Visual Cortex Research Articles

Response sub-additivity and variability quenching in visual cortex.

Sub-additivity and variability are ubiquitous response motifs in the primary visual cortex (V1). Response sub-additivity enables the construction of useful interpretations of the visual environment, whereas response variability indicatesthe factors that limit the precision with which the brain can do this. There is increasing evidence that experimental manipulations that elicit response sub-additivity often also quench response variability. Here, we provide an overview of these phenomena and suggest that theymay have common origins. We discuss empirical findings and recent model-based insights into the functional operations, computational objectives and circuit mechanisms underlying V1 activity. These differentmodelling approaches all predict that response sub-additivity and variability quenchingoften co-occur. The phenomenology of these two response motifs, as well as many of the insights obtained about them in V1, generalize to other cortical areas.Thus, the connection between response sub-additivity and variability quenching may be a canonical motif across the cortex.

Rodents' visual gamma as a biomarker of pathological neural conditions.

Neural gamma oscillations (indicatively 30-100Hz) are ubiquitous: they are associated with a broad range of functions in multiple cortical areas and across many animal species. Experimental and computational works established gamma rhythms as a global emergent property of neuronal networks generated by the balanced and coordinated interaction of excitation and inhibition. Coherently, gamma activity is strongly influenced by the alterations of synaptic dynamics which are often associated with pathological neural dysfunctions. We argue therefore that these oscillations are an optimal biomarker for probing the mechanism of cortical dysfunctions. Gamma oscillations are also highly sensitive to external stimuli in sensory cortices, especially the primary visual cortex (V1), where the stimulus dependence of gamma oscillations has been thoroughly investigated. Gamma manipulation by visual stimuli tuning is particularly easy in rodents, which have become a standard animal model for investigating the effects of network alterations on gamma oscillations. Overall, gamma in the rodents' visual cortex offers an accessible probe on dysfunctional information processing in pathological conditions. Beyond vision-related dysfunctions, alterations of gamma oscillations in rodents were indeed also reported in neural deficits such as migraine, epilepsy and neurodegenerative or neuropsychiatric conditions such as Alzheimer's, schizophrenia and autism spectrum disorders. Altogether, the connections between visual cortical gamma activity and physio-pathological conditions in rodent models underscore the potential of gamma oscillations as markers of neuronal (dys)functioning.

Adaptation-induced sharpening of orientation tuning curves in the mouse visual cortex.

Orientation selectivity is an emergent property of visual neurons across species with columnar and noncolumnar organization of the visual cortex. The emergence of orientation selectivity is more established in columnar cortical areas than in noncolumnar ones. Thus, how does orientation selectivity emerge in noncolumnar cortical areas after an adaptation protocol? Adaptation refers to the constant presentation of a nonoptimal stimulus (adapter) to a neuron under observation for a specific time. Previously, it had been shown that adaptation has varying effects on the tuning properties of neurons, such as orientation, spatial frequency, motion and so on. We recorded the mouse primary visual neurons (V1) at different orientations in the control (preadaptation) condition. This was followed by adapting neurons uninterruptedly for 12 min and then recording the same neurons postadaptation. An orientation selectivity index (OSI) for neurons was computed to compare them pre- and post-adaptation. We show that 12-min adaptation increases the OSI of visual neurons ( n = 113), that is, sharpens their tuning. Moreover, the OSI postadaptation increases linearly as a function of the OSI preadaptation. The increased OSI postadaptation may result from a specific dendritic neural mechanism, potentially facilitating the rapid learning of novel features.

Rapid color categorization revealed by frequency-tagging-based EEG

There has been much debate on whether color categories affect how we perceive color. Recent theories have put emphasis on the role of top-down influence on color perception that the original continuous color space in the visual cortex may be transformed into categorical encoding due to top-down modulation. To test the influence of color categories on color perception, we adopted an RSVP paradigm, where color stimuli were presented at a fast speed of 100 ms per stimulus and were forward and backward masked by the preceding and following stimuli. Moreover, no explicit color naming or categorization was required. In theory, backward masking with such a short interval in a passive viewing task should constrain top-down influence from higher-level brain areas. To measure any potentially subtle differences in brain response elicited by different color categories, we embedded a sensitive frequency-tagging-based EEG paradigm within the RSVP stimuli stream where the oddball color stimuli were encoded with a different frequency from the base color stimuli. We showed that EEG responses to cross-category oddball colors at the frequency where the oddball stimuli were presented was significantly larger than the responses to within-category oddball colors. Our study suggested that the visual cortex can automatically and implicitly encode color categories when color stimuli are presented rapidly.

Pattern electroretinography response in amblyopic adults

IntroductionAmblyopia is generally a unilateral disorder, defined by at least a difference of two lines of visual acuity between both eyes with the best-corrected visual acuity, a decrease in contrast sensitivity, and a decrease in stereopsis. Pattern electroretinogram (PERG) is a noninvasive technique that provides a retinal biopotential and is a highly sensitive indicator of changes in the macular area. Our aim was to evaluate if there are differences in the retinal response of an amblyopic eye compared with a normal eye (NE).MethodsWe evaluated twenty-four adult volunteers, twelve amblyopes (mean 43.42 ± 12.72 years old), and twelve subjects with NE (mean 35.58 ± 12.85 years old). None of the subjects in the two groups had comorbidities. A complete optometric examination was performed including parameters such as visual acuity (VA) by far and near with ETDRS chart, eye alignment with cover test, and evaluation of retinal cells response with PERG.ResultsThe refractive error found in the NE group of subjects had a mean of − 0.95 ± 1.65D, while the amblyopic group showed a mean of − 2.03 ± 4.29D. The VA in amblyopic eyes had a mean of 0.38 ± 0.20 logMAR. Analyzing PERG data, we observed significant differences in the P50-N95 amplitudes of the amblyopic group compared with the NE group (p < 0.0001–amblyopic eye vs. NE; p = 0.039–fellow eye vs. NE).DiscussionThese findings suggest that amblyopic patients may also present other impairments beyond the visual cortex. PERGs seem to be an important complementary examination in the diagnosis of other impairments in amblyopia.

Working memory signals in early visual cortex are present in weak and strong imagers.

It has been suggested that visual images are memorized across brief periods of time by vividly imagining them as if they were still there. In line with this, the contents of both working memory and visual imagery are known to be encoded already in early visual cortex. If these signals in early visual areas were indeed to reflect a combined imagery and memory code, one would predict them to be weaker for individuals with reduced visual imagery vividness. Here, we systematically investigated this question in two groups of participants. Strong and weak imagers were asked to remember images across brief delay periods. We were able to reliably reconstruct the memorized stimuli from early visual cortex during the delay. Importantly, in contrast to the prediction, the quality of reconstruction was equally accurate for both strong and weak imagers. The decodable information also closely reflected behavioral precision in both groups, suggesting it could contribute to behavioral performance, even in the extreme case of completely aphantasic individuals. Our data thus suggest that working memory signals in early visual cortex can be present even in the (near) absence of phenomenal imagery.

Parafoveal vision reveals qualitative differences between fusiform face area and parahippocampal place area.

The center-periphery visual field axis guides early visual system organization with enhanced resources devoted to central vision leading to reduced peripheral performance relative to that of central vision (i.e., behavioral eccentricity effect) for many visual functions. The center-periphery organization extends to high-order visual cortex where, for example, the well-studied face-sensitive fusiform face area (FFA) shows sensitivity to central vision and the place-sensitive parahippocampal place area (PPA) shows sensitivity to peripheral vision. As we have recently found that face perception is more sensitive to eccentricity than place perception, here we examined whether these behavioral findings reflect differences in FFA's and PPA's sensitivities to eccentricity. We assumed FFA would show higher sensitivity to eccentricity than PPA would, but that both regions' modulation by eccentricity would be invariant to the viewed category. We parametrically investigated (fMRI, n = 32) how FFA's and PPA's activations are modulated by eccentricity (≤8°) and category (upright/inverted faces/houses) while keeping stimulus size constant. As expected, FFA showed an overall higher sensitivity to eccentricity than PPA. However, both regions' activation modulations by eccentricity were dependent on the viewed category. In FFA, a reduction of activation with growing eccentricity ("BOLD eccentricity effect") was found (with different amplitudes) for all categories. In PPA however, qualitatively different BOLD eccentricity effect modulations were found (e.g., at 8° mild BOLD eccentricity effect for houses but a reverse BOLD eccentricity effect for faces and no modulation for inverted faces). Our results emphasize that peripheral vision investigations are critical to further our understanding of visual processing.

Dynamic fading memory and expectancy effects in the monkey primary visual cortex

In order to investigate the involvement of the primary visual cortex (V1) in working memory (WM), parallel, multisite recordings of multi-unit activity were obtained from monkey V1 while the animals performed a delayed match-to-sample (DMS) task. During the delay period, V1 population firing rate vectors maintained a lingering trace of the sample stimulus that could be reactivated by intervening impulse stimuli that enhanced neuronal firing. This fading trace of the sample did not require active engagement of the monkeys in the DMS task and likely reflects the intrinsic dynamics of recurrent cortical networks in lower visual areas. This renders an active, attention-dependent involvement of V1 in the maintenance of WM contents unlikely. By contrast, population responses to the test stimulus depended on the probabilistic contingencies between sample and test stimuli. Responses to tests that matched expectations were reduced which agrees with concepts of predictive coding.

Neuropil Variation in the Prefrontal, Motor, and Visual Cortex of Six Felids

Introduction: Felids have evolved a specialized suite of morphological adaptations for obligate carnivory. Although the musculoskeletal anatomy of the Felidae has been studied extensively, the comparative neuroanatomy of felids is relatively unexplored. Little is known about how variation in the cerebral anatomy of felids relates to species-specific differences in sociality, hunting strategy, or activity patterns. Methods: We quantitatively analyzed neuropil variation in the prefrontal, primary motor, and primary visual cortices of six species of Felidae (Panthera leo, Panthera uncia, Panthera tigris, Panthera leopardus, Acinonyx jubatus, Felis sylvestris domesticus) to investigate relationships with brain size, neuronal cell parameters, and select behavioral and ecological factors. Neuropil is the dense, intricate network of axons, dendrites, and synapses in the brain, playing a critical role in information processing and communication between neurons. Results: There were significant species and regional differences in neuropil proportions, with African lion, cheetah, and tiger having more neuropil in all three cortical regions in comparison to the other species. Based on regression analyses, we find that the increased neuropil fraction in the prefrontal cortex supports social and behavioral flexibility, while in the primary motor cortex, this facilitates the neural activity needed for hunting movements. Greater neuropil fraction in the primary visual cortex may contribute to visual requirements associated with diel activity patterns. Conclusion: These results provide a cross-species comparison of neuropil fraction variation in the Felidae, particularly the understudied Panthera, and provide evidence for convergence of the neuroanatomy of Panthera and cheetahs.

Visuo-frontal interactions during social learning in freely moving macaques

Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by distributing socially relevant information among neurons in each area. Decoding population activity showed that viewing social cues influences the decision to cooperate. Learning social events increased coordinated spiking between visual and prefrontal cortical neurons, which was associated with improved accuracy of neural populations to encode social cues and the decision to cooperate. These results indicate that the visual-frontal cortical network prioritizes relevant sensory information to facilitate learning social interactions while freely moving macaques interact in a naturalistic environment.

Predicting Single Neuron Responses of the Primary Visual Cortex with Deep Learning Model.

Modeling neuron responses to stimuli can shed light on next-generation technologies such as brain-chip interfaces. Furthermore, high-performing models can serve to help formulate hypotheses and reveal the mechanisms underlying neural responses. Here the state-of-the-art computational model is presented for predicting single neuron responses to natural stimuli in the primary visual cortex (V1) of mice. The algorithm incorporates object positions and assembles multiple models with different train-validation data, resulting in a 15%-30% improvement over the existing models in cross-subject predictions and ranking first in the SENSORIUM 2022 Challenge, which benchmarks methods for neuron-specific prediction based on thousands of images. Importantly, The model reveals evidence that the spatial organizations of V1 are conserved across mice. This model will serve as an important noninvasive tool for understanding and utilizing the response patterns of primary visual cortex neurons.

Bounded contribution of human early visual cortex to the topographic anisotropy in spatial extent perception

To interact successfully with objects, it is crucial to accurately perceive their spatial extent, an enclosed region they occupy in space. Although the topographic representation of space in the early visual cortex (EVC) has been favored as a neural correlate of spatial extent perception, its exact nature and contribution to perception remain unclear. Here, we inspect the topographic representations of human individuals’ EVC and perception in terms of how much their anisotropy is influenced by the orientation (co-axiality) and radial position (radiality) of stimuli. We report that while the anisotropy is influenced by both factors, its direction is primarily determined by radiality in EVC but by co-axiality in perception. Despite this mismatch, the individual differences in both radial and co-axial anisotropy are substantially shared between EVC and perception. Our findings suggest that spatial extent perception builds on EVC’s spatial representation but requires an additional mechanism to transform its topographic bias.

Rat superior colliculus encodes the transition between static and dynamic vision modes

The visual continuity illusion involves a shift in visual perception from static to dynamic vision modes when the stimuli arrive at high temporal frequency, and is critical for recognizing objects moving in the environment. However, how this illusion is encoded across the visual pathway remains poorly understood, with disparate frequency thresholds at retinal, cortical, and behavioural levels suggesting the involvement of other brain areas. Here, we employ a multimodal approach encompassing behaviour, whole-brain functional MRI, and electrophysiological measurements, for investigating the encoding of the continuity illusion in rats. Behavioural experiments report a frequency threshold of 18±2 Hz. Functional MRI reveal that superior colliculus signals transition from positive to negative at the behaviourally-driven threshold, unlike thalamic and cortical areas. Electrophysiological recordings indicate that these transitions are underpinned by neural activation/suppression. Lesions in the primary visual cortex reveal this effect to be intrinsic to the superior colliculus (under a cortical gain effect). Our findings highlight the superior colliculus’ crucial involvement in encoding temporal frequency shifts, especially the change from static to dynamic vision modes.

Preferential transduction of parvalbumin-expressing cortical neurons by AAV-mDLX5/6 vectors.

A major goal of modern neuroscience is to understand the functions of the varied neuronal types that comprise the mammalian brain. Toward this end, some types of neurons can be targeted and manipulated with enhancer-bearing AAV vectors. These vectors hold great promise to advance basic and translational neuroscience, but to realize this potential, their selectivity must be characterized. In this study, we investigated the selectivity of AAV vectors carrying an enhancer of the murine Dlx5 and Dlx6 genes. Vectors were injected into the visual cortex of two macaque monkeys, the frontal cortex of two others, and the somatosensory/motor cortex of three rats. Post-mortem immunostaining revealed that parvalbumin-expressing neurons were transduced efficiently in all cases but calretinin-expressing neurons were not. We speculate that this specificity is a consequence of differential activity of this DLX5/6 enhancer in adult neurons of different developmental lineages.

Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain's response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain's electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

Functional connectivity interacts with visual perceptual learning for visual field recovery in chronic stroke

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.

40 Hz light flickering promotes sleep through cortical adenosine signaling

Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of a neurochemical underpinning has hampered its therapeutic development. Here, we demonstrate that light flickering triggered an immediate and sustained increase (up to 3 h after flickering) in extracellular adenosine levels in the primary visual cortex (V1) and other brain regions, as a function of light frequency and intensity, with maximal effects observed at 40 Hz frequency and 4000 lux. We uncovered cortical (glutamatergic and GABAergic) neurons, rather than astrocytes, as the cellular source, the intracellular adenosine generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), and adenosine efflux mediated by equilibrative nucleoside transporter-2 (ENT2) as the molecular pathway responsible for extracellular adenosine generation. Importantly, 40 Hz (but not 20 and 80 Hz) light flickering for 30 min enhanced non-rapid eye movement (non-REM) and REM sleep for 2–3 h in mice. This somnogenic effect was abolished by ablation of V1 (but not superior colliculus) neurons and by genetic deletion of the gene encoding ENT2 (but not ENT1), but recaptured by chemogenetic inhibition of V1 neurons and by focal infusion of adenosine into V1 in a dose-dependent manner. Lastly, 40 Hz light flickering for 30 min also promoted sleep in children with insomnia by decreasing sleep onset latency, increasing total sleep time, and reducing waking after sleep onset. Collectively, our findings establish the ENT2-mediated adenosine signaling in V1 as the neurochemical basis for 40 Hz flickering-induced sleep and unravel a novel and non-invasive treatment for insomnia, a condition that affects 20% of the world population.

Dynamic predictive coding: A model of hierarchical sequence learning and prediction in the neocortex.

We introduce dynamic predictive coding, a hierarchical model of spatiotemporal prediction and sequence learning in the neocortex. The model assumes that higher cortical levels modulate the temporal dynamics of lower levels, correcting their predictions of dynamics using prediction errors. As a result, lower levels form representations that encode sequences at shorter timescales (e.g., a single step) while higher levels form representations that encode sequences at longer timescales (e.g., an entire sequence). We tested this model using a two-level neural network, where the top-down modulation creates low-dimensional combinations of a set of learned temporal dynamics to explain input sequences. When trained on natural videos, the lower-level model neurons developed space-time receptive fields similar to those of simple cells in the primary visual cortex while the higher-level responses spanned longer timescales, mimicking temporal response hierarchies in the cortex. Additionally, the network's hierarchical sequence representation exhibited both predictive and postdictive effects resembling those observed in visual motion processing in humans (e.g., in the flash-lag illusion). When coupled with an associative memory emulating the role of the hippocampus, the model allowed episodic memories to be stored and retrieved, supporting cue-triggered recall of an input sequence similar to activity recall in the visual cortex. When extended to three hierarchical levels, the model learned progressively more abstract temporal representations along the hierarchy. Taken together, our results suggest that cortical processing and learning of sequences can be interpreted as dynamic predictive coding based on a hierarchical spatiotemporal generative model of the visual world.

Functional blindsight and its diagnosis.

Even when brain scans fail to detect a striate lesion, functional evidence for blindsight can be adduced. In the aftermath of an automobile accident, JK became blind. Results of ophthalmic exams indicated that the blindness must be cortical. Nevertheless, multiple MRI scans failed to detect structural damage to the striate cortex. Prior to the accident JK had been an athlete; after the accident he retained some athletic abilities, arousing suspicions that he might be engaged in fraud. His residual athletic abilities-e.g., hitting a handball or baseball, or catching a Frisbee-coupled with his experienced blindness, suggested blindsight. But due to the apparent absence of striate lesions, we designed a series of tasks for temporal and spatial dimensions in an attempt to detect functional evidence of his disability. Indeed, test results revealed compelling neural evidence that comport with his subjective reports. This spatiotemporal task-related method that includes contrasts with healthy controls, and detailed understanding of the patient's conscious experience, can be generalized for clinical, scientific and forensic investigations of blindsight.

Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex.

Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.