Mapping brain abnormalities in boys with autism.

Children with autism spectrum disorder (ASD) exhibit characteristic cognitive and behavioral differences, but no systematic pattern of neuroanatomical differences has been consistently found. Recent neurodevelopmental models posit an abnormal early surge in subcortical white matter growth in at least some autistic children, perhaps normalizing by adulthood, but other studies report subcortical white matter deficits. To investigate the profile of these alterations in 3D, we mapped brain volumetric differences using a relatively new method, tensor-based morphometry. 3D T1-weighted brain MRIs of 24 male children with ASD (age: 9.5 years +/- 3.2 SD) and 26 age-matched healthy controls (age: 10.3 +/- 2.4 SD) were fluidly registered to match a common anatomical template. Autistic children had significantly enlarged frontal lobes (by 3.6% on the left and 5.1% on the right), and all other lobes of the brain were enlarged significantly, or at trend level. By analyzing the applied deformations statistically point-by-point, we detected significant gray matter volume deficits in bilateral parietal, left temporal and left occipital lobes (P = 0.038, corrected), trend-level cerebral white matter volume excesses, and volume deficits in the cerebellar vermis, adjacent to volume excesses in other cerebellar regions. This profile of excesses and deficits in adjacent regions may (1) indicate impaired neuronal connectivity, resulting from aberrant myelination and/or an inflammatory process, and (2) help to understand inconsistent findings of regional brain tissue excesses and deficits in autism.

Three-dimensional mapping of the lateral ventricles in autism.

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1+/-3.5 years) and 22 male control subjects (age: 10.7+/-2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life.

Detection and mapping of hippocampal abnormalities in autism.

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.

Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia.

CONTEXT: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. OBJECTIVE: To map gray matter loss rates across the medial hemispheric surface, including the cingulate and medial frontal cortex, in the same cohort studied previously. DESIGN: Five-year longitudinal study. SETTING: National Institute of Mental Health, Bethesda, Md. Subjects Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ-matched subjects with psychosis not otherwise specified. INTERVENTIONS: Three-dimensional magnetic resonance imaging at baseline and follow-up. MAIN OUTCOME MEASURES: Gyral pattern and shape variations encoded by means of high-dimensional elastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. RESULTS: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. CONCLUSION: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia.