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CONNECTOME:
A NEW PARADIGM FOR UNDERSTANDING
BRAIN FUNCTION
Emilie Lommers
Neurologie, Juin 2014
Network as models of complex systems
The Brain - A complex network
Brain organization :
segregation and integration
Segregation
• Specialized neurons and brain areas in performing
specific mental operations
• Specific response to specific input features or
conjunction of features
• Anatomical and functional
F. Gall, P. Broca, …
K. Brodmann, …
Is something important missing?
C. Golgi, P. Flechsing, K. Wernicke, …
• Segregated and specialized neuronal units do not operate in
isolation
• Perceptual and cognitive states requires the coordinated
activation of neurons within the cerebral cortex
- precise dynamical coordination between segregated elements
- through intact axonal and synaptic connectivity
Functional Integration
CONNECTOME
The Brain - A complex network
BRAIN FUNCTION
SEGREGATION INTEGRATION
BRAIN NETWORK
Brain connectivity: multiple modes
• Structural connectivity: pattern of structural connections
between neurons, neuronal populations, or brain regions.
• Functional connectivity: Pattern of statistical
dependencies (e.g. correlations) between distinct (often
remote) neuronal elements.
• Effective connectivity: Network of causal effects,
combination of functional connectivity and structural
model.
Honey et al., 2007
Brain connectivity: multiple scales
• Microscale: Single neurons and their synaptic connections
• Mesoscale: Connections within and between microcolumns or other types of local
cell assemblies
• Macroscale: Anatomically segregated brain regions and their projections
C. Elegans …
Extraction of Brain Networks from empirical data
Hagmann et
al. 2008
Graph Theory: Basic definitions
Segregation
Clustering
Motifs
Integration
Distance
Path Length
Influence
Degree
Centrality (Hubs)
Backbone of the structural connectivity of
human cerebral cortex
Hagmann et al. 2008
Network analyses of the human connectome
Each functionally specialized
cortical region has a unique
connectional fingerprint –
a unique set of inputs and outputs.
Structural modules : nodes that
have similar connections with other
nodes.
Structural modules reflect
functional specificities
Connector hubs: links between
multiple modules
Connectors tend to be areas of
multimodal and association
cortex
In some networks, highly connected/central hub nodes have a
tendency to be highly connected to each other (“rich-club”
organization).
RC members include:
precuneus, superior
parietal and frontal
cortex, insula, medial
temporal regions
Large proportion of short
communication paths
travel trough RC
RC damage has
disproportionate effects
on network integrityvan den Heuvel et al. 2011
Concluding Remarks
• Connectome provides a powerful method to quantitatively describe
the topological organisation of brain connectivity.
• Disrupted functional and structural connectivities have been
associated with several neurological and psychiatric disorders
(dementia, ALS, MS, schizophrenia,…)
• Connectome could improve understanding of brain diseases in
term of aetiopathogeny, clinical manifestations, repair and
adaptative mechanisms,…
TO BE CONTINUED…
Thank you
for your attention!

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Connectome

  • 1. CONNECTOME: A NEW PARADIGM FOR UNDERSTANDING BRAIN FUNCTION Emilie Lommers Neurologie, Juin 2014
  • 2. Network as models of complex systems
  • 3. The Brain - A complex network Brain organization : segregation and integration
  • 4. Segregation • Specialized neurons and brain areas in performing specific mental operations • Specific response to specific input features or conjunction of features • Anatomical and functional
  • 5. F. Gall, P. Broca, …
  • 7. Is something important missing? C. Golgi, P. Flechsing, K. Wernicke, …
  • 8. • Segregated and specialized neuronal units do not operate in isolation • Perceptual and cognitive states requires the coordinated activation of neurons within the cerebral cortex - precise dynamical coordination between segregated elements - through intact axonal and synaptic connectivity Functional Integration
  • 9. CONNECTOME The Brain - A complex network BRAIN FUNCTION SEGREGATION INTEGRATION BRAIN NETWORK
  • 10. Brain connectivity: multiple modes • Structural connectivity: pattern of structural connections between neurons, neuronal populations, or brain regions. • Functional connectivity: Pattern of statistical dependencies (e.g. correlations) between distinct (often remote) neuronal elements. • Effective connectivity: Network of causal effects, combination of functional connectivity and structural model.
  • 12. Brain connectivity: multiple scales • Microscale: Single neurons and their synaptic connections • Mesoscale: Connections within and between microcolumns or other types of local cell assemblies • Macroscale: Anatomically segregated brain regions and their projections
  • 14. Extraction of Brain Networks from empirical data Hagmann et al. 2008
  • 15. Graph Theory: Basic definitions Segregation Clustering Motifs Integration Distance Path Length Influence Degree Centrality (Hubs)
  • 16. Backbone of the structural connectivity of human cerebral cortex Hagmann et al. 2008
  • 17. Network analyses of the human connectome Each functionally specialized cortical region has a unique connectional fingerprint – a unique set of inputs and outputs. Structural modules : nodes that have similar connections with other nodes. Structural modules reflect functional specificities Connector hubs: links between multiple modules Connectors tend to be areas of multimodal and association cortex
  • 18. In some networks, highly connected/central hub nodes have a tendency to be highly connected to each other (“rich-club” organization).
  • 19. RC members include: precuneus, superior parietal and frontal cortex, insula, medial temporal regions Large proportion of short communication paths travel trough RC RC damage has disproportionate effects on network integrityvan den Heuvel et al. 2011
  • 20. Concluding Remarks • Connectome provides a powerful method to quantitatively describe the topological organisation of brain connectivity. • Disrupted functional and structural connectivities have been associated with several neurological and psychiatric disorders (dementia, ALS, MS, schizophrenia,…) • Connectome could improve understanding of brain diseases in term of aetiopathogeny, clinical manifestations, repair and adaptative mechanisms,… TO BE CONTINUED…
  • 21. Thank you for your attention!

Notas do Editor

  1. Pour étudier le fonctionnement cérébral
  2. A graph is a mathematical description of a network, consisting of a collection of nodes and connections.
  3. La segregation c’est la spécialisation, anatomique et fonctionnelle, de neurones et d’aires cérébrale, dans la réalisation de certaines tâches, en réponse à des stimuli spécifiques Ce principe de segregation est connu de longue date et a été étudié par de nombreux scientifiques.
  4. EN 1810, Franz Gall énonce sa théorie selon laquelle les traits de caractère ont des situations très précises au niveau du cortex. On peut donc connaître le caractère de quelqu’un en analysant son relief crânien : la bosse des maths. Bien que la phrénologie ait été qualifiée de pseudo-science, Gall est le premier à avoir évoqué le modèle de somatotopie corticale C'est en étudiant le cerveau d'un homme ayant perdu l'usage de la parole après une lésion cérébrale que Broca fut convaincu que les différentes fonctions cérébrales pouvaient siéger dans des régions particulières du cerveau. Aphasie motrice décrite en 1861: 2 cas
  5. En 1905, Brodmann réalise une cartographie détaillée des différences cytoarchitecturales du cortex cérébral (1905). Ces nombreuses observations ont renforcé l’hypothèse ségrégationiste pendant de nombreuses années et ont influencés les recherches futures dans le domaine des neurosciences.
  6. Avec l’évolution des techniques histo, électrophysiologiques, imagerie … on s’est rendu compte que l’hypothèse ségrégationiste ne pouvait à elle seule expliquer l’ensemble du fonctionnement cérébral. Bien avant cela, certains scientifiques, contemporains de Brodman, etaient déjà de fervents défenseurs de l’aspect intégratif du fonctionnement cérébral. Golgi décrit input et output à l’hippocampe (1906) par la coloration argentique 10 ans après Broca, Wernicke met en évidence l’aire de Wernicke, reliant l’aire de Broca par le faisceau arqué
  7. Segregation: local processing of information - Integration: effective coordination Connectome: tentative de cartographie des groupes neuronaux et de leurs interconnections permettant une analyse quantitative de la connectivité cérébrale avec des outils neuroinformatiques et mathematiques. A la base, définition d’une connectome structurel (sporns 2005). Matrice de connectivité, graphique de connectivité
  8. modes of brain connectivity. structural connectivity (fiber pathways), functional connectivity (correlations), and effective connectivity (information flow) among four brain regions in macaque cortex. (see Honey et al., 2007).  
  9. When sporns first define connectome, he distinguished 3 relevant scales of organization. Image of neuronal connectivity in mouse hippocampus. Livet et al
  10. 302 neurons: sujet excellent pour étudier le réseau neuronal. Seul organisme qui a son connectome réalisé aux 3 échelles neurons connected by synapses. Red, sensory neurons; blue, interneurons; green, motorneurons. Ceci a apporté des informations importantes sur la longueur totale des connexions. Dans un si petit organisme, la nécessité de minimaliser le cablage influence directement la topographie neuronale et la connectivité locale.
  11. A graph is a mathematical description of a network, consisting of a collection of nodes and connections. Graph metrics providing us quantitative data about local and global connectivity c) The clustering coeffi cient describes the tendency of nodes to form local triangles, providing insight into the local organisation of the network. d) The shortest path length describes the minimum number of steps needed to travel between two nodes, and provides insight into the capacity of the network to communicate between remote regions. e) The degree of a node describes its number of connections. The existence of a small set of high-degree nodes with a central position in the network can suggest the existence of hub nodes.
  12. Nodes (998 regions of interest) are code in red according to node strenght and edges (4000) are code in blue according to he connection strength (fiber density)
  13. Analyses de modularité MODULES: frontal, temporopariétal, médial cortical regions Connector hubs: localisés médialement : cortex cingulaire, lobule paracentral, précunéus