The hubs of the human connectome are generally implicated in the anatomy of brain disorders

Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-dist...

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Published in:Brain (London, England : 1878) Vol. 137; no. Pt 8; p. 2382
Main Authors: Crossley, Nicolas A, Mechelli, Andrea, Scott, Jessica, Carletti, Francesco, Fox, Peter T, McGuire, Philip, Bullmore, Edward T
Format: Journal Article
Language:English
Published: England 01.08.2014
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ISSN:1460-2156, 1460-2156
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Abstract Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders.
AbstractList Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders.Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders.
Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders.
Author Carletti, Francesco
Bullmore, Edward T
Scott, Jessica
McGuire, Philip
Fox, Peter T
Mechelli, Andrea
Crossley, Nicolas A
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  fullname: Crossley, Nicolas A
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  organization: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK nicolas.crossley@kcl.ac.uk
– sequence: 2
  givenname: Andrea
  surname: Mechelli
  fullname: Mechelli, Andrea
  organization: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK
– sequence: 3
  givenname: Jessica
  surname: Scott
  fullname: Scott, Jessica
  organization: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK
– sequence: 4
  givenname: Francesco
  surname: Carletti
  fullname: Carletti, Francesco
  organization: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK
– sequence: 5
  givenname: Peter T
  surname: Fox
  fullname: Fox, Peter T
  organization: 2 Research Imaging Institute and Department of Radiology, The University of Texas Health Science Centre at San Antonio, San Antonio, TX 78229, USA
– sequence: 6
  givenname: Philip
  surname: McGuire
  fullname: McGuire, Philip
  organization: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK
– sequence: 7
  givenname: Edward T
  surname: Bullmore
  fullname: Bullmore, Edward T
  organization: 3 University of Cambridge, Behavioural & Clinical Neuroscience Institute, Department of Psychiatry, Cambridge CB2 0SZ, UK4 Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge CB21 5EF, UK5 GlaxoSmithKline, ImmunoPsychiatry, Alternative Discovery and Development, Stevenage SG1 2NY, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25057133$$D View this record in MEDLINE/PubMed
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References 25057132 - Brain. 2014 Aug;137(Pt 8):2117-8. doi: 10.1093/brain/awu148.
26205839 - Brain. 2015 Aug;138(Pt 8):e374. doi: 10.1093/brain/awv122.
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Snippet Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports...
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SubjectTerms Adult
Brain - anatomy & histology
Brain - pathology
Brain - physiopathology
Computer Simulation
Connectome - methods
Diffusion Tensor Imaging - methods
Female
Humans
Male
Nerve Net - anatomy & histology
Nerve Net - pathology
Nerve Net - physiopathology
Title The hubs of the human connectome are generally implicated in the anatomy of brain disorders
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