Differences in Adolescent Cortex Related to Age and Sex ...€¦ · NCANDA Baseline MRI Findings In...
Transcript of Differences in Adolescent Cortex Related to Age and Sex ...€¦ · NCANDA Baseline MRI Findings In...
Differences in Adolescent Cortex Related to Age and Sex: Initial Findings from the
National Consortium on Alcohol & NeuroDevelopment in Adolescence
Adolf Pfefferbaum, M.D.
Center for Health Sciences, SRI International Department of Psychiatry & Behavioral Sciences, Stanford
University School of Medicine
Research Society on Alcoholism San Antonio, TX 22 June 2015
NCANDA FUNDING: NIAAA, NIDA, NIMH, NICHD
FINANCIAL INTEREST DISCLOSURES
Adolf Pfefferbaum, M.D.
Salary and research support:
Center for Health Sciences
Differences in Adolescent Cortex Related to Age and Sex: Initial Findings from the
National Consortium on Alcohol & NeuroDevelopment in Adolescence
Research Society on Alcoholism San Antonio, TX 22 June 2015
Adolf Pfefferbaum, Torsten Rohlfing, Kilian M. Pohl, Barton Lane, Weiwei Chu, Sandra A. Brown, Susan F. Tapert, Kevin Cummins, Wesley K. Thompson, Ty Brumback, M.J. Meloy, Terry L. Jernigan, Anders Dale, Ian M. Colrain, Fiona C. Baker, Devin Prouty, Michael D. De Bellis, James T. Voyvodic, Duncan B. Clark, Beatriz Luna, Tammy Chung, Bonnie Nagel, Edith V. Sullivan
NCANDA FUNDING: NIAAA, NIDA, NIMH, NICHD
Teenage and Young Adulthood Binge drinking Drunk driving Unsafe sex
Photo courtesy of Teresa Kellerman
Prenatal Fetal Alcohol Syndrome
Life span and excessive alcohol consumption
Adulthood Hypertension Breast cancer Liver disease Job and family
Nielsen et al, IntJCancer, 2007.
Maturity Brain damage Cognitive impairment
NCANDA MRI
Age Headsize / Supratentorial Volume Sex Ethnicity Prior Alcohol Exposure
Human Brain Growth after Birth
Brain weight increases fourfold from birth to about 10 years of age
Gray matter, white matter, and CSF volumes expand but at different rates in different regions of brain
Rise and Fall of Cortical Gray Matter Volume
5 10 15 20 25 30 Age (years)
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90
100
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170
0
Cor
tical
Gra
y M
atte
r Vol
ume
(cc)
53 years
1 Year
1 Month
2 Years 4 Years
10 Years
14 Years
21 years
71 years
18 Years
Pfefferbaum et al. Archives of Neurology 1994
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90
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150
160
170
0 5 10 15 20 25 30 Age
Volu
me
(cc)
Gray Matter
Cortical Tissue Volumes
30
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60
70
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90
100
0 5 10 15 20 25 30
Age
Male Female
White Matter
Gray to White Matter Ratio Gray : White
1
2
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4
0 5 10 15 20 25 30
Age
Volu
me
(cc)
Male Female
Development of Cortex Age Differences in PET Local Glucose Metabolism
Chugani Preventive Medicine 1998
9 mo 1.5 yr 3 yr 4 yr 12 yr 6 yr Neuropsychology Review December 2012 cover
Brain Development after Birth Heterochronicity of Structural Modeling
NCANDA Prospective Study
National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA)
5 U.S. recruitment sites 647 no/low drinking
– 334 male, 340 female 134 exceeded criteria Age 12-14, 15-17, 18-21 years Baseline + annual visits
– Clinical interview – Neuropsychological testing – 3T MRI, DTI, resting state-fMRI
NCANDA Sample
Sex Ethnicity
Basic NCANDA MRI Protocol
Anomalies Identified on Clinical Readings in 95 Adolescents*
24 mega cysterna magna 15 subarachnoid cysts (primarily temporal and frontal) 12 pineal cysts 11 white matter anomalies (primarily corpus cysts) 6 tonsilar ectopias 5 very prominent perivascular spaces 5 gray matter heterotopias 4 pituitary masses (primarily cysts) 4 abnormally large or asymmetrical lateral ventricles 4 cavum septum pellucidum 3 developmental venous anomalies (DVA) 1 severe cranio-cervical junction stenosis (10/30 mm) 1 *right parietal cortical mass (3 cm) 1 *bilateral tonsillar herniation, medullary distortion (Chiari 1 malformation) *excluded from NCANDA cohort
95/833 adolescents = 11.4% 23 excluded from parcellation *2 excluded from the study
Subependymal heterotopia Probable congenital Rathke's cleft cyst vs. craniopharyngioma
Anomalies Identified on Clinical Readings
Large ventricles with possible cyst Cranio-cervical junction stenosis
Anomalies Identified on Clinical Readings Some Precluding Automated Quantification
Mega cisterna magna in a 15.5 year old boy
Subarachnoid cyst in a 17.0 year old girl
Abnormalities on Clinical Readings Excluded from Further Study
Chiari 1 malformation
bilateral tonsillar herniation with medullary distortion
right parietal cortical mass
T1-weighted
T2-weighted
NCANDA Data Analysis Team
Torsten Rohlfing, Ph.D.
NCANDA Data Analysis Team
Torsten Rohlfing, Ph.D.
Nolan Nichols, Ph.D.
Kilian Pohl, Ph.D.
Yong Zheng, Ph.D. Dongjin Kwon, Ph.D.
Lateral Ventricle Volume Lateral Ventricle Volume
Freq
uenc
y (N
=808
)
cc
10 Boys 14.5 to 15.5 years old
Structural MRI Quantitative Measures of Regional Brain Tissue
white matter
gray matter
CSF
Tissue Segmentation
Structural MRI
FreeSurfer Gray Matter Regions
Frontal Parietal
Temporal Occipital
Cingulate
Subcortical white matter
Corpus callosum
Pons
SRI24 White Matter Regions
Frontal Superior Frontal Rostral and Caudal Middle Frontal Pars Opercularis, Pars Triangularis, and Pars Orbitalis Lateral and Medial Orbitofrontal Precentral Paracentral Frontal Pole Temporal Superior, Middle, and Inferior Temporal Banks of the Superior Temporal Sulcus Fusiform Transverse Temporal Entorhinal Temporal Pole Parahippocampal Insula
Parietal Superior Parietal Inferior Parietal Supramarginal Postcentral Precuneus Occipital Lateral Occipital Lingual Cuneus Pericalcarine Cingulate Rostral Anterior (Frontal) Caudal Anterior (Frontal) Posterior (Parietal) Isthmus (Parietal)
Frontal Parietal
Temporal Occipital
Cingulate
Structural MRI FreeSurfer Cortical Lobar Volume, Surface & Thickness
IR-Prep SPGR vs. MPRAGE
GE GE GE Siemens Siemens
Human Phantom across Site/Scanner Harmonization Across 3 GE Sites and 2 Siemens Sites
NCANDA MRI
Linear: braini ~ 0 + 1agei + 2mfgi + 3sesi + 4ethnicityi + 5sexi + ∑i
Non-linear: braini ~ S0(agei)+ 1mfgi + 2sesi + 3ethnicityi + 4sexi + ∑i
General Additive Model (GAM)
Brain region ~ age + covariates (sex, ethnicity, SES, etc)
Cross-platform Harmonization done with GAM
NCANDA MRI
Age Headsize / Supratentorial Volume Sex Ethnicity Prior Alcohol Exposure
NCANDA Cohort Baseline MRI by Age and Sex
Pons
Adju
sted
Vol
ume
(cc)
Age (years)
Adju
sted
Vol
ume
(cc)
Age (years)
Subcortical White Matter
Adju
sted
Vol
ume
(cc)
Age (years)
Corpus Callosum
Subcortical white matter
Corpus callosum
Pons Regional White Matter Volumes
NCANDA Cohort Baseline MRI by Age and Sex
Frontal
Temporal
NCANDA Cohort Baseline MRI by Age and Sex
Frontal
Temporal
NCANDA Cohort Baseline MRI by Age and Sex
Regional Cortical Thickness Frontal Temporal
Regional Cortical Volumes Frontal Temporal
Age (years) Age (years)
Age (years) Age (years)
Frontal
Temporal
Adju
sted
Vol
ume
(cc)
Adju
sted
Vol
ume
(cc)
Adju
sted
Thi
ckne
ss (m
m)
Adju
sted
Thi
ckne
ss (m
m)
NCANDA Cohort Baseline MRI by Age and Sex
Regional Cortical Thickness Frontal Temporal
Regional Cortical Volumes Frontal Temporal
Age (years) Age (years)
Age (years) Age (years)
Frontal
Temporal
Adju
sted
Vol
ume
(cc)
Adju
sted
Vol
ume
(cc)
Adju
sted
Thi
ckne
ss (m
m)
Adju
sted
Thi
ckne
ss (m
m)
Age (years)
Age (years)
Regional Cortical Thickness
NCANDA Cohort Baseline MRI by Age and Sex
Frontal
Temporal
NCANDA MRI
Age Headsize / Supratentorial Volume Sex Ethnicity Prior Alcohol Exposure
Sex Differences in Brain Size Ad
just
ed V
olum
e (c
c)
Supratentorial Volume
Age (years)
Sex
Size Metrics and Supratentorial Volume
Frontal Gray Matter Volume
Adju
sted
Vol
ume
(cc)
Supratentorial Volume (cc)
Frontal Cortical Surface Area
Adju
sted
Are
a (c
m2 )
Supratentorial Volume (cc)
Frontal Cortical Thickness
Adju
sted
Thi
ckne
ss (m
m)
Supratentorial Volume (cc)
Frontal
NCANDA MRI
Age Headsize / Supratentorial Volume Sex Ethnicity Prior Alcohol Exposure
NCANDA Cohort Baseline MRI by Age and Sex
Regional Cortical Volumes Frontal Temporal
Age (years) Age (years)
Frontal
Temporal
Adju
sted
Vol
ume
(cc)
Adju
sted
Vol
ume
(cc)
Frontal
Svol
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uste
d Vo
lum
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c)
Age (years)
Svol
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uste
d Vo
lum
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c)
Age (years)
Temporal
Supratentorial Volume -Adjusted Regional Cortical Volumes
NCANDA MRI
Age Headsize / Supratentorial Volume Sex Ethnicity Prior Alcohol Exposure
Frontal Cortex Baseline MRI by Age, Sex, Ethnicity
Frontal Thickness
Frontal Volume
Age (years)
Age (years)
Frontal Ad
just
ed V
olum
e (c
c)
Adju
sted
Thi
ckne
ss (m
m)
Frontal Cortex Baseline MRI by Age, Sex, Ethnicity
Frontal Thickness
Age (years)
Frontal Ad
just
ed T
hick
ness
(mm
)
Age (years)
Svol
Adj
uste
d Vo
lum
e (c
c) Frontal Volume
Adjusted for supratentorial volume
% Difference per Year (N=631)
Pubertal Development Ad
just
ed V
olum
e (c
c)
PDS score
Frontal Gray Matter Volume
Adju
sted
Thi
ckne
ss (m
m)
PDS score
Frontal Cortical Thickness
PDS
scor
e
Age (years)
Frontal
Are the data generalizable? Frontal
Temporal
NCANDA and PING Cortical Volume and Thickness
NCANDA: National Consortium on Alcohol & NeuroDevelopment in Adolescence PING: Pediatric Imaging, Neurocognition, and Genetics
NCANDA and PING Cortical Volume and Thickness
PING NCANDA
Parietal
Occipital
Cingulate
Parietal
Occipital
Cingulate
Adj.
Volu
me
(cc)
Ad
j. Vo
lum
e (c
c)
Adj.
Volu
me
(cc)
Adj.
Thic
k (m
m)
Adj.
Thic
k (m
m)
Adj.
Thic
k (m
m)
Volume Cortical Thickness
Alcohol and Drug Use Criteria No/low vs. Exceeds
0
20
40
60
80
100
12 13 14 15 16 17 18 19 20 21
Other Drugs
Alcohol
Marijuana
Cigarettes
Exceeds Criteria Group (N=134)
Moderate/high Alcohol Regional Cortical Volumes and Thickness
Age (years)
Svol
Adj
uste
d Sc
ore
(cc)
Total Cortical Volume Frontal Cortical Volume
Age (years) Age (years)
Total Cortical Thickness
Age (years)
Svol
Adj
uste
d Sc
ore
(mm
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Frontal Cortical Thickness
Age (years)
Temporal Cortical Thickness Cingulate Cortical Thickness
Age (years)
Temporal
Frontal
Binge Drinking and Cortical Thickness
Binge Episodes in Past Year
Svol
Adj
uste
d Sc
ore
(cc)
Frontal Cortical Thickness Parietal Cortical Thickness
Binge Episodes in Past Year
Svol
Adj
uste
d Sc
ore
(cc)
Parietal Frontal
NCANDA Baseline MRI Findings In 833 with MRIs, clinical readings identified structural anomalies in
95 individuals (11.4%), ~3% precluding automated quantification.
Regional volume and surface, but not thickness, measures showed sex and ethnicity effects that were minimized with adjustment for variation in supratentorial volume.
NCANDA and PING data showed similar age-related differences in regional cortical volumes and thickness.
Relative to no/low drinking youth, moderate/high alcohol drinking youth had smaller and thinner cortices in frontal, temporal, and cingulate regions.
Youth who binged had thinner frontal and parietal cortices than no/low drinking youth.
NCANDA Clinical MRI Findings Baseline
A note of caution ....
NCANDA Clinical MRI Findings Baseline
NCANDA Clinical MRI Findings 1-year Followup
NCANDA Clinical MRI Findings 1-year Followup
Even in a group of healthy highly screened participants with normal brain structure at study entry, pathology will emerge in a sample this size.