Three-dimensional topography of eye-specific domains in the lateral geniculate nucleus of pigmented and albino rats.

We previously revealed the presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of pigmented rats. On the other hand, previous studies have shown that the ipsilateral-eye domains of the dorsal lateral geniculate nucleus (dLGN) are segregated into a handful of patches in pigmented rats. To investigate the three-dimensional (3D) topography of the eye-specific patches of the dLGN and its relationship with ODCs, we injected different tracers into the right and left eyes and examined strain difference, development, and plasticity of the patches. Furthermore, we applied the tissue clearing technique to reveal the 3D morphology of the LGN and were able to observe entire retinotopic map of the rat dLGN at a certain angle. Our results show that the ipsilateral domains of the dLGN appear mesh-like at any angle and are developed at around time of eye-opening. Their development was moderately affected by abnormal visual experience, but the patch formation was not disrupted. In albino Wistar rats, ipsilateral patches were observed in the dLGN, but they were much fewer, especially near the central visual field. These results provide insights into how ipsilateral patches of the dLGN arise, and how the geniculo-cortical arrangement is different between rodents and primates.

Linking individual differences in human primary visual cortex to contrast sensitivity around the visual field.

A central question in neuroscience is how the organization of cortical maps relates to perception, for which human primary visual cortex (V1) is an ideal model system. V1 nonuniformly samples the retinal image, with greater cortical magnification (surface area per degree of visual field) at the fovea than periphery and at the horizontal than vertical meridian. Moreover, the size and cortical magnification of V1 varies greatly across individuals. Here, we used fMRI and psychophysics in the same observers to quantify individual differences in V1 cortical magnification and contrast sensitivity at the four polar angle meridians. Across observers, the overall size of V1 and localized cortical magnification positively correlated with contrast sensitivity. Moreover, greater cortical magnification and higher contrast sensitivity at the horizontal than the vertical meridian were strongly correlated. These data reveal a link between cortical anatomy and visual perception at the level of individual observer and stimulus location.

Predictive masking of an artificial scotoma is associated with a system-wide reconfiguration of neural populations in the human visual cortex.

The visual brain has the remarkable capacity to complete our percept of the world even when the information extracted from the visual scene is incomplete. This ability to predict missing information based on information from spatially adjacent regions is an intriguing attribute of healthy vision. Yet, it gains particular significance when it masks the perceptual consequences of a retinal lesion, leaving patients unaware of their partial loss of vision and ultimately delaying diagnosis and treatment. At present, our understanding of the neural basis of this masking process is limited which hinders both quantitative modeling as well as translational application. To overcome this, we asked the participants to view visual stimuli with and without superimposed artificial scotoma (AS). We used fMRI to record the associated cortical activity and applied model-based analyzes to track changes in cortical population receptive fields and connectivity in response to the introduction of the AS. We found that throughout the visual field and cortical hierarchy, pRFs shifted their preferred position towards the AS border. Moreover, extrastriate areas biased their sampling of V1 towards sections outside the AS projection zone, thereby effectively masking the AS with signals from spared portions of the visual field. We speculate that the signals that drive these system-wide population modifications originate in extrastriate visual areas and, through feedback, also reconfigure the neural populations in the earlier visual areas.

Development of the visual white matter pathways mediates development of electrophysiological responses in visual cortex.

The latency of neural responses in the visual cortex changes systematically across the lifespan. Here, we test the hypothesis that development of visual white matter pathways mediates maturational changes in the latency of visual signals. Thirty-eight children participated in a cross-sectional study including diffusion magnetic resonance imaging (MRI) and magnetoencephalography (MEG) sessions. During the MEG acquisition, participants performed a lexical decision and a fixation task on words presented at varying levels of contrast and noise. For all stimuli and tasks, early evoked fields were observed around 100 ms after stimulus onset (M100), with slower and lower amplitude responses for low as compared to high contrast stimuli. The optic radiations and optic tracts were identified in each individual's brain based on diffusion MRI tractography. The diffusion properties of the optic radiations predicted M100 responses, especially for high contrast stimuli. Higher optic radiation fractional anisotropy (FA) values were associated with faster and larger M100 responses. Over this developmental window, the M100 responses to high contrast stimuli became faster with age and the optic radiation FA mediated this effect. These findings suggest that the maturation of the optic radiations over childhood accounts for individual variations observed in the developmental trajectory of visual cortex responses.

A strategy for mapping biophysical to abstract neuronal network models applied to primary visual cortex.

A fundamental challenge for the theoretical study of neuronal networks is to make the link between complex biophysical models based directly on experimental data, to progressively simpler mathematical models that allow the derivation of general operating principles. We present a strategy that successively maps a relatively detailed biophysical population model, comprising conductance-based Hodgkin-Huxley type neuron models with connectivity rules derived from anatomical data, to various representations with fewer parameters, finishing with a firing rate network model that permits analysis. We apply this methodology to primary visual cortex of higher mammals, focusing on the functional property of stimulus orientation selectivity of receptive fields of individual neurons. The mapping produces compact expressions for the parameters of the abstract model that clearly identify the impact of specific electrophysiological and anatomical parameters on the analytical results, in particular as manifested by specific functional signatures of visual cortex, including input-output sharpening, conductance invariance, virtual rotation and the tilt after effect. Importantly, qualitative differences between model behaviours point out consequences of various simplifications. The strategy may be applied to other neuronal systems with appropriate modifications.

Unveiling functions of the visual cortex using task-specific deep neural networks.

The human visual cortex enables visual perception through a cascade of hierarchical computations in cortical regions with distinct functionalities. Here, we introduce an AI-driven approach to discover the functional mapping of the visual cortex. We related human brain responses to scene images measured with functional MRI (fMRI) systematically to a diverse set of deep neural networks (DNNs) optimized to perform different scene perception tasks. We found a structured mapping between DNN tasks and brain regions along the ventral and dorsal visual streams. Low-level visual tasks mapped onto early brain regions, 3-dimensional scene perception tasks mapped onto the dorsal stream, and semantic tasks mapped onto the ventral stream. This mapping was of high fidelity, with more than 60% of the explainable variance in nine key regions being explained. Together, our results provide a novel functional mapping of the human visual cortex and demonstrate the power of the computational approach.

Sensory coding and the causal impact of mouse cortex in a visual decision.

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by steering a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs,proportionally to each site's encoding of the visual stimulus, and at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, sensory signals localized in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.

Heritable functional architecture in human visual cortex.

How much of the functional organization of our visual system is inherited? Here we tested the heritability of retinotopic maps in human visual cortex using functional magnetic resonance imaging. We demonstrate that retinotopic organization shows a closer correspondence in monozygotic (MZ) compared to dizygotic (DZ) twin pairs, suggesting a partial genetic determination. Using population receptive field (pRF) analysis to examine the preferred spatial location and selectivity of these neuronal populations, we estimate a heritability around 10-20% for polar angle preferences and spatial selectivity, as quantified by pRF size, in extrastriate areas V2 and V3. Our findings are consistent with heritability in both the macroscopic arrangement of visual regions and stimulus tuning properties of visual cortex. This could constitute a neural substrate for variations in a range of perceptual effects, which themselves have been found to be at least partially genetically determined. These findings also add convergent evidence for the hypothesis that functional map topology is linked with cortical morphology.

Emergence of local and global synaptic organization on cortical dendrites.

Synaptic inputs on cortical dendrites are organized with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where nearby synapses are significantly correlated, and globally with distance to the soma. We propose a biophysically motivated synaptic plasticity model to dissect the mechanistic origins of this organization during development and elucidate synaptic clustering of different stimulus features in the adult. Our model captures local clustering of orientation in ferret and receptive field overlap in mouse visual cortex based on the receptive field diameter and the cortical magnification of visual space. Including action potential back-propagation explains branch clustering heterogeneity in the ferret and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, by combining activity-dependent synaptic competition and species-specific receptive fields, our framework explains different aspects of synaptic organization regarding stimulus features and spatial scales.

The structural and functional connectivity neural underpinnings of body image.

How we perceive our bodies is fundamental to our self-consciousness and our experience in the world. There are two types of interrelated internal body representations-a subjective experience of the position of a limb in space (body schema) and the subjective experience of the shape and size of the limb (body image). Body schema has been extensively studied, but there is no evidence of the brain structure and network dynamics underpinning body image. Here, we provide the first evidence for the extrastriate body area (EBA), a multisensory brain area, as the structural and functional neural substrate for body shape and size. We performed a multisensory finger-stretch illusion that elongated the index finger. EBA volume and functional connectivity to the posterior parietal cortex are both related to the participants' susceptibility to the illusion. Taken together, these data suggest that EBA structure and connectivity encode body representation and body perception disturbances.

Unraveling the mechanisms of surround suppression in early visual processing.

This paper uses mathematical modeling to study the mechanisms of surround suppression in the primate visual cortex. We present a large-scale neural circuit model consisting of three interconnected components: LGN and two input layers (Layer 4Ca and Layer 6) of the primary visual cortex V1, covering several hundred hypercolumns. Anatomical structures are incorporated and physiological parameters from realistic modeling work are used. The remaining parameters are chosen to produce model outputs that emulate experimentally observed size-tuning curves. Our two main results are: (i) we discovered the character of the long-range connections in Layer 6 responsible for surround effects in the input layers; and (ii) we showed that a net-inhibitory feedback, i.e., feedback that excites I-cells more than E-cells, from Layer 6 to Layer 4 is conducive to producing surround properties consistent with experimental data. These results are obtained through parameter selection and model analysis. The effects of nonlinear recurrent excitation and inhibition are also discussed. A feature that distinguishes our model from previous modeling work on surround suppression is that we have tried to reproduce realistic lengthscales that are crucial for quantitative comparison with data. Due to its size and the large number of unknown parameters, the model is computationally challenging. We demonstrate a strategy that involves first locating baseline values for relevant parameters using a linear model, followed by the introduction of nonlinearities where needed. We find such a methodology effective, and propose it as a possibility in the modeling of complex biological systems.

Multiple Visuotopically Organized Subdivisions of the Lateral Pulvinar/Central Lateral Inferior Pulvinar Project into Thin and Thick Stripe Compartments of V2 in Macaques.

The lateral and central lateral inferior pulvinar (PL/PIcl) of primates has been implicated in playing an important role in visual processing, but its physiological and anatomical characteristics remain to be elucidated. It has been suggested that there are two complete visuotopic maps in the PL/PIcl, each of which sends afferents into V2 and V4 in primates. Given that functionally distinct thin and thick stripes of V2 both receive inputs from the PL/PIcl, this raises the possibility of a presence of parallel segregated pathways within the PL/PIcl. To address this question, we selectively injected three types of retrograde tracers (CTB-488, CTB-555, and BDA) into thin or thick stripes in V2 and examined labeling in the PL/PIcl in macaques. As a result, we found that every cluster of retrograde labeling in the PL/PIcl included all three types of signals next to each other, suggesting that thin stripe- and thick stripe-projecting compartments are not segregated into domains. Unexpectedly, we found at least five topographically organized retrograde labeling clusters in the PL/PIcl, indicating the presence of more than two V2-projecting maps. Our results suggest that the PL/PIcl exhibits greater compartmentalization than previously thought. They may be functionally similar but participate in multiple cortico-pulvinar-cortical loops.

Primate extrastriate cortical area MST: a gateway between sensation and cognition.

Primate visual cortex consists of dozens of distinct brain areas, each providing a highly specialized component to the sophisticated task of encoding the incoming sensory information and creating a representation of our visual environment that underlies our perception and action. One such area is the medial superior temporal cortex (MST), a motion-sensitive, direction-selective part of the primate visual cortex. It receives most of its input from the middle temporal (MT) area, but MST cells have larger receptive fields and respond to more complex motion patterns. The finding that MST cells are tuned for optic flow patterns has led to the suggestion that the area plays an important role in the perception of self-motion. This hypothesis has received further support from studies showing that some MST cells also respond selectively to vestibular cues. Furthermore, the area is part of a network that controls the planning and execution of smooth pursuit eye movements and its activity is modulated by cognitive factors, such as attention and working memory. This review of more than 90 studies focuses on providing clarity of the heterogeneous findings on MST in the macaque cortex and its putative homolog in the human cortex. From this analysis of the unique anatomical and functional position in the hierarchy of areas and processing steps in primate visual cortex, MST emerges as a gateway between perception, cognition, and action planning. Given this pivotal role, this area represents an ideal model system for the transition from sensation to cognition.

Unsupervised neural network models of the ventral visual stream.

Deep neural networks currently provide the best quantitative models of the response patterns of neurons throughout the primate ventral visual stream. However, such networks have remained implausible as a model of the development of the ventral stream, in part because they are trained with supervised methods requiring many more labels than are accessible to infants during development. Here, we report that recent rapid progress in unsupervised learning has largely closed this gap. We find that neural network models learned with deep unsupervised contrastive embedding methods achieve neural prediction accuracy in multiple ventral visual cortical areas that equals or exceeds that of models derived using today's best supervised methods and that the mapping of these neural network models' hidden layers is neuroanatomically consistent across the ventral stream. Strikingly, we find that these methods produce brain-like representations even when trained solely with real human child developmental data collected from head-mounted cameras, despite the fact that these datasets are noisy and limited. We also find that semisupervised deep contrastive embeddings can leverage small numbers of labeled examples to produce representations with substantially improved error-pattern consistency to human behavior. Taken together, these results illustrate a use of unsupervised learning to provide a quantitative model of a multiarea cortical brain system and present a strong candidate for a biologically plausible computational theory of primate sensory learning.

Survey of spiking in the mouse visual system reveals functional hierarchy.

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory2-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli. Using cross-correlation analysis, we reveal that the organization of inter-area functional connectivity during visual stimulation mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas3. We find that four classical hierarchical measures-response latency, receptive-field size, phase-locking to drifting gratings and response decay timescale-are all correlated with the hierarchy. Moreover, recordings obtained during a visual task reveal that the correlation between neural activity and behavioural choice also increases along the hierarchy. Our study provides a foundation for understanding coding and signal propagation across hierarchically organized cortical and thalamic visual areas.

A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.

The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.

The claustrum of the sheep and its connections to the visual cortex.

The present study analyses the organization and selected neurochemical features of the claustrum and visual cortex of the sheep, based on the patterns of calcium-binding proteins expression. Connections of the claustrum with the visual cortex have been studied by tractography. Parvalbumin-immunoreactive (PV-ir) and Calbindin-immunoreactive (CB-ir) cell bodies increased along the rostro-caudal axis of the nucleus. Calretinin (CR)-labeled somata were few and evenly distributed along the rostro-caudal axis. PV and CB distribution in the visual cortex was characterized by larger round and multipolar cells for PV, and more bitufted neurons for CB. The staining pattern for PV was the opposite of that of CR, which showed densely stained but rare cell bodies. Tractography shows the existence of connections with the caudal visual cortex. However, we detected no contralateral projection in the visuo-claustral interconnections. Since sheep and goats have laterally placed eyes and a limited binocular vision, the absence of contralateral projections could be of prime importance if confirmed by other studies, to rule out the role of the claustrum in stereopsis.

Projections between visual cortex and pulvinar in the rat.

The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar, is poorly understood. The pulvinar is thought to modulate information flow between cortical areas, and has been implicated in cognitive tasks like directing visually guided actions. In order to better understand the underlying circuitry, we performed retrograde injections of modified rabies virus in the visual cortex and pulvinar of the Long-Evans rat. We found a relatively small population of cells projecting to primary visual cortex (V1), compared to a much larger population projecting to higher visual cortex. Reciprocal corticothalamic projections showed a similar result, implying that pulvinar does not play as big a role in directly modulating rodent V1 activity as previously thought.

Reconsidering the Border between the Visual and Posterior Parietal Cortex of Mice.

The posterior parietal cortex (PPC) contributes to multisensory and sensory-motor integration, as well as spatial navigation. Based on primate studies, the PPC is composed of several subdivisions with differing connection patterns, including areas that exhibit retinotopy. In mice the composition of the PPC is still under debate. We propose a revised anatomical delineation in which we classify the higher order visual areas rostrolateral area (RL), anteromedial area (AM), and Medio-Medial-Anterior cortex (MMA) as subregions of the mouse PPC. Retrograde and anterograde tracing revealed connectivity, characteristic for primate PPC, with sensory, retrosplenial, orbitofrontal, cingulate and motor cortex, as well as with several thalamic nuclei and the superior colliculus in the mouse. Regarding cortical input, RL receives major input from the somatosensory barrel field, while AM receives more input from the trunk, whereas MMA receives strong inputs from retrosplenial, cingulate, and orbitofrontal cortices. These input differences suggest that each posterior PPC subregion may have a distinct function. Summarized, we put forward a refined cortical map, including a mouse PPC that contains at least 6 subregions, RL, AM, MMA and PtP, MPta, LPta/A. These anatomical results set the stage for a more detailed understanding about the role that the PPC and its subdivisions play in multisensory integration-based behavior in mice.

Anatomy of nerve fiber bundles at micrometer-resolution in the vervet monkey visual system.

Although the primate visual system has been extensively studied, detailed spatial organization of white matter fiber tracts carrying visual information between areas has not been fully established. This is mainly due to the large gap between tracer studies and diffusion-weighted MRI studies, which focus on specific axonal connections and macroscale organization of fiber tracts, respectively. Here we used 3D polarization light imaging (3D-PLI), which enables direct visualization of fiber tracts at micrometer resolution, to identify and visualize fiber tracts of the visual system, such as stratum sagittale, inferior longitudinal fascicle, vertical occipital fascicle, tapetum and dorsal occipital bundle in vervet monkey brains. Moreover, 3D-PLI data provide detailed information on cortical projections of these tracts, distinction between neighboring tracts, and novel short-range pathways. This work provides essential information for interpretation of functional and diffusion-weighted MRI data, as well as revision of wiring diagrams based upon observations in the vervet visual system.