V1 Responses Research Articles

Learning a Model of Shape Selectivity in V4 Cells Reveals Shape Encoding Mechanisms in the Brain.

The mechanisms involved in transforming early visual signals to curvature representations in V4 are unknown. We propose a hierarchical model that reveals V1/V2 encodings that are essential components for this transformation to the reported curvature representations in V4. Then, by relaxing the often-imposed prior of a single Gaussian, V4 shape selectivity is learned in the last layer of the hierarchy from Macaque V4 responses. We found that V4 cells integrate multiple shape parts from the full spatial extent of their receptive fields with similar excitatory and inhibitory contributions. Our results uncover new details in existing data about shape selectivity in V4 neurons that with additional experiments can enhance our understanding of processing in this area. Accordingly, we propose designs for a stimulus set that allow removing shape parts without disturbing the curvature signal to isolate part contributions to V4 responses.SIGNIFICANCE STATEMENT Selectivity to convex and concave shape parts in V4 neurons has been repeatedly reported. Nonetheless, the mechanisms that yield such selectivities in the ventral stream remain unknown. We propose a hierarchical computational model that incorporates findings of the various visual areas involved in shape processing and suggest mechanisms that transform the shape signal from low-level features to convex/concave part representations. Learning shape selectivity from Macaque V4 responses in the final processing stage in our model, we found that V4 neurons integrate shape parts from the full spatial extent of their receptive field with both facilitatory and inhibitory contributions. These results reveal hidden information in existing V4 data that with additional experiments can enhance our understanding of processing in V4.

Model-Based Approach Shows ON Pathway Afferents Elicit a Transient Decrease of V1 Responses.

Neurons in the primary visual cortex (V1) receive excitation and inhibition from distinct parallel pathways processing lightness (ON) and darkness (OFF). V1 neurons overall respond more strongly to dark than light stimuli, consistent with a preponderance of darker regions in natural images, as well as human psychophysics. However, it has been unclear whether this "dark-dominance" is because of more excitation from the OFF pathway or more inhibition from the ON pathway. To understand the mechanisms behind dark-dominance, we record electrophysiological responses of individual simple-type V1 neurons to natural image stimuli and then train biologically inspired convolutional neural networks to predict the neurons' responses. Analyzing a sample of 71 neurons (in anesthetized, paralyzed cats of either sex) has revealed their responses to be more driven by dark than light stimuli, consistent with previous investigations. We show that this asymmetry is predominantly because of slower inhibition to dark stimuli rather than to stronger excitation from the thalamocortical OFF pathway. Consistent with dark-dominant neurons having faster responses than light-dominant neurons, we find dark-dominance to solely occur in the early latencies of neurons' responses. Neurons that are strongly dark-dominated also tend to be less orientation-selective. This novel approach gives us new insight into the dark-dominance phenomenon and provides an avenue to address new questions about excitatory and inhibitory integration in cortical neurons.SIGNIFICANCE STATEMENT Neurons in the early visual cortex respond on average more strongly to dark than to light stimuli, but the mechanisms behind this bias have been unclear. Here we address this issue by combining single-unit electrophysiology with a novel machine learning model to analyze neurons' responses to natural image stimuli in primary visual cortex. Using these techniques, we find slower inhibition to light than to dark stimuli to be the leading mechanism behind stronger dark responses. This slower inhibition to light might help explain other empirical findings, such as why orientation selectivity is weaker at earlier response latencies. These results demonstrate how imbalances in excitation versus inhibition can give rise to response asymmetries in cortical neuron responses.

Contextual drive of neuronal responses in mouse V1 in the absence of feedforward input.

Neurons in the primary visual cortex (V1) respond to stimuli in their receptive field (RF), which is defined by the feedforward input from the retina. However, V1 neurons are also sensitive to contextual information outside their RF, even if the RF itself is unstimulated. Here, we examined the cortical circuits for V1 contextual responses to gray disks superimposed on different backgrounds. Contextual responses began late and were strongest in the feedback-recipient layers of V1. They differed between the three main classes of inhibitory neurons, with particularly strong contextual drive of VIP neurons, indicating a contribution of disinhibitory circuits to contextual drive. Contextual drive was strongest when the gray disk was perceived as figure, occluding its background, rather than a hole. Our results link contextual drive in V1 to perceptual organization and provide previously unknown insight into how recurrent processing shapes the response of sensory neurons to facilitate figure perception.

Identification of a novel link between adiposity and visuospatial perception.

Recent work has reported a negative association between BMI and performance on the Penn Line Orientation Task. To determine the reliability of this effect, a comprehensive assessment of visual function in individuals with healthy weight (HW) and those with overweight/obesity (OW/OB) was performed. Visual acuity/contrast, Penn Line Orientation Task, and higher-order visuospatial function were measured in 80 (40 with HW, 40 with OW/OB) case-control study participants. Adiposity, fasting glucose, hemoglobin A1c, diet, physical activity, and heart rate variability were also assessed. A subgroup of 22 participants plus 5 additional participants (n=27) underwent functional magnetic resonance imaging scanning. Compared with those with HW, individuals with OW/OB performed worse on tasks requiring judgments of line orientation. This effect was mediated by body fat percentage and was unrelated to other measures. Functional magnetic resonance imaging revealed a negative association between BMI and response in the primary visual cortex (V1) during line orientation judgment. Performance was unrelated to V1 response but positively correlated with response in a network of regions, including the lateral occipital cortex, when BMI was accounted for in the model. These results demonstrate a selective deficit in line orientation perception associated with adiposity and blunted activation in the V1 that cannot be attributed to visual acuity and does not generalize to other visuospatial tasks.

Circadian time- and sleep-dependent modulation of cortical parvalbumin-positive inhibitory neurons.

Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show invivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.

Near-additive temporal dynamics of sub-threshold population responses in macaque V1

Near-additive temporal dynamics of sub-threshold population responses in macaque V1

Erratum: Popovkina and Pasupathy, "Task Context Modulates Feature-Selective Responses in Area V4".

In the article “Task Context Modulates Feature-Selective Responses in Area V4,” by Dina V. Popovkina and Anitha Pasupathy, which appeared on pages [6408–6423][1] of the August 17, 2022 issue, because of a production error, an incorrect reference was cited on page 6421. “David et al., 2006

Temporal frequency dependence of the polarity inversion between upper and lower visual field in the pattern-onset steady-state visual evoked potential

PurposeAccording to the cruciform model, the upper and lower halves of the visual field representation in the primary visual cortex are located mainly on the opposite sides of the calcarine sulcus. Such a shape would have consequences for the surface-recorded visual evoked potential (VEP), as V1 responses to stimulation of the upper and lower hemifield manifest with opposite polarity (i.e., polarity inversion). However, the steady-state VEP results from a complex superposition of response components from different cortical sources, which can obscure the inversion of polarity. The present study assesses the issue for different stimulation frequencies which result in different patterns of superposition in the steady-state response.MethodsSequences of brief pattern-onset stimuli were presented at different stimulation rates ranging from 2 Hz (transient VEP) to 13 Hz (steady-state VEP). The upper and lower hemifields were tested separately and simultaneously. The data were assessed both in the time domain and in the frequency domain.ResultsComparing the responses to the stimulation of upper and lower hemifield, polarity inversion was present within a limited time interval following individual stimulus onsets. With increasing frequency, this resulted in an approximate inversion of the full steady-state response and consequently in a phase shift of approximately 180° in the time-domain response. Polarity inversion was more prominent at electrode Pz, also for transient responses. Our data also demonstrated that the sum of the hemifield responses is a good approximation of the full-field response.ConclusionWhile the basic phenomenon of polarity inversion occurs irrespective of the stimulus frequency, its relative impact on the steady-state response as a whole is the largest for high stimulation rates. We propose that this is because longer-lasting response components from other visual areas are not well represented in the steady-state VEP at higher frequencies.

Adaptive processing and perceptual learning in visual cortical areas V1 and V4

Neurons in visual cortical areas primary visual cortex (V1) and V4 are adaptive processors, influenced by perceptual task. This is reflected in their ability to segment the visual scene into task-relevant and task-irrelevant stimulus components and by changing their tuning to task-relevant stimulus properties according to the current top-down instruction. Differences between the information represented in each area were seen. While V1 represented detailed stimulus characteristics, V4 filtered the input from V1 to carry the binary information required for the two-alternative judgement task. Neurons in V1 were activated at locations where the behaviorally relevant stimulus was placed well outside the grating-mapped receptive field. By systematically following the development of the task-dependent signals over the course of perceptual learning, we found that neuronal selectivity for task-relevant information was initially seen in V4 and, over a period of weeks, subsequently in V1. Once the learned information was represented in V1, on any given trial, task-relevant information appeared initially in V1 responses, followed by a 12-ms delay in V4. We propose that the shifting representation of learned information constitutes a mechanism for systems consolidation of memory.

In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules

The brain's connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations? We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations. Remarkably, the magnitude and selectivity of connectivity weights followed a specific order across most of the inferred connectivity configurations. We argue that this order stems from the specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning. Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than their magnitudes, represent a connectivity motif supporting canonical V1 computations.

Macaque V1 responses to 2nd-order contrast-modulated stimuli and the possible subcortical and cortical contributions.

Natural images comprise contours and boundaries defined by 1st-order luminance-modulated (LM) cues that are readily encoded by V1 neurons, and 2nd-order contrast-modulated (CM) cues that carry local, but not over-the-space, luminance changes. The neurophysiological foundations for CM processing remain unsolved. Here we used two-photon calcium imaging to demonstrate that V1 superficial-layer neurons respond to both LM and CM gratings in awake, fixating, macaques, with overall LM responses stronger than CM responses. Furthermore, adaptation experiments revealed that LM responses were similarly suppressed by LM and CM adaptation, with moderately larger effects by iso-orientation adaptation than by orthogonal adaptation, suggesting that LM and CM orientation responses likely share a strong orientation-non-selective subcortical origin. In contrast, CM responses were substantially more suppressed by iso-orientation than by orthogonal LM and CM adaptation, likely suggesting stronger orientation-specific intracortical influences for CM responses than for LM responses, besides shared orientation-non-selective subcortical influences. These results thus may indicate a subcortical-to-V1 filter-rectify-filter mechanism for CM processing: Local luminance changes in CM stimuli are initially encoded by orientation-non-selective subcortical neurons, and the outputs are half-wave rectified, and then summed by V1 neurons to signal CM orientation, which may be further substantially refined by intracortical influences.

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat-/- mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). In particular, retinoid treatment enhanced responses from the ipsilateral eye, restoring the normal balance of eye-specific responses in V1. Additionally, the treatment rescued the modulation of cortical responses by arousal. These findings illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases.

Distinguishing externally from saccade-induced motion in visual cortex

Distinguishing sensory stimuli caused by changes in the environment from those caused by an animal’s own actions is a hallmark of sensory processing1. Saccades are rapid eye movements that shift the image on the retina. How visual systems differentiate motion of the image induced by saccades from actual motion in the environment is not fully understood2. Here we discovered that in mouse primary visual cortex (V1) the two types of motion evoke distinct activity patterns. This is because, during saccades, V1 combines the visual input with a strong non-visual input arriving from the thalamic pulvinar nucleus. The non-visual input triggers responses that are specific to the direction of the saccade and the visual input triggers responses that are specific to the direction of the shift of the stimulus on the retina, yet the preferred directions of these two responses are uncorrelated. Thus, the pulvinar input ensures differential V1 responses to external and self-generated motion. Integration of external sensory information with information about body movement may be a general mechanism for sensory cortices to distinguish between self-generated and external stimuli.

Cascaded normalizations for spatial integration in the primary visual cortex of primates.

Spatial integration of visual information is an important function in the brain. However, neural computation for spatial integration in the visual cortex remains unclear. In this study, we recorded laminar responses in V1 of awake monkeys driven by visual stimuli with grating patches and annuli of different sizes. We find three important response properties related to spatial integration that are significantly different between input and output layers: neurons in output layers have stronger surround suppression, smaller receptive field (RF), and higher sensitivity to grating annuli partially covering their RFs. These interlaminar differences canbe explained by a descriptive model composed of two global divisions (normalization) and a local subtraction. Our results suggest suppressions with cascaded normalizations (CNs) are essential for spatial integration and laminar processing in the visual cortex. Interestingly, the features of spatial integration in convolutional neural networks, especially in lower layers, are different from our findings in V1.

Task Context Modulates Feature-Selective Responses in Area V4.

Feature selectivity of visual cortical responses measured during passive fixation provides only a partial view of selectivity because it does not account for the influence of cognitive factors. Here we focus on primate area V4 and ask how neuronal tuning is modulated by task engagement. We investigated whether responses to colored shapes during active shape discrimination are simple, stimulus-agnostic, scaled versions of responses during passive fixation, akin to results from attentional studies. Alternatively, responses could be subject to stimulus-specific scaling, that is, responses to different stimuli are modulated differently, resulting in changes in underlying shape/color selectivity. Among 83 well-isolated V4 neurons in two male macaques, only a minority (16 of 83), which were weakly tuned to both shape and color, displayed responses during fixation and discrimination tasks that could be related by stimulus-agnostic scaling. The majority (67 of 83), which were strongly tuned to shape, color, or both, displayed stimulus-dependent response changes during discrimination. For some of these neurons (39 of 83), the shape or color of the stimulus dictated the magnitude of the change, and for others (28 of 83) it was the combination of stimulus shape and color. Importantly, for neurons with one strong and one weak tuning dimension, stimulus-dependent response changes during discrimination were associated with a relative increase in selectivity along the stronger tuning dimension, without changes in tuning peak. These results reveal that more strongly tuned V4 neurons may also be more flexible in their selectivity, and imbalances in selectivity are amplified during active task contexts.SIGNIFICANCE STATEMENT Tuning for stimulus features is typically characterized by recording responses during passive fixation, but cognitive factors, including attention, influence responses in visual cortex. To determine how behavioral engagement influences neuronal responses in area V4, we compared responses to colored shapes during passive fixation and active behavior. For a large fraction of neurons, differences in responses between passive fixation and active behavior depended on the identity of the visual stimulus. For a subgroup of strongly feature-selective neurons, this response modulation was associated with enhanced selectivity for one feature at the expense of selectivity for the other. Such flexibility in tuning strength could improve performance in tasks requiring active judgment of stimuli.

Dynamic causal communication channels between neocortical areas

Processing of sensory information depends on the interactions between hierarchically connected neocortical regions, but it remains unclear how the activity in one area causally influences the activity dynamics in another and how rapidly such interactions change with time. Here, we show that the communication between the primary visual cortex (V1) and high-order visual area LM is context-dependent and surprisingly dynamic over time. By momentarily silencing one area while recording activity in the other, we find that both areas reliably affected changing subpopulations of target neurons within one hundred milliseconds while mice observed a visual stimulus. The influence of LM feedback on V1 responses became even more dynamic when the visual stimuli predicted a reward, causing fast changes in the geometry of V1 population activity and affecting stimulus coding in a context-dependent manner. Therefore, the functional interactions between cortical areas are not static but unfold through rapidly shifting communication subspaces whose dynamics depend on context when processing sensory information.

PO-673-03 ANODAL CAPTURE DURING LEFT BUNDLE AREA PACING OVERCOMES DELAYED RIGHT VENTRICULAR ACTIVATION BUT DOES NOT OFFER ANY HAEMODYNAMIC ADVANTAGE

The use of Left bundle area pacing is rapidly growing for both bradycardia and CRT indications. It offers physiological activation of the left ventricle, but right ventricular activation may be delayed. It is often possible to shorten QRS duration and eliminate the R wave in V1 by adjusting pacing output and/or configuration. It is not clear whether the reduction in QRS occurs as a result of bi-bundle capture or due to RV septal capture and it is not known whether programming this configuration offers an advantage in cardiac function. To assess the mechanism of QRS reduction and R prime elimination during left bundle area pacing (ECGi mapping) and whether this confers any haemodynamic benefit. Patients implanted with a LBAP lead were recruited if they exhibited R prime in lead V1 response to pacing and R prime could be eliminated by changing pacing output or configuration (e.g. switch from unipolar to bipolar pacing). We used ECGi mapping to determine ventricular activation (septal myocardial capture or bibundle capture) and a high precision haemodynamic protocol to measure systolic blood pressure change for each capture type. 15 patients were recruited (11 male), mean age 68 ± 11 years. Bradycardia was the pacing indication in 4 (27%) patients, heart failure in 11 (73%).ECGi mapping suggested that the mechanism of shortening of QRS duration was due to RV septal myocardial capture, rather than bi-bundle capture in all of our patients.Left bundle plus right septal capture was associated with significantly narrower QRS duration compared to left bundle only capture (-11.7ms, 95% CI: -15.7 to -7.6 ms, P<0.0001). However, this response required higher pacing outputs (mean threshold 3.28 V ± 2.16 at 0.4ms vs 0.69 V ± 0.25 at 0.4ms, p=0.0004) (Figure 1).Despite the narrower QRS duration, there was no significant difference in systolic blood pressure between the two capture types (-0.96 mm Hg; 95% CI: -3.3 to 1.4 mm Hg; P>0.05). (Figure 1). During left bundle branch pacing it is often possible to deliver earlier right ventricular activation achieved by right septal capture. However, this requires significantly higher pacing outputs without any haemodynamic advantage. When programming these devices, the lowest threshold that achieves left bundle capture is acceptable.

Stimulating both eyes with matching stimuli enhances V1 responses

SummaryNeurons in the primary visual cortex (V1) of primates play a key role in combining monocular inputs to form a binocular response. Although much has been gleaned from studying how V1 responds to discrepant (dichoptic) images, equally important is to understand how V1 responds to concordant (dioptic) images in the two eyes. Here, we investigated the extent to which concordant, balanced, zero-disparity binocular stimulation modifies V1 responses to varying stimulus contrast using intracranial multielectrode arrays. On average, binocular stimuli evoked stronger V1 activity than their monocular counterparts. This binocular facilitation scaled most proportionately with contrast during the initial transient. As V1 responses evolved, additional contrast-mediated dynamics emerged. Specifically, responses exhibited longer maintenance of facilitation for lower contrast and binocular suppression at high contrast. These results suggest that V1 processes concordant stimulation of both eyes in at least two sequential steps: initial response enhancement followed by contrast-dependent control of excitation.

Perceptual Weighting of V1 Spikes Revealed by Optogenetic White Noise Stimulation.

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice of both sexes while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel, an unbiased, temporally precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for understanding how patterns of spiking in neuronal populations are decoded in generating perception and action.SIGNIFICANCE STATEMENT During visually guided actions, continuous chains of neurons connect our retinas to our motoneurons. To unravel circuit contributions to behavior, it is crucial to establish the relative functional position(s) that different neural structures occupy in processing and relaying the signals that support rapid, precise responses. To address this question, we randomly inhibited activity in mouse V1 throughout the stimulus-response cycle while the animals did many repetitions of a visual task. The period that led to impaired performance corresponded to the earliest stimulus-driven response in V1, with no effect of inhibition immediately before or during late stages of the stimulus-driven response. This approach offers experimenters a powerful method for uncovering the temporal weighting of spikes from stimulus to response.

NMDA receptors in visual cortex are necessary for normal visuomotor integration and skill learning.

The experience of coupling between motor output and visual feedback is necessary for the development of visuomotor skills and shapes visuomotor integration in visual cortex. Whether these experience-dependent changes of responses in V1 depend on modifications of the local circuit or are the consequence of circuit changes outside of V1 remains unclear. Here, we probed the role of N-methyl-d-aspartate (NMDA) receptor-dependent signaling, which is known to be involved in neuronal plasticity, in mouse primary visual cortex (V1) during visuomotor development. We used a local knockout of NMDA receptors and a photoactivatable inhibition of CaMKII in V1 during the first visual experience to probe for changes in neuronal activity in V1 as well as the influence on performance in a visuomotor task. We found that a knockout of NMDA receptors before, but not after, first visuomotor experience reduced responses to unpredictable stimuli, diminished the suppression of predictable feedback in V1, and impaired visuomotor skill learning later in life. Our results demonstrate that NMDA receptor-dependent signaling in V1 is critical during the first visuomotor experience for shaping visuomotor integration and enabling visuomotor skill learning.