Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 duplication Syndrome of Autism

Abstract

Extracting common patterns of neural circuit computations in autism spectrum and pinning them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in human subjects with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To be able to study these processes with single-cell precision and exhaustive neuronal population coverage, we developed the visual bi-stable perception task for mice. Our task is based on plaid patterns consisting of two transparent gratings drifting at an angle of 120 degrees relative to each other. This results in spontaneous reversals of the perception between local component motion (motion of the plaid perceived as two separate moving grating components) and integrated global pattern motion (motion of the plaid perceived as a fused moving texture). This robust paradigm does not depend on the explicit report of the mouse, as the direction of the optokinetic nystagmus (OKN, rapid eye movements driven by either pattern or component motion) is used to infer the dominant percept. Using this paradigm, we found that the rate of perceptual reversals between global and local motion interpretations of the stimulus is reduced in MECP2 duplication mouse model of autism. Moreover, the stability of local motion percepts is greatly increased in MECP2 duplication mice at the expense of global motion percepts. Thus, our model reproduces a subclass of core features in human autism (reduced rate of visual rivalry and atypical perception of visual motion). This further offers a well-controlled approach for dissecting neuronal circuits underlying these core features if combined with mesoscale 2-photon imaging and optogenetic manipulation of neuronal circuits.

A Burst-dependent Thalamocortical Substrate for Visual Rivalry

“…Our neurobiological approach to modelling allowed us to: i) explore whether the cellular-level mechanism of visual awareness discovered in a rodent model could recover the lawlike psychophysical relationships (known as Levelt’s laws) between stimulus properties and the perceptual phenomenology known to characterise visual rivalry (Brascamp et al, 2015); ii) validate the basic mechanism of perceptual competition and suppression in our model by comparing outputs of the model to genetic perturbations of E/I balance in a rodent model of visual rivalry. In agreement with empirical findings (Bogatova et al, 2022), a shift towards a high excitation regime led to a slowing of perceptual reversals. Crucially, this prediction is in contradiction to many large-scale (i.e.…”

“…Having confirmed that our model conforms to key psychophysical constraints, we next sought to test the model's mechanism of perceptual competition and suppression by comparing simulated E/I balance perturbations to genetic perturbations of E/I balance in a rodent model of visual rivalry (Bogatova et al, 2022). Specifically, Bogatova et al (2022) found that compared to non-transgenic litter mates, mice with a MECP2-duplication, which has been shown to reduce inhibitory IPSP currents (Chao et al, 2010), have a reduced perceptual reversal rate (Fig 2A).…”

“…Having confirmed that our model conforms to key psychophysical constraints, we next sought to test the model's mechanism of perceptual competition and suppression by comparing simulated E/I balance perturbations to genetic perturbations of E/I balance in a rodent model of visual rivalry (Bogatova et al, 2022). Specifically, Bogatova et al (2022) found that compared to non-transgenic litter mates, mice with a MECP2-duplication, which has been shown to reduce inhibitory IPSP currents (Chao et al, 2010), have a reduced perceptual reversal rate (Fig 2A). Crucially, this result is in direct contradiction to the predictions of a number of prominent mean field models of rivalry which all predict the exact opposite effect (e.g., Curtu et al, 2008;Laing & Chow, 2002;Wilson, 2007) -namely, that decreasing inhibition should increase perceptual reversal rate through an increase in capacity of the suppressed population to escape from inhibition.…”

“… A ) Comparison of empirical data acquired from figure 1 of Bogatova et al, (2022) showing reversal frequency between mice with and without a MECP2 -duplication (which predominantly effects GABAergic signalling; Chao et al, 2010) with model output for I → E = 4.25 and I → E = 5. B) Effect of EI balance on perceptual reversal frequency across external drive frequencies.…”

“…In addition, visual rivalry has been studied extensively in both empirical (Alais & Blake, 2005;Blake & Tong, 2008;Carmel et al, 2010;Tong et al, 2006) and computational (Grossberg et al, 2008;Laing et al, 2010;Laing & Chow, 2002;Safavi & Dayan, 2022;Shpiro et al, 2007Shpiro et al, , 2009Wilson, 2003Wilson, , 2007Wilson, , 2017 settings, thereby imposing a wealth of constraints on the modelling process. Importantly, due to the highly robust nature of visual rivalry and recent advances in experimental paradigms, the subjective contents of perception can be reliably inferred from involuntary eye-movements without the need for subjective reports (Frassle et al, 2014;Kapoor et al, 2022;Naber et al, 2011) making it possible to study aspects of visual rivalry in mice (Bogatova et al, 2022;Palagina et al, 2017) as well as in human and non-human primates. This allows us to propose testable predictions about the neurobiological basis of perceptual awareness at both microscopic, mesoscopic, and behavioural scales.…”