Transcript Preliminary results cortical meGa analysis

ENIGMA
OCD working group
Teleconference
August 25th, 2016
1 PM GMT (Greenwich Mean Time)
Amsterdam/Barcelona/Berlin/Milan/Munich/Rome/Zurich 3 PM
Oxford 2 PM
Sao Paulo 10 AM
Tokyo/Kyoto/Seoul 10 PM
Cape Town 3 PM
Los Angeles 6 AM
New York/Toronto/Michigan/Boston 9 AM
Bangalore 6.30 PM
Agenda
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New ENIGMA OCD collaborators
Results Cortical meTa analysis
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Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Status Structural Covariance analysis
Secondary Research proposal Clyde Francks (Lateralization)
DTI connectomics project
MeGa database
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis
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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Status Structural Covariance analysis
Secondary Research proposal Clyde Francks (Lateralization)
DTI connectomics project
MeGa database
Jan Buitelaar, M.D., Ph.D.
Professor of Psychiatry and Child & Adolescent
Psychiatry
 Radboud University Nijmegen, The Netherlands
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Donders Institute for Brain, Cognition and Behaviour
Department of Cognitive Neuroscience
Karakter Child and Adolescent Psychiatry University Centre
Paediatric data
 Co-workers
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Daan van Rooij
Evelyn Stewart, M.D.
Assistant Professor of Psychiatry
 Director-Pediatric OCD Program, B.C. Children’s
Hospital
 University of British Columbia, Vancouver, BC Canada
 Paediatric data
 Co-workers
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Fern Jaspers-Fayer
Sarah Yao Lin
Pedro Morgado, M.D., Ph.D.
Assistant Professor
 University of Minho, Braga, Portugal
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School of Health Science
Clinical Academic Centre Hospital de Braga
Adult data
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis
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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Status Structural Covariance analysis
Secondary Research proposal Clyde Francks (Lateralization)
DTI connectomics project
MeGa database
Main group comparison
adult OCD vs HC (meTa)
↓ SA of left transverse temporal gyrus
 No effects for CT
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No effects interaction group by age
 No effects interaction group by sex
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CONFIDENTIAL
Medication (MeTa)
CONFIDENTIAL
Medicated patients versus healthy controls
↓ SA of left transverse temporal gyrus
↓ average CT in left hemisphere
↓ CT in left pars opercularis, frontal pole, rostral middle
frontal gyrus, bank of the superior temporal sulcus, middle
temporal and superior frontal gyrus
↓ CT in right fusiform gyrus
↓ CT in orbitofrontal cortex, caudal middle frontal gyrus
and inferior temporal gyrus bilaterally
Note that CT effects disappear when corrected for avgT
CONFIDENTIAL
Medicated patients versus HC (MeTa)
↓ CT
Frontal and temporal areas (d ≈ - 0.2, PFDR < 0.05)
10
Medication (MeTa)
CONFIDENTIAL
Medicated patients versus non medicated patients
No significant results for SA
↓ average CT in left hemisphere in medicated patients
↓ CT in frontal and temporal areas in medicated patients
↓ CT caudal middle frontal gyrus bilaterally in medicated
patients
Note that CT effects disappear when corrected for avgT
Medicated patients versus non
CONFIDENTIAL
medicated (MeTa)↓ CT
Frontal and temporal areas (d ≈ - 0.2 to - 0.3, PFDR < 0.05)
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AO (MeTa)
Late age of onset versus HC
 ↓ SA of left pars opercularis
 No effects for CT
CONFIDENTIAL
Severity (MeTa)
CONFIDENTIAL
Y-BOCS correlation
 No significant results for CT
 ↓ total SA of left hemisphere
 ↓ total SA of right hemisphere
 ↓ SA of frontal, temporal, parietal and cingulate
cortex
Note: severity correlates negatively with tSA
Note that these effects disappear when corrected for tSA
Results
Severity (MeTa) ↓SA
CONFIDENTIAL
Frontal, temporal, parietal and cingulate cortex (d ≈ - 0.1, PFDR < 0.05)
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Comorbidities (MeTa)
CONFIDENTIAL
Patients with comorbid anxiety versus HC
 No significant results for SA
 ↓CT in the left superior frontal gyrus (d = - 0.31, PFDR =
0.031)
 ↓CT in the right middle temporal gyrus (d = - 0.34, PFDR
= 0.031)
CONFIDENTIAL
Summary (adult MeTa-analysis)
SA
OCD < HC
Med < HC
Transverse temporal (L)
Average CT (L)
Fusiform gyrus ( R)
Transverse temporal (L) OFC (L&R)
Caudal middle frontal (L&R)
Inferior temporal (L&R)
Med < Non-med
Late onset OCD < HC
Y-BOCS
Anxiety comorbidity < HC
CT
Average CT (L)
Caudal middle frontal (L&R)
Pars opercularis (L)
Total SA (L&R)
Superior frontal (L)
Middle temporal ( R)
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis
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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
Main group comparison
CONFIDENTIAL
pediatric OCD vs HC (MeTa)
No effects for SA
 No effects for CT
 No effects of interaction group by age
 No effects of interaction group by sex
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Medication (ped. MeTa)
CONFIDENTIAL
Medicated ped. patients versus healthy controls
 no effects in CT
↓ average SA bilaterally
↓ SA in left pars lateral orbitofrontal, rostral middle
frontal gyrus, precuneus and rostral anterior cingulate
↓ SA in right pars triangularis, posterior cingulate, cuneus,
paracentral region and lateral occipital
↓ SA in superior frontal regions and medial orbitofrontal
regions bilaterally
Note that these effects disappear when corrected for tSA
Medication (ped. MeTa)
CONFIDENTIAL
Medicated patients versus non mediated patients
 no effects in CT
↓ SA right pericalcarine
Note that this effect disappears when corrected for tSA
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis
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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
Main group comparison
CONFIDENTIAL
adult MeGa analysis OCD vs HC
↓ SA transverse temporal lobe bilaterally
 ↓ average CT
 ↓ CT in the inferior parietal cortex bilaterally
 ↓ CT in mean fusiform gyrus, OFC, middle temporal
gyrus, precuneus and rostral middle frontal region
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No effects of group by age interaction
 No effects of diagnosis by gender interaction
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Medication (adult MeGa)
CONFIDENTIAL
Medicated patients versus healthy controls
↓ SA transverse temporal lobe bilaterally
↓ average CT bilaterally
↓ CT in almost all regions
Unmedicated patients versus healthy controls
 no effects in CT
 no effects in SA
Medication (adult MeGa)
CONFIDENTIAL
Medicated patients versus non mediated patients
 no effects in SA
↓ average CT lower in medicated patients
↓CT caudal middle frontal, inferior temporal, OFC, middle
temporal, pars orbitalis, pars triangularis, superior frontal, superior
temporal, insula bilaterally
Please, give input on:
1. Medication effects (present both in children and adults)
- related to comorbidity?
(CT effect frontal/temporal mainly in adult OCD with comorbid anxiety)
- related to disease duration?
(but AO plays not role in CT in adult OCD)
- status related to disease severity?
(but severity mainly related to SA, not CT)
2. yes/no correction for total CT/SA or average CT/SA?
Please, give input on:
3. Option to:
- combine SA and CT in order to compare with VBM
results of OCD Brain Imaging Consortium (OBIC) (de
Wit et al. 2014)?
- run tensor-based FreeSurfer, in order to compare with
FreeSurfer results OBIC (de Fouche et al. 2016)? > we
than need the raw data of all sites
- run VBM (on raw data, as we did in OBIC)
Planning cortical meGa analysis
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Adult meGa analysis
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Pediatric meGa analysis
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Work in progress
Expected to be finished mid September
Manuscript writing (including both MeTa and MeGa
results)
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September/October
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis


3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Status (in progress):
Site
PI
Preprocessing
Preprocessing QC
Processing
Processing QC
ROI extraction
Cohen's d
Amsterdam
Odile van den Heuvel
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Cape Town
Dan Stein
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Barcelona
Jose Menchon
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Seoul
Jun Soo Kwon
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Shangai
Zhen Wang
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Kyoto
Takashi Nakamae
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Munich
Kathrin Koch
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Kunming
Yuqi Cheng
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Fukuoka
Tomohiro Nakao
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Bangalore
Reddy Janardhan
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Milan
Francesco Benedetti
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Rome
Gianfranco Spalletta
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Berlin
Jan-Carl Beucke
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New York
Blair Simpson
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Zurich
Susanne Walitza
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Sao Paulo
Marcelo Batistuzzo
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Centrally processed data (Rome)
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CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Available data:
TBSS-based FA of 19 bilateral and 5 unilateral white matter
labels (plus average FA) based on the John Hopkins University –
ICBM-DTI-81 white matter labels atlas
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Available data:
TBSS-based FA of 19 bilateral and 5 unilateral white matter
labels (plus average FA) based on the John Hopkins University –
ICBM-DTI-81 white matter labels atlas
Effect size estimates (Cohen’s d) computed using age, sex, age
by sex interaction, age2 and age2 by sex interaction as
covariates since linear and non-linear age and sex interactions
have been reported for FA (Kochunov et al., 2012)
Meta-analyzed using CMA (Rstudio next step)
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Results: random effects
*
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Significance level: * =p<.05
** =p<.002 surviving Bonferroni correction 0.05/24
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Sagittal Striatum
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Posterior Thalamic Radiation
CONFIDENTIAL
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Corpus Callosum
Posterior Corona Radiata
Genu of Corpus Callosum
Uncinate Fasciculus
DOMAIN – OCD DTI meta-analysis
Fabrizio Piras – Gianfranco Spalletta’s group, Rome
Heterogeneity is a critical aspect
Next Steps:
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Completing all sites
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Using Rstudio
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Analysing diffusivity measures
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Investigating laterality
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Investigating moderator variables (AoO, DoI, Medication,
Symptom Severity)
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis


3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
Structural Covariance
CONFIDENTIAL
ENIGMA-OCD Structural Covariance (Kwon JS and Yun JY et al.): 2016/AUG/25
1. Participants: meta-analytical approach
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Comprised of a total of 37 dataset (31/37 included for now)
Additional information needs to be gathered from other 6 dataset
o cortical-subcortical id match needed (Reddy, Fitzgerald)
o subcortical data available? (Nurmi)
Structural Covariance
CONFIDENTIAL
ENIGMA-OCD Structural Covariance (Kwon JS and Yun JY et al.): 2016/AUG/25
2. Construction of structural covariance matrix
• ROI: 33 CSAM + 33 CTM + 6 subcort_volM  72 ROIs
 Exclusion of entorhinal cortices & nucleus accumbens (poor parcellation)
• Inclusion criteria for participants for each study sites (for meta-)
‘or(isnan(ROIL)==0, isnan(ROIR)==0)==1’ for all of the 72 ROIs, so that
computation of ROIM(mean) value available
• To regress-out effect of age, sex and ICV/mean CT/whole CSA
• Z-score transform the ‘r’ using MHC/SDHC of given ROIM
• Calculation of individualized structural covariance matrix
 1./exp((X(i,j)-X(i,k))^2)
Yun JY and Kwon JS et al., (2015, 2016)
3. Graph theory analysis
• For adults & pediatric dataset
• Global characteristics (K=0.10-0.25): compare AUC values
• Regional characteristics; community structure; rich-club phenomena
ENIGMA-OCD Structural Covariance (Kwon JS and Yun JY et al.): 2016/AUG/25
4. Meta-analytic integration
CONFIDENTIAL
4-1. Global characteristics in adult (OCD vs. HC)
(other results to be shared in next TC)
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis

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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
Secondary Research Proposal Clyde Francks
Altered lateralization in people with OCD
 In collaboration with the Lateralization working group
 Analysis Plan in progress (to send around to all
members after the holiday of Clyde Francks for
approval/comments)
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Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis
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3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database
10Kin1day:
http://www.myconnectome.nl/10Kin1day/
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ENIGMA-DCL-NCU Connectome Event
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Utrecht, The Netherlands, October 28-30, 2016
Connectomics workshop by Martijn van den Heuvel, Ph.D.
Connectome reconstruction and analysis
Analysis on the Dutch National Supercomputer (41000
computer cores)
Detailed analysis plan will be send to you in September.
Who registered already?
Who would like to register in case there is place?
For all other people, Odile and Premika can process your
data if you upload the data to the Utrecht system prior to the
course (instructions follow).
Agenda
1.
2.
New ENIGMA OCD collaborators
Results Cortical meTa analysis


3.
4.
5.
6.
7.
8.
9.
Adult meTa analysis
Pediatric meTa analysis
Preliminary results cortical meGa analysis
Planning cortical meGa analysis
Preliminary results DTI meta analysis
Structural Covariance
Secondary Research proposal Clyde Francks (Lateralization)
Secondary DTI connectomics project
MeGa database : ethical issues
MeGa database
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Copy of IC used in all studies
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Highlight permission to share raw MRI/genetic data
Translate important statements on sharing raw data to
English
Send it to Odile and Premika a.s.a.p
Next TC
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Thursday, October 20 (same time)