Mapping the Brain the Face and Neurocognitive Function in FASD (U01) Elizabeth R. Sowell, Ph.D. USC Professor of Pediatrics Director, Developmental Cognitive Neuroimaging Laboratory (DCNL)

CIFASD II Progress 5 Manuscripts in 2012 8 abstracts in 2012-13

Cortical thickness increase in FASD: More is not necessarily better Yang et al., 2011, CIFASD

The face is a window to the brain Kids with smaller PFL have smaller callosal thickness in both the genu and isthmus of the CC than kids with bigger eye openings. Palpebral Fissure Length (PFL) Yang et al. & CIFASD, ACER 2011

Frontostriatal connectivity is decreased in prenatal alcohol exposure (PAE) Functional connectivity between caudate and frontal Cortex in PAE Roussotte et al. 2012

Longitudinal trajectories in FASD Trajectories of cortical volume change within children and youth with prenatal alcohol exposure (PAE) differed from those of unexposed control subjects. While control children (black) appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, the alcohol-exposed participants (blue) showed primarily volume loss in several posterior brain regions, demonstrating decreased plasticity. Furthermore, smaller volume change between scans was associated with lower intelligence and worse facial morphology in both groups, and was related to the amount of PAE during each trimester of pregnancy in the exposed group. These results are encouraging in that interventions aimed at altering “experience” over time may improve brain trajectories in individuals with heavy PAE, and possibly other neurodevelopmental disorders. Shaw et al., Nature 2006 Lebel et al., Journal of Neuroscience, In Press. 2012 CIFASD 8

Lebel et al., Journal of Neuroscience, In Press. 2012 CIFASD

Longitudinal Change It is not just damage to the brain that occurs prenatally from alcohol exposure, where we know when the “insult” to the brain occured. Change over time throughout childhood happens differently in children with prenatal alcohol exposure. Experience dependent plasticity?

What if I taught you to juggle (at age 46, or 55)? What if I taught you to juggle at age 10? More brain plasticity may make interventions more effective. Scholz, et al., 2009, Nature Neuroscience.

CIFASD II Works in Progress Longitudinal fMRI Gyrification Sex differences in white matter integrity Longitudinal change in cognitive function and white matter volume

Multisite longitudinal investigation of working memory changes in children with fetal alcohol spectrum disorders (Gautam et al., in preparation) Figure 1: Statistical maps showing group differences in change in activation between time 1 and time 2 on the visuospatial N-back task. All regions shown in color were statistically significant in the SA sample , in red were overlapping regions between SA and SD, and in blue overlapping between SA and L.A. Longitudinal data was available for 61 (30-alcohol exposed, 31- controls) subjects in Cape Town, 22 subjects (11-alcohol exposed, 11-controls) subjects in Los Angeles, and 15 subjects in San Diego (8 alcohol exposed, 8 controls). Controls: Orange, FASD: Blue Gautam et al. Presented at SFN 2012

Abnormal Patterns of Gyrification in Fetal Alcohol Spectrum Disorder, Joshi et al. HBM 2013

Joshi et al., To be presented at HBM, 2013

AE>C AE>C Boys: Girls: Sexually dimorphic alterations in structural connectivity in adolescents with a FASD: preliminary findings, Uban et al., RSA 2013 AE>C p’s <0.05 AE>C p’s <0.05 Boys: Girls: R L Uban et al., to be presented at RSA 2013

Brain Imaging Spin-off Projects Modeling of Joint Face-Brain dysmorphology in Fetal Alcohol Spectrum Disorder (K99 AA021407, Under Review, Joshi PI) Effects of in utero alcohol exposure on adolescent brain connectivity (F32 NRSA 1F32AA022561-01, Under Review, Uban PI)

In the Works: Moscow Russia Russian Academy of Medical Sciences: Scientific Center of Children Health “In 2014 we start MRI of the brain on the 3T scan, we will also use an additional spectrography regimen.” “Currently, we are conducting 1,5 T MRI studies of the brain. Additionally we are working with diffusion tensor and functional MRI (the latter starting from autumn 2012).”

Specific Aims CIFASD III: Brain Imaging Connectivity Aim 1: To evaluate cross-sectionally and longitudinally the effects of prenatal alcohol exposure on brain morphology and connectivity using high-resolution T1- and T2-wieghted MRI datasets. Aim 2. To evaluate cross-sectionally and longitudinally the effects of prenatal alcohol exposure on functional connectivity using resting state (rs) fMRI. Aim 3. To evaluate cross-sectionally and longitudinally the effects of prenatal alcohol exposure on structural connectivity using diffusion tensor imaging (DTI).

CIFASD III Progress IRB Pilot scans Human Phantom (Dr. Katherine Narr) Neurobehavior certification Recruitment

CIFASD III – Progress: First Quarter USC/CHLA SDSU UMN Emory IRB X x Human Phantom Jan 2013 Feb 2013 Pilot scan approved Neurobehavior approved Wait list/available FASD subjects ~30 Image data collected N = 3 Start Jan 2013

CIFASD III Plans Continue data collection Multi-project integration Continue data analysis from CIFASD II Some highlights below