The Critical Importance of the Adolescent Stage of Brain Development

Beatriz Luna, PhD Staunton Professor of Psychiatry and Pediatrics Laboratory of Neurocognitive Development University of Pittsburgh Medical Center

Disclosure

There are no conflicts of interests to report

New Yorker

Adolescence

1 • Stage of development when sexual maturation associated with pubertal hormonal changes

• Hormones affect brain maturation • Hormones affect behavior • Socialization, mating, independence

Age of Onset of Psychiatric Disorders

Paus et al., 2008

• Major psychopathology emerges and intensifies during adolescence • Reward and cognitive systems are compromised in psychopathology • Reward and cognitive systems mature through adolescence

Sex Differences

Females Males •Mood, anxiety, and eating •Risk taking: accidental disorders deaths, suicide, substance abuse, and violent offenses

•Earlier brain maturation. •Males have protracted development. frontal GM

•Greater negative affect to •Greater physiological stress reactivity to stress.

•Greater engagement of insula •Males show less functional (interoception) to stress reactivity to angry faces in . Ordaz & Luna 2012

2 Adolescence: Vulnerabilities

• There is a peak in sensation seeking – Sensation seeking can lead to risk-taking undermining survival • Despite peak physical health there is a twofold increase in mortality (Dahl 2004) • Substance abuse, unprotected sex, extreme sports, suicide

Adolescence: Vulnerabilities

• There is a peak in sensation seeking that can lead to risk-taking undermining survival • Despite peak physical health there is a twofold increase in mortality (Dahl 2004) -Substance abuse, unprotected sex, extreme sports, suicide • Present across societies and species – Biologival Adaptive Stage

SAMHSA

Adolescence: Adaptive Development

• Sensation seeking is present across species and cultures • It is an adaptive manner to obtain skills needed to survive as an independent adult • Sensation seeking is necessary for optimally sculpting the brain to fit its environment

3 Adolescence and Young Adulthood

2015

• 18-25 years of age

Neurodevelopment

Silbereis et al., 2016

4 Brain Maturation

Functional Specificity • (Huttenlocher et al,1990) enhances local computations supporting complex processing

• Myelination (Yakovlev and Functional Integration Lecours,1968, Benes 1999) speeds neuronal transmission allowing for the integration of distant brain regions and top down modulation of

behavior 2

Adolescence

Prefrontal Executive Limbic Motivational Processes Emotional Processes Abstract reasoning, Reward processing, impulse control, planning emotion regulation

5 Dual Systems

B. Maturational Imbalance Model A. Dual Systems Model C. Driven Dual Systems Model (Casey et al., 2008) (Steinberg, 2008) (Luna & Wright, 2015) Strength Strength Strength

Age Age Age Cognitive Control System Affective System

Shulman et al., 2016 (Steinberg and Chein)

Outline • Executive systems – PFC – HPC • Sz • Affective Systems – Reward – DA • depression • Connectivity: – DTI, DSI • Sz – Rest

Brain Imaging Approaches

Mehta & Parasuraman, 2013.

6 Neuroimaging Approaches MRI MEG PET

DA fMRI rsfMRI Oscillations

DWI MRSI

EXECUTIVE SYSTEM

Executive Function Cognitive Control

• Goal directed purposeful behavior • Endogenously & voluntarily driven • Engages working memory, , and cognitive flexibility • plays a critical role due to its widely distributed connectivity and unique neural computations

7 Adolescence

Prefrontal Executive Processes Abstract reasoning, impulse control, planning

Magnetic Resonance Imaging

Normal off- RF Pulse spin

0.0003% of wikidoc protons aligned per Tesla of B0

Structural no function

Structural MRI

T1 images – FAT

T2 images – FAT and WATER http://casemed.case.edu/clerkships/neurology/Web %20Neurorad/MRI%20Basics.htm

8 http://www.martinos.org/neurorecovery/technology.htm

Gray Matter Thins

Child Adolescence

Adult

Giedd lab

Neocortical GM thins with development in association areas including but not exclusive to PFC

Brain Processes

Neuron Synaptic Pruning

Synapse

Axon

Neurotransmitter

Dendrite

9 Synaptic Pruning

(Shore & Rima 1997)

Synaptogenesis occurs in the first years of life followed by pruning of unused synapses and strengthening of used ones

Adolescence

10 Brain Structure: PFC pruning

Synaptic Pruning

Huttenlocher et al., 1990 0 6m 1 7 10y 16y Adul Synaptic Density y Visiony Language Reasoningt

Occ Temp FrontalHuttenlocher, 1990

Petanjek et al., 2011

Mechanisms of Brain Maturation

• Glial cells play a critical role in synaptic pruning and maturation – Microglia (cytokine) (complement) • synaptic pruning & maturation (ASD, SZ)

Schafer and Stevens 2015

Abnormal Pruning

• Persistent pruning is associated with schizophrenia – Impaired mechanisms of closing critical period plasticity (perineuronal nets, complement cascade system) – Believed to underlie reductions in cortical thickness – Genetics indicate that genes involved in synaptic pruning are present in schizophrenia (Sekar et al., 2016)

11 Cognitive Development • The ability to stop an automatic response –

• The ability to retain information on line in working memory – Making planned goal driven responses

fMRI

Capillary Bed - - + + - + + - - baseline - + + - + + + - - +

+ + - + - ++ + + activation + - + + + + + + + + - + + +

Blood Oxygen Level Dependent (BOLD) response

Timecourse of BOLD Response to Task vs. Fixation

Fixation Saccade

+

12 Hemodynamic Response Function

• The BOLD response is slow with approximately a

6 sec delay from neuronal Stimulus (“Neural”) HRF Predicted Data firing • Temporal Resolution is at  = the level of seconds • Spatial resolution is at the level of millimeters • Tasks last 3-10mins • BLOCK more power because averaging across trials • ER repeat task many times to obtain sufficient trials (40-60)

Inhibitory Control: Antisaccade Task

Don’t look Preparation

+ Response Inhibition

Sarah Ordaz, PhD N=139 - 8-28yo (356, 1-6 visits) Instructor, Stanford University Errors

Age

• dACC function was associated with performance, and mediated the association between age and inhibitory control

13 Working Memory: Memory Guided Saccade Task Encoding

Maintenance

+ + Retrieval

Daniel Simmonds, PhD Working Memory Medical Student

Simmonds et al., In Press

DLPFC Visual Assoc Cortex

30

al al (beta) 20 10 0 10 15 20 25 BOLD sign

PFC functioning

5 15 25 Age

14 Schizophrenia: Working Memory

DLPFC

DLPFC/ACC

ACC

(Jalbrzikowski et al., 2017) DLPFC is compromised in psychosis including that may undermine ACC performance monitoring.

Mean Performance

Variability in Performance

Latency Accuracy tency SD of MGS SD ofMGS La SD of MGS Accuracy SD ofMGS

• In addition to mean performance (accuracy and RT) improving with age, variability in responses decreases with age

15 Development through Variability in Brain Function

David Montez, PhD Encode Maintain Retrieve (Montez et al., 2017)

Brain State Var X Behavior Var WM Brain State Var X Age Encoding Maintenance Retrieval

n.s.

p<.001e-6 p<.001e-7

PFC functioning

5 15 25 Age

16 Hippocampus

HPC-PFC Model of Adolescence

Finn Calabro PhD Research Instructor

Vishnu Murty PhD Assistant Prof

Murty, Calabro, & Luna NBR 2016

• During adolescence PFC/HPC integration supports memory/experience driven guidance of executive function and is enhanced by mesolimbic function

17 Hippocampal-Prefrontal Functional Connectivity

Finn Calabro PhD Research Instructor

Methods (Calabro et al., under review)

A Prosaccades Antisaccades

+ + + > 0 36 157.5 205.5 327 366

• Off-period connectivity 15s from task (Fair et al, 2007)

• Subjects (n=143, ages 8-32, 78 female) were tested longitudinally, with up to 10 yearly visits (455 total scans, mean 3.2 scans/subject)

PFC and HPC ROIs

vmPFC vlPFC dlPFC Ant/Post HPC VTA

• ROIs for PFC and anterior and posterior HPC were partitioned based on anatomical atlases: PFC (Mackey and Petrides, 2014), HPC (Harvard-Oxford), and VTA using a probabilistic atlas of (Murty et al., 2014).

18 Development of HPC Connectivity to: vmPFC, vlPFC, and dlPFC

Anterior HPC Posterior HPC * *

ns ns

• Age related changes in HPC connectivity were only evident with vmPFC

Replication of HPC Connectivity to: vmPFC, vlPFC, and dlPFC on PNC

Anterior HPC Posterior HPC * *

ns ns

• Results were replicated cross-sectionally on 807 10-22yo subjects from the Philadelphia Neurodevelopmental Cohort (PNC) resting state fMRI dataset

HPC-vmPFC vlPFC dlPFC and Cognition

• CANTAB tasks (Luciana, 2003):

• Delayed Match to Sample (DMS) • Spatial Span (SSP) • Stockings of Cambridge (SOC)

• Memory guided saccade (MGS) task

19 HPC-vmPFC vlPFC dlPFC and Cognition aHPC pHPC * *

12 SOC 10

Spatial Planning 8

Task 6 SOC Performance 4 14 20 26 32 Age • HPC-vmPFC connectivity predicts performance on Stockings of Cambridge (: WM, future planning) task after controlling for age

DA role (VTA/PFC) in HPC/PFC connectivity

• VTA/vmPFC functional connectivity mediated increases with age in anterior and posterior HPC/vmPFC functional connectivity

Conclusions

• DA changes in adolescence increase HPC- vmPFC connectivity facilitating the integration of context and encoding supporting developmental improvements in executive function

20 PFC and HPC development/DA

5 15 25 Age

AFFECTIVE SYSTEM

21 Sensation seeking

• Drive to take risks (physical, legal) to obtain "varied, novel, complex and intense” experiences (Zuckerman, 2007) • Sensation Seeking Scale – Degree of sensory stimulation to reach optimal level of arousal – Thrill and adventure seeking (extreme sports) – Experience seeking (novelty: substance use) – Disinhibition (relinquish control: wild parties) – Boredom (intolerance of predictability) • Dopaminergic System

SS peaks in Adolescence

Romer & Hennessy, 2007

• Sensation seeking peaks around 16 in females and 19 in males (Romer & Hennessy, 2007) and other countries (Duell et al., 2016).

Basal Ganglia Brain Structure Maturation riatum St

15yo 8yo

9yo 12yo Sowell et al., 1999

Raznahan et al., 2014 • Females peak earlier than males • Striatal volume peaks after cortical volume has already begun to decline • Subregions expand/contract with development (VS contracts)

22 Adolescence

Limbic Motivational DA Emotional Processes Reward processing, emotion regulation Strength Adolescence

Age

Preparation Rewards +

Geier et al., 2009 Assoc Prof Penn State

Overactive Reward System

Adult VS Child Teen Adult Teen

OFC

Galvan, 2006 Geier,, 2010 Van Leijenhorst, 2010

•Teens show greater VS reactivity to rewards compared to adults or children •VS reactivity is associated with increased risk taking Galvan, 2006

23 Rewards on Cognitive Control N = 30: 10 Adults (18-25yrs); 10 Teens(14-17yrs); 10 Children (8-13yrs)

$ $ $ +

Neutral Reward Padmanabhan et al., 2011

Children Adolescents Adults *

*

•Performance is faster with rewards but only kids and teens improve performance •Only teens show increased VS reactivity with concomitant increases in action regions

Preparation Rewards +

VS

Neutral Rewards

Adult Teen

FEF

Rate of Correct Responses Correct of Rate Teens Adults Geier et al, 2010 Paulsen et al., 2014

•Adolescents show greater reactivity to rewards pushing the brain systems that support reward receipt (Geier et al., 2009, Padmanabhan et al., 2011, Paulsen et al., 2014)

Rewarded State

Background Connectivity

24 Baseline v. Reward Mesolimbic Function

Reward Context VS Teens Adults Baseline

Geier et al, 2010 f Function f Degree o Function Degree of

Context-dependent mesolimbic function

Ballard, Murty et al., 2011

• Reward cues in the environment engage the VTA via top-down modulation by the lateral PFC enhancing VTA connectivity to the NAcc • Thus, VTA connectivity can provide a putative marker for the effects of reward context on mesolimbic function

We probed developmental differences in mesolimbic function during rewarded and non-rewarded contexts

Methods (Murty et al., under review) Rewarded Antisacade fMRI Task

Rest (5m eyes closed) vs. +

• 180 10-30yo (84 F) up to 3 18mo visits • Background Connectivity (Al-Aidroos et al., 2012; Norman-Haignere et al., 2012; Duncan et al., 2014) • Remove task activation to assess task (reward) state • Compared to rest • Age differences in VTA/NAcc functional connectivity

25 *Significant difference in slopes across Neutral and Reward contexts (p<0.01) • VTA-NAcc but not VTA-CN coupling decreased in reward context from adolescence to adulthood but not in neutral context.

Conclusions

Core components of mesolimbic function are mature by adolescence while those related to integrating a rewarded context are enhanced

Peer Influence

Crashes

Ventral Chein et al., 2011

VS.

•Adolescents by themselves performed the same as adults. •Adolescents with peers observing, had more crashes and activated the reward region to a greater degree

26 Emotional Processing is Immature Emotional Regulation Amygdala PFC

Social Emotional Processing Processing of Intentions Guilt Assessing intentions Embarrassment and causality

•Adolescents show immature brain activity when processing emotional information, social emotional information (guilt), and understanding intentions •Adolescents have a heightened response to emotion and less executive regulation of emotion.

Driven Dual Systems Model

Cognitive Control System Affective System Strength Adolescence

Age (Luna & Wright, 2015)

Measuring Striatal Neurophysiology by Measuring Iron (Ferritin) in the Brain

• Iron is stored in oligodendrocytes and as ferritin • Basal ganglia and midbrain have the greatest concentration of iron • Iron supports: – production, cellular oxidative metabolism, D2 receptor density, DA transporters, DA synthesis • MRI time-averaged T2* (taT2*) weighted images are sensitive to tissue iron

27 True vs. Predicted Age

Bart Larsen Graduate Student Correlation coefficient Correlation

Larsen & Luna under review

• Support vector regression (SVR) multivariate pattern analysis (MVPA) of striatal taT2* generated age predictions in 10-25yo that accounted for over 60% of the sample variance in VS and its subregions.

taT2* across the Brain

Whole-brain searchlight analysis

Greatest association between taT2* and age in:

• Ventral striatum • Midbrain, including substantia nigra • Superior frontal gyrus • Perigenual anterior cingulate • Medial PFC • Central gyrus • Dentate nucleus of the cerebellum

• Regions overlap with prominent pathways

Age prediction was led by increases in TaT2* in VS and decreases in DS.

28 Animal Models of developmental changes in DA processes

The DA system is not a generalized system but complex

Methods • Molecular MRI (mMR) – Simultaneous PET and MRI • 140 12-30 yo – R2’ measure of tissue iron • Transverse relaxation rate measuring tissue iron • Tissue iron contributes to DA synthesis (TH) • Related to postmortem tissue iron (Sedlacik et al. 2014) • 80 18-30 PET (bolus plus infusion) – Raclopride • Baseline binding potential • Postsynaptic D2/3 receptor density – DTBZ • Vesicular monoamine transporter (VMAT2) density • Presynaptic terminal density and vesicular DA

PET

• Goal: Identify neurotransmitter (NT)- specific properties of the brain

• Subjects are injected with a chemical tracer designed to bind to specific NT receptors. Tracers are “tagged” by a radioactive isotope (e.g., carbon-11), which emits gamma radiation that can be detected by the PET scanner.

• By determining where the radiation came from, we can identify where the tracer is bound in the brain. Regions with greater receptor density will emit more radiation, allow us to map NT receptor systems

29 Tissue Iron VMAT

D2/3

• Postsynaptic D2/3 receptor density decreases through adulthood

Association between Tissue Iron and PET Measures

VMAT X Tissue Iron D2/3 X Tissue Iron

• Tissue iron was best associated with presynaptic DA measures

VTA/vmPFC VTA/NAcc Rew

HPC/vmPFC

90

30 Conclusions

• Similar to animal models, human neuroimaging suggests: – Earlier establishment of receptor density with continuous increase in DA concentration. – Changes are most predominant in dorsal/cognitive v. ventral/reward parts of striatum • In adolescence there is a greater number of DA receptors with less available DA • The change in ratio of pre/postsynaptic DA processing with development may reflect specialization

Conclusions

• Taken together adolescence is a time of enhanced motivation (background connectivity) that attenuates into adulthood with increased integration of prefrontal systems.

Driven Dual Systems

PFC Executive System Mesolimbic Motivation System Adolescence

31 SYSTEMS LEVEL INTEGRATION

Brain Maturation

Functional Specificity • Regional Mechanisms: – Synaptic pruning (Huttenlocher et al,1990) enhances local computations supporting complex processing

• Systems Level Mechanisms Functional Integration • Myelination (Yakovlev and Lecours,1968) speeds neuronal transmission allowing for the integration of distant brain regions and top down modulation of behavior

2

Myelination

Yakovlev and Lecours, 1967

32 White Matter

Diffusion Weighted Imaging (DWI) Diffusion Tensor Imaging (DTI) Diffusion Spectral Imaging (DSI)

Diffusion Weighted Imaging (DTI)

• Amount of Myelination

• Connection between Brain Regions

33 Water molecules move freely but when constrained by a tract, they will move in the direction of the pathway showing coherence.

Crossing Fibers

Fibers Crossing Fibers

Tensor Model Orientation Approach

Zuo et al., 2012

DWI Analysis Approaches

34 DWI Analysis Approaches

DWI Measures TENSOR Assumes a single fiber direction. RD FA - fractional anisotropy. Overall diffusion in a single direction. FA=AD/RD AD AD - axial diffusivity. Coherence in the main direction of the tract (i.e., down the )

RD - radial diffusivity. Coherence perpendicular to the direction of the tract, ie., its radius

ORIENTATION DISTRIBUTION Multiple fiber directions are identified to better resolve crossing fibers. QA - quantitative anisotropy. Identifies the main direction of diffusion to calculate its coherence while controlling for isotropic diffusion.

35 Myelination • Predominantly but not exclusively increases through development • Continues throughout adulthood (learning) • Its impairment is associated with mental illness – neuroinflammation

Mechanisms of Brain Maturation

• Glial cells play a critical role in myelination – Oligodendrocytes & astrocytes • myelination and remodeling

Fields 2005

DTI Tensor Model

36 Lebel & Beaulieu, 2011

Daniel Simmonds, PhD Medical Student •128 8-29 yo (61 males) scanned 1-5 times for a total of 322 scans.

•Mixed-effects regression - Visits – random effect •Greatest overall growth occurs between10-16y

•Hierarchical maturation RTZ: •Maturing into adolescence BG PL •RTZ: F, T, P, & BG FL •Last to Mature

WM Tracts WM TL •Cingulum & Uncinate SM Fasciculus CG •Males show greater and more UF protracted WM growth than females

Different WM Trajectories

FA

RD Low FA AD

High FA Simmonds et al, 2014

While FA increases RD and AD predominantly decrease

37 FA/RD/AD

• FA is the ratio of AD and RD – FA = AD/RD. • If RD decreases faster with age than AD, FA will increase with age.

RD

AD

QSDR Orientation Distribution Function

Adolescence

Prefrontal Executive Limbic Motivational Processes Emotional Processes Abstract reasoning, Reward processing, impulse control, planning emotion regulation

38 Dual Systems

B. Maturational Imbalance Model A. Dual Systems Model C. Driven Dual Systems Model (Casey et al., 2008) (Steinberg, 2008) (Luna & Wright, 2015) Strength Strength Strength

Age Age Age

Cognitive Control System Affective System

Shulman et al., 2016 (Steinberg and Chein)

Striatal Integration of Affective and Cognitive Control Systems

Larsen et al., (2017)

Ventral Attention Frontoparietal Dorsal Attention

Affect Cognitive

Affect

Cog

Amygdala-VMPFC connectivity Jalbrzikowski et al, 2016

Maria Jalbrzikowski Functional & Structural Functional Amy/PFC Connectivity Age

• Amygdala vmPFC functional and structural connectivity decreases with age

39 Development of White Matter

• FA increases reflecting a general increase in integrity of fibers that support faster and more integral neural conduction • QA decreases in affective regions reflects specialization of specific fibers that may be decreasing in integrity • These changes may be underlied by myelination and axonal caliber and influenced by synaptic pruning

First Episode Psychosis

41 First Episode Psychosis v. 32 Controls (14-35 yo)

Diffusion Spectrum Imaging:

Diffusion Spectral Imaging

First Episode Psychosis

41 First Episode Psychosis v. 32 Controls (14-35 yo)

Diffusion Spectrum Imaging: FEP CON

Integrity of White Matter Tracts

15 20 25 30 Age • Reduced FEP white matter integrity is evident in early adolescence but not in young adulthood. • Psychosis is underlied by diminished WM integrity

40 Functional Task Connectivity

Effective Functional Connectivity: Granger Causality Kai Hwang, PhD • Granger Causality – How region X could influence the activity in region Y based on the ability to predict Y from the past history of X. – Only Unidirectional measures • ROIs – Past Studies (Luna et al 2001) (Dosenbach et al 2006, 2007) • Antisaccade and Prosaccade Blocks • Functional Connectivity (confirmatory) + . • 26 Children 8-12 years • 25 Adolescents 13-17 years • 26 Adults 18-27 years (Hwang et al., 2010)

Cognitive Circuitry •PFC connectivity becomes established by adolescence and strengthens into adulthood.

+ .

Top-Down on line Childhood only Adulthood only (Hwang et al., 2010) Bottom-Up on line Adolescence only Stronger Connection

41 Whole Brain MEG Resting State Connectivity

Magnetoencephalography (MEG)

• MEG is sensitive to magnetic fields generated by electrical current produced by a large group of neurons

• MEG has superior temporal resolution compared to MRI (1ms).

• Magnetic fields are detected by sensors in the MEG helmet.

• To determine the anatomical origin of the signal, we solve the forward solution and inverse solution and correlate with MRI

FEF Alpha (10-18Hz) Antisaccade Prosaccade

(Hwang et al., 2016) ts

Adul * m baseline m *

NS % signal changefro Adolescents

• Adults and not adolescents showed greater alpha power for antisaccade v. prosaccade trials, reflecting inhibitory control signals.

42 MFG/FEF Connectivity

Adults Adolescents Adults - Adolescents

MFG Hz

•Compared to adolescents, adults showed stronger cross frequency amplitude coupling between DLPFC beta power and FEF alpha power (Granger Causality)

Resting State Connectivity

rs-fcMRI signal

Vogel et al., 2010 •Correlation of spontaneous fluctuations •Human Connectdome Project (HCP)

Resting State Functional Connectivity: Hub Architecture (Hwang et al., 2012) Children 8-12y

Adolescents 13-17y worldness Small Adults 18-27y Threshold for Density

Hwang et al., 2012 N=87; 5min eyes closed rest

Established by childhood (graph analyses): •Hub number, location, degree density (number of connections), average strength, and betweenness centrality, the relative significance of a hub in supporting a high degree of connection paths •Efficient and stable small-world network (path length and clustering coefficient)

43 Hub to Non-Hub Connection Strength

•The foundational network is in place early in development •Specialization to top down connectivity occurs from childhood to adolescence •From adolescence to adulthood areas come on line that allow for fine tuning, precision, and control

FP CO/Sal Network PC Age CON VN DMN AS RT SMN

CO/Sal Network PC

• Network organization is well established by childhood. Integration between networks continues to strengthen through adolescence in association with cognitive control.

Conclusions

• The foundational architecture of the brain is established by childhood

• The adolescent period is characterized by the specialization of network integration

44 Rest MEG

• 68 14-31 yo • 300 seconds (eyes closed) • ROI defined from rsfMRI data using Gordon et al., 2014 parcellation • PLV for every ROI pair (1-49Hz, 1Hz intervals) • MNE source localization • Motion corrected

More coupled

More decoupled

45 Neurotransmitter Changes

Lewis Lab

Common Neural Correlates of Psychiatric Risk

Philadelphia Neurodevelopmental Cohort (PNC) 716 (9-22 years)

K-SADS-PL - Symptom severity: Depression (DEP); Generalized Anxiety (GAD); Agoraphobia (AGR); Panic (PAN); Specific Phobia (PHB); Social Phobia (SOC); Attention Deficit Disorder (ADHD); Conduct Disorder (CDD); Oppositional Defiant Disorder (ODD)

Correlation between symptom severity and rest connectivity in ROI-ROI pair for all disorders.

Factor analysis of symptom-severity connectomes. Luna Normative Developmental Sample 167 (10-31 years)

46 • Expression of transdiagnostic risk changes during adolescence for factors related to basal ganglia and OFC (factor 3) and the ACC (factor 4).

Adolescent Critical Period for Specialization of Association Cortices

Bart Larsen PhD Student

• Adolescence as a time of unique plasticity to specialize brain processes specific to higher order cognition • Vulnerabilities • Opportunities

Adult Modes of Genes Operation

Adolescent Brain Maturation

Environment

47 Normative Neurocognitive Developmental Growth Chart

Adolescence

Resilience/Treatment lopment D) 2S - (Mean +/ (Mean

Vulnerability to Psychopathology Neurocognitive Deve Neurocognitive

August 30-September 1, 2018 Berlin, Germany

Ulman Lindenberger Eveline Crone Silvia Bunge Max Planck Institute Leiden University UC Berkeley for Human Development Program Chair Program Co-Chair Host Chair

Laboratory of Neurocognitive Development

•Michael Hallquist PhD-Faculty Penn State •Finn Calabro PhD - Faculty •Will Foran- MS •Dani Simmonds – MD/PhD Student •Raj Chahal – Res Assistant •Bart Larsen – PhD Student •Julia Lekht -Res Assistant Supported by: •Scott Marek – PhD Student •Jen Fedor-Res Assistant MH067924 •David Montez – PhD Student MH080243 •Brenden Tervo-Clemmens – PhD Student K23 NS 052234 K01 MH081191 K01 MH082123

PSYCHOLOGY

48 49