Avery Voos

Neural signatures of autism

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Brain mechanisms for processing affective touch.

Despite the crucial role of touch in social development, there is very little functional magnetic resonance imaging (fMRI) research on brain mechanisms underlying social touch processing. The “skin as a social organ” hypothesis is supported by the discovery of C‐tactile (CT) nerves that are present in hairy skin and project to the insular cortex. CT‐fibers respond specifically well to slow, gentle touch such as that which occurs during close social interactions. Given the social significance of such touch researchers have proposed that the CT‐system represents an evolutionarily conserved mechanism important for normative social development. However, it is currently unknown whether brain regions other than the insula are involved in processing CT‐targeted touch. In the current fMRI study, we sought to characterize the brain regions involved in the perception of CT‐supported affective touch. Twenty‐two healthy adults received manual brush strokes to either the arm or palm. A direct contrast of the blood‐oxygenation‐level‐dependent (BOLD) response to gentle brushing of the arm and palm revealed the involvement of a network of brain regions, in addition to the posterior insula, during CT‐targeted affective touch to the arm. This network included areas known to be involved in social perception and social cognition, including the right posterior superior temporal sulcus and the medial prefrontal cortex (mPFC)/dorso anterior cingulate cortex (dACC). Connectivity analyses with an mPFC/dACC seed revealed coactivation with the left insula and amygdala during arm touch. These findings characterize a network of brain regions beyond the insula involved in coding CT‐targeted affective touch. Hum Brain Mapp, 2013.

Brain Mechanisms for Processing Affective (and Nonaffective) Touch Are Atypical in Autism

C-tactile (CT) afferents encode caress-like touch that supports social-emotional development, and stimulation of the CT system engages the insula and cortical circuitry involved in social-emotional processing. Very few neuroimaging studies have investigated the neural mechanisms of touch processing in people with autism spectrum disorder (ASD), who often exhibit atypical responses to touch. Using functional magnetic resonance imaging, we evaluated the hypothesis that children and adolescents with ASD would exhibit atypical brain responses to CT-targeted touch. Children and adolescents with ASD, relative to typically developing (TD) participants, exhibited reduced activity in response to CT-targeted (arm) versus non-CT-targeted (palm) touch in a network of brain regions known to be involved in social-emotional information processing including bilateral insula and insular operculum, the right posterior superior temporal sulcus, bilateral temporoparietal junction extending into the inferior parietal lobule, right fusiform gyrus, right amygdala, and bilateral ventrolateral prefrontal cortex including the inferior frontal and precentral gyri, suggesting atypical social brain hypoactivation. Individuals with ASD (vs. TD) showed an enhanced response to non-CT-targeted versus CT-targeted touch in the primary somatosensory cortex, suggesting atypical sensory cortical hyper-reactivity.

Action representation in the superior temporal sulcus in children and adults: an fMRI study

The superior temporal sulcus (STS) plays an important role in the perception of biological motion and in the representation of higher order information about others goals and intentions. Using a rapid event related functional magnetic resonance imaging paradigm (fMRI), children (n=37, mean age 11.0) and adults (n=17, mean age 25.3) viewed congruent or incongruent actions. Congruency (and incongruency) of a reach toward an object was a function of whether the object had just previously received positive or negative regard. Relative to congruent trials, both children and adults showed an increase in activation in the posterior STS bilaterally, in response to incongruent trials. In children, these STS regions exhibited developmental changes. Specifically, the differential response to incongruent trials relative to congruent trials was larger in older children in both hemispheres.

White Matter Abnormalities in Autism and Unaffected Siblings

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (fMRI), with its excellent spatial resolution and ability to visualize networks of neuroanatomical structures involved in complex information processing, has become the dominant technique for the study of brain function and its development. The accessibility of in-vivo pediatric brain-imaging techniques together with the revolution in modern molecular genetic and epigenetic techniques offers the developmental scientist an unprecedented opportunity to enact a truly developmental perspective, allowing the experimentalist to understand and integrate multiple levels of analysis in the study of developing children. Here, we review how fMRI works along with a critical issue in the use of fMRI to study cognition and its development—the necessity to carefully control movement in the scanner. We then provide a primer on strategies implemented in our laboratory to successfully scan children as young as 4 years of age while they are awake and engaged in cognitive tasks. We conclude with a practical discussion of the potential risks of fMRI and ways to maximize participant safety and comfort.

Neurogenetic analysis of childhood disintegrative disorder

BackgroundChildhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences.MethodsWe pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces.ResultsWe observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces.ConclusionsGiven that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level.

Developmental Neuroscience of Social Perception

This chapter focuses on the development of social perception, a critical aspect of social cognition. This chapter presents a review of the neuroanatomical substrates and development of several aspects of social perception including (1) recognition of other people, (2) perception and experience of emotion, (3) perception of biological motion, (4) representation of the self and the other, and (5) thinking about the thoughts of others. This chapter concludes with a presentation of a developmental model of social perception.