The Teen Brain. Jay Giedd, MD - The Teenage Brain. Adolescence what age range? What is Adolescence. Adolescence = time of change

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1 The Teen Brain Jay N. Giedd, MD UC San Diego / Rady Children s Hospital Chair Child and Adolescent Psychiatry Johns Hopkins Bloomberg School of Public Health (Department of Family and Reproductive Medicine) University of Fukui Slides Available What is Adolescence Proto-Indo-European roots ad- ( to, toward ) + al ( ripen, nourish ) The Latin suffix escere added to al conveys in the process of becoming (i.e. inchoate form) So from an etymological perspective adolescence means in the process of moving toward ripeness Adolescence what age range? Begins with biological event of puberty Ends with social event of independent functioning as an adult Ages may vary from person to person Adolescence conflicting forces A time when most mental illness emerges And a time when physical health, strength, speed, agility, are at their peak. A time of reckless and often puzzling behavior And a time of great leaps in cognitive abilities and motor skills A time of increased drives of sex and aggression And a time of intense passions and convictions Adolescence = time of change By its very nature this ripening process is a time of change Changes in body, behavior, and as we have more recently discovered a time of changes in the brain. These dynamic changes make adolescence a time of vulnerability but also of opportunity. 1

2 Short talk, huh? Oh, you mean they found one? Isn t that a contradiction of terms? What is your next talk on the Loch Ness Monster? 2

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4 The adolescent brain is not a broken or defective adult brain! It is exquisitely forged by the forces of our evolutionary history to have different features compared to children or adults. Adolescent Behavioral Changes in Social Mammals Hall of Human Origins Smithsonian Museum, Washington DC Increased risk taking Increased sensation seeking Greater peer affiliation Facilitate separation from natal family? Less inbreeding = evolutionary advantage? Brain volume increase driven by change in environment 4

5 The Double Edged Sword of Adolescent Brain Plasticity Trajectories AR Genotype X & Y Dosage Effects Vulnerability Opportunity GOAL: To explore the path, mechanisms, and influences on brain development in health and illness through longitudinal studies combining brain imaging, genetics, and psychological/behavioral assessments. Twins Pediatric Neuroimaging Data Base Longitudinal Assessment (~ 2 year intervals) Imaging (smri, fmri, DTI, MTI) Genetics (blood, saliva) Neuropsychological / Clinical 10,000+ Scans from Subjects ~ ¼ Typically-Developing Singletons ~ ¼ Typically-Developing Twins 25 Clinical Populations ADHD, Autism, Childhood Onset Schizophrenia, Sex Chromosome Variations (XXY, XXX, XXY, XXYY, XXXXY), 3 Key Points of Brain Maturation The brain matures by becoming more connected (white matter) and more specialized (gray matter). A changing prefrontal/limbic balance affects reward circuitry, hot vs cold cognition, temporal discounting, and decision making Enormous plasticity confers both vulnerability and opportunity 3 Key Points of Brain Maturation White Matter The brain matures by becoming more connected (white matter) and more specialized (gray matter). Nucleus White Matter A changing prefrontal/limbic balance affects reward circuitry, hot vs cold cognition, temporal discounting, and decision making Axon Oligodendroglia Enormous plasticity confers both vulnerability and opportunity Male (152 scans from 90 subjects) Female (91 scans from 55 subjects) 95% Confidence Intervals Age in years 5

6 Myelin Increased Bandwidth Speed 100x, Refractory Period 1/30x More than just maximizing speed Synchrony Plasticity Sensitive Periods Integration Signal hops between nodes of Ranvier Facets of Connectivity Long Term Potentiation (LTP) White Matter EEG coherence fmri coactivation Temporally coupled developmental trajectories fire together wire together grow together? Similarly affected by same genetic/environmental factors Graph Theory (nodes and edges) Maturational Coupling Echoes White Matter and FMRI Connectivity Fire together Wire together Grow together GRAY MATTER CHANGE Raznahan, 2011, Neuron WHITE MATTER rsfmri Honey, 2009, PNAS Facets of Connectivity Long Term Potentiation (LTP) White Matter EEG coherence fmri coactivation Temporally coupled developmental trajectories fire together wire together grow together? Similarly affected by same genetic/environmental factors Graph Theory (nodes and edges) CC area 17% less in abused / neglected subjects CC area 11% less than psychiatric controls 6

7 Graph Theory: Is it a small world after all? (strangers linked by mutual acquaintance) Disrupted modularity and local connectivity in childhood onset schizophrenia Nodes and Edges Alexander-Bloch, Giedd, Bullmore (2010) 3 Key Points of Brain Maturation White Matter vs Gray Matter The brain matures by becoming more connected (white matter) and more specialized (gray matter). A changing prefrontal/limbic balance affects reward circuitry, hot vs cold cognition, temporal discounting, and decision making Enormous plasticity confers both vulnerability and opportunity White Matter Linear increase Not different by region Gray Matter Inverted U Regionally specific Gray Matter Development in Healthy Children & Adolescents (1412 Scans from 540 Subjects) Frontal Lobe Gray Matter 240 Volume in ml Age in years 7

8 Cortical Gray Matter Ages 4 to 25 years Prefrontal Cortex Executive functions Long term strategy Planning Organization Impulse control Integrates input from rest of the brain social brain circuitry Time Travel Multi tasking bottle neck? anatomical coupling correlates with vocabulary scores in linguistically relevant regions 3 Key Points of Brain Maturation The brain matures by becoming more connected (white matter) and more specialized (gray matter). A changing prefrontal/limbic balance affects reward circuitry, hot vs cold cognition, temporal discounting, and decision making Lee, Giedd et al Enormous plasticity confers both vulnerability and opportunity Limbic circuitry ignites at puberty Scientific American, September

9 3 Key Points of Brain Maturation Pruning / Specialization The brain matures by becoming more connected (white matter) and more specialized (gray matter). A changing prefrontal/limbic balance affects reward circuitry, hot vs cold cognition, temporal discounting, and decision making Enormous plasticity confers both vulnerability and opportunity Zits cartoons Zits Partnership If we understood influences 9

10 Adolescent Brain Cognitive Development (ABCD) 12,000 9 and 10 year olds recruited for 10 year longitudinal study Brain imaging, genetics, biosamples, cognitive/behavioral and mobile assessments 22 sites / epidemiological sampling ~$500 million in funding from NIH GOAL: UNDERSTAND CONTRIBUTORS TO HEALTHY DEVELOPMENT How does screen time affect social and brain development? How do sleep patterns affect academic What are effects of earlier experience on brain development.? Do extracurricular activities or other experiences help children do better in school and feel happier? What are the long-term effects of ADHD medications on academics and health? achievement? The Double Edged Sword of Adolescent Brain Plasticity Vulnerability Opportunity Time of dramatic change in brain, body, and behavior Time of peak emergence of: Schizophrenia Depression Anxiety Substance Abuse Eating Disorders Not Autism, ADHD, Alzheimer s Moving parts get broken? 10

11 Why Adolescence: Schizophrenia Is schizophrenia related to an exaggeration of typical regressive changes of adolescence? Gray Matter thickness changes in Childhood Onset Schizophrenia Delta sleep (synaptic pruning?) (Feinberg 1982) Membrane phospholipids (Pettegrew et al. 1991) Prefrontal metabolism (Andreasen et al. 1992) Density of synaptic spines (Garey et al. 1998) Neuropil (Selemon et al. 1995) Expression of synaptic marker synaptophysin (Eastwood et al. 1995) Frontal cortical gray matter (Sporn et al. 2003) Percentage Change in Regional Cortical Gray Matter Volumes Between Healthy Volunteers (N=34) and Childhood-Onset Schizophrenics (N=15) Ages Decrease Increase 50% by 14 75% by 20 Adolescent Depression 1 in 7 adolescents experience 1 in 10 any form of treatment The Double Edged Sword of Adolescent Brain Plasticity Vulnerability Average time between onset of symptoms and treatment = 10.8 years Opportunity 11

12 Digital Revolution Remarkable advances in technologies that enable the distribution and utilization of information encoded as sequences of 1s and 0s have dramatically changed our way of life. The Digital Revolution: Impact The way we learn, play, and interact with each other has changed more in the last 15 years than in the previous 570 years since Gutenberg s popularization of the printing press. Adolescents Young enough to embrace change Old enough to master the technology Multitasking Smartphones, Fitbit, Wearable Sensors 12

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