Hower Kwon

White matter structure in autism: preliminary evidence from diffusion tensor imaging.

BACKGROUND Individuals with autism have severe difficulties in social communication and relationships. Prior studies have suggested that abnormal connections between brain regions important for social cognition may contribute to the social deficits seen in autism. METHODS In this study, we used diffusion tensor imaging to investigate white matter structure in seven male children and adolescents with autism and nine age-, gender-, and IQ-matched control subjects. RESULTS Reduced fractional anisotropy (FA) values were observed in white matter adjacent to the ventromedial prefrontal cortices and in the anterior cingulate gyri as well as in the temporoparietal junctions. Additional clusters of reduced FA values were seen adjacent to the superior temporal sulcus bilaterally, in the temporal lobes approaching the amygdala bilaterally, in occipitotemporal tracts, and in the corpus callosum. CONCLUSIONS Disruption of white matter tracts between regions implicated in social functioning may contribute to impaired social cognition in autism.

The Amygdala Is Enlarged in Children But Not Adolescents with Autism; the Hippocampus Is Enlarged at All Ages

Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. Thus, the amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children. Children with autism, with and without mental retardation, also had a larger right hippocampal volume than typically developing controls, even after controlling for total cerebral volume. Children with autism but without mental retardation also had a larger left hippocampal volume relative to controls. These cross-sectional findings indicate an abnormal program of early amygdala development in autism and an abnormal pattern of hippocampal development that persists through adolescence. The cause of amygdala and hippocampal abnormalities in autism is currently unknown.

Neural basis of protracted developmental changes in visuo-spatial working memory

Developmental studies have shown that visuo-spatial working memory (VSWM) performance improves throughout childhood and adolescence into young adulthood. The neural basis of this protracted development is poorly understood. In this study, we used functional MRI (fMRI) to examine VSWM function in children, adolescents, and young adults, ages 7–22. Subjects performed a 2-back VSWM experiment that required dynamic storage and manipulation of spatial information. Accuracy and response latency on the VSWM task improved gradually, extending into young adulthood. Age-related increases in brain activation were observed in focal regions of the left and right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex (including Brocas area), left premotor cortex, and left and right posterior parietal cortex. Multiple regression analysis was used to examine the relative contributions of age, accuracy, and response latency on activation. Our analysis showed that age was the most significant predictor of activation in these brain regions. These findings provide strong evidence for a process of protracted functional maturation of bilateral fronto-parietal neural networks involved in VSWM development. At least two neural systems involved in VSWM mature together: (i) a right hemisphere visuo-spatial attentional system, and (ii) a left hemisphere phonological storage and rehearsal system. These observations suggest that visually and verbally mediated mnemonic processes, and their neural representations, develop concurrently during childhood and adolescence and into young adulthood.

COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome

Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMTL) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome.

Williams syndrome (WS) is a neurogenetic-neurodevelopmental disorder characterized by a highly variable and enigmatic profile of cognitive and behavioral features. Relative to overall intellect, affected individuals demonstrate disproportionately severe visual-spatial deficits and enhanced emotionality and face processing. In this study, high-resolution magnetic resonance imaging data were collected from 43 individuals with WS and 40 age- and gender-matched healthy controls. Given the distinct cognitive-behavioral dissociations associated with this disorder, we hypothesized that neuroanatomical integrity in WS would be diminished most in regions comprising the visual-spatial system and most “preserved” or even augmented in regions involved in emotion and face processing. Both volumetric analysis and voxel-based morphometry were used to provide convergent approaches for detecting the hypothesized WS neuroanatomical profile. After adjusting for overall brain volume, participants with WS showed reduced thalamic and occipital lobe gray matter volumes and reduced gray matter density in subcortical and cortical regions comprising the human visual-spatial system compared with controls. The WS group also showed disproportionate increases in volume and gray matter density in several areas known to participate in emotion and face processing, including the amygdala, orbital and medial prefrontal cortices, anterior cingulate, insular cortex, and superior temporal gyrus. These findings point to specific neuroanatomical correlates for the unique topography of cognitive and behavioral features associated with this disorder.

Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome

Efforts to examine the structural neuroanatomy of autism by using traditional methods of imaging analysis have led to variable findings, often based on methodological differences in image acquisition and analysis. A voxel-based computational method of whole-brain anatomy allows examination of small patterns of tissue differences between groups. High-resolution structural magnetic resonance images were acquired for nine males with high-functioning autism (HFA; mean age 14y [SD3y 4mo]), 11 with Asperger syndrome (ASP; mean age 13y 6mo [SD2y 5mo]), and 13 comparison (COM) participants (mean age 13y 7mo [SD 3y 1mo]). Using statistical parametric mapping, we examined contrasts of gray matter differences between the groups. Males with HFA and ASP had a pattern of decreased gray matter density in the ventromedial regions of the temporal cortex in comparison with males from an age-matched comparison group. Examining contrasts revealed that the COM group had increased gray matter density compared with the ASP or combined HFA and ASP group in the right inferior temporal gyrus, entorhinal cortex, and rostral fusiform gyrus. The ASP group had less gray matter density in the body of the cingulate gyrus in comparison with either the COM or HFA group. The findings of decreased gray matter density in ventromedial aspects of the temporal cortex in individuals with HFA and ASP lends support to theories suggesting an involvement of these areas in the pathophysiology of autism, particularly in the integration of visual stimuli and affective information.

Functional brain activation during cognition is related to FMR1 gene expression

Fragile X syndrome, the most common known cause of inherited mental retardation, is caused by alterations of the FMR1 gene encoding the FMRP protein. We investigated the relation between FMRP protein levels and functional brain activation during a working memory task. Our study provides the first evidence for a relation between FMR1 gene expression and neural activity during higher-order cognition. More broadly, our findings provide the first demonstration of how gene-brain-behavior investigations can help to bridge the gap between molecular and systems neuroscience.

Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndrome

Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well‐substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty‐seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age‐matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI–VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult.