Responses In Primary Visual Cortex Research Articles

The representational geometry for naturalistic textures in macaque V1 and V2.

Our understanding of visual cortical processing has relied primarily on studying the selectivity of individual neurons in different areas. A complementary approach is to study how the representational geometry of neuronal populations differs across areas. Though the geometry is derived from individual neuronal selectivity, it can reveal encoding strategies difficult to infer from single neuron responses. In addition, recent theoretical work has begun to relate distinct functional objectives to different representational geometries. To understand how the representational geometry changes across stages of processing, we measured neuronal population responses in primary visual cortex (V1) and area V2 of macaque monkeys to an ensemble of synthetic, naturalistic textures. Responses were lower dimensional in V2 than V1, and there was a better alignment of V2 population responses to different textures. The representational geometry in V2 afforded better discriminability between out-of-sample textures. We performed complementary analyses of standard convolutional network models, which did not replicate the representational geometry of cortex. We conclude that there is a shift in the representational geometry between V1 and V2, with the V2 representation exhibiting features of a low-dimensional, systematic encoding of different textures and of different instantiations of each texture. Our results suggest that comparisons of representational geometry can reveal important transformations that occur across successive stages of visual processing.

Data-driven modelling of visual receptive fields: comparison between the generalized quadratic model and the nonlinear input model

Objective: Neurons in primary visual cortex (V1) display a range of sensitivity in their response to translations of their preferred visual features within their receptive field: from high specificity to a precise position through to complete invariance. This visual feature selectivity and invariance is frequently modeled by applying a selection of linear spatial filters to the input image, that define the feature selectivity, followed by a nonlinear function that combines the filter outputs, that defines the invariance, to predict the neural response. We compare two such classes of model, that are both popular and parsimonious, the generalized quadratic model (GQM) and the nonlinear input model (NIM). These two classes of model differ primarily in that the NIM can accommodate a greater diversity in the form of nonlinearity that is applied to the outputs of the filters. Approach: We compare the two model types by applying them to data from multielectrode recordings from cat primary visual cortex in response to spatially white Gaussian noise After fitting both classes of model to a database of 342 single units (SUs), we analyze the qualitative and quantitative differences in the visual feature processing performed by the two models and their ability to predict neural response. Main results: We find that the NIM predicts response rates on a held-out data at least as well as the GQM for 95% of SUs. Superior performance occurs predominantly for those units with above average spike rates and is largely due to the NIMs ability to capture aspects of the model’s nonlinear function cannot be captured with the GQM rather than differences in the visual features being processed by the two different models. Significance: These results can help guide model choice for data-driven receptive field modelling.

Normalization by orientation-tuned surround in human V1-V3.

An influential account of neuronal responses in primary visual cortex is the normalized energy model. This model is often implemented as a multi-stage computation. The first stage is linear filtering. The second stage is the extraction of contrast energy, whereby a complex cell computes the squared and summed outputs of a pair of the linear filters in quadrature phase. The third stage is normalization, in which a local population of complex cells mutually inhibit one another. Because the population includes cells tuned to a range of orientations and spatial frequencies, the result is that the responses are effectively normalized by the local stimulus contrast. Here, using evidence from human functional MRI, we show that the classical model fails to account for the relative responses to two classes of stimuli: straight, parallel, band-passed contours (gratings), and curved, band-passed contours (snakes). The snakes elicit fMRI responses that are about twice as large as the gratings, yet a traditional divisive normalization model predicts responses that are about the same. Motivated by these observations and others from the literature, we implement a divisive normalization model in which cells matched in orientation tuning ("tuned normalization") preferentially inhibit each other. We first show that this model accounts for differential responses to these two classes of stimuli. We then show that the model successfully generalizes to other band-pass textures, both in V1 and in extrastriate cortex (V2 and V3). We conclude that even in primary visual cortex, complex features of images such as the degree of heterogeneity, can have large effects on neural responses.

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1)-a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence-a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations-and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that although basic adaptation to redundant stimuli was present early (50ms) in layer 4 responses, DD emerged later (150-230ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7Hz) and high-gamma (70-80Hz) oscillations in L2/3 and decreased beta oscillations (26-36Hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, whereas "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

Parabolic avalanche scaling in the synchronization of cortical cell assemblies

Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced E/I-networks. The corresponding time course of an inverted parabola with exponent of χ = 2 described cortical avalanches of coincident firing for up to 5 s duration over an area of 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches.

Convolutional neural network classifies visual stimuli from cortical response recorded with wide-field imaging in mice

Objective. The optic nerve is a good location for a visual neuroprosthesis. It can be targeted when a subject cannot receive a retinal prosthesis and it is less invasive than a cortical implant. The effectiveness of an electrical neuroprosthesis depends on the combination of the stimulation parameters which must be optimized, and an optimization strategy might be performing closed-loop stimulation using the evoked cortical response as feedback. However, it is necessary to identify target cortical activation patterns and to associate the cortical activity with the visual stimuli present in the visual field of the subjects. Visual stimuli decoding should be performed on large areas of the visual cortex, and with a method as translational as possible to shift the study to human subjects in the future. The aim of this work is to develop an algorithm that meets these requirements and can be leveraged to automatically associate a cortical activation pattern with the visual stimulus that generated it. Approach. Three mice were presented with ten different visual stimuli, and their primary visual cortex response was recorded using wide-field calcium imaging. Our decoding algorithm relies on a convolutional neural network (CNN), trained to classify the visual stimuli from the correspondent wide-field images. Several experiments were performed to identify the best training strategy and investigate the possibility of generalization. Main results. The best classification accuracy was 75.38% ± 4.77%, obtained pre-training the CNN on the MNIST digits dataset and fine-tuning it on our dataset. Generalization was possible pre-training the CNN to classify Mouse 1 dataset and fine-tuning it on Mouse 2 and Mouse 3, with accuracies of 64.14% ± 10.81% and 51.53% ± 6.48% respectively. Significance. The combination of wide-field calcium imaging and CNNs can be used to classify the cortical responses to simple visual stimuli and might be a viable alternative to existing decoding methodologies. It also allows us to consider the cortical activation as reliable feedback in future optic nerve stimulation experiments.

Brightness illusions evoke pupil constriction preceded by a primary visual cortex response in rats.

The mind affects the body via central nervous system (CNS) control of the autonomic nervous system (ANS). In humans, one striking illustration of the "mind-body" connection is that illusions, subjectively perceived as bright, drive pupil constriction. The CNS network driving this pupil response is unknown and requires an animal model for investigation. However, the pupil response to this illusion has long been thought to occur only in humans. Here, we report that the same brightness illusion that evokes pupil constriction in humans also does so in rats. We surveyed the role of most of rat cortex in this "mind-body" connection by recording cortex-wide EEG. These recordings revealed that, compared to a luminance-matched control stimulus, the illusion of brightness for a specific stimulus color and size, evoked a larger response in primary visual cortex (V1) and not in secondary visual, parietal, or frontal cortex. The response preceded pupil constriction suggesting a potential causal role of V1 on the pupil. Our results provide evidence that this "mind-body" connection is not confined to humans and that V1 may be part of a mammalian CNS network for bodily reactions to illusions.

Visuomotor Mismatch Responses as a Hallmark of Explaining Away in Causal Inference.

How are visuomotor mismatch responses in primary visual cortex embedded into cortical processing? We here show that mismatch responses can be understood as the result of a cooperation of motor and visual areas to jointly explain optic flow. This cooperation requires that optic flow is not explained redundantly by both areas, meaning that optic flow inputs to V1 that are predictable from motor neurons should be canceled (i.e., explained away). As a result, neurons in V1 represent only external causes of optic flow, which could allow the animal to easily detect movements that are independent of its own locomotion. We implement the proposed model in a spiking neural network, where coding errors are computed in dendrites and synaptic weights are learned with voltage-dependent plasticity rules. We find that both positive and negative mismatch responses arise, providing an alternative to the prevailing idea that visuomotor mismatch responses are linked to dedicated neurons for error computation. These results also provide a new perspective on several other recent observations of cross-modal neural interactions in cortex.

Juvenile depletion of microglia reduces orientation but not high spatial frequency selectivity in mouse V1

Microglia contain multiple mechanisms that shape the synaptic landscape during postnatal development. Whether the synaptic changes mediated by microglia reflect the developmental refinement of neuronal responses in sensory cortices, however, remains poorly understood. In postnatal life, the development of increased orientation and spatial frequency selectivity of neuronal responses in primary visual cortex (V1) supports the emergence of high visual acuity. Here, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to rapidly and durably deplete microglia in mice during the juvenile period in which increased orientation and spatial frequency selectivity emerge. Excitatory and inhibitory tuning properties were measured simultaneously using multi-photon calcium imaging in layer II/III of mouse V1. We found that microglia depletion generally increased evoked activity which, in turn, reduced orientation selectivity. Surprisingly, microglia were not required for the emergence of high spatial frequency tuned responses. In addition, microglia depletion did not perturb cortical binocularity, suggesting normal depth processing. Together, our finding that orientation and high spatial frequency selectivity in V1 are differentially supported by microglia reveal that microglia are required normal sensory processing, albeit selectively.

Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism.SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential "hypo-priors" theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.

The human primary visual cortex (V1) encodes the perceived position of static but not moving objects

Brain activity in retinotopic cortex reflects illusory changes in stimulus position. Is this neural signature a general code for apparent position? Here we show that responses in primary visual cortex (V1) are consistent with perception of the Muller-Lyer illusion; however, we found no such signature for another striking illusion, the curveball effect. This demonstrates that V1 does not encode apparent position per se.

A cortical circuit for audio-visual predictions

Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these interactions are mediated or at what level of the processing hierarchy they occur. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices in mice. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons that are responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be communicated by long-range cortical connections and that, with learning, these cross-modal connections function to suppress responses to predictable input.

BOLD signal response in primary visual cortex to flickering checkerboard increases with stimulus temporal frequency in older adults.

Many older adults have difficulty seeing brief visual stimuli which younger adults can easily recognize. The primary visual cortex (V1) may induce this difficulty. However, in neuroimaging studies, the V1 response change to the increase of temporal frequency of visual stimulus in older adults was unclear. Here we investigated the association between the temporal frequency of flickering stimuli and the BOLD activity within V1 in older adults, using surface-based fMRI analysis. The fMRI data from 29 healthy older participants stimulated by contrast-reversing checkerboard at temporal flicker frequencies of 2, 4, and 8 Hz were obtained. The participants also performed a useful field of view (UFOV) test. The slope coefficient of BOLD activity regarding the temporal frequency of the visual stimulus averaged within V1 regions of interest was positive and significantly different from zero. Group analysis in the V1 showed significant clusters with positive slope and no significant clusters with a negative slope. The correlation coefficient between the slope coefficient and UFOV performance was not significant. The results indicated that V1 BOLD response to a flickering visual stimulus increases as the stimulus temporal frequency increases from 2 to 8 Hz in older adults.

Spatial modulation of dark versus bright stimulus responses in the mouse visual system

A fundamental task of the visual system is to respond to both increases and decreases of luminance with action potentials (ON and OFF responses1-4). OFF responses are stronger, faster, and more salient than ON responses in primary visual cortex (V1) of both cats5,6 and primates,7,8 but in ferrets9 and mice,10 ON responses can be stronger, weaker,11 or balanced12 in comparison to OFF responses. These discrepancies could arise from differences in species, experimental techniques, or stimulus properties, particularly retinotopic location in the visual field, as has been speculated;9 however, the role of retinotopy for ON/OFF dominance has not been systematically tested across multiple scales of neural activity within species. Here, we measured OFF versus ON responses across large portions of visual space with silicon probe and whole-cell patch-clamp recordings in mouse V1 and lateral geniculate nucleus (LGN). We found that OFF responses dominated in the central visual field, whereas ON and OFF responses were more balanced in the periphery. These findings were consistent across local field potential (LFP), spikes, and subthreshold membrane potential in V1, and were aligned with spatial biases in ON and OFF responses in LGN. Our findings reveal that retinotopy may provide a common organizing principle for spatial modulation of OFF versus ON processing in mammalian visual systems.

Differential activation of c-Fos and Egr1 during development of the mouse visual cortex

Background: Critical periods (CP) in brain development are characterized by heightened neural plasticity in the relevant brain regions. They are associated with changes in gene expression cascades, in particular with altered expression of genes involved in plasticity regulation, such as immediate early genes. Here we examine the expression of the immediate early genes c-Fos and Egr1 at different stages of mouse visual cortex (VC) development. Methods: Mice 11, 25, and 50 days of age were maintained under standard light-dark conditions, deprived of light for 5 days, or deprived of light for 5 days and then exposed to light for 90 min. Their brains were analyzed at PND16 (before the onset of the CP), PND30 (during the CP) and PND55 (after the CP) to determine the changes in the number of cells expressing c-Fos and Egr1 in the binocular primary visual and primary somatosensory cortices. Results: We found highly specific induction of c-Fos expression in the primary VC in response to light. We also observed transient cross-modal activation of c-Fos in the barrel field of the primary somatosensory cortex in response to light before and during the CP; such activation disappeared after the CP. Expression of Egr1 was not induced by light in the VC before the CP, but was evident during and after the CP, although the induction was much less pronounced than that of c-Fos. Conclusions: Dynamic changes in c-Fos and Egr1 expression may reflect their contribution to the VC plasticity during the CPs of postnatal brain development.

Cortical Reorganization: Reallocated Responses without Rewiring

Summary Is the brain able to reorganise following loss of sensory input? New work on individuals with sight loss shows that, while brain areas normally allocated to vision respond to other sensory stimuli, those responses are unlikely to mean the brain has rewired.

Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice

Retinal degeneration (rd) is one of the leading causes of blindness in the modern world today. Various strategies including electrical stimulation are being researched for the restoration of partial or complete vision. Previous studies have demonstrated that the effectiveness of electrical stimulation in somatosensory, frontal and visual cortices is dependent on stimulation parameters including stimulation frequency and brain states. The aim of the study is to investigate the effect of applying a prolonged electrical stimulation on the eye of rd mice with various stimulation frequencies, in awake and anesthetized brain states. We recorded spontaneous electrocorticogram (ECoG) neural activity in prefrontal cortex and primary visual cortex in a mouse model of retinitis pigmentosa (RP) after prolonged (5-day) transcorneal electrical stimulation (pTES) at various frequencies (2, 10, and 20 Hz). We evaluated the absolute power and coherence of spontaneous ECoG neural activities in contralateral primary visual cortex (contra Vcx) and contralateral pre-frontal cortex (contra PFx). Under the awake state, the absolute power of theta, alpha and beta oscillations in contra Vcx, at 10 Hz stimulation, was higher than in the sham group. Under the anesthetized state, the absolute power of medium-, high-, and ultra-high gamma oscillations in the contra PFx, at 2 Hz stimulation, was higher than in the sham group. We also observed that the ultra-high gamma band coherence in contra Vcx-contra PFx was higher than in the sham group, with both 10 and 20 Hz stimulation frequencies. Our results showed that pTES modulates rd brain oscillations in a frequency and brain state-dependent manner. These findings suggest that non-invasive electrical stimulation of retina changes patterns of neural oscillations in the brain circuitry. This also provides a starting point for investigating the sustained effect of electrical stimulation of the retina to brain activities.

Residual contrast response in primary visual cortex of rats with inherited retinal degeneration

Rhodopsin S334ter-3 retinal degeneration rats have been widely used to investigate degenerative diseases of the retina. In this model, morphological and electrophysiological changes have been observed in the retina, superior colliculus and primary visual cortex (V1). However, no study so far has examined rhodopsin S334ter-3 rats with regards to their contrast response in V1 — a fundamental property of visual information processing. In this study, experimental rats (S334ter-3) carried one copy of the mutant transgene. We compared responses to spatio-temporal variations in luminance contrast in the primary visual cortex of these rats with those in Long-Evans (LE) rats to elucidate the degeneration-specific activity changes in this part of the visual pathway. We measured extracellular responses to different stimulus contrasts at the preferred parameters of each recorded cell under classical receptive field (CRF) stimulation. Our results show that V1 cells in the S334ter-3 group exhibit stronger spontaneous activity but weaker stimulus-evoked responses at medium and high contrasts. By fitting responses to a sigmoid function, we found that the S334ter-3 group had a lower Rmax but a larger exponent N than the LE group. However, we did not find a significant difference in C50 value. These results indicate the decrease in discriminating the stimuli contrast and loss in responses and lower signal to noise ratio after retinal degeneration. Our study supports the notion that a considerable degree of plasticity is found in cortex after retinal degeneration, indicating that visual restoration therapies would succeed if the retina could send useful signals to the brain.

Pull-push neuromodulation of cortical plasticity enables rapid bi-directional shifts in ocular dominance.

Neuromodulatory systems are essential for remodeling glutamatergic connectivity during experience-dependent cortical plasticity. This permissive/enabling function of neuromodulators has been associated with their capacity to facilitate the induction of Hebbian forms of long-term potentiation (LTP) and depression (LTD) by affecting cellular and network excitability. In vitro studies indicate that neuromodulators also affect the expression of Hebbian plasticity in a pull-push manner: receptors coupled to the G-protein Gs promote the expression of LTP at the expense of LTD, and Gq-coupled receptors promote LTD at the expense of LTP. Here we show that pull-push mechanisms can be recruited in vivo by pairing brief monocular stimulation with pharmacological or chemogenetical activation of Gs- or Gq-coupled receptors to respectively enhance or reduce neuronal responses in primary visual cortex. These changes were stable, inducible in adults after the termination of the critical period for ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation.

Concomitant modulation of BOLD responses in white matter pathways and cortex

In response to a flickering visual stimulus, the BOLD response in primary visual cortex varies with the flickering frequency and is maximal when it is close to 8Hz. In previous studies we demonstrated that BOLD signals in specific white matter (WM) pathways covary with the alternations between stimulus conditions in a block design in similar manner to gray matter (GM) regions. Here we investigated whether WM tracts show varying responses to changes in flicker frequency and are modulated in the same manner as cortical areas. We used a Fourier analysis of BOLD signals to measure the signal amplitude and phase at the fundamental frequency of a block-design task in which flickering visual stimuli alternated with blank presentations, avoiding the assumption of any specific hemodynamic response function. The BOLD responses in WM pathways and the primary visual cortex were evaluated for flicker frequencies varying between 2 and 14Hz. The variations with frequency of BOLD signals in specific WM tracts followed closely those in primary visual cortex, suggesting that variations in cortical activation are directly coupled to corresponding BOLD signals in connected WM tracts. Statistically significant differences in the timings of BOLD responses were also measured between visual cortex and specific WM bundles. These results confirm that when cortical BOLD responses are modulated by selecting different task parameters, relevant WM tracts exhibit corresponding BOLD signals that are also affected.