Pediatric Imaging, Neurocognition and Genetics. The PING Study

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P I N G Pediatric Imaging, Neurocognition and Genetics The PING Study Natacha Akshoomoff, Ph.D. Associate Professor Department of Psychiatry and Center for Human Development University of California, San Diego

I have no financial interests to disclose

P I N G Pediatric Imaging, Neurocognition and Genetics NIDA Recovery Act Grand Opportunity: Creating a Pediatric Imaging Genomics Data Resource RC2 DA029475 Demographic, developmental, family history, cognitive, and neuroimaging phenotypes. Genome-wide genotyping >1200 typically developing children aged 3 to 20 years

Terry Jernigan, Ph.D., UC San Diego Anders Dale, Ph.D., UC San Diego Linda Chang, M.D. University of Hawaii and Queen s Medical Center Thomas Ernst, Ph.D., University of Hawaii and Queen s Medical Center Sarah Murray, Ph.D, Scripps Translational Science Institute Cinnamon Bloss, Ph.D., Scripps Translational Science Institute Natacha Akshoomoff, Ph.D., UC San Diego David Amaral, Ph.D., UC Davis B.J. Casey, Ph.D., Weill Medical College of Cornell University David Kennedy, Ph.D. University of Massachusetts Medical School Jean Frazier, M.D., University of Massachusetts Medical School Jeffrey Gruen, M.D., Yale University School of Medicine Tal Kenet, Ph.D., Massachusetts General Hospital, Harvard University Walter Kaufmann, M.D. Kennedy Krieger Institute, Johns Hopkins University Stewart Mostofsky, M.D., Kennedy Krieger Institute, Johns Hopkins University Bruce R. Rosen, M.D., Ph.D., Massachusetts General Hospital, Harvard University Elizabeth Sowell, Ph.D., UCLA and Children's Hospital of Los Angeles

Subdomain EXECUTIVE FUNCTION The NIH Toolbox Cognition Measures Flanker Inhibitory Control and Attention Test Dimensional Change Card Sort Test ATTENTION Flanker Inhibitory Control and Attention Test EPISODIC MEMORY Picture Sequence Memory Test LANGUAGE Picture Vocabulary Test Oral Reading Recognition Test PROCESSING SPEED Pattern Comparison Processing Speed Test WORKING MEMORY List Sorting Working Memory Test

PING sample characteristics Age Group Mean Age Males Females Total 3-5 years 4.17 24 24 48 5-7 years 5.98 50 50 100 7-9 years 7.96 68 61 129 9-11 years 9.94 73 71 144 11-14 years 12.55 114 82 196 14-17 years 15.47 193 106 193 17-20 years 19.18 99 111 210 M = 12.48 N = 534 N = 486 N = 1020 Akshoomoff et al., 2014

Subdomain EXECUTIVE FUNCTION The NIH Toolbox Cognition Measures Flanker Inhibitory Control and Attention Test Dimensional Change Card Sort Test ATTENTION Flanker Inhibitory Control and Attention Test EPISODIC MEMORY Picture Sequence Memory Test LANGUAGE Picture Vocabulary Test Oral Reading Recognition Test PROCESSING SPEED Pattern Comparison Processing Speed Test WORKING MEMORY List Sorting Working Memory Test

Generalized Additive Models Base Model: Smoothed effect of age, sex, age x sex interaction Base + SES: Household Income, Highest Parental Education, Highest Parental Occupation added to model Base + SES + GAFs: Genetic ancestry factors (coefficients for european, african, amerindian, central asia, eastern asia, oceania) added to model

Genetic Estimates of Ancestry

Generalized Additive Model Results R 2 Base R 2 Base + SES R 2 Base + SES + GAF DCCS 0.6651 0.6806 0.6854 Flanker 0.6800 0.6903 0.6946 Attention 0.5822 0.5928 0.60123 PSMT 0.5379 0.5538 0.5698 List Sorting 0.621 0.6411 0.6485 Picture Vocab. 0.6427 0.7059 0.7292 Oral Reading 0.7341 0.7565 0.7665 Pattern Comp. 0.5725 0.5819 0.5883 Akshoomoff et al., 2014

Flanker: Sustained Attention Akshoomoff et al., 2014

Flanker: Inhibitory Control Akshoomoff et al., 2014

Dimensional Change Card Sort: Cognitive Flexibility S * F > M Akshoomoff et al., 2014

Picture Sequence Memory Test Akshoomoff et al., 2014

Picture Vocabulary Test Akshoomoff et al., 2014

Oral Reading Recognition Test Akshoomoff et al., 2014

Pattern Comparison Processing Speed Test S * F > M Akshoomoff et al., 2014

List Sorting Working Memory S * M > F Akshoomoff et al., 2014

Summary All measures show strong sensitivity to age, but age-functions varied across measures Flanker and DCCS tasks exhibit bimodality in the youngest children SES and GAFs explain modest, but significant, proportions of variability in most measures; % of age-residualized variability was sometimes substantial.

Neuroanatomical Assessment of Biological Maturity Brown et al., 2012

nature neuroscience

Figure 9.