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3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry.

ABSTRACT: Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/-1.58 S.D., 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/-2.2 S.D., 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p = 0.001) and lateral ventricle volumes (19% higher; p = 0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p = 0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the Fragile X mental retardation protein (FMRP; Spearman's r < -0.5 locally). Decreased FMRP correlated with ventricular expansion (p = 0.042; permutation test), and anterior cingulate tissue reductions (p = 0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated by performing statistics after logarithmic transformation, which may be more appropriate for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment.

SUBMITTER: Lee AD

PROVIDER: S-EPMC1995408 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry.

Lee Agatha D AD Leow Alex D AD Lu Allen A Reiss Allan L AL Hall Scott S Chiang Ming-Chang MC Toga Arthur W AW Thompson Paul M PM

NeuroImage 20061208 3

Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/-1.58 S.D., 18 females/18 males) ...[more]

PMID: 17161622

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Project description:22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Dataset Information

3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry.

Publications

3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry.

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