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B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Neuroimagerie cognitive
défis, enjeux
Bernard Mazoyer
bernard.mazoyer@u-bordeaux.fr
Groupe d’Imagerie Neurofonctionnelle,
UMR5296, CEA, CNRS, UBxS
http://www.cnrs.gin.fr
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Neuroimaging. Genesis
A i s ( ‘ ys ’ = viscus) + liquid secretion
brain
Edwin Smith Surgical papyrus, 1700 BC – Rare book room, New York Academy of Medicine
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
19th century: the anatomo-clinical approach
The « tan » case (1861) P. Broca (1824-1880)
« I make enquiries about the character,
vivacity, skills, …, and diseases of my patients
before they die; … I trustfully record all
informations I get. When the patient is dead, I
do the autopsy and I look carefully at the
brain … » V. Malacarne (1744-1816)
« Tell me where is fancie bred,
Or in the heart, Or in the head »
W.T. Shakespeare (1596)
The Merchant of Venice, III,64
1441
Cells and dualism
Neuroimaging. Cognitive and clinical
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
1980’s Physics
Detection/production of e.m.f.
(magnets/antennas, cristals/PMTs,)
Computer science Digital image acquisition & processing
(processors, allgorithms, memories) +
Neuroimaging. E.M. spectrum and techniques
Hz 1021 1018 1015 1014 1010 108 105 10 1 10-7
radio radar Visible light X e.m.f.
MEG EEG MRI OPT X-SCAN PET
eV 106 103 1 10-5 10-7 10-10 10-14 10-22
+ techniques ultra sonores et endoscopiques
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Neuroimaging. Techniques and brain targets
HEMODYNAMIC IMAGING (vessels)
fMRI: functional magnetic resonance imaging
METABOLIC IMAGING (astrocytes, neurons)
PET: positron emission tomography (FDG)
MOLECULAR IMAGING (synapses)
PET (C11 or F11 labeled proteins)
ELECTROMAGNETIC IMAGING (membranes)
EEG/MEG: electro/magneto encephalography msec
STRUCTURAL IMAGING (grey matter, fibres)
T1-MRI: T1-magnetic resonance imaging (T1),
DTI: diffusion tensor imaging (DTI)
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
GIN, UMR5296 CNRS-CEA UBx
Neuroimaging. Techniques and brain targets: Functional Magnetic Resonance
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
BRAIN
/
MIND
Functional networks hemodynamic/metabolic imaging
fMRI, PET, NIRS
Who?
Structures anatomical imaging
MRI (T1), DTI
Where?
Neurotransmission neurochemical imaging
PET
How?
Chronometry, oscillations electromagnetic imaging
MEG, EEG
When?
Neuroimaging. Biological issues: WWWH
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Science • Neuroscience: brain morpho-functional macroscopic architecture
• Psychology: brain/mind/cognition models
• Robotics: in silico brain
Education & training
• Updated and personalized pedagogy
• Enhanced skills through improved training methods (neurofeedback)
Forensic & Ethics
• Image-based evidence (brain disease, brain death, …): neuroimage in the court
• Neuroimage-based lie detection, brain decoding
Healthcare • Improving diagnostic, therapy evaluation, and prevention: imaging biomarkers
• Designing new treatments: image guided therapy, neurofeedback
Economy • Marketing, decision making
Philosophy • Theories, beliefs, religion
Neuroimaging. Issues
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Understanding signal origin
• Mediators and modulators of hemodynamic signals
• Hemodynamic versus electromagnetic signals
• Multiscale integration
Multimodal integration • FMRI and DTI: functional and structural connectomics
• MRI & MEEG: spatio-temporal mapping
• FMRI/MEEG & PET: neurochemical cognitive neuroimaging
Neuroimaging. Challenges
Enhanced signal acquisition • Ultra high-field MRI (7T+): magnet, gradients, antennas
• New contrast agents and radiopharmaceuticals
Advanced image processing and statistical analysis • Segmentation, classification, pattern recognition, graph analysis
• Multivariate-highdimensional statistical analysis
• Data visualisation, and data mining
Identification/quantification of sources of brain phenotypes variability
• development, education, training, aging, genetic
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
3 current challenges/issues in neuroimaging
Imaging genetics Connectomics Variability sources
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Imaging genetics Connectomics Variability sources
3 current challenges/issues in neuroimaging
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Variability sources
3 current challenges/issues in neuroimaging
• Numerous
Genetic, age, sex, education, practice, lifestyle, life events, pathologies, …
• Phenotype dependent (or not?)
Behavior (exophenotype) versus morphology and function (endophenotypes)
Global versus local (target areas)
• Hard to estimate
Intrinsic higher variability than average statistics
Confounding factors
Needs large and balanced samples
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Hemispheric specialization or
the embodiement of dualism and manicheism
“The murder of ABEL”
Marc Chagall, 1960
“Night of the hunter”
Charles Laughton, 1955 Advertisement for luxury cars, 2014
Identification of brain phenotype sources of variability
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Anatomical asymmetries
Petalia & torque
(Toga 2003)
Global brain
asymmetry (85% in hominids
25% in great apes)
Rolando genu
(Rumeau et al, 1994)
Handedness and
manual skills
Left
hemisphere
Heschl gyrus and planum
temporale
(Geschwind & Levisty, 1968)
Language
Left
hemisphere
90% right-handed 90% left-hemisphere
dominant for language
Identification of brain phenotype sources of variability
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
SAMPLE 194 RH 80 LH
170 FS- 128 42
104 FS+ 66 38
(Tzourio-Mazoyer Cerebral Cortex 2009)
Left PT
(mm2) RH LH
FS- 668 704
FS+ 628 599
Right PT
(mm2) RH LH
FS- 470 480
FS+ 471 482
**
*
n.s. n.s.
n.s
.
MRI defined PT Handedness and structural marker of language
hemispheric dominance
Identification of brain phenotype sources of variability
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Hemisheric Functional Lateralization Index
P(H
FLI)
Right-handed
Left-handed
Atyp Ambi Typ
12%
15% 7% 78%
88%
(Mazoyer PLoS One 2014)
FMRI derived language network
Left-handed enriched sample (BIL&GIN)
297 participants (153 left-handed)
P (HFLI) = p iN (mi,s i
2 )i=1
i=n
å
Hemispheric Functional Lateralization Index HFLIk= (Actgauche – Actdroite) / (Actgauche + Actdroite)
Multi-Gaussian modeling
Handedness and functional marker of language hemispheric dominance
Identification of brain phenotype sources of variability
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Imaging genetics Connectomics Variability sources
3 current challenges/issues in neuroimaging
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
T1 imaging
Diffusion imaging
Cortical thickness
Target VOI
WM
tractography WM
connectivity
GM density
WM density
3D morphology
Intrinsic
connectivity
(resting state)
F F F T T T T
Cognitive networks
(task related)
Effective/functio
nal connectivity
Functional
Structural
Connectivity. MRI-derived phenotypes
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
While you are listening,
No rest!
Activation of your speech listening
neural network
Recruitment of ~40 cc of cortex
5% increase of local blood flow and
glucose consumption
Stable local oxygen consumption
BOLD signal
Connectomics of the resting state (RS)
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
But: during the last hour, your brain
consumed:
• 5,4g of sugar and 4,5l of oxygen
•delivered by 45l of blood!
Q: What for?
A: For « sustaining » a background
brain activity named « brain default
mode », associated with a « mind in a
resting state » behaviour
Minor changes in your cerebral global metabolism:
•blood flow: +1 ml/min on top of 750 ml/min
•glucose consumption: +0,1 mg/min on top of 90 mg/min
While you are listening,
Connectomics. The resting state (RS) paradox
Goal directed activity
Intrinsic activity
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Power spectrum
Connectomics. Brain networks during RS: intrinsic connectivity
Large scale networks with low frequency
synchroneous hemodynamic random fluctuations
Fox et al, PNAS, 2005
BIL&GIN database, N=282
BOLD fMRI, 8 min resting-state
Naveau, Neuroinformatics 2012
Doucet, Neuroimage 2012
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Connectomics. Modeling intrinsic functionnal connectivity
Doucet, Neuroimage 2012 Naveau, HBM 2012
Hub of degree
and betweeness
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Connectomics. The new neuroimaging paradigm
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Imaging genetics Connectomics Variability sources
3 current challenges/issues in neuroimaging
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Brain phenotype/genotype association studies
Imaging genetics. The multidimensional challenge
106 brain voxels x 107 SNP
= 1013 tests …
➞ very large sample > 105
subjects
➞ automated analysis
✽ high throughput
genome sequencing
✽ automated brain
morphometry
Medland et al2014
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Cross-sectional multi consortium study
n = 9,234 for discovery + 2,322 for replication
Imaging genetics. Finding genes influencing hippocampus size
Bis et al. 2012
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Nature Genetics 2012
Imaging genetics: finding genes influencing hippocampus size
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
SNP’s are from genes involved in
• apoptosis (HRK),
• embryo development (WIF1)
• oxydative stress (MSR3B)
Nature Genetics 2012
Imaging genetics: finding genes influencing hippocampus size
B Mazoyer – Neuroimagerie – Colloque Imagerie Bio-Santé– CNRS – 17 Juillet2014
Groupe d’Imagerie Neurofonctionnelle , UMR5296
Scientists
Fabrice Crivello
Isabelle Hesling
Gael Jobard
Marc Joliot
Bernard Mazoyer
Emmanuel Mellet
Laurent Petit
Nathalie Tzourio-Mazoyer
Laure Zago
Postdocs
Pierre-Yves Hervé
V Budisavljevic
Technical staff
Anita Foro
Gaelle Leroux
Kristel Lozach’meur
Guy Perchey
PhD students
Quentin Duriez
Janice Hau
Damien Marie
Main collaborations
INSERM U708 (Neuroimaging cohorts)
MPI Nijmegen (Genetics of language)
ICBM consortium (Neuroimaging methods)
CHARGE consortium (Aging brain genetic biomarkers)
ENIGMA consortium (Genetics of brain asymmetry)
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