Disrupted axonal fiber connectivity in schizophrenia

Zalesky, Andrew, Fornito, Alex, Seal, Marc L., Cocchi, Luca, Westin, Carl-Fredrik, Bullmore, Edward T., Egan, Gary F. and Pantelis, Christos (2011) Disrupted axonal fiber connectivity in schizophrenia. Biological Psychiatry, 69 1: 80-89. doi:10.1016/j.biopsych.2010.08.022

Author Zalesky, Andrew
Fornito, Alex
Seal, Marc L.
Cocchi, Luca
Westin, Carl-Fredrik
Bullmore, Edward T.
Egan, Gary F.
Pantelis, Christos
Title Disrupted axonal fiber connectivity in schizophrenia
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2011-01
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2010.08.022
Volume 69
Issue 1
Start page 80
End page 89
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2012
Language eng
Formatted abstract
Background: Schizophrenia is believed to result from abnormal functional integration of neural processes thought to arise from aberrant brain connectivity. However, evidence for anatomical dysconnectivity has been equivocal, and few studies have examined axonal fiber connectivity in schizophrenia at the level of whole-brain networks.

Methods: Cortico-cortical anatomical connectivity at the scale of axonal fiber bundles was modeled as a network. Eighty-two network nodes demarcated functionally specific cortical regions. Sixty-four direction diffusion tensor-imaging coupled with whole-brain tractography was performed to map the architecture via which network nodes were interconnected in each of 74 patients with schizophrenia and 32 age- and gender-matched control subjects. Testing was performed to identify pairs of nodes between which connectivity was impaired in the patient group. The connectional architecture of patients was tested for changes in five network attributes: nodal degree, smallworldness, efficiency, path length, and clustering.

Results: Impaired connectivity in the patient group was found to involve a distributed network of nodes comprising medial frontal, parietal/occipital, and the left temporal lobe. Although small-world attributes were conserved in schizophrenia, the cortex was interconnected more sparsely and up to 20% less efficiently in patients. Intellectual performance was found to be associated with brain efficiency in control subjects but not in patients.

Conclusions: This study presents evidence of widespread dysconnectivity in white- matter connectional architecture in a large sample of patients with schizophrenia. When considered from the perspective of recent evidence for impaired synaptic plasticity, this study points to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms.
Keyword Axonal connectivity
diffusion tensor imaging
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Available online 29 October 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
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