Area V1 Research Articles

A non-canonical visual cortical-entorhinal pathway contributes to spatial navigation

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.

Neural Correlates of Crowding in Macaque Area V4.

Visual crowding refers to the phenomenon where a target object that is easily identifiable in isolation becomes difficult to recognize when surrounded by other stimuli (distractors). Many psychophysical studies have investigated this phenomenon and proposed alternative models for the underlying mechanisms. One prominent hypothesis, albeit with mixed psychophysical support, posits that crowding arises from the loss of information due to pooled encoding of features from target and distractor stimuli in the early stages of cortical visual processing. However, neurophysiological studies have not rigorously tested this hypothesis. We studied the responses of single neurons in macaque (one male, one female) area V4, an intermediate stage of the object-processing pathway, to parametrically designed crowded displays and texture statistics-matched metameric counterparts. Our investigations reveal striking parallels between how crowding parameters-number, distance, and position of distractors-influence human psychophysical performance and V4 shape selectivity. Importantly, we also found that enhancing the salience of a target stimulus could alleviate crowding effects in highly cluttered scenes, and this could be temporally protracted reflecting a dynamical process. Thus, a pooled encoding of nearby stimuli cannot explain the observed responses, and we propose an alternative model where V4 neurons preferentially encode salient stimuli in crowded displays. Overall, we conclude that the magnitude of crowding effects is determined not just by the number of distractors and target-distractor separation but also by the relative salience of targets versus distractors based on their feature attributes-the similarity of distractors and the contrast between target and distractor stimuli.

Visual cortical area contributions to the transient, multifocal and steady-state VEP: A forward model-informed analysis

Abstract Central to our understanding of how visual-evoked potentials (VEPs) contribute to visual processing is the question of where their anatomical sources are. Three well-established measures of low-level visual cortical activity are widely used: the first component (“C1”) of the transient and multifocal VEP, and the steady-state VEP (SSVEP). Although primary visual cortex (V1) activity has often been implicated in the generation of all three signals, their dominant sources remain uncertain due to the limited resolution and methodological heterogeneity of source modelling. Here, we provide the first characterisation of all three signals in one analytic framework centred on the “cruciform model”, which describes how scalp topographies of V1 activity vary with stimulus location due to the retinotopy and unique folding pattern of V1. We measured the transient C1, multifocal C1, and SSVEPs driven by an 18.75 Hz and 7.5 Hz flicker, and regressed them against forward models of areas V1, V2, and V3 generated from the Benson-2014 retinotopy atlas. The topographic variations of all four VEP signals across the visual field were better captured by V1 models, explaining between 2 and 6 times more variance than V2/V3. Models with all three visual areas improved fit further, but complementary analyses of temporal dynamics across all three signals indicated that the bulk of extrastriate contributions occur considerably later than V1. Overall, our data support the use of peak C1 amplitude and SSVEPs to probe V1 activity, although the SSVEP contains stronger extrastriate contributions. Moreover, we provide elaborated heuristics to distinguish visual areas in VEP data based on signal lateralisation as well as polarity inversion.

Temporal Sensitivity for Achromatic and Chromatic Flicker across the Visual Cortex.

The retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic postreceptoral channels. The goal of the current study was to determine temporal sensitivity across the three postreceptoral channels in subcortical and cortical regions involved in human vision. We measured functional magnetic resonance imaging (fMRI) responses at 7 T from three participants (two males, one female) viewing a high-contrast, flickering, spatially uniform wide field (∼140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L + M + S, L - M, and S - (L + M) cone combinations. These measurements were used to create temporal sensitivity functions of the primary visual cortex (V1) across eccentricity and spatially averaged responses from the lateral geniculate nucleus (LGN), and the V2/V3, hV4, and V3A/B regions. fMRI responses reflected the known properties of the visual system, including higher peak temporal sensitivity to achromatic versus chromatic stimuli and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. The comparison of measured cortical responses to a model of the integrated retinal output to our stimuli demonstrates that extensive filtering and amplification are applied to postretinal signals.

Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit.

Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.

Are we aware of neural activity in primary visual cortex? A neuropsychological case study.

According to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC). We provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved. Visual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC. These results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Multiple objects evoke fluctuating responses in several regions of the visual pathway.

How neural representations preserve information about multiple stimuli is mysterious. Because tuning of individual neurons is coarse (e.g., visual receptive field diameters can exceed perceptual resolution), the populations of neurons potentially responsive to each individual stimulus can overlap, raising the question of how information about each item might be segregated and preserved in the population. We recently reported evidence for a potential solution to this problem: when two stimuli were present, some neurons in the macaque visual cortical areas V1 and V4 exhibited fluctuating firing patterns, as if they responded to only one individual stimulus at a time (Jun et al., 2022). However, whether such an information encoding strategy is ubiquitous in the visual pathway and thus could constitute a general phenomenon remains unknown. Here, we provide new evidence that such fluctuating activity is also evoked by multiple stimuli in visual areas responsible for processing visual motion (middle temporal visual area, MT), and faces (middle fundus and anterolateral face patches in inferotemporal cortex - areas MF and AL), thus extending the scope of circumstances in which fluctuating activity is observed. Furthermore, consistent with our previous results in the early visual area V1, MT exhibits fluctuations between the representations of two stimuli when these form distinguishable objects but not when they fuse into one perceived object, suggesting that fluctuating activity patterns may underlie visual object formation. Taken together, these findings point toward an updated model of how the brain preserves sensory information about multiple stimuli for subsequent processing and behavioral action.

Dissociable components of attention exhibit distinct neuronal signatures in primate visual cortex.

Attention can be deployed in multiple forms and facilitates behavior by influencing perceptual sensitivity and choice bias. Attention is also associated with a myriad of changes in sensory neural activity. Yet, the relationship between the behavioral components of attention and the accompanying changes in neural activity remains largely unresolved. We examined this relationship by quantifying sensitivity and bias in monkeys performing a task that dissociated eye movement responses from the focus of covert attention. Unexpectedly, bias, not sensitivity, increased at the focus of covert attention, whereas sensitivity increased at the location of planned eye movements. Furthermore, neuronal activity within visual area V4 varied robustly with bias, but not sensitivity, at the focus of covert attention. In contrast, correlated variability between neuronal pairs was lowest at the location of planned eye movements, and varied with sensitivity, but not bias. Thus, dissociable behavioral components of attention exhibit distinct neuronal signatures within the visual cortex.

Transformations of sensory information in the brain suggest changing criteria for optimality.

Neurons throughout the brain modulate their firing rate lawfully in response to sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization in which neurons aim to robustly and efficiently represent sensory information. Our understanding of how this optimization varies across different areas in the brain, however, is still in its infancy. Here, we show that neural sensory responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation towards optimizing for perceptual discrimination. Focusing on the representation of binocular disparities-the slight differences in the retinal images of the two eyes-we re-analyze measurements characterizing neuronal tuning curves in brain areas V1, V2, and MT (middle temporal) in the macaque monkey. We compare these to measurements of the statistics of binocular disparity typically encountered during natural behaviors using a Fisher Information framework. The differences in tuning curve characteristics across areas are consistent with a shift in optimization goals: V1 and V2 population-level responses are more consistent with maximizing the information encoded about naturally occurring binocular disparities, while MT responses shift towards maximizing the ability to support disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective areas of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings emphasize the need to consider not just information preservation and neural resources, but also relevance to behavior, when assessing the optimality of neural codes.

Paying attention to natural scenes in area V1

Natural scene responses in the primary visual cortex are modulated simultaneously by attention and by contextual signals about scene statistics stored across the connectivity of the visual processing hierarchy. We hypothesized that attentional and contextual signals interact in V1 in a manner that primarily benefits the representation of natural stimuli, rich in high-order statistical structure. Recording from two macaques engaged in a spatial attention task, we found that attention enhanced the decodability of stimulus identity from population responses evoked by natural scenes, but not by synthetic stimuli lacking higher-order statistical regularities. Population analysis revealed that neuronal responses converged to a low-dimensional subspace only for natural stimuli. Critically, we determined that the attentional enhancement in stimulus decodability was captured by the natural-scene subspace, indicating an alignment between the attentional and natural stimulus variance. These results suggest that attentional and contextual signals interact in V1 in a manner optimized for natural vision.

Construction of Objects from Pixels — Cortical Coding in Intermediate-level Visual Area V4

Construction of Objects from Pixels — Cortical Coding in Intermediate-level Visual Area V4

Attention modulates early visual processing: An association between subjective contrast perception and early C1 ERP component.

The question of whether spatial attention can modulate initial afferent activity in area V1, as measured by the earliest visual event-related potential (ERP) component "C1", is still the subject of debate. Because attention always enhances behavioral performance, previous research has focused on finding evidence of attention-related enhancements in visual neural responses. However, recent psychophysical studies revealed a complex picture of attention's influence on visual perception: attention amplifies the perceived contrast of low-contrast stimuli while dampening the perceived contrast of high-contrast stimuli. This evidence suggests that attention may not invariably augment visual neural responses but could instead exert inhibitory effects under certain circumstances. Whether this bi-directional modulation of attention also manifests in C1 and whether the modulation of C1 underpins the attentional influence on contrast perception remain unknown. To address these questions, we conducted two experiments (N = 67 in total) by employing a combination of behavioral and ERP methodologies. Our results did not unveil a uniform attentional enhancement or attenuation effect of C1 across all subjects. However, an intriguing correlation between the attentional effects of C1 and contrast appearance for high-contrast stimuli did emerge, revealing an association between attentional modulation of C1 and the attentional modulation of contrast appearance. This finding offers new insights into the relationship between attention, perceptual experience, and early visual neural processing, suggesting that the attentional effect on subjective visual perception could be mediated by the attentional modulation of the earliest visual cortical response.

Functional connectivity via total correlation: Analytical results in visual areas

Recent studies invoke the superiority of the multivariate Total Correlation concept over the conventional pairwise measures of functional connectivity in biological networks. Those seminal works certainly show that empirical measures of Total Correlation lead to connectivity patterns that differ from what is obtained using the most popular measure, linear correlation, or its higher order and nonlinear alternative Mutual Information. However, they do not provide analytical results that explain the differences beyond the obvious multivariate versus bivariate definitions. Moreover, the accuracy of the empirical estimators could not be addressed directly because no controlled scenario with known analytical result was provided either. This point is critical because empirical estimation of information theory measures is always challenging.As opposed to previous empirical approaches, in this work we present analytical results to prove the advantages of Total Correlation over Mutual Information to describe the functional connectivity. In particular, we do it in neural networks for early vision (retina–LGN–cortex) which are realistic but simple enough to get analytical results. The presented analytical setting is also useful to check empirical estimates of Total Correlation. Therefore, once certain estimate can be trusted, one can explore the behavior with natural signals where the analytical results (that assume Gaussian signals), may not be valid. In this regard, as applications (a) we explore the effect of connectivity and feedback in the analytical retina–LGN–cortex network with natural images, and (b) we assess the functional connectivity in visual areas V1–V2–V3–V4 from actual fMRI recordings.

Normative tDCS over V5 and FEF reveals practice-induced modulation of extraretinal smooth pursuit mechanisms, but no specific stimulation effect

The neural networks subserving smooth pursuit eye movements (SPEM) provide an ideal model for investigating the interaction of sensory processing and motor control during ongoing movements. To better understand core plasticity aspects of sensorimotor processing for SPEM, normative sham, anodal or cathodal transcranial direct current stimulation (tDCS) was applied over visual area V5 and frontal eye fields (FEF) in sixty healthy participants. The identical within-subject paradigm was used to assess SPEM modulations by practice. While no specific tDCS effects were revealed, within- and between-session practice effects indicate plasticity of top-down extraretinal mechanisms that mainly affect SPEM in the absence of visual input and during SPEM initiation. To explore the potential of tDCS effects, individual electric field simulations were computed based on calibrated finite element head models and individual functional localization of V5 and FEF location (using functional MRI) and orientation (using combined EEG/MEG) was conducted. Simulations revealed only limited electric field target intensities induced by the applied normative tDCS montages but indicate the potential efficacy of personalized tDCS for the modulation of SPEM. In sum, results indicate the potential susceptibility of extraretinal SPEM control to targeted external neuromodulation (e.g., personalized tDCS) and intrinsic learning protocols.

Behavioral examination of the role of the primary visual cortex in the perceived size representation

Previous research has shown that neural activity in the primary visual cortex (V1) and V1 surface area may be linked with subjective experience of size illusions. Here, we behaviorally measured the hallway illusion with experimental manipulations as a proxy of V1’s influence on size perception. We first tested whether the hallway illusion can persist without further recurrent processing by using backward masking. Next, we examined relations among the hallway illusion magnitude and other perceptual measures that have been suggested to be correlated with V1 surface area. In Experiment 1, the magnitude of the hallway illusion was not affected by the stimulus duration and visual masking when the hallway context was previewed (i.e., complex depth information is already processed). It suggests that V1 activity could support the size illusion to some extent even when recurrent processing between V1 and higher areas is disturbed. In Experiment 2, the hallway illusion magnitude was correlated with the Vernier acuity threshold, but not with physical size discriminability. Our results provide converging evidence with the previous findings in that neural activity in V1 may contribute to size illusions and that V1 surface area is not the sole factor that mediates size perception and visual precision.

Targeted V1 comodulation supports task-adaptive sensory decisions

Sensory-guided behavior requires reliable encoding of stimulus information in neural populations, and flexible, task-specific readout. The former has been studied extensively, but the latter remains poorly understood. We introduce a theory for adaptive sensory processing based on functionally-targeted stochastic modulation. We show that responses of neurons in area V1 of monkeys performing a visual discrimination task exhibit low-dimensional, rapidly fluctuating gain modulation, which is stronger in task-informative neurons and can be used to decode from neural activity after few training trials, consistent with observed behavior. In a simulated hierarchical neural network model, such labels are learned quickly and can be used to adapt downstream readout, even after several intervening processing stages. Consistently, we find the modulatory signal estimated in V1 is also present in the activity of simultaneously recorded MT units, and is again strongest in task-informative neurons. These results support the idea that co-modulation facilitates task-adaptive hierarchical information routing.

Visual experience induces 4–8 Hz synchrony between V1 and higher-order visual areas

Visual perceptual experience induces persistent 4-8Hz oscillations in the mouse primary visual cortex (V1), encoding visual familiarity. Recent studies suggest that higher-order visual areas (HVAs) are functionally specialized and segregated into information streams processing distinct visual features. However, whether visual memories are processed and stored within the distinct streams is not understood. We report here that V1 and lateromedial (LM), but not V1 and anterolateral, become more phase synchronized in 4-8Hz after the entrainment of visual stimulus that maximally induces responses in LM. Directed information analysis reveals changes in the top-down functional connectivity between V1 and HVAs. Optogenetic inactivation of LM reduces post-stimulus oscillation peaks in V1 and impairs visual discrimination behavior. Our results demonstrate that 4-8Hz familiarity-evoked oscillations are specific for the distinct visual features and are present in the corresponding HVAs, where they may be used for the inter-areal communication with V1 during memory-related behaviors.

Joint encoding of stimulus and decision in monkey primary visual cortex.

We investigated whether neurons in monkey primary visual cortex (V1) exhibit mixed selectivity for sensory input and behavioral choice. Parallel multisite spiking activity was recorded from area V1 of awake monkeys performing a delayed match-to-sample task. The monkeys had to make a forced choice decision of whether the test stimulus matched the preceding sample stimulus. The population responses evoked by the test stimulus contained information about both the identity of the stimulus and with some delay but before the onset of the motor response the forthcoming choice. The results of subspace identification analysis indicate that stimulus-specific and decision-related information coexists in separate subspaces of the high-dimensional population activity, and latency considerations suggest that the decision-related information is conveyed by top-down projections.

Laminar compartmentalization of attention modulation in area V4 aligns with the demands of visual processing hierarchy in the cortex

Attention selectively enhances neural responses to low contrast stimuli in visual area V4, a critical hub that sends projections both up and down the visual hierarchy. Veridical encoding of contrast information is a key computation in early visual areas, while later stages encoding higher level features benefit from improved sensitivity to low contrast. How area V4 meets these distinct information processing demands in the attentive state is unknown. We found that attentional modulation in V4 is cortical layer and cell-class specific. Putative excitatory neurons in the superficial layers show enhanced boosting of low contrast information, while those of deep layers exhibit contrast-independent scaling. Computational modeling suggested the extent of spatial integration of inhibitory neurons as the mechanism behind such laminar differences. Considering that superficial neurons are known to project to higher areas and deep layers to early visual areas, our findings suggest that the interactions between attention and contrast in V4 are compartmentalized, in alignment with the demands of the visual processing hierarchy.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents.

JOURNAL/nrgr/04.03/01300535-202408000-00038/figure1/v/2023-12-16T180322Z/r/image-tiff Memory deficit, which is often associated with aging and many psychiatric, neurological, and neurodegenerative diseases, has been a challenging issue for treatment. Up till now, all potential drug candidates have failed to produce satisfactory effects. Therefore, in the search for a solution, we found that a treatment with the gene corresponding to the RGS14414 protein in visual area V2, a brain area connected with brain circuits of the ventral stream and the medial temporal lobe, which is crucial for object recognition memory (ORM), can induce enhancement of ORM. In this study, we demonstrated that the same treatment with RGS14414 in visual area V2, which is relatively unaffected in neurodegenerative diseases such as Alzheimer's disease, produced long-lasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer's disease. Furthermore, we found that the prevention of memory deficits was mediated through the upregulation of neuronal arborization and spine density, as well as an increase in brain-derived neurotrophic factor (BDNF). A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer's disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits. These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer's disease. Therefore, our findings of RGS14414 gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.