will, in part, replicate the averaged evoked response results obtained in the current project period in a younger independent cohort and will extend the prior project period aim by examining task-evoked neural oscillations allowing us to capture theta and beta oscillations related to cognitive control. Aim 2 will examine resting neural oscillations and resting functional network connectivity using both MEG and fMRI. Recent results indicate that resting functional network connectivity patterns differ by clinical disorders. Aim 3 will examine this question directly by linking the results from Aim 1 and Aim 2 as well as behavioral measures of inhibitory functioning in these children to determine what functional brain measures predict inhibitory functioning in children with FASD and healthy controls. Project 5 is complementary to each of the other projects in this center grant with neural oscillations in mouse and rat models examined in Projects 3&4. Furthermore, autonomic nervous system response will be assessed through heart rate variability in support of project 2. Combined, these projects will provide translational results to take measurable steps toward developing mechanistic-based interventions for children with FASD.