Area V1 Research Articles

Resilience of FEF neuronal saccade code to V4 perturbations.

The frontal eye field (FEF) plays a key role in initiating rapid eye movements known as saccades. Accumulation models have been proposed to explain the dynamic of these neurons and how they may enable the initiation of saccades. To update the scope of the viability of this model, we studied single neurons recorded from the FEF of two rhesus monkeys while they performed a memory-guided saccade task. We evaluated the degree to which each type of FEF neuron complied with these models by quantifying how precisely their discharge predicted an imminent saccade based on their immediate presaccadic activity. We found that decoders trained on single neurons with a stronger motor component performed better than decoders trained on neurons with a stronger visual component in predicting the saccade. Importantly, despite a dramatic effect on the reaction times, the perturbations delivered to the FEF neurons via area V4 did not impact their saccade predictability. Our results demonstrate a high degree of resilience of the FEF neuronal presaccadic discharge patterns, fulfilling the predictions of accumulation models.NEW & NOTEWORTHY We studied neurons in the brain's frontal eye field (FEF) to understand how these neurons predict swift eye shifts called saccades. We found that neurons with more movement-related activity were better at predicting saccades than those with sensory-related activity. Interestingly, electrical disruptions of this region strongly impacted saccade onset times but did not affect the individual neuron's saccade predictability, consistent with models suggesting that a specific threshold in neural activity triggers the saccade.

Rapid compensatory plasticity revealed by dynamic correlated activity in monkeys in vivo.

To produce adaptive behavior, neural networks must balance between plasticity and stability. Computational work has demonstrated that network stability requires plasticity mechanisms to be counterbalanced by rapid compensatory processes. However, such processes have yet to be experimentally observed. Here we demonstrate that repeated optogenetic activation of excitatory neurons in monkey visual cortex (area V1) induces a population-wide dynamic reduction in the strength of neuronal interactions over the timescale of minutes during the awake state, but not during rest. This new form of rapid plasticity was observed only in the correlation structure, with firing rates remaining stable across trials. A computational network model operating in the balanced regime confirmed experimental findings and revealed that inhibitory plasticity is responsible for the decrease in correlated activity in response to repeated light stimulation. These results provide the first experimental evidence for rapid homeostatic plasticity that primarily operates during wakefulness, which stabilizes neuronal interactions during strong network co-activation.

Enhanced behavioral performance through interareal gamma and beta synchronization

Cognitive functioning requires coordination between brain areas. Between visual areas, feedforward gamma synchronization improves behavioral performance. Here, we investigate whether similar principles hold across brain regions and frequency bands, using simultaneous electrocorticographic recordings from 15 areas of two macaque monkeys during performance of a selective attention task. Short behavioral reaction times (RTs), suggesting efficient interareal communication, occurred when occipital areas V1, V2, V4, and DP showed gamma synchronization, and fronto-central areas S1, 5, F1, F2, and F4 showed beta synchronization. For both area clusters and corresponding frequency bands, deviations from the typically observed phase relations increased RTs. Across clusters and frequency bands, good phase relations occurred in a correlated manner specifically when they processed the behaviorally relevant stimulus. Furthermore, the fronto-central cluster exerted a beta-band influence onto the occipital cluster whose strength predicted short RTs. These results suggest that local gamma and beta synchronization and their inter-regional coordination jointly improve behavioral performance.

Feedforward attentional selection in sensory cortex

Salient objects grab attention because they stand out from their surroundings. Whether this phenomenon is accomplished by bottom-up sensory processing or requires top-down guidance is debated. We tested these alternative hypotheses by measuring how early and in which cortical layer(s) neural spiking distinguished a target from a distractor. We measured synaptic and spiking activity across cortical columns in mid-level area V4 of male macaque monkeys performing visual search for a color singleton. A neural signature of attentional capture was observed in the earliest response in the input layer 4. The magnitude of this response predicted response time and accuracy. Errant behavior followed errant selection. Because this response preceded top-down influences and arose in the cortical layer not targeted by top-down connections, these findings demonstrate that feedforward activation of sensory cortex can underlie attentional priority.

The role of neural oscillations in visuo-motor communication at the time of saccades

Saccadic eye-movements are fundamental for active vision, allowing observers to purposefully scan the environment with the high-resolution fovea. In this brief perspective we outline a series of experiments from our laboratories investigating the role of eye-movements and their consequences to active perception. We show that saccades lead to suppression of visual sensitivity at saccadic onset, and that this suppression is accompanied by endogenous neural oscillations in the delta range. Similar oscillations are initiated by purposeful hand movements, which lead to measurable changes in responsivity in area V1, and in the connectivity with motor area M1. Saccades also lead to clear distortions in apparent position, but only for verbal reports, not when participants respond with rapid pointing, consistent with the action of two separate visual systems in neurotypical adults. At the time of saccades, serial dependence, the positive influence on perception of previous stimulus attributes (such as orientation) is particularly strong. Again, these processes are accompanied by neural oscillations, in the alpha and low beta range. In general, oscillations seem to be tightly linked to serial dependence in perception, both in auditory judgments (around 10 Hz), and for visual judgements of face gender (14 Hz for female, 17 Hz for male). Taken together, the studies show that neural oscillations play a fundamental role in dynamic, active vision.

Predicting the temporal-dynamic trajectories of cortical neuronal responses in non-human primates based on deep spiking neural network.

Deep convolutional neural networks (CNNs) are commonly used as computational models for the primate ventral stream, while deep spiking neural networks (SNNs) incorporated with both the temporal and spatial spiking information still lack investigation. We compared performances of SNN and CNN in prediction of visual responses to the naturalistic stimuli in area V4, inferior temporal (IT), and orbitofrontal cortex (OFC). The accuracies based on SNN were significantly higher than that of CNN in prediction of temporal-dynamic trajectory and averaged firing rate of visual response in V4 and IT. The temporal dynamics were captured by SNN for neurons with diverse temporal profiles and category selectivities, and most sensitively captured around the time of peak responses for each brain region. Consistently, SNN activities showed significantly stronger correlations with IT, V4 and OFC responses. In SNN, correlations with neural activities were stronger for later time-step features than early time-step features. The temporal-dynamic prediction was also significantly improved by considering preceding neural activities during the prediction. Thus, our study demonstrated SNN as a powerful temporal-dynamic model for cortical responses to complex naturalistic stimuli.

Feature-based Attentional Amplitude Modulations of the Steady-state Visual Evoked Potentials Reflect Blood Oxygen Level Dependent Changes in Feature-sensitive Visual Areas.

Recent EEG studies have investigated basic principles of feature-based attention by means of frequency-tagged random dot kinematograms in which different colors are simultaneously presented at different temporal frequencies to elicit steady-state visual evoked potentials (SSVEPs). These experiments consistently showed global facilitation of the to-be-attended random dot kinematogram-a basic principle of feature-based attention. SSVEP source estimation suggested that posterior visual cortex from V1 to area hMT+/V5 is broadly activated by frequency-tagged stimuli. What is presently unknown is whether the feature-based attentional facilitation of SSVEPs is a rather unspecific neural response including all visual areas that follow the "on/off," or whether SSVEP feature-based amplitude enhancements are driven by activity in visual areas most sensitive to a specific feature, such as V4v in the case of color. Here, we leverage multimodal SSVEP-fMRI recordings in human participants and a multidimensional feature-based attention paradigm to investigate this question. Attending to shape produced significantly greater SSVEP-BOLD covariation in primary visual cortex compared with color. SSVEP-BOLD covariation during color selection increased along the visual hierarchy, with greatest values in areas V3 and V4. Importantly, in area hMT+/V5, we found no differences between shape and color selection. Results suggest that SSVEP amplitude enhancements in feature-based attention is not an unspecific enhancement of neural activity in all visual areas following the "on/off." These findings open new avenues to investigating neural dynamics of competitive interactions in specific visual areas sensitive to a certain feature in a more economical way and better temporal resolution compared with fMRI.

Alice in wonderland syndrome – A medical enigma

Alice in Wonderland syndrome (AIWS) is a disorder in which patients report distorted visual perception and an impaired sense of time. It was first described in 1955 by the British psychiatrist John Todd, who associated these symptoms with disorders such as migraine and epilepsy. Before Todd’s observations, many symptoms of this disorder had made appearances in literature describing hysteria. Similar symptoms were observed in soldiers with occipital wounds after World Wars I and II. Patients with AIWS experience a plethora of symptoms such as, “kinetopsia” – Stationary objects appear to be moving, “total microsomatognosia” – Body parts appear unusually smaller. “Depersonalization” – Feeling of strangeness in perceiving one’s body image is common in AIWS. Often, this is accompanied by “derealisation” – Patients start perceiving their surroundings and the people around them as unreal. However, the patient is aware that this state of consciousness is not normal- which is what differentiates it from the state of psychosis. Other symptoms include: Dyschronometria, dysmorphops, macropsia, micropsia, kinetopsia, prosopometamorphopsia, and plagiopsia. In migraine patients, the prevalence rate of these symptoms increases to about 15%. Most symptoms of AIWS are ascribed to neurons of the central nervous system and cell columns that respond to specific sensory inputs (Ex- like visionary inputs of cortical areas V1–V5). Area V4 of the extrastriata visual cortex, particularly responds to the colors, whereas area V5 responds to movement. V4 and V5 also respond to shape and depth, but the bilateral loss of function of V4 results in achromatopsia (the inability to visualize color), and bilateral loss of V5 results in akinetopsia (the inability to visualize motion). Anatomically speaking, a critical region for developing this syndrome is the junction of three major areas, i.e., temporooccipital, parieto-occipital, and temporo-parietal junctions, known as the temporoparietal-occipital carrefour, point where our visual and somatosensory perceptions of the world are integrated to develop an external and internal representation of ourselves. AIWS remains a poorly understood and usually misdiagnosed syndrome. It is mostly associated with Epstein–Barr virus infection in children. Most cases of AIWS are expected to have a full remission of symptoms; sometimes, this may occur spontaneously with/without proper treatment. However, in cases with an associated chronic disease, like migraines and epilepsy, symptoms tend to occur in accordance with the active phases of these diseases. The number of fascinating disorders that surround and confound the medical community has no limit. The journey into the human brain is about as daunting and baffling as Alice’s journey into Wonderland. Efforts to understand the functioning and physiology of this extraordinary organ will keep both doctors and scientists on their toes for many years to come.

Investigation of layer-specific BOLD signal in the human visual cortex during visual attention

Directing spatial attention towards a particular stimulus location enhances cortical responses at corresponding regions in cortex. How attention modulates the laminar response profile within the attended region remains unclear, however. In this paper, we use high-field (7T) functional magnetic resonance imaging to investigate the effects of attention on laminar activity profiles in areas V1–V3 both when a stimulus was presented to the observer and in the absence of visual stimulation. Replicating previous findings, we find robust increases in the overall BOLD response for attended regions in cortex, both with and without visual stimulation. When analysing the BOLD response across the individual layers in visual cortex, we observed no evidence for laminar-specific differentiation with attention. We offer several potential explanations for these results, including theoretical, methodological and technical reasons. Additionally, we provide all data and pipelines openly in order to promote analytic consistency across layer-specific studies and improve reproducibility.

The representation of occluded image regions in area V1 of monkeys and humans

Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons' receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode individual scenes and could be predicted from those elicited by non-occluded images, indicating that there is an overlap between visually driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with functional magnetic resonance imaging (fMRI). Our results reveal that contextual influences rapidly alter V1 spiking activity in monkeys over distances of several degrees in the visual field, carry information about individual scenes, and resemble those in human V1.

Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.

The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs. We conducted a case-control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups. We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.

Neural patterns of conscious visual awareness in the Riddoch syndrome

The Riddoch syndrome is one in which patients blinded by lesions to their primary visual cortex can consciously perceive visual motion in their blind field, an ability that correlates with activity in motion area V5. Our assessment of the characteristics of this syndrome in patient ST, using multimodal MRI, showed that: 1. ST’s V5 is intact, receives direct subcortical input, and decodable neural patterns emerge in it only during the conscious perception of visual motion; 2. moving stimuli activate medial visual areas but, unless associated with decodable V5 activity, they remain unperceived; 3. ST’s high confidence ratings when discriminating motion at chance levels, is associated with inferior frontal gyrus activity. Finally, we report that ST’s Riddoch Syndrome results in hallucinatory motion with hippocampal activity as a correlate. Our results shed new light on perceptual experiences associated with this syndrome and on the neural determinants of conscious visual experience.

Laminar mechanisms of saccadic suppression in primate visual cortex

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

Visual cortical processing—From image to object representation

Image understanding is often conceived as a hierarchical process with many levels, where complexity and invariance of object representation gradually increase with level in the hierarchy. In contrast, neurophysiological studies have shown that figure-ground organization and border ownership coding, which imply understanding of the object structure of an image, occur at levels as low as V1 and V2 of the visual cortex. This cannot be the result of back-projections from object recognition centers because border-ownership signals appear well-before shape selective responses emerge in inferotemporal cortex. Ultra-fast border-ownership signals have been found not only for simple figure displays, but also for complex natural scenes. In this paper I review neurophysiological evidence for the hypothesis that the brain uses dedicated grouping mechanisms early on to link elementary features to larger entities we might call “proto-objects”, a process that is pre-attentive and does not rely on object recognition. The proto-object structures enable the system to individuate objects and provide permanence, to track moving objects and cope with the displacements caused by eye movements, and to select one object out of many and scrutinize the selected object. I sketch a novel experimental paradigm for identifying grouping circuits, describe a first application targeting area V4, which yielded negative results, and suggest targets for future applications of this paradigm.

Investigations of the subarachnoid space as a potential link between aura and headache in migraine: A case-control MRI study

Background The connection between migraine aura and headache is poorly understood. Some patients experience migraine aura without headache, and patients with migraine aura with headache commonly experience milder headaches with age. The distance between the cerebral cortex and the overlying dura mater has been hypothesized to influence development of headache following aura. We tested this hypothesis by comparing approximated distances between visual cortical areas and overlying dura mater between female patients with migraine aura without headache and female patients with migraine aura with headache. Methods Twelve cases with migraine aura without headache and 45 age-matched controls with migraine aura with headache underwent 3.0 T MRI. We calculated average distances between the occipital lobes, between the calcarine sulci, and between the skull and visual areas V1, V2 and V3a. We also measured volumes of corticospinal fluid between the occipital lobes, between the calcarine sulci, and overlying visual areas V2 and V3a. We investigated the relationship between headache status, distances and corticospinal fluid volumes using conditional logistic regression. Results Distances between the occipital lobes, calcarine sulci and between the skull and V1, V2 and V3a did not differ between patients with migraine aura with headache and patients with migraine aura without headache. We found no differences in corticospinal fluid volumes between groups. Conclusion We found no indication for a connection between visual migraine aura and headache based on cortico-cortical, cortex-to-skull distances, or corticospinal fluid volumes overlying visual cortical areas. Longitudinal studies with imaging sequences optimized for measuring the cortico-dural distance and a larger sample of patients are needed to further investigate the hypothesis.

Empirically validated theoretical analysis of visual-spatial perception under change of nervous system arousal.

Visual-spatial perception is a process for extracting the spatial relationship between objects in the environment. The changes in visual-spatial perception due to factors such as the activity of the sympathetic nervous system (hyperactivation) or parasympathetic nervous system (hypoactivation) can affect the internal representation of the external visual-spatial world. We formulated a quantitative model of the modulation of visual-perceptual space under action by hyperactivation or hypoactivation-inducing neuromodulating agents. We showed a Hill equation based relationship between neuromodulator agent concentration and alteration of visual-spatial perception utilizing the metric tensor to quantify the visual space. We computed the dynamics of the psilocybin (hyperactivation-inducing agent) and chlorpromazine (hypoactivation-inducing agent) in brain tissue. Then, we validated our quantitative model by analyzing the findings of different independent behavioral studies where subjects were assessed for alterations in visual-spatial perception under the action of psilocybin and under chlorpromazine. To validate the neuronal correlates, we simulated the effect of the neuromodulating agent on the computational model of the grid-cell network, and also performed diffusion MRI-based tractography to find the neural tracts between the cortical areas involved: V2 and the entorhinal cortex. We applied our computational model to an experiment (where perceptual alterations were measured under psilocybin) and found that for n (Hill-coefficient) = 14.8 and k = 1.39, the theoretical prediction followed experimental observations very well (χ2 test robustly satisfied, p > 0.99). We predicted the outcome of another psilocybin-based experiment using these values (n = 14.8 and k = 1.39), whereby our prediction and experimental outcomes were well corroborated. Furthermore, we found that also under hypoactivation (chlorpromazine), the modulation of the visual-spatial perception follows our model. Moreover, we found neural tracts between the area V2 and entorhinal cortex, thus providing a possible brain network responsible for encoding visual-spatial perception. Thence, we simulated the altered grid-cell network activity, which was also found to follow the Hill equation. We developed a computational model of visuospatial perceptual alterations under altered neural sympathetic/parasympathetic tone. We validated our model using analysis of behavioral studies, neuroimaging assessment, and neurocomputational evaluation. Our quantitative approach may be probed as a potential behavioral screening and monitoring methodology in neuropsychology to analyze perceptual misjudgment and mishaps by highly stressed workers.

Categorical working memory codes in human visual cortex

Working memory contents are represented in neural activity patterns across multiple regions of the cortical hierarchy. A division of labor has been proposed where more anterior regions harbor increasingly abstract and categorical representations while the most detailed representations are held in primary sensory cortices. Here, using fMRI and multivariate encoding modeling, we demonstrate that for color stimuli categorical codes are already present at the level of extrastriate visual cortex (V4 and VO1), even when subjects are neither implicitly nor explicitly encouraged to categorize the stimuli. Importantly, this categorical coding was observed during working memory, but not during perception. Thus, visual working memory is likely to rely at least in part on categorical representations. Significance statementWorking memory is the representational basis for human cognition. Recent work has demonstrated that numerous regions across the human brain can represent the contents of working memory. We use fMRI brain scanning and machine learning methods to demonstrate that different regions can represent the same content differently during working memory. Reading out the neural codes used to store working memory contents, we show that already in sensory cortex, areas V4 and VO1 represent color in a categorical format rather than a purely sensory fashion. Thereby, we provide a better understanding of how different regions of the brain might serve working memory and cognition.

The normalization model predicts responses during object-based attention in the human visual cortex.

Divisive normalization of the neural responses by the activity of the neighboring neurons has been proposed as a fundamental operation in the nervous system based on its success in predicting neural responses recorded in primate electrophysiology studies. Nevertheless, experimental evidence for the existence of this operation in the human brain is still scant. Here, using functional MRI, we explored the role of normalization across the visual hierarchy in the human visual cortex. Using stimuli form the two categories of human bodies and houses, we presented objects in isolation or in clutter and asked participants to attend or ignore the stimuli. Focusing on the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA, we first modeled single-voxel responses using a weighted sum, a weighted average, and a normalization model and demonstrated that although the weighted sum and weighted average models also made acceptable predictions in some conditions, the response to multiple stimuli could generally be better described by a model that takes normalization into account. We then explored the observed effects of attention on cortical responses and demonstrated that these effects were predicted by the normalization model, but not by the weighted sum or the weighted average models. Our results thus provide evidence that the normalization model can predict responses to objects across shifts of visual attention, suggesting the role of normalization as a fundamental operation in the human brain.

Parvalbumin as a neurochemical marker of the primate optic radiation

Parvalbumin (PV) is a calcium-binding protein that labels neuronal cell bodies in the magno and parvocellular layers of the primate lateral geniculate nucleus (LGN). Here we demonstrate that PV immunohistochemistry can also be used to trace the optic radiation (OR) of the marmoset monkey (Callithrix jacchus) from its LGN origin to its destinations in the primary visual cortex (V1), thus providing a high-resolution method for identification of the OR with single axon resolution. The emergence of fibers from LGN, their entire course and even the entry points to V1 were clearly defined in coronal, parasagittal, and horizontal sections of marmoset brain. In all cases, the trajectory revealed by PV staining paralleled that defined by high-resolution diffusion tensor imaging (DTI). We found that V1 was the exclusive target for the PV-containing fibers, with abrupt transitions in staining observed in the white matter at the border with area V2, and no evidence of PV-labeled axons feeding into other visual areas. Changes in the pattern of PV staining in the OR were detected following V1 lesions, demonstrating that this method can be used to assess the progress of retrograde degeneration of geniculocortical projections. These results suggest a technically simple approach to advance our understanding of a major white matter structure, which provides a cellular resolution suitable for the detection of microstructural variations during development, health and disease. Understanding the relationship between PV staining and DTI in non-human primates may also offer clues for improving the specificity and sensitivity of OR tractography for clinical purposes.

Intrinsic timescales in the visual cortex change with selective attention and reflect spatial connectivity

Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 in male monkeys performing spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales may arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.