Biology subjects

Wade, A. R.

Publications and source records attributed to Wade, A. R..

13 recordsLinked to original sources

bioRxiv2026

The development of coarse and fine feature tuning in infant visual cortex

Objects can be recognized from visual features at multiple spatial scales, from coarse global shape to fine local detail. How infant visual cortex encodes these features across the visual hierarchy, however, remains unknown. We combined awake infant fMRI with developmentally inspired deep neural networks (DNNs) trained and tested with different levels of image blur to probe cortical tuning to coarse and fine visual features. V1 showed mature tuning to coarse and fine features by 2 months. In contrast, infant extrastriate cortex (V2-V4) followed a protracted developmental trajectory and was biased toward coarse object features relative to adults. This relative bias persisted at 9 months and was not readily explained by developing acuity. The sustained coarse-feature bias contrasted with DNNs, in which low-spatial-frequency representations took longest to converge with visual cortex during training, revealing distinct developmental biases in object-feature tuning in biological and artificial visual systems.

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bioRxiv2024

Measuring the effects of age on contrast suppression

The apparent contrast of a suprathreshold central stimulus can be reduced by a surrounding stimulus - a phenomenon known as surround suppression. When stimuli are presented at the fovea, this effect reportedly increases in strength with age. The underlying mechanism proposed for this age dependence, a change in the balance of inhibition and excitation in cortex, makes this phenomenon potentially interesting as a biomarker of neurological dysfunction. Here, we attempt to repeat these measurements, but we use stimuli designed to control for untuned overlay masking, a different form of suppression thought to be of pre-cortical origin. We measured contrast matching thresholds in twenty younger (< 30) and seventeen older (>60) observers. Across all observers, we find weak suppression that has little or no orientation tuning and, importantly, no dependence on age. Our findings contradict those from earlier studies and suggest that effects relating to age may be dependent on the temporal parameters of this stimulus, and could arise from effects on other pre-cortical mechanisms.

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bioRxiv2024

Binocular combination in the autonomic nervous system

Pupil diameters are regulated by the autonomic nervous system, which combines light signals across the eyes independently of the visual cortex. Distinct classes of retinal photoreceptor are involved in this process, with cones and rods driving the initial constriction and intrinsically photosensitive retinal ganglion cells main-taining diameter over prolonged time periods. We investigated binocular combination by targeting different photoreceptor pathways using a novel binocular multiprimary system to modulate the input spectra via silent substitution. At the first harmonic of the modulation frequency, luminance and S-cone responses showed strong binocular facilitation, and weak interocular suppression. Melanopsin responses were invariant to the number of eyes stimulated. The L-M pathway involved binocular inhibition, whereby responses to binocular stimulation were weaker than for monocular stimulation. The second harmonic involved strong interocular suppression in all pathways, but with some evidence of binocular facilitation. Our results are consistent with a computational model of binocular signal combination (implemented in a Bayesian hierarchical framework), in which the weight of interocular suppression differs across pathways. We also find pathway differences in response phase, consistent with different lag times for phototransduction. These results provide evidence that binocular interactions in the pupillary pathway differ across photoreceptor-directed modulations and across harmonic components of the response.

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bioRxiv2023

PySilSub: An open-source Python toolbox for implementing the method of silent substitution in vision and nonvisual photoreception research

The normal human retina contains several classes of photosensitive cell--rods for low-light vision, three cone classes for daylight vision, and intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin for non-image-forming functions including pupil control, melatonin suppression and circadian photoentrainment. The spectral sensitivities of the photoreceptors overlap significantly, which means that most lights will stimulate all photoreceptors, to varying degrees. The method of silent substitution is a powerful tool for stimulating individual photoreceptor classes selectively and has found much use in research and clinical settings. The main hardware requirement for silent substitution is a spectrally calibrated light stimulation system with at least as many primaries as there are photoreceptors under consideration. Device settings that will produce lights to selectively stimulate the photoreceptor(s) of interest can be found using a variety of analytic and algorithmic approaches. Here we present PySilSub (https://github.com/PySilentSubstitution/pysilsub), a novel Python package for silent substitution featuring flexible object-oriented support for individual colorimetric observer models (including human and mouse observers), multi-primary stimulation devices, and solving silent substitution problems with linear algebra and constrained numerical optimisation. The toolbox is registered with the Python Package Index and includes example data sets from various multi-primary systems. We hope that PySilSub will facilitate the application of silent substitution in research and clinical settings.

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bioRxiv2023

The emergence of tuning to global shape properties of radial frequency patterns in the ventral visual pathway

Radial frequency patterns - created by sinusoidal modulations of a circles radius - are processed globally when radial frequency is low. These closed shapes therefore offer a useful way to interrogate the human visual system for global processing of curvature. Radial frequency patterns elicit greater responses than those to radial gratings in V4 and more anterior face selective regions of the ventral visual pathway. This is largely consistent with work on non-human primates showing curvature processing emerges in V4, but is evident also higher up the ventral visual stream. Rather than contrasting radial frequency patterns with other stimuli, we presented them at varied frequencies in a regimen that allowed tunings to radial frequency to be derived from 8 human participants (3 female). We found tuning to low radial frequency in lateral occipital areas and to some extent in V4. In a control experiment we added a high frequency ripple to the stimuli disrupting the local contour. Low frequency tuning to these stimuli remained in the ventral visual stream underscoring its role in global processing of shape curvature. We then used representational similarity analysis to show that in lateral occipital areas the neural representation was related to stimulus similarity, when it was computed with a model that captured how stimuli are perceived. We show therefore that global processing of shape curvature emerges in the ventral visual stream as early as V4, but is found more strongly in lateral occipital regions, which exhibit responses and representations that relate well to perception.

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bioRxiv2023

Temporal Dynamics of Normalization Reweighting

1For decades, neural suppression in early visual cortex has been thought to be fixed. But recent work has challenged this assumption by showing that suppression can be reweighted based on recent history; when pairs of stimuli are repeatedly presented together, suppression between them strengthens. Here we investigate the temporal dynamics of this process using a steady-state visual evoked potential (SSVEP) paradigm that provides a time-resolved, direct index of suppression between pairs of stimuli flickering at different frequencies (5 and 7Hz). Our initial analysis of an existing EEG dataset (N=100) indicated that suppression increases substantially during the first 2-5 seconds of stimulus presentation (with some variation across stimulation frequency). We then collected new EEG data (N=100) replicating this finding for both monocular and dichoptic mask arrangements in a preregistered study designed to measure reweighting. A third experiment (N=20) used source localized MEG, and found that these effects are apparent in primary visual cortex (V1), consistent with results from neurophysiological work. Because long-standing theories propose inhibition/excitation differences in autism, we also compared reweighting between individuals with high vs low autistic traits, and with and without an autism diagnosis, across our 3 data sets (total N=220). We find no compelling differences in reweighting that are associated with autism. Our results support the normalization reweighting model, and indicate that for prolonged stimulation, increases in suppression occur on the order of 2-5 seconds after stimulus onset.

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bioRxiv2023

Different rules for binocular combination of luminance flicker in cortical and subcortical pathways

1How does the human brain combine information across the eyes? It has been known for many years that cortical normalisation mechanisms implement ocularity invariance: equalising neural responses to spatial patterns presented either monocularly or binocularly. Here we used a novel combination of electrophysiology, psychophysics, pupillometry and computational modelling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is therefore not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalisation algorithm for different visual functions by adjusting the amount of interocular suppression.

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bioRxiv2022

The effect of combined dexmedetomidine and isoflurane anaesthesia on visually evoked responses in rats -- an electrophysiological study

The purpose of this study was to pilot an anaesthetic regime with the potential to be used for blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) of the visual system. We used electrophysiology to explore the effect of an anaesthesia regime, combining dexmedetomidine and isoflurane, on the visual system of female Sprague-Dawley rats. This paradigm is hypothesised to affect neural signalling less than other paradigms, and thus may be suitable for studies using BOLD fMRI. Electrodes were implanted bilaterally in the visual cortex (VC) and superior colliculus (SC) of 16 rats. Visual evoked potentials (VEPs) and steady-state VEPs (SSVEPs) were recorded during 1 Hz and 14 Hz light stimulation, respectively. As a control experiment an exploration of the wash-out of isoflurane was performed. The combined anaesthetic regime showed, that the visually evoked responses were almost completely abolished at the initiation of anaesthesia, but gradually recovered to baseline levels over time in the SC. In contrast, the evoked response in the VC only partially recovered, staying significantly below baseline condition. BOLD fMRI results from a previously published study supports this finding.

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bioRxiv2021

eQTLs are key players in the integration of genomic and transcriptomic data for phenotype prediction

Multi-omics represent a promising link between phenotypes and genome variation. Few studies yet address their integration to understand genetic architecture and improve predictability. Our study used 241 poplar genotypes, phenotyped in two common gardens, with their xylem and cambium RNA sequenced at one site, yielding large phenotypic, genomic and transcriptomic datasets. For each trait, prediction models were built with genotypic or transcriptomic data and compared to concatenation integrating both omics. The advantage of integration varied across traits and, to understand such differences, we made an eQTL analysis to characterize the interplay between the genome and the transcriptome and classify the predicting features into CIS or TRANS relationships. A strong and significant negative correlation was found between the change in predictability and the change in predictor importance for eQTLs (both TRANS and CIS effects) and CIS regulated transcripts, and mostly for traits showing beneficial integration and evaluated in the site of transcriptomic sampling. Consequently, beneficial integration happens when redundancy of predictors is decreased, leaving the stage to other less prominent but complementary predictors. An additional GO enrichment analysis appeared to corroborate such statistical output. To our knowledge, this is a novel finding delineating a promising way to explore data integration. One-sentence summarySuccessful multi-omics integration when predicting phenotypes makes redundant the predictors that are linked to ubiquitous connections between the omics, according to biological and statistical approaches

genetics↗

bioRxiv2021

Electrophysiological measures of visual suppression

In the early visual system, suppression occurs between neurons representing different stimulus properties. This includes features such as orientation (cross-orientation suppression), eye-of-origin (interocular suppression) and spatial location (surround suppression), which are thought to involve distinct anatomical pathways. We asked if these separate routes to suppression can be differentiated by their pattern of gain control on the contrast response function measured in human participants using steady-state electroencephalography. Changes in contrast gain shift the contrast response function laterally, whereas changes in response gain scale the function vertically. We used a Bayesian hierarchical model to summarise the evidence for each type of gain control. A computational meta-analysis of 16 previous studies found the most evidence for contrast gain effects with overlaid masks, but no clear evidence favouring either response gain or contrast gain for other mask types. We then conducted two new experiments, comparing suppression from four mask types (monocular and dichoptic overlay masks, and aligned and orthogonal surround masks) on responses to sine wave grating patches flickering at 5Hz. At the occipital pole, there was strong evidence for contrast gain effects in all four mask types at the first harmonic frequency (5Hz). Suppression generally became stronger at more lateral electrode sites, but there was little evidence of response gain effects. At the second harmonic frequency (10Hz) suppression was stronger overall, and involved both contrast and response gain effects. Although suppression from different mask types involves distinct anatomical pathways, gain control processes appear to serve a common purpose, which we suggest might be to suppress less reliable inputs.

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bioRxiv2019

Feature-specific patterns of attention and functional connectivity in human visual cortex

Attending to different features of a scene can alter the responses of neurons in early- and mid- level visual areas but the nature of this change depends on both the (top down) attentional task and the (bottom up) visual stimulus. One outstanding question is the spatial scale at which cortex is modulated by attention to low-level stimulus features such as shape, contrast and orientation. It is unclear whether the recruitment of neurons to particular tasks occurs at an area level or at the level of intra-areal sub-populations, or whether the critical factor is a change in the way that areas communicate with each other. Here we use functional magnetic resonance imaging (fMRI) and psychophysics, to ask how areas known to be involved in processing different visual features (orientation, contrast and shape) are modulated as participants switch between tasks based on those features while the visual stimulus itself is effectively constant. At a univariate level, we find almost no feature-specific bottom-up or top-down responses in the areas we examine. However, multivariate analyses reveal a complex pattern of voxel-level modulation driven by attentional task. Connectivity analyses also demonstrate flexible and selective patterns of connectivity between early visual areas as a function of attentional focus. Overall, we find that attention alters the sensitivity and connectivity of neuronal subpopulations within individual early visual areas but, surprisingly, not the univariate response amplitudes of the areas themselves.

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bioRxiv2019

Decoding the neuronal correlates of motion-in-depth from EEG

Two stereoscopic cues that underlie the perception of motion-in-depth (MID) are changes in retinal disparity over time (CD) and interocular velocity differences (IOVD). These cues have independent spatiotemporal sensitivity profiles, depend upon different low-level stimulus properties, and are potentially processed along separate cortical pathways. Here, we ask whether these MID cues code for different motion directions: do they give rise to discriminable patterns of neural signals, and is there evidence for their convergence onto a single motion-in-depth pathway? To answer this, we use a decoding algorithm to test whether, and when, patterns of electroencephalogram (EEG) signals measured from across the full scalp, generated in response to CD- and IOVD-isolating stimuli moving towards or away in depth can be distinguished. We find that both MID cue type and 3D-motion direction can be decoded at different points in the EEG timecourse and that direction decoding cannot be accounted for by static disparity information. Remarkably, we find evidence for late processing convergence: IOVD motion direction can be decoded relatively late in the timecourse based on a decoder trained on CD stimuli, and vice versa. We conclude that early CD and IOVD direction decoding performance is dependent upon fundamentally different low-level stimulus features, but that later stages of decoding performance may be driven by a central, shared pathway that is agnostic to these features. Overall, these data are the first to show that neural responses to CD and IOVD cues that move towards and away in depth can be decoded from EEG signals, and that different aspects of MID-cues contribute to decoding performance at different points along the EEG timecourse.

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bioRxiv2018

Autism sensory dysfunction in an evolutionarily conserved system

There is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here we instead assay another functional domain - sensory processing - known to be affected in autism to test a novel genetic autism model in Drosophila melanogaster. We show similar visual response alterations and a similar development trajectory in Nhe3 mutant flies (total N=72) and in autistic human participants (total N=154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.

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