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Network hubs in the human brain



Brain: anatomically differentiated, functionally specialized (early times) Specializa

tion fully account most functions

Integrative process, dynamic interaction underpin cognitive processes

Whats the neural substrate of integration?

1. Neural communication: synchronization, information flow

2. Specific brain regions & anatomical connections: complex & diverse response, l
evel hierarchy, confluence zones


Approach: complex network

Neural system: graphs, networks

Network map, connectome: structural basis for dynamic interactions

1. unravel its architecture

2. explain how structural network topology shape & modulate function

Connectome: diverse; modularity (specialization)+communication (integration)

Network hub ensure integration: high degree connectivity, central placement

1. Methodological Aspects: Detection and

Classification of Hubs in Brain Networks

Brain Network as Graphs

Nodes- neuronal elements

Edges- their interconnections

Pair-wise couplings: connection matrix

Arrangement: topology

Graph theory offer data-driven measures to characterize network topology

Identifies network elements having strong influence on the global network functio

Hub Detection

Network hub: nodes that make strong contributions to global network function

Detected by

1. Node degree (degree centrality): # of edges maintained by each node

2. Eigenvector centrality (pagerank centrality): favor nodes that connect to other hi

ghly central nodes

3. Closeness centrality: average distance btw a given node and the rest of the netw

4. Betweenness centrality: # of short communication paths a node (or edge) partici

pates in

5. Vulnerability: node deletion impact on global network communication

6. Dynamic importance: synchronization; graph metrics before & after deletion

Rankings of nodes: highly correlated aggregate rankings

4&5: identify central edges

Hub Detection

Network community(=module): nodes more densely linked among each other than wit
h nodes in other communities

Participation coefficient: differentiates provincial hubs (single module) from connector

hubs (multiple modules)

Peripheral nodes: low-degree, connects within own module, participation coefficient

Hub nodes highly interconnected than by chance?

Rich club: collectives of high-degree nodes and their interconnecting edges facilitate
mutual interactions

Structural core: recursive pruning of nodes of increasing degree resilient nodes (den
sely interconnected)

Structural Network

Functional Network

anatomical connectivity: Relatively sta

ble (sec~min); plasticity (h~day)

Derived from statistical descriptions of

time series data

Edges: physical links; infrastructure for

neuronal signaling & communication

fMRI linear (Pearson) cross-correlati


Time dependent, modulated by stimul

i and task context, non-stationary fluc
tuations even at rest

Edges: represent anatomical connec


Links many structurally unconnected n

ode pairs, prone to transitivity overconnection & high clustering

Reflection of signaling & communicati

on unfolded in structural network

Define Hubs based on networks com

munity structure

2. Empirical Results: Candidate Hubs in the

Structural and Functional Connectome

Structural Hubs

Betweenness centrality: dorsal superior frontal(I), precuneus(II), occipital gyrus(III)

Group-averaged: Precuneus(a), anterior(b) & posterior cingulate(c), superior front

al(d), dorsolateral prefrontal(e), insular(f), occipital(g), temporual gyrus(h)

Other measures: structural vulnerability, node degree, multiple centrality metrics ra

nkings (medial parietal, frontal & insular)

Their Integrative & diversive properties central embedding within connection top

Functional properties are shaped by connectional fingerprint

Structural Hubs

Also maintain # of anatomical connections among each other

Hub regions: more densely interconnected (wrt degree alone)

rich club (densely interconneted core)

1. Inter-hub communication robustness

2. Promote efficient communication & integration across the brain

Other aspects for classification of hubs as rich

Structural network hubs & connections

1. wiring volume, white matter (efficiency, cost)

Direct communication path, transmission delay, robustness

2. metabolic active

3. complex cellular & microcircuit properties

Shaped by trade-offs btw wiring cost, spatial &metabolic constraint & efficiency

Location of hubs: consistent

High-degree regions: parietal, frontal, insular cortices

Network hubs: universal feature of connectome organization

Functional Hubs

Mearuse density (concentration) of local & global network functional connectivity

Functional interactions: precuneus, (posterior) cingulate gyrus, inferior parietal, ve

ntromedial frontal cortex

significant overlap w/ default mode network

Recent approach: characterization of functional heterogeneity

1. Assess coactivation levels from various cognitive tasks

2. Participation of hubs in multiple functional domains

3. examination of functional paths layout within the networks

functional connectivity pattern

:step-wise connectivity approach (unimodalhigher-order)

Multimodal & Functional hubs: superior parietal, superior frontal cortex,

cingulate gyrus, anterior insula (portion): part of resting-state network

Functional Hubs

Other approach: examine participation across multiple functional networks & level of overl
ap btw different functional domain

Primary regions (primary motor, visual & auditory): single or small # of functional networks

Putative hub regions (medial superior frontal, anterior cingulate, precuneus/posterior cing
ulate gyrus): multiple functional networks

Flexible network hubs: capacity to link & interact w/ diverse brain regions adaptively (+time
& temporal variability)

frontoparietal, medial parietal & posterior cingulate

Detection based on graph analysis: pair-wise statistical relationships

(correlation coefficient btw recorded time series)

Identification depends on

1. Network edge estimation methodology

2. Graph metrics expressing functional centrality

Spatial overlap w/ default mode network: central role

due to local interactions within them &

functional degree biased by the network size

Individual Differences and Development of Hu


connectivity profile & functional coupling level variation: intelligence, performance

in different cognitive domains, interhemispheric integration, personality traits

Intelligence: medial parietal & prefrontal

Cognitive control & intellectual performance: frontal

Personality: medial parietal & cingulate

Functional connectivity topology (high density): heritable

Genetic influence

structural integrity of long-range white matter tracts

Individual Differences and Development of Hu


Structural hubs emerge early, but functionally immature, confined to primary visual
& motor

Hub regions remain relatively stable; their interaction undergo developmental chan

1. Functional connectivity among association areas

2. Spatially localized globally distributed functional network through brain devel


Sex-related difference in hormone (eg. LH) level affect white matter brain connect

Genetic & environmental factors individual variation on connectivity cognition

& behavior variation

Hubs in Brain Dysfunction

Abnormal connectivity & functioning: cognitive impairment computational netw

ork studies

Schizophrenia: frontal hub connectivity, disturbed rich club formation-long-standi

ng dysconnectivity hypothesis

Childhood-onset schizophrenia: disrupted modular architecture & disturbed conne

ctivity in multimodal association cortex

Autism: altered intra- & intermodular connectivity of densely connected limbic, tem
poral & frontal regions

Alzheimers: medial parietal

Frontotemporal dementia (FTD): frontal

Hubs in Brain Dysfunction

Focal damage affect behavioral & cognitive functioning

Lesions at functional connector hubs: disruption of modular organization

Cognitive decline associated with white matter damage & network integrity

Damage to long-distance connections network function & cognitive disruption

Hubs in Brain Dysfunction

Reduced levels of consciousness related to disruption of hub connectivity

Metabolic activity in parietal precuneus & posterior cingulate hub

Coma: random reorganization of functional hubs

Vegetative & minimally conscious: persisting functional connectivity level

3. Conceptual Framework: Role of Hu

bs in Communication and Integration

Hubs and Network Communication

Neural hubs derive their influence from their strong participation in dynamic interactio
ns due to neuronal signaling

Infer communication patterns focusing on layout of short paths & centrality of nodes (r
elative to these paths)

Structural & functional hubs play a central role in global brain communication

Hub regions may also render them potential neural bottlenecks of information flow: s
et upper bounds for integration, chaining & serializing mental operations

Mental disorders structural & functional connectivity disturbances

Limitations intrinsic to network models; reflect our ignorance & lack of data

1. capture only inter-regional projections,

include local circuits (transformation & recording)

2. fully predict dynamic patterns of communication (local firing rates of neurons,

Level of activity, external input, coherent phase relations, synaptic efficiency)

some nodes may preferentially engage in neural communication; others rarely or never

3. assume nodes connect along most efficient paths, are accessible, dominant criterion

Require detailed studies that track actual network paths of information flow

Hubs as Sources and Sinks

Some cortical hub regions maintain an unequal balance of incoming and outgoing

Receivers (sink): frontal & paracingulate cortex

Emitters (source): cingulate, entorhineal, insular cortex

Consistent w/ inferred directionality of functional interactions

Hub Connections

edge-centric perspective: focus influence of edge on network organization

Hub-hub & hub-(non-hub) edges: proportion of long-distance connections

1. Short communication relays: transmission delay, interference & noise, faster s


Small world; shortcuts randomly placed; aggregate at hub nodes

2. efficient neural communication

3. robustness of inter-hub communication

Strong hub connections (in white matter): structural modules & functional restingstate networks vulnerability

Hubs and Cross-modal Integration

Brain hubs & their connections: convergent structure for integration of informatio
n, forming putative substrate for functional global workspace

cognitive architecture in which segregated functional systems can share & integr
ate information neuronal interactions

Connective core hypothesis: interconnected hub regions topologically central offer

an important substrate for cognitive integration: broadcasting, dynamic coupling,
offering arena for dynamic cooperation and competition

Confluence (convergence) zones: hub regions across multiple functional domain o

verlapping area

involvement of hub nodes in intermodular connectivity

Hubs in Computational Models of Brain Dyna


Enable level functional diversity & synchronization

Central hub nodes engage on more variable or noisy dynamics structural rewiring

Highly connected hub nodes & connections dominate systems dynamical organizatio

: desynchronized centrally synchronized dynamics

Scale-free architecture: functional diversity

Hub nodes and edges lesions: most disruptive for network organization & functioning

Network hubs: loci of high variability & plasticity (+maintaining the cortical synchroniz
ation, modularity structure, functional dynamics)

Thank You for listening!

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