Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
Background: An intriguing characteristic of the human brain is that neural activity in functionally related cortical areas fluctuates spontaneously in a correlated/synchronized manner during rest and sleep. Such synchronized activity, in the complete absence of stimulus or task, is thought to be a feature of neural networks that share a common sensory, motor, or cognitive function and may be a product of strong anatomical connections linking functionally related brain areas. A prominent feature of this synchronization is its anatomical selectivity. In particular, the strongest synchronization occurs between corresponding inter-hemispheric cortical sites (e.g. right and left auditory cortex).
It has been hypothesized that some of the atypical behavioral symptoms in autism may arise from a reduction in long-range cortical connections needed for normally synchronized cortical activity. Several recent studies have reported reduced functional connectivity in adults with autism, but this issue has not been addressed in babies with autism.
Objectives: To characterize and compare inter-hemispheric functional connectivity patterns between toddlers with autism ages 12-42 months and age matched typical controls.
Methods: Using a prospective population based screening method (Pierce et al., in review), 20 toddlers at-risk for autism and 20 typical controls 12-42 months old were recruited and participated in functional and structural MRI scans during natural sleep. Toddlers at-risk for autism were tracked until their 3rd birthday and only those with confirmed diagnoses were included in this experiment. fMRI pre-processing included standard motion correction, spatial smoothing, removal of the global mean, and removal of linear trends. During the fMRI scan, children were exposed to a soft auditory soundtrack. However, we extracted evoked auditory responses by “projecting out” all brain responses correlated with the experiment design. Several bilateral anatomical regions of interest were defined including inferior frontal gyrus (Broca’s area), superior temporal gyrus (Wernicke’s area), lateral occipital cortex, anterior intraparietal sulcus, and primary motor cortex. We computed the correlation between right and left ROIs in each subject separately and averaged across individuals of each group. Functional connectivity maps were created between each of the ROIs and the rest of the cortex in each group separately so as to compare the spatial selectivity of inter-hemispheric correlations.
Results: Both toddlers with autism and typically developing controls showed strong and selective inter-hemispheric correlations in several brain areas including occipital, parietal, and motor regions. These correlations were similar in strength and spatial selectivity to those reported in adult subjects. However, toddlers with autism exhibited reduced inter-hemispheric correlations in a subset of cortical areas, which included insular cortex and putative language-related Broca’s and Wernicke’s areas.
Conclusions: Children as young as 12-42 months old already exhibit adult-like inter-hemispheric correlations indicative of a somewhat mature functional organization. However, children with autism, already at this young age, exhibited a difference in the functional organization of the cortex characterized by reduced inter-hemispheric synchronization in language areas during sleep. This neural characteristic may serve as an early biomarker of autism and may be useful for predicting developmental outcome.
It has been hypothesized that some of the atypical behavioral symptoms in autism may arise from a reduction in long-range cortical connections needed for normally synchronized cortical activity. Several recent studies have reported reduced functional connectivity in adults with autism, but this issue has not been addressed in babies with autism.
Objectives: To characterize and compare inter-hemispheric functional connectivity patterns between toddlers with autism ages 12-42 months and age matched typical controls.
Methods: Using a prospective population based screening method (Pierce et al., in review), 20 toddlers at-risk for autism and 20 typical controls 12-42 months old were recruited and participated in functional and structural MRI scans during natural sleep. Toddlers at-risk for autism were tracked until their 3rd birthday and only those with confirmed diagnoses were included in this experiment. fMRI pre-processing included standard motion correction, spatial smoothing, removal of the global mean, and removal of linear trends. During the fMRI scan, children were exposed to a soft auditory soundtrack. However, we extracted evoked auditory responses by “projecting out” all brain responses correlated with the experiment design. Several bilateral anatomical regions of interest were defined including inferior frontal gyrus (Broca’s area), superior temporal gyrus (Wernicke’s area), lateral occipital cortex, anterior intraparietal sulcus, and primary motor cortex. We computed the correlation between right and left ROIs in each subject separately and averaged across individuals of each group. Functional connectivity maps were created between each of the ROIs and the rest of the cortex in each group separately so as to compare the spatial selectivity of inter-hemispheric correlations.
Results: Both toddlers with autism and typically developing controls showed strong and selective inter-hemispheric correlations in several brain areas including occipital, parietal, and motor regions. These correlations were similar in strength and spatial selectivity to those reported in adult subjects. However, toddlers with autism exhibited reduced inter-hemispheric correlations in a subset of cortical areas, which included insular cortex and putative language-related Broca’s and Wernicke’s areas.
Conclusions: Children as young as 12-42 months old already exhibit adult-like inter-hemispheric correlations indicative of a somewhat mature functional organization. However, children with autism, already at this young age, exhibited a difference in the functional organization of the cortex characterized by reduced inter-hemispheric synchronization in language areas during sleep. This neural characteristic may serve as an early biomarker of autism and may be useful for predicting developmental outcome.