Dataset Information

Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2.

ABSTRACT: Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower [corrected] eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.

SUBMITTER: Dennis EL

PROVIDER: S-EPMC3420970 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2.

Dennis Emily L EL Jahanshad Neda N Rudie Jeffrey D JD Brown Jesse A JA Johnson Kori K McMahon Katie L KL de Zubicaray Greig I GI Montgomery Grant G Martin Nicholas G NG Wright Margaret J MJ Bookheimer Susan Y SY Dapretto Mirella M Toga Arthur W AW Thompson Paul M PM

Brain connectivity 20110101 6

Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After ...[more]

PMID: 22500773

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Project description:BackgroundAutism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.MethodsUsing functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays-depicting biological versus non-biological motion-in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females-i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm.ResultsWe observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies.LimitationsWe were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position.ConclusionsThese methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD.

Project description:Cannabis is one of the most used and commodified illicit substances worldwide, especially among young adults. The neurobiology mechanism of cannabis is yet to be identified particularly in youth. The purpose of this study was to concurrently measure alterations in brain structural and functional connectivity in cannabis users using resting-state functional magnetic resonance images (rs-fMRI) and diffusion-weighted images (DWI) from a group of 73 cannabis users (age 22-36, 19 female) in comparison with 73 healthy controls (age 22-36, 14 female) from Human Connectome Project (HCP). Several significant differences were observed in local structural/functional network measures (e.g. degree and clustering coefficient), being prominent in the insular and frontal opercular cortex and lateral/medial temporal cortex. The rich-club organization of structural networks revealed a normal trend, distributed within bilateral frontal, temporal and occipital regions. However, minor differences were found between the two groups in the superior and inferior temporal gyri. Functional rich-club nodes were mostly located within parietal and posterior areas, with minor differences between the groups found mainly in the centro-temporal and parietal regions. Regional network measures of structural/functional networks were associated with times used cannabis (TUC) in several regions. Although the structural/functional network in both groups showed small-world property, no differences between cannabis users and healthy controls were found regarding the global network measures, showing no association with cannabis use. After FDR correction, all of the significant associations between network measures and TUC were found to be insignificant, except for the association between degree and TUC within the presubiculum region. To recap, our findings revealed alterations in local topological properties of structural and functional networks in cannabis users, although their global brain network organization remained intact.

Dataset Information

Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2.

Publications

Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2.

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