Activity In Primary Visual Cortex Research Articles

Visually Driven Neuropil Activity and Information Encoding in Mouse Primary Visual Cortex.

Cortical neuropil modulations recorded by calcium imaging reflect the activity of large aggregates of axo-dendritic processes and synaptic compartments from a large number of neurons. The organization of this activity impacts neuronal firing but is not well understood. Here we used in vivo 2-photon imaging with Oregon Green Bapta (OGB) and GCaMP6s to study neuropil visual responses to moving gratings in layer 2/3 of mouse area V1. We found neuropil responses to be strongly modulated and more reliable than neighboring somatic activity. Furthermore, stimulus independent modulations in neuropil activity, i.e., noise correlations, were highly coherent across the cortical surface, up to distances of at least 200 μm. Pairwise neuropil-to-neuropil-patch noise correlation strength was much higher than cell-to-cell noise correlation strength and depended strongly on brain state, decreasing in quiet wakefulness relative to light anesthesia. The profile of neuropil noise correlation strength decreased gently with distance, dropping by ~11% at a distance of 200 μm. This was comparatively slower than the profile of cell-to-cell noise correlations, which dropped by ~23% at 200 μm. Interestingly, in spite of the “salt & pepper” organization of orientation and direction encoding across mouse V1 neurons, populations of neuropil patches, even of moderately large size (radius ~100 μm), showed high accuracy for discriminating perpendicularly moving gratings. This was commensurate to the accuracy of corresponding cell populations. The dynamic, stimulus dependent, nature of neuropil activity further underscores the need to carefully separate neuropil from cell soma activity in contemporary imaging studies.

Basal forebrain activation enhances between-trial reliability of low-frequency local field potentials (LFP) and spiking activity in tree shrew primary visual cortex (V1).

Brain state has profound effects on neural processing and stimulus encoding in sensory cortices. While the synchronized state is dominated by low-frequency local field potential (LFP) activity, low-frequency LFP power is suppressed in the desynchronized state, where a concurrent enhancement in gamma power is observed. Recently, it has been shown that cortical desynchronization co-occurs with enhanced between-trial reliability of spiking activity in sensory neurons, but it is currently unclear whether this effect is also evident in LFP signals. Here, we address this question by recording both spike trains and LFP in primary visual cortex during natural movie stimulation, and using isoflurane anesthesia and basal forebrain (BF) electrical activation as proxies for synchronized and desynchronized brain states. We show that indeed, low-frequency LFP modulations ("LFP events") also occur more reliably following BF activation. Interestingly, while being more reliable, these LFP events are smaller in amplitude compared to those generated in the synchronized brain state. We further demonstrate that differences in reliability of spiking activity between cortical states can be linked to amplitude and probability of LFP events. The correlated temporal dynamics between low-frequency LFP and spiking response reliability in visual cortex suggests that these effects may both be the result of the same neural circuit activation triggered by BF stimulation, which facilitates switching between processing of incoming sensory information in the desynchronized and reverberation of internal signals in the synchronized state.

Activity of primate V1 neurons during the gap saccade task.

When a saccadic eye movement is made toward a visual stimulus, the variability in accompanying primary visual cortex (V1) activity is related to saccade latency in both humans and simians. To understand the nature of this relationship, we examined the functional link between V1 activity and the initiation of visually guided saccades during the gap saccade task, in which a brief temporal gap is inserted between the turning off of a fixation stimulus and the appearance of a saccadic target. The insertion of such a gap robustly reduces saccade latency and facilitates the occurrence of extremely short-latency (express) saccades. Here we recorded single-cell activity from macaque V1 while monkeys performed the gap saccade task. In parallel with the gap effect on saccade latency the neural latency (time of first spike) of V1 response elicited by the saccade target became shorter, and the firing rate increased as the gap duration increased. Similarly, neural latency was shorter and firing rate was higher before express saccades relative to regular-latency saccades. In addition to these posttarget changes, the level of spontaneous spike activity during the pretarget period was negatively correlated with both neural and saccade latencies. These results demonstrate that V1 activity correlates with the gap effect and indicate that trial-to-trial variability in the state of V1 accompanies the variability of neural and behavioral latencies.NEW & NOTEWORTHY The link between neural activity in monkey primary visual cortex (V1) and visually guided behavioral response is confirmed with the gap saccade paradigm. Results indicated that the variability in neural latency of V1 spike activity correlates with the gap effect on saccade latency and that the trial-to-trial variability in the state of V1 before the onset of saccade target correlates with the variability in neural and behavioral latencies.

Volumetric two-photon imaging of neurons using stereoscopy (vTwINS).

Two-photon laser scanning microscopy of calcium dynamics using fluorescent indicators is a widely used imaging method for large scale recording of neural activity in vivo. Here we introduce volumetric Two-photon Imaging of Neurons using Stereoscopy (vTwINS), a volumetric calcium imaging method that employs an elongated, V-shaped point spread function to image a 3D brain volume. Single neurons project to spatially displaced “image pairs” in the resulting 2D image, and the separation distance between images is proportional to depth in the volume. To demix the fluorescence time series of individual neurons, we introduce a novel orthogonal matching pursuit algorithm that also infers source locations within the 3D volume. We illustrate vTwINS by imaging neural population activity in mouse primary visual cortex and hippocampus. Our results demonstrate that vTwINS provides an effective method for volumetric two-photon calcium imaging that increases the number of neurons recorded while maintaining a high frame-rate.

Recent Visual Experience Shapes Visual Processing in Rats through Stimulus-Specific Adaptation and Response Enhancement

From an ecological point of view, it is generally suggested that the main goal of vision in rats and mice is navigation and (aerial) predator evasion [1-3]. The latter requires fast and accurate detection of a changein the visual environment. An outstanding question is whether there are mechanisms in the rodent visual system that would support and facilitate visual change detection. An experimental protocol frequently used to investigate change detection in humans is the oddball paradigm, in which a rare, unexpected stimulus is presented in a train of stimulus repetitions [4]. A popular "predictive coding" theory of cortical responses states that neural responses should decrease for expected sensory input and increase for unexpected input [5, 6]. Despite evidence for response suppression and enhancement in noninvasive scalp recordings in humans with this paradigm [7, 8], it has proven challenging to observe both phenomena in invasive action potential recordings in other animals [9-11]. During a visual oddball experiment, we recorded multi-unit spiking activity in rat primary visual cortex (V1) and latero-intermediate area (LI), which is a higher area of the rodent ventral visual stream. In rat V1, there was only evidence for response suppression related to stimulus-specific adaptation, and not for response enhancement. However, higher up in area LI, spiking activity showed clear surprise-based response enhancement in addition to stimulus-specific adaptation. These results show that neural responses along the rat ventral visual stream become increasingly sensitive to changes in the visual environment, suggesting a system specialized in the detection of unexpected events.

Layer-specificity in the effects of attention and working memory on activity in primary visual cortex

Neuronal activity in early visual cortex depends on attention shifts but the contribution to working memory has remained unclear. Here, we examine neuronal activity in the different layers of the primary visual cortex (V1) in an attention-demanding and a working memory task. A current-source density analysis reveales top-down inputs in the superficial layers and layer 5, and an increase in neuronal firing rates most pronounced in the superficial and deep layers and weaker in input layer 4. This increased activity is strongest in the attention task but it is also highly reliable during working memory delays. A visual mask erases the V1 memory activity, but it reappeares at a later point in time. These results provide new insights in the laminar circuits involved in the top-down modulation of activity in early visual cortex in the presence and absence of visual stimuli.

Independent effects of motivation and spatial attention in the human visual cortex.

Motivation and attention constitute major determinants of human perception and action. Nonetheless, it remains a matter of debate whether motivation effects on the visual cortex depend on the spatial attention system, or rely on independent pathways. This study investigated the impact of motivation and spatial attention on the activity of the human primary and extrastriate visual cortex by employing a factorial manipulation of the two factors in a cued pattern discrimination task. During stimulus presentation, we recorded event-related potentials and pupillary responses. Motivational relevance increased the amplitudes of the C1 component at ∼70 ms after stimulus onset. This modulation occurred independently of spatial attention effects, which were evident at the P1 level. Furthermore, motivation and spatial attention had independent effects on preparatory activation as measured by the contingent negative variation; and pupil data showed increased activation in response to incentive targets. Taken together, these findings suggest independent pathways for the influence of motivation and spatial attention on the activity of the human visual cortex.

Functional neuroimaging of visuo-vestibular interaction

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues.

Apparent Motion Suppresses Responses in Early Visual Cortex: A Population Code Model.

Two stimuli alternately presented at different locations can evoke a percept of a stimulus continuously moving between the two locations. The neural mechanism underlying this apparent motion (AM) is thought to be increased activation of primary visual cortex (V1) neurons tuned to locations along the AM path, although evidence remains inconclusive. AM masking, which refers to the reduced detectability of stimuli along the AM path, has been taken as evidence for AM-related V1 activation. AM-induced neural responses are thought to interfere with responses to physical stimuli along the path and as such impair the perception of these stimuli. However, AM masking can also be explained by predictive coding models, predicting that responses to stimuli presented on the AM path are suppressed when they match the spatio-temporal prediction of a stimulus moving along the path. In the present study, we find that AM has a distinct effect on the detection of target gratings, limiting the maximum performance at high contrast levels. This masking is strongest when the target orientation is identical to the orientation of the inducers. We developed a V1-like population code model of early visual processing, based on a standard contrast normalization model. We find that AM-related activation in early visual cortex is too small to either cause masking or to be perceived as motion. Our model instead predicts strong suppression of early sensory responses during AM, consistent with the theoretical framework of predictive coding.

Enhanced Spatial Resolution During Locomotion and Heightened Attention in Mouse Primary Visual Cortex.

We do not fully understand how behavioral state modulates the processing and transmission of sensory signals. Here, we studied the cortical representation of the retinal image in mice that spontaneously switched between a state of rest and a constricted pupil, and one of active locomotion and a dilated pupil, indicative of heightened attention. We measured the selectivity of neurons in primary visual cortex for orientation and spatial frequency, as well as their response gain, in these two behavioral states. Consistent with prior studies, we found that preferred orientation and spatial frequency remained invariant across states, whereas response gain increased during locomotion relative to rest. Surprisingly, relative gain, defined as the ratio between the gain during locomotion and the gain during rest, was not uniform across the population. Cells tuned to high spatial frequencies showed larger relative gain compared with those tuned to lower spatial frequencies. The preferential enhancement of high-spatial-frequency information was also reflected in our ability to decode the stimulus from population activity. Finally, we show that changes in gain originate from shifts in the operating point of neurons along a spiking nonlinearity as a function of behavioral state. Differences in the relative gain experienced by neurons with high and low spatial frequencies are due to corresponding differences in how these cells shift their operating points between behavioral states. How behavioral state modulates the processing and transmission of sensory signals remains poorly understood. Here, we show that the mean firing rate and neuronal gain increase during locomotion as a result in a shift of the operating point of neurons. We define relative gain as the ratio between the gain of neurons during locomotion and rest. Interestingly, relative gain is higher in cells with preferences for higher spatial frequencies than those with low-spatial-frequency selectivity. This means that, during a state of locomotion and heightened attention, the population activity in primary visual cortex can support better spatial acuity, a phenomenon that parallels the improved spatial resolution observed in human subjects during the allocation of spatial attention.

Orbitofrontal Cortex and the Early Processing of Visual Novelty in Healthy Aging.

Event-related potential (ERP) studies have previously found that scalp topographies of attention-related ERP components show frontal shifts with age, suggesting an increased need for compensatory frontal activity to assist with top-down facilitation of attention. However, the precise neural time course of top-down attentional control in aging is not clear. In this study, 20 young (mean: 22 years) and 14 older (mean: 64 years) adults completed a three-stimulus visual oddball task while high-density ERPs were acquired. Colorful, novel distracters were presented to engage early visual processing. Relative to young controls, older participants exhibited elevations in occipital early posterior positivity (EPP), approximately 100 ms after viewing colorful distracters. Neural source models for older adults implicated unique patterns of orbitofrontal cortex (OFC; BA 11) activity during early visual novelty processing (100 ms), which was positively correlated with subsequent activations in primary visual cortex (BA 17). Older adult EPP amplitudes and OFC activity were associated with performance on tests of complex attention and executive function. These findings are suggestive of age-related, compensatory neural changes that may driven by a combination of weaker cortical efficiency and increased need for top-down control over attention. Accordingly, enhanced early OFC activity during visual attention may serve as an important indicator of frontal lobe integrity in healthy aging.

Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters

Objective. A traditional goal of neural recording with extracellular electrodes is to isolate action potential waveforms of an individual neuron. Recently, in brain–computer interfaces (BCIs), it has been recognized that threshold crossing events of the voltage waveform also convey rich information. To date, the threshold for detecting threshold crossings has been selected to preserve single-neuron isolation. However, the optimal threshold for single-neuron identification is not necessarily the optimal threshold for information extraction. Here we introduce a procedure to determine the best threshold for extracting information from extracellular recordings. We apply this procedure in two distinct contexts: the encoding of kinematic parameters from neural activity in primary motor cortex (M1), and visual stimulus parameters from neural activity in primary visual cortex (V1). Approach. We record extracellularly from multi-electrode arrays implanted in M1 or V1 in monkeys. Then, we systematically sweep the voltage detection threshold and quantify the information conveyed by the corresponding threshold crossings. Main Results. The optimal threshold depends on the desired information. In M1, velocity is optimally encoded at higher thresholds than speed; in both cases the optimal thresholds are lower than are typically used in BCI applications. In V1, information about the orientation of a visual stimulus is optimally encoded at higher thresholds than is visual contrast. A conceptual model explains these results as a consequence of cortical topography. Significance. How neural signals are processed impacts the information that can be extracted from them. Both the type and quality of information contained in threshold crossings depend on the threshold setting. There is more information available in these signals than is typically extracted. Adjusting the detection threshold to the parameter of interest in a BCI context should improve our ability to decode motor intent, and thus enhance BCI control. Further, by sweeping the detection threshold, one can gain insights into the topographic organization of the nearby neural tissue.

Rivalry-Like Neural Activity in Primary Visual Cortex in Anesthetized Monkeys.

When visual input is ambiguous, for example, in viewing bistable images, human subjects normally perceive one of the interpretations at a particular moment. Previous studies have shown that both low-level visual processing and high-level attention contribute to the establishment of the final visual perception. However, it is not clear whether attention is indispensable in such a process. Here we show that rivalry-like neural activity persisted in monkey V1 when the monkeys were anesthetized and viewed binocularly incongruent stimuli. Such activity has many key features similar to those observed in conscious human subjects. These findings indicate that low-level visual processes play a critical role in solving visual ambiguity such as binocular rivalry.

SMA Selectively Codes the Active Accumulation of Temporal, Not Spatial, Magnitude.

Estimating duration depends on the sequential integration (accumulation) of temporal information in working memory. Using fMRI, we directly compared the accumulation of information in temporal versus spatial domains. Participants estimated either the duration or distance of the dynamic trajectory of a moving dot or, in a control condition, a static line stimulus. Comparing the duration versus distance of static lines activated an extensive cortico-striatal network. By contrast, comparing the duration versus distance of dynamic trajectories, both of which required sequential integration of information, activated SMA alone. Indeed, activity in SMA, as well as right inferior occipital cortex, increased parametrically as a function of stimulus duration and also correlated with individual differences in the propensity to overestimate stimulus duration. By contrast, activity in primary visual cortex increased parametrically as a function of stimulus distance. Crucially, a direct comparison of the parametric responses to duration versus distance revealed that activity in SMA increased incrementally as a function of stimulus duration but not as a function of stimulus distance. Collectively, our results indicate that SMA responds to the active accumulation of information selectively in the temporal domain.

Peripheral sounds rapidly activate visual cortex: evidence from electrocorticography

Neurophysiological studies with animals suggest that sounds modulate activity in primary visual cortex in the presence of concurrent visual stimulation. Noninvasive neuroimaging studies in humans have similarly shown that sounds modulate activity in visual areas even in the absence of visual stimuli or visual task demands. However, the spatial and temporal limitations of these noninvasive methods prevent the determination of how rapidly sounds activate early visual cortex and what information about the sounds is relayed there. Using spatially and temporally precise measures of local synaptic activity acquired from depth electrodes in humans, we demonstrate that peripherally presented sounds evoke activity in the anterior portion of the contralateral, but not ipsilateral, calcarine sulcus within 28 ms of sound onset. These results suggest that auditory stimuli rapidly evoke spatially specific activity in visual cortex even in the absence of concurrent visual stimulation or visual task demands. This rapid auditory-evoked activation of primary visual cortex is likely to be mediated by subcortical pathways or direct cortical projections from auditory to visual areas.

The role of the different layers of primary visual cortex in working memory

Imaging studies have revealed a neuronal correlate of working memory in primary visual cortex (Harrison & Tong, Nature, 2009). However, it is unknown if working memories influence spiking activity in the primary visual cortex. To address this question, we recorded neuronal activity in the primary visual cortex of monkeys trained to perform attentional and working memory tasks with a probe that records activity in all the cortical layers. We found a consistent working memory trace in the spiking activity in the superficial and deep layers of monkey V1, and only a weak memory representation in input layer 4. This V1 memory trace could be disrupted with a visual mask, but it then quickly recovered. The advantage of the laminar probe is that is also gives insight into the current-source density, which reveals the putative synaptic sources of memory activity. The current-source density measurements revealed a characteristic signature of feedback processing with putative synaptic inputs in the superficial and deep layers for working memory. This signature resembles the signature of selective attention, supporting the view that top-down modulation of activity in primary visual cortex underlies both working memory and attention. Our results provide new insights into the role of early visual cortex in working memory.

In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse.

In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1.

Phosphene Perception Relates to Visual Cortex Glutamate Levels and Covaries with Atypical Visuospatial Awareness.

Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy. We further examined whether phosphene thresholds would relate to the visuospatial phenomenology of grapheme-color synesthesia, a condition characterized by atypical binding and involuntary color photisms. Phosphene thresholds negatively correlated with glutamate concentrations in visual cortex, with lower thresholds associated with elevated glutamate. This relationship was robust, present in both controls and synesthetes, and exhibited neurochemical, topographic, and threshold specificity. Projector synesthetes, who experience color photisms as spatially colocalized with inducing graphemes, displayed lower phosphene thresholds than associator synesthetes, who experience photisms as internal images, with both exhibiting lower thresholds than controls. These results suggest that phosphene perception is driven by interindividual variation in glutamatergic activity in primary visual cortex and relates to cortical processes underlying individual differences in visuospatial awareness.

Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections.

The medial prefrontal cortex (mPFC) exerts top-down control of primary visual cortex (V1) activity. As there is no direct neuronal projection from mPFC to V1, this functional connection may use an indirect route, i.e., via basalo-cortical cholinergic projections. The cholinergic projections to V1 originate from neurons in the horizontal limb of the diagonal band of Broca (HDB), which receive neuronal projections from the ventral part of the mPFC, composed of prelimbic (PrL) and infralimbic cortices (IL). Therefore, the objective of this study was to determine whether electrical stimulation of mice mPFC subregions activate (1) V1 neurons; and (2) HDB cholinergic neurons, suggesting that the HDB serves as a relay point in the mPFC-V1 interaction. Neuronal activation was quantified using c-Fos immunocytochemistry or thallium autometallography for each V1 layer using automated particle analysis tools and optical density measurement. Stimulation of IL and PrL induced significantly higher c-Fos expression or thallium labeling in layers II/III and V of V1 in the stimulated hemisphere only. A HDB cholinergic neuron-specific lesion by saporin administration reduced IL-induced c-Fos expression in layers II/III of V1 but not in layer V. However, there was no c-Fos expression or thallium labeling in the HDB neurons, suggesting that this area was not activated by IL stimulation. Stimulation of another mPFC subarea, the anterior cingulate cortex (AC), which is involved in attention and receives input from V1, activated neither V1 nor HDB. The present results indicate that IL and PrL, but not AC, stimulation activates V1 with the minor involvement of the HDB cholinergic projections. These results suggest a functional link between the ventral mPFC and V1, but this function is only marginally supported by HDB cholinergic neurons and may involve other brain regions.

Functional PET Scan in Four Patients with Higher Order Neglect-Like Cognitive Dysfunction Associated to Chiasm Related Pathology

Cognitive disturbances with neglect-like features have been reported occasionally in patients with chiasmal disorders, so far however with no obvious substrate by conventional brain imaging. Thus, there were no right hemisphere lesions that could explain the lateralised visual inattention as observed in particular during monocular visual acuity testing. On this background, we further examined four adult patients who consented to functional 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) scan. In three there were no significant findings. The fourth patient, a 26-year-old male with cognitive defects after surgery for craniopharyngioma, will be discussed in more detail. His PET scan demonstrated a widespread reduction of regional metabolic activity in left hemisphere primary visual cortex and higher order visual areas, despite absence of explanatory pathological signal changes on MRI. As present in only one out of four patients, however, the findings do not allow specific pathogenetic mechanisms to be suggested, nor generally to substantiate involvement of higher cerebral circuits. Obviously, even developed imaging has its limits, and in the very theory the visual dysfunctions observed might still depend on higher brain centres’ faulty adaptation to loss of pre-geniculate visual information.