We are interested in understanding the biological basis of autism. What changes in the brain are associated with the development of this disorder? Recent studies about autism suggest that it is not caused by a local dysfunction of one particular brain area, but rather by numerous subtle changes in multiple areas of the brain. In our current research efforts we are utilizing MRI, fMRI, DTI, and EEG to compare brain function and structure across individuals with autism and matched controls. We are focusing on the following issues:

freesurferAnatomy – Are there anatomical differences between individuals with and without autism? We use anatomical MRI scans to compare measures of volume, cortical thickness, cortical area, and cortical folding across individuals with and without autism. We segment the brain into gray and white matter and align the brain of each subject to an anatomical atlas, which allows us to identify different brain areas in each participant. This allows us to then compare the anatomy of specific brain areas across different subject groups. In the figure on the right you can see the brain of an individual with autism after marking specific brain areas with different colors according to an anatomical atlas.

wm_tractsWhite matter integrity – Neurons in different parts of the brain communicate by sending long  myelinated axons that reach distant brain areas and form the white matter of the brain. Using diffusion tensor imaging (DTI) it is possible to identify white tracts containing many axons and assess their quality, geometry, and volume. In the figure to the left you can see the three main language white-matter tracts of an individual with autism who was scanned in the lab.

Sensory systems function – Since autism is a developmental disorder that is likely to affect brain development in a diffused and distributed manner, studying sensory systems in autism is likely to reveal important clues about autism patho-physiology. Sensory systems are by far the best understood systems in the human brain and assessing their responses can reveal critical insights about basic neural functioning (e.g. neural response reliability, adaptation, selectivity, etc…). In a recent study we found that visual, auditory, and somatosensory fMRI responses in autism are about 30% less reliable (i.e. more variable/”noisy”) than those of matched controls. We are currently studying whether other basic neural characteristics are altered in autism.

Neural response reliability – We are currently performing several studies to better understand the reliability of basic sensory neural responses in the general population. To accomplish this we are using EEG to measure trial-by-trial variability to visual, auditory, and somatosensory stimuli in individuals of different ages. We plan to understand how response reliability changes across life and determine its relationship with different cognitive measures such as IQ, working memory, and attention on a subject-by-subject level.

connectivity_toddlersFunctional connectivity – Distant brain areas with similar function (e.g. auditory cortical areas) exhibit activity changes that are correlated over time. It has been hypothesized that brains with different pathologies may exhibit specific changes in these correlations and that autism, in particular, is a disorder of abnormal functional connectivity/synchronization. In a recent study in collaboration with the Courchesne lab in UCSD we reported that inter-hemispheric functional connectivity is weak in 2-3 year old toddlers with autism in a manner, which is correlated with their autism severity. We are currently examining whether this measure allows us to predict the developmental outcome of individual toddlers. In the figure to the right you can see the specific cortical area that exhibited weak inter-hemispheric connectivity in a large percentage of toddlers with autism.

There are two main goals to these different research directions, which are intimately related to one another. The first goal is to better understand what are the biological mechanisms that underlie the emergence of the strange and unique cognitive and social behaviors that are exhibited by individuals with autism. Can we relate particular structural or functional characteristics to specific abnormal behaviors and identify the vague “limits” of typical brain development? The second goal is to identify objective biological measures that will enable early and accurate clinical diagnosis of autism, which would be able to replace or at least complement the subjective behavioral measures that are currently used for diagnosis. Characterizing the underlying mechanisms of autism will also be a critical step in identifying appropriate targets for novel forms of therapy.