Rhoshel Lenroot Chair of Infant, Child and Adolescent ......2015/08/06  · Understanding the...

Understanding the teenage brain of today

Rhoshel LenrootChair of Infant, Child and Adolescent PsychiatryUNSW and Neurosciences Research Australia

Clinical Director of Child and Adolescent Mental Health ServicesSoutheastern Sydney Local Health District

Adolescence

• Beginning of puberty till achieve self-sufficiency

• Developmental tasks: – Individuation– Formation of intimate relationships outside the

family

Teens are not defective adults

• Evolutionarily conserved– Increased risk taking– Socializing with peers– Fighting with parents– Increased ethanol intake

(Spear Dev Cog Sci 2010)

• 2005 Youth Risk Behavior Survey1:– 13, 000 adolescent deaths in

US each year– 70% from

1 Eaton et al, Youth risk behavior surveillance – United State, 2005, surveillance summmaries. Morbidity and Mortality Weekly Report, 2006

• Motor vehicle crashes• Unintentional injuries

• Homicide• Suicide

• Lifelong adverse consequences• Due to individual choices: preventable

Early onset of psychiatric disorders:50% age 14; 75% by age 24

What do we know about the teenage

brain?I. Differences in functionII. Developmental changes III. Influences

I. DIFFERENCES IN TEENAGE BRAIN FUNCTION

Observations

• Improvements in cognition– Multitasking– Social cognition

• Interactions between cognition and emotion – both positive and negative

Somerville et al, J Cogn Sci 2011

Dreyfuss et al, Dev Neurosci 2014

Social exclusion

• Cyberball task

Social exclusion

Younger and mid adolescent decreased mood; younger also increased anxiety (from Sebastian et al, Brain Cog 2010)

Learning

(From Casey, Ann Rev Psych 2015)

Effects of peers on risk taking

Chein et al, Dev Sci 2014

Neurobiologic models of adolescence

Casey, Ann Rev Psych 2015

Triadic model

Pictures “Inside out”, Pixar

Giedd, Sci Amer 2015

II. DEVELOPMENTAL CHANGES

Growth during childhood and adolescence

• Mean volume by age in years for males ( 588 scans) and females (375 scans)

Cortical Thickness

Changes in cortical thickness ages 4-22Gogtay et al, PNAS 2004

Prolonged development

More focal activation with maturation: increased

efficiency?

Comparison of activation during inhibition in go-nogo task7 boys participated twice at 9yo and 11yoRegion in red correlated with increased task performance

Blue: Dec activationRed: Inc activation

Durston et al, Developmental Science 2006 (1-20)

Decreases in cerebral blood flow with

maturation• Arterial spin labeling: use MRI for noninvasive

quantification of cerebral perfusion• Cross-sectional study of 922 youth ages 8-22• Map changes in blood flow according to age and

to pubertal stage (self-reported Tanner stage)• Satterthwaite et al, PNAS 2014

Main effect of age on cerebral perfusion.

Satterthwaite T D et al. PNAS 2014;111:8643-8648

©2014 by National Academy of Sciences

Adolescent maturation: increasing the

integration of brain networks

• Structural connectivity:• Post-mortem tracts• Diffusion tensor

imaging• Correlations between

brain regions

Functional connectivity: statistical dependence

between activity in groups of neurons

• Functional imaging techniques:– Functional magnetic resonance imaging– EEG/MEG

• Functional imaging has discussed networks obtained using two different methods:– Set of regions grouped because of correlated

activity; for example default network– Networks formally defined from sets of pair-wise

interactions: graph theory

• Nodes and Edges• Degrees: number of other nodes 

(k) that a node is connected to.

• Hub: Node with higher than average degrees – hubs more efficient than everything being connected

• Path length:  distance between any two nodes – shorter path interpreted as measure of integration 

Small world networks‐Many short regional connections‐ A few long connections‐ Highly efficient

Changes in network properties measured using DTI in 483 subjects 12-30yoNode size proportional to number of connections (degree)

Decreases in path lengthMore hubs

Dennis et al, Neuroimage 2013

Copyright ©2008 by the National Academy of Sciences

Fair, Damien A. et al. (2008) Proc. Natl. Acad. Sci. USA 105, 4028-4032

Functional: Developmental changes in resting networks

Developmental patterns of functional connectivity associated with inhibitory control.

Hwang K et al. J. Neurosci. 2010;30:15535-15545

©2010 by Society for Neuroscience

Compare developmental changes in brain activity associated with eye saccadestowards a target with saccades away from a target – measure of inhibitory control

Increased connections between frontal regions and other brain regions with ageduring inhibitory activity; fewer local connections

Networks and Peer Pressure

• Assess resistance to peer influence – (RPI) with questionnaire

• Use fMRI to determine strength of brain response to angry or neutral stimuli

• Compare those with higher versus lower RPI scores• Individuals with higher RPI scores

– Had pattern of less reaction to angry stimuli in non-cognitive brain regions and stronger reaction in executive function regions areas

• Suggests increased integration of brain regions may be associated with more mature ability to resist peer influence

Grosbras et al, J Neuroscience 2007

III. INFLUENCES

Hormones and adolescent brain

development

• Puberty: complex onset• Many areas of brain rich in sex steroid

receptors– Limbic – hippocampus, amygdala– Motivation and reward systems– Cortex

Effects of hormones on brain development:

organization/activation

• Two-stage model – Early organizational effects– Pubertal activation– Now: recognition that organizational

effects also occur to less extent during puberty

Growth during childhood and adolescence

• Mean volume by age in years for males ( 588 scans) and females (375 scans)

Netherland twins cohort

• Cohort of twins followed longitudinally • 7 years onward (Peper et al, 2008, 2009)• Measure sex steroids levels and MRI• Luteinizing hormone when twins aged 9: levels

predicted WM volumes • Estradiol and testosterone aged 10-15

– Estradiol had negative correlation with GM volume in females

– Testosterone had positive correlation in boys– Girls slightly older: different point in development?

Pubertal changes

• Complex: – different aspects of puberty occur at different

rates– measuring steroid levels that are undergoing

circadian changes– Relating to non-linear brain changes

• Evidence however that organizational effects occurring during adolescence

Changes in heritability with age

Schmitt et al, PNAS 2014

Environment

Surface area in 1,099 children and youth aged 3-20Affected areas also correlate with performanceNoble et al, Nat Neuro2015

CONCLUSION

Conclusions

• Neuroimaging techniques:– window into adolescent brain

• Structural and functional changes continue throughout adolescence

• Development ≠ Growth: integration and efficiency increase, plasticity decreases

Adolescent behavioral changes present across

species

Ability to take risks adaptive

“Scaffolding”

• Today’s environment has different risks –- Driving- Access to drugs

• Working with teens to find their path -safely