Visual processing in genetic conditions linked to autism: A behavioral study of binocular rivalry in individuals with 16p11.2 deletions and age-matched controls.

Close phenotypic characterization of individuals with genetic conditions linked to autism provides a promising approach to navigating the heterogeneity of autism spectrum conditions. The current study investigated sensory processing in individuals with a rare genetic event that is highly penetrant for autism, 16p11.2 deletions, using a well-characterized visual paradigm, binocular rivalry, which is thought to be a non-invasive index of excitatory/inhibitory balance in the visual cortex. We characterized rivalry dynamics in 45 adolescent and adult individuals (19 individuals with 16p11.2 deletions, 26 age-matched neurotypical controls). We found that binocular rivalry perceptual transition rates were significantly slower for individuals with 16p11.2 deletions, relative to controls. Importantly, these results could not be accounted for by differences in motor response latencies or perceptual decision criteria, which were matched between groups. Results should be interpreted with caution given the unmatched psychometric features between groups, such as IQ. Future studies should study visual processing in other genetic groups linked to autism beyond 16p to understand the specificity of these findings. These results highlight the importance of characterizing sensory functions in individuals with genetic alterations associated with autism.

Brief Report: Differences in Naturalistic Attention to Real-World Scenes in Adolescents with 16p.11.2 Deletion.

Sensory differences are nearly universal in autism, but their genetic origins are poorly understood. Here, we tested how individuals with an autism-linked genotype, 16p.11.2 deletion ("16p"), attend to visual information in immersive, real-world photospheres. We monitored participants' (N = 44) gaze while they actively explored 360° scenes via headmounted virtual reality. We modeled the visually salient and semantically meaningful information in scenes and quantified the relative bottom-up vs. top-down influences on attentional deployment. We found, when compared to typically developed control (TD) participants, 16p participants' attention was less dominantly predicted by semantically meaningful scene regions, relative to visually salient regions. These results suggest that a reduction in top-down relative to bottom-up attention characterizes how individuals with 16p.11.2 deletions engage with naturalistic visual environments.

Reduced social attention in autism is magnified by perceptual load in naturalistic environments.

Individuals with autism spectrum conditions (ASC) describe differences in both social cognition and sensory processing, but little is known about the causal relationship between these disparate functional domains. In the present study, we sought to understand how a core characteristic of autism-reduced social attention-is impacted by the complex multisensory signals present in real-world environments. We tested the hypothesis that reductions in social attention associated with autism would be magnified by increasing perceptual load (e.g., motion, multisensory cues). Adult participants (N = 40; 19 ASC) explored a diverse set of 360° real-world scenes in a naturalistic, active viewing paradigm (immersive virtual reality + eyetracking). Across three conditions, we systematically varied perceptual load while holding the social and semantic information present in each scene constant. We demonstrate that reduced social attention is not a static signature of the autistic phenotype. Rather, group differences in social attention emerged with increasing perceptual load in naturalistic environments, and the susceptibility of social attention to perceptual load predicted continuous measures of autistic traits across groups. Crucially, this pattern was specific to the social domain: we did not observe differential impacts of perceptual load on attention directed toward nonsocial semantic (i.e., object, place) information or low-level fixation behavior (i.e., overall fixation frequency or duration). This study provides a direct link between social and sensory processing in autism. Moreover, reduced social attention may be an inaccurate characterization of autism. Instead, our results suggest that social attention in autism is better explained by "social vulnerability," particularly to the perceptual load of real-world environments.

Neuroscout, a unified platform for generalizable and reproducible fMRI research.

Functional magnetic resonance imaging (fMRI) has revolutionized cognitive neuroscience, but methodological barriers limit the generalizability of findings from the lab to the real world. Here, we present Neuroscout, an end-to-end platform for analysis of naturalistic fMRI data designed to facilitate the adoption of robust and generalizable research practices. Neuroscout leverages state-of-the-art machine learning models to automatically annotate stimuli from dozens of fMRI studies using naturalistic stimuli-such as movies and narratives-allowing researchers to easily test neuroscientific hypotheses across multiple ecologically-valid datasets. In addition, Neuroscout builds on a robust ecosystem of open tools and standards to provide an easy-to-use analysis builder and a fully automated execution engine that reduce the burden of reproducible research. Through a series of meta-analytic case studies, we validate the automatic feature extraction approach and demonstrate its potential to support more robust fMRI research. Owing to its ease of use and a high degree of automation, Neuroscout makes it possible to overcome modeling challenges commonly arising in naturalistic analysis and to easily scale analyses within and across datasets, democratizing generalizable fMRI research.

Active vision in immersive, 360° real-world environments.

How do we construct a sense of place in a real-world environment? Real-world environments are actively explored via saccades, head turns, and body movements. Yet, little is known about how humans process real-world scene information during active viewing conditions. Here, we exploited recent developments in virtual reality (VR) and in-headset eye-tracking to test the impact of active vs. passive viewing conditions on gaze behavior while participants explored novel, real-world, 360° scenes. In one condition, participants actively explored 360° photospheres from a first-person perspective via self-directed motion (saccades and head turns). In another condition, photospheres were passively displayed to participants while they were head-restricted. We found that, relative to passive viewers, active viewers displayed increased attention to semantically meaningful scene regions, suggesting more exploratory, information-seeking gaze behavior. We also observed signatures of exploratory behavior in eye movements, such as quicker, more entropic fixations during active as compared with passive viewing conditions. These results show that active viewing influences every aspect of gaze behavior, from the way we move our eyes to what we choose to attend to. Moreover, these results offer key benchmark measurements of gaze behavior in 360°, naturalistic environments.

Slower Binocular Rivalry in the Autistic Brain.

Autism has traditionally been regarded as a disorder of the social brain. Recent reports of differences in visual perception have challenged this notion, but little evidence for altered visual processing in the autistic brain exists. We have previously observed slower behaviorally reported rates of a basic visual phenomenon, binocular rivalry, in autism [1, 2]. During rivalry, two images-one presented to each eye-vie for awareness, alternating back and forth in perception. This competition is modeled to rely, in part, on the balance of excitation and inhibition in visual cortex [3-8], which may be altered in autism [2, 9-14]. Yet direct neural evidence for this potential marker of excitation/inhibition (E/I) balance in autism is lacking. Here, we report a striking alteration in the neural dynamics of binocular rivalry in individuals with autism. Participants viewed true and simulated frequency-tagged binocular rivalry displays while steady-state visually evoked potentials (SSVEPs) were measured over occipital cortex using electroencephalography (EEG). First, we replicate our prior behavioral findings of slower rivalry and reduced perceptual suppression in individuals with autism compared with controls. Second, we provide direct neural evidence for slower rivalry in autism compared with controls, which strongly predicted individuals' behavioral switch rates. Finally, using neural data alone, we were able to predict autism symptom severity (ADOS) and correctly classify individuals' diagnostic status (autistic versus control; 87% accuracy). These findings clearly implicate atypical visual processing in the neurobiology of autism. Down the road, this paradigm may serve as a non-verbal marker of autism for developmental and cross-species research.

GABAergic Inhibition Gates Perceptual Awareness During Binocular Rivalry.

Binocular rivalry is a classic experimental tool to probe the neural machinery of perceptual awareness. During rivalry, perception alternates between the two eyes, and the ebb and flow of perception is modeled to rely on the strength of inhibitory interactions between competitive neuronal populations in visual cortex. As a result, rivalry has been suggested as a noninvasive perceptual marker of inhibitory signaling in visual cortex, and its putative disturbance in psychiatric conditions, including autism. Yet, direct evidence causally implicating inhibitory signaling in the dynamics of binocular rivalry is currently lacking. We previously found that people with higher GABA levels in visual cortex, measured using magnetic resonance spectroscopy, have stronger perceptual suppression during rivalry. Here, we present direct causal tests of the impact of GABAergic inhibition on rivalry dynamics, and the contribution of specific GABA receptors to these dynamics. In a crossover pharmacological design with male and female adult participants, we found that drugs that modulate the two dominant GABA receptor types in the brain, GABAA (clobazam) and GABAB (arbaclofen), increase perceptual suppression during rivalry relative to a placebo. Crucially, these results could not be explained by changes in reaction times or response criteria, as determined through rivalry simulation trials, suggesting a direct and specific influence of GABA on perceptual suppression. A full replication study of the GABAB modulator reinforces these findings. These results provide causal evidence for a link between the strength of inhibition in the brain and perceptual suppression during rivalry and have implications for psychiatric conditions including autism.SIGNIFICANCE STATEMENT How does the brain accomplish perceptual gating? Here we use a direct and causal pharmacological manipulation to present insight into the neural machinery of a classic illusion of perceptual awareness: binocular rivalry. We show that drugs that increase GABAergic inhibition in the brain, clobazam (GABAA modulator) and arbaclofen (GABAB modulator), increase perceptual suppression during rivalry relative to a placebo. These results present the first causal link between GABAergic inhibition and binocular rivalry in humans, complementing classic models of binocular rivalry, and have implications for our understanding of psychiatric conditions, such as autism, where binocular rivalry is posited as a behavioral marker of disruptions in inhibitory signaling in the brain.