Abnormal Anatomical Connectivity between the Amygdala and Orbitofrontal Cortex in Conduct Disorder
Abstract
Objective: Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD. Methods: Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography. Results: Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts. Conclusions: These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.
Additional Information
© 2012 Passamonti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: June 11, 2012; Accepted: October 1, 2012; Published: November 7, 2012. We would like to thank our volunteers for participating in this study and to the radiographers at the MRC Cognition and Brain Sciences Unit for their invaluable help with data acquisition. We also thank the Cambridge Youth Offending Service, and the schools and pupil referral units for their assistance with participant recruitment. Dr. Passamonti was funded by the Betty Behrens Research Fellowship at the Clare Hall College of the University of Cambridge. This study was supported by the Wellcome Trust (Project Grant #083140 to Professor Goodyer and Dr. Fairchild) and by Medical Research Council (Project Code MC_US_A060_5PQ50 to Dr. Calder). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contributions: Conceived and designed the experiments: LP GF AC IG. Performed the experiments: LP GF CH. Analyzed the data: LP AF. Contributed reagents/materials/analysis tools: AF INS. Wrote the paper: LP GF CH AC IG. The authors have declared that no competing interests exist.Attached Files
Published - journal.pone.0048789.PDF
Supplemental Material - journal.pone.0048789.s001.DOC
Supplemental Material - journal.pone.0048789.s002.DOC
Supplemental Material - journal.pone.0048789.s003.DOC
Supplemental Material - journal.pone.0048789.s004.DOC
Supplemental Material - journal.pone.0048789.s005.DOC
Supplemental Material - journal.pone.0048789.s006.DOC
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Additional details
- PMCID
- PMC3492256
- Eprint ID
- 101557
- Resolver ID
- CaltechAUTHORS:20200225-135944675
- Betty Behrens Research Fellowship
- 083140
- Wellcome Trust
- MC_US_A060_5PQ50
- Medical Research Council (UK)
- Created
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2020-02-26Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field