Elizabeth Walter

Neuroanatomical Differences in Toddler Boys With Fragile X Syndrome and Idiopathic Autism

CONTEXT Autism is an etiologically heterogeneous neurodevelopmental disorder for which there is no known unifying etiology or pathogenesis. Many conditions of atypical development can lead to autism, including fragile X syndrome (FXS), which is presently the most common known single-gene cause of autism. OBJECTIVE To examine whole-brain morphometric patterns that discriminate young boys with FXS from those with idiopathic autism (iAUT) as well as control participants. DESIGN Cross-sectional, in vivo neuroimaging study. SETTING Academic medical centers. PATIENTS Young boys (n = 165; aged 1.57-4.15 years) diagnosed as having FXS or iAUT as well as typically developing and idiopathic developmentally delayed controls. MAIN OUTCOME MEASURES Univariate voxel-based morphometric analyses, voxel-based morphometric multivariate pattern classification (linear support vector machine), and clustering analyses (self-organizing map). RESULTS We found that frontal and temporal gray and white matter regions often implicated in social cognition, including the medial prefrontal cortex, orbitofrontal cortex, superior temporal region, temporal pole, amygdala, insula, and dorsal cingulum, were aberrant in FXS and iAUT as compared with controls. However, these differences were in opposite directions for FXS and iAUT relative to controls; in general, greater volume was seen in iAUT compared with controls, who in turn had greater volume than FXS. Multivariate analysis showed that the overall pattern of brain structure in iAUT generally resembled that of the controls more than FXS, both with and without AUT. CONCLUSIONS Our findings demonstrate that FXS and iAUT are associated with distinct neuroanatomical patterns, further underscoring the neurobiological heterogeneity of iAUT.

A Specific Autistic Trait that Modulates Visuospatial Illusion Susceptibility

Although several accounts of autism have predicted that the disorder should be associated with a decreased susceptibility to visual illusions, previous experimental results have been mixed. This study examined whether a link between autism and illusion susceptibility can be more convincingly demonstrated by assessing the relationships between susceptibility and the extent to which several individual autistic traits are exhibited as a continuum in a population of college students. A significant relationship was observed between the systemizing trait and susceptibility to a subset of the tested illusions (the rod-and-frame, Roelofs, Ponzo and Poggendorff illusions). These results provide support for the idea that autism involves an imbalance between the processing of local and global cues, more heavily weighted toward local features than in the typically developed individual.

Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation

BACKGROUND Fragile X syndrome (FXS) is the most common known heritable cause of intellectual disability. Prior studies in FXS have observed a plateau in cognitive and adaptive behavioral development in early adolescence, suggesting that brain development in FXS may diverge from typical development during this period. METHODS In this study, we examined adolescent brain development using structural magnetic resonance imaging data acquired from 59 individuals with FXS and 83 typically developing control subjects aged 9 to 22, a subset of whom were followed up longitudinally (1-5 years; typically developing: 17, FXS: 19). Regional volumes were modeled to obtain estimates of age-related change. RESULTS We found that while structures such as the caudate showed consistent volume differences from control subjects across adolescence, prefrontal cortex (PFC) gyri showed significantly aberrant maturation. Furthermore, we found that PFC-related measures of cognitive functioning followed a similarly aberrant developmental trajectory in FXS. CONCLUSIONS Our findings suggest that aberrant maturation of the PFC during adolescence may contribute to persistent or increasing intellectual deficits in FXS.

Neural Correlates of Humor Detection and Appreciation in Children

Humor is a vital component of human well-being. Neuroimaging studies conducted with adults indicate that humor activates specific brain regions, including the temporo-occipito-parietal junction (TOPJ), involved in incongruity resolution, and mesolimbic regions, involved in reward processing. However, no study to date has used neuroimaging to examine humor in typically developing children. Here, we illuminate the neural network involved in the detection and appreciation of humor in childhood. Fifteen typically developing children (ages, 6–12 years) were invited to watch and respond to video clips while neural activity was imaged with a 3T GE Discovery MR750 scanner. Before presentation during functional imaging, the clips were evaluated by age-matched controls and were representative of three categories: Funny, Positive (enjoyable but not funny), and Neutral (not intended to evoke any emotional response). We found TOPJ and mesolimbic activation in childrens response to humor, suggesting these regions may form a humor-essential neural network already present in childhood. Furthermore, in a novel comparison of Funny to Positive stimuli, we found that bilateral TOPJ activation may be specific to humor processing and not part of a general constellation of neural activity in response to reward. Finally, we observed greater activation in the inferior frontal gyrus and nucleus accumbens in younger participants, indicating humor activation intensity changes during development. By providing a crucial link in studying the neurodevelopment of humor processing across the lifespan, our findings contribute valuable information about the evolution of how children understand their world.

Visuospatial contextual processing in the parietal cortex: An fMRI investigation of the induced Roelofs effect

Neighboring contextual elements can dramatically affect the manner in which the brain processes the perceptual characteristics of an object. Indeed, many well-known visual illusions rely on misleading contextual cues to create misperceptions of size, length or orientation (e.g., in the Ebbinghaus, Muller-Lyer or rod-and-frame illusions, respectively). However, little is known about the brain regions underlying these integrative computations. The current study used fMRI to delineate the brain areas responsible for processing visuospatial contextual information. Participants were asked to determine whether a small target was positioned left or right of midline in the presence of an offset rectangle designed to induce a shift in the participants perception of straight-ahead (the induced Roelofs effect). We found localized, bilateral regions in superior parietal cortex and precuneus that were specifically active when participants judged the target location in the presence of this shifted context; significantly less activation was present when a color judgment was made with identical stimuli, or when the location judgment was made without a Roelofs-inducing frame. We propose that this portion of parietal cortex is selectively involved in processing visuospatial contextual information. Additional findings support the notion that perceptual judgments of target location based on an egocentric frame of reference fall within the purview of the dorsal stream of visual processing, rather than the ventral stream.

Activation in a Frontoparietal Cortical Network Underlies Individual Differences in the Performance of an Embedded Figures Task

The Embedded Figures Test (EFT) requires observers to search for a simple geometric shape hidden inside a more complex figure. Surprisingly, performance in the EFT is negatively correlated with susceptibility to illusions of spatial orientation, such as the Roelofs effect. Using fMRI, we previously demonstrated that regions in parietal cortex are involved in the contextual processing associated with the Roelofs task. In the present study, we found that similar parietal regions (superior parietal cortex and precuneus) were more active during the EFT than during a simple matching task. Importantly, these parietal activations overlapped with regions found to be involved during contextual processing in the Roelofs illusion. Additional parietal and frontal areas, in the right hemisphere, showed strong correlations between brain activity and behavioral performance during the search task. We propose that the posterior parietal regions are necessary for processing contextual information across many different, but related visuospatial tasks, with additional parietal and frontal regions serving to coordinate this processing in participants proficient in the task.

The neural basis of auditory temporal discrimination in girls with fragile X syndrome

Fragile X syndrome (FXS) is a common genetic disorder in which temporal processing may be impaired. To our knowledge however, no studies have examined the neural basis of temporal discrimination in individuals with FXS using functional magnetic resonance imaging (fMRI). Ten girls with fragile X syndrome and ten developmental age-matched typically developing controls performed an auditory temporal discrimination task in a 3T scanner. Girls with FXS showed significantly greater brain activation in a left-lateralized network, comprising left medial frontal gyrus, left superior and middle temporal gyrus, left cerebellum, and left brainstem (pons), when compared to a developmental age-matched typically developing group of subjects who had similar in-scanner task performance. There were no regions that showed significantly greater brain activation in the control group compared to individuals with FXS. These data indicate that networks of brain regions involved in auditory temporal processing may be dysfunctional in FXS. In particular, it is possible that girls with FXS employ left hemispheric resources to overcompensate for relative right hemispheric dysfunction.

Fragments of the Roelofs effect: a bottom-up effect equal to the sum of its parts.

The Roelofs effect is a distortion of perceived space that occurs when a large frame whose center is offset left or right from the objective midline is presented visually to an observer and causes a bias in the observer’s subjective judgment of midline. Experiments were designed to test whether an isolated fragment (left or right end) of a Roelofs-inducing frame was capable of generating the Roelofs effect and to determine whether prior experience with intact frames would provide a top-down influence that would bias the Roelofs effect resulting from fragment presentation. Although the fragments did induce an effect, top-down information did not play a significant role even after a 5-day training paradigm. Instead, we found that the effect generated by an intact frame was equal in magnitude to the sum of the effects generated by the individual fragments. In addition, perception was found to be differentially affected by the two ends of the frame, with fragments falling in the right visual field causing a larger effect than those falling in the left.

Semantic guidance of attention within natural scenes

When viewing real-world scenes composed of a myriad of objects, detecting changes can be quite difficult, especially when transients are masked. In general, changes are noticed more quickly and accurately if they occur at the currently (or a recently) attended location. Here, we examine the effects of explicit and implicit semantic cues on the guidance of attention in a change detection task. Participants first attempted to read aloud a briefly presented prime word, then looked for a difference between two alternating versions of a real-world scene. Helpful primes named the object that changed, while misdirecting primes named another (unchanging) object in the picture. Robust effects were found for both explicit and implicit priming conditions, with helpful primes yielding faster change detection times than misdirecting or neutral primes. This demonstrates that observers are able to use higher order semantic information as a cue to guide attention within a natural scene, even when the semantic information is presented outside of explicit awareness.