Sensory perception in autism Robertson, Caroline E; Baron-Cohen, Simon
Nature reviews. Neuroscience,
11/2017, Letnik:
18, Številka:
11
Journal Article
Recenzirano
Autism is a complex neurodevelopmental condition, and little is known about its neurobiology. Much of autism research has focused on the social, communication and cognitive difficulties associated ...with the condition. However, the recent revision of the diagnostic criteria for autism has brought another key domain of autistic experience into focus: sensory processing. Here, we review the properties of sensory processing in autism and discuss recent computational and neurobiological insights arising from attention to these behaviours. We argue that sensory traits have important implications for the development of animal and computational models of the condition. Finally, we consider how difficulties in sensory processing may relate to the other domains of behaviour that characterize autism.
An imbalance between excitatory/inhibitory neurotransmission has been posited as a central characteristic of the neurobiology of autism 1, inspired in part by the striking prevalence of seizures ...among individuals with the disorder 2. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies 3–7, fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals 8, 9, and GABAergic signaling is disrupted across heterogeneous mouse models of autism 10. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry 11, a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex 12–15. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition.
•Behavioral marker of inhibitory/excitatory neurotransmission is perturbed in autism•Marker predicts higher-order autistic symptom severity•Inhibitory and excitatory neurotransmitters measured in the brain predict behavior•Action of the inhibitory neurotransmitter, GABA, is reduced the autistic brain
An imbalance in inhibitory/excitatory neurotransmission is proposed to affect the autistic brain, but empirical evidence in humans is lacking. Robertson et al. report a link between a robust autistic perceptual symptom and reduced action of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in the brains of autistic individuals.
Color ignites visual experience, imbuing the world with meaning, emotion, and richness. As soon as an observer opens their eyes, they have the immediate impression of a rich, colorful experience that ...encompasses their entire visual world. Here, we show that this impression is surprisingly inaccurate. We used head-mounted virtual reality (VR) to place observers in immersive, dynamic real-world environments, which they naturally explored via saccades and head turns. Meanwhile, we monitored their gaze with in-headset eye tracking and then systematically altered the visual environments such that only the parts of the scene they were looking at were presented in color and the rest of the scene (i.e., the visual periphery) was entirely desaturated. We found that observers were often completely unaware of these drastic alterations to their visual world. In the most extreme case, almost a third of observers failed to notice when less than 5% of the visual display was presented in color. This limitation on perceptual awareness could not be explained by retinal neuroanatomy or previous studies of peripheral visual processing using more traditional psychophysical approaches. In a second study, we measured color detection thresholds using a staircase procedure while a set of observers intentionally attended to the periphery. Still, we found that observers were unaware when a large portion of their field of view was desaturated. Together, these results show that during active, naturalistic viewing conditions, our intuitive sense of a rich, colorful visual world is largely incorrect.
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.
•Binocular rivalry is slower in the autistic brain•Potential marker of E/I balance in visual cortex•Predicts clinical symptoms and classifies diagnostic status (autism versus controls)•Non-verbal measure, which may be suitable for infant and cross-species research
Robertson et al. report that a basic visual phenomenon, binocular rivalry, is altered in the autistic brain. This result firmly implicates the visual cortex in the neurobiology of autism and may reflect an imbalance in E/I neurotransmission. As a non-verbal paradigm, this marker of autism may be suitable for future infant and cross-species studies.
The neural systems supporting scene-perception and spatial-memory systems of the human brain are well-described. But how do these neural systems interact? Here, using fine-grained individual-subject ...fMRI, we report three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with spatial memory systems during naturalistic scene understanding. These "place-memory areas" offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation.
Models of healthy brain function and psychiatric conditions assume that excitatory and inhibitory activity are balanced in the human brain at multiple spatial and temporal scales. In human ...neuroimaging, concentrations of the major excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters are measured in vivo using magnetic resonance spectroscopy (MRS). However, despite the central importance of E/I balance to theories of brain function, a relationship between regional glutamate and GABA levels in the human brain has not been shown. We addressed this question in a large corpus of edited MRS data collected at 19 different sites (n = 220). Consistent with the notion of E/I balance, we found that levels of glutamate+glutamine (Glx) and GABA+ were highly correlated (R = 0.52, p = 2.86 x 10−14). This relationship held when controlling for site, scanner vendor, and demographics. Controlling for neurochemicals associated with neuronal density and metabolism (i.e. N-acetylaspartate and creatine) significantly reduced the correlation between GABA+ and Glx, suggesting that the levels of GABA+ and Glx may be critically linked to regional metabolism. These results are consistent with the notion that excitation and inhibition are balanced in the human brain.
•Concentrations of glutamate + glutamine and GABA + are correlated in a large cohort (N = 220).•Acquisition site, demographics, and data quality do not explain the relationship.•Controlling for the concentration of NAA and Cr diminished the correlation.•Suggests that regional metabolism may mediate this relationship.
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.
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, GABA
(clobazam) and GABA
(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 GABA
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.
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 (GABA
modulator) and arbaclofen (GABA
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.
The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders ...such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.
Slower rate of binocular rivalry in autism Robertson, Caroline E; Kravitz, Dwight J; Freyberg, Jan ...
The Journal of neuroscience,
10/2013, Letnik:
33, Številka:
43
Journal Article
Recenzirano
Odprti dostop
An imbalance between cortical excitation and inhibition is a central component of many models of autistic neurobiology. We tested a potential behavioral footprint of this proposed imbalance using ...binocular rivalry, a visual phenomenon in which perceptual experience is thought to mirror the push and pull of excitatory and inhibitory cortical dynamics. In binocular rivalry, two monocularly presented images compete, leading to a percept that alternates between them. In a series of trials, we presented separate images of objects (e.g., a baseball and a broccoli) to each eye using a mirror stereoscope and asked human participants with autism and matched control subjects to continuously report which object they perceived, or whether they perceived a mixed percept. Individuals with autism demonstrated a slower rate of binocular rivalry alternations than matched control subjects, with longer durations of mixed percepts and an increased likelihood to revert to the previously perceived object when exiting a mixed percept. Critically, each of these findings was highly predictive of clinical measures of autistic symptomatology. Control "playback" experiments demonstrated that differences in neither response latencies nor response criteria could account for the atypical dynamics of binocular rivalry we observed in autistic spectrum conditions. Overall, these results may provide an index of atypical cortical dynamics that may underlie both the social and nonsocial symptoms of autism.
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