Robust Coding of Eye Position in Posterior Parietal Cortex despite Context-Dependent Tuning.

Neurons in posterior parietal cortex (PPC) encode many aspects of the sensory world (e.g., scene structure), the posture of the body, and plans for action. For a downstream computation, however, only some of these dimensions are relevant; the rest are "nuisance variables" because their influence on neural activity changes with sensory and behavioral context, potentially corrupting the read-out of relevant information. Here we show that a key postural variable for vision (eye position) is represented robustly in male macaque PPC across a range of contexts, although the tuning of single neurons depended strongly on context. Contexts were defined by different stages of a visually guided reaching task, including (1) a visually sparse epoch, (2) a visually rich epoch, (3) a "go" epoch in which the reach was cued, and (4) during the reach itself. Eye position was constant within trials but varied across trials in a 3 × 3 grid spanning 24° × 24°. Using demixed principal component analysis of neural spike-counts, we found that the subspace of the population response encoding eye position is orthogonal to that encoding task context. Accordingly, a context-naive (fixed-parameter) decoder was nevertheless able to estimate eye position reliably across contexts. Errors were small given the sample size (∼1.78°) and would likely be even smaller with larger populations. Moreover, they were comparable to that of decoders that were optimized for each context. Our results suggest that population codes in PPC shield encoded signals from crosstalk to support robust sensorimotor transformations across contexts.SIGNIFICANCE STATEMENT Neurons in posterior parietal cortex (PPC) which are sensitive to gaze direction are thought to play a key role in spatial perception and behavior (e.g., reaching, navigation), and provide a potential substrate for brain-controlled prosthetics. Many, however, change their tuning under different sensory and behavioral contexts, raising the prospect that they provide unreliable representations of egocentric space. Here, we analyze the structure of encoding dimensions for gaze direction and context in PPC during different stages of a visually guided reaching task. We use demixed dimensionality reduction and decoding techniques to show that the coding of gaze direction in PPC is mostly invariant to context. This suggests that PPC can provide reliable spatial information across sensory and behavioral contexts.

Motion Perception in the Common Marmoset.

Visual motion processing is a well-established model system for studying neural population codes in primates. The common marmoset, a small new world primate, offers unparalleled opportunities to probe these population codes in key motion processing areas, such as cortical areas MT and MST, because these areas are accessible for imaging and recording at the cortical surface. However, little is currently known about the perceptual abilities of the marmoset. Here, we introduce a paradigm for studying motion perception in the marmoset and compare their psychophysical performance with human observers. We trained two marmosets to perform a motion estimation task in which they provided an analog report of their perceived direction of motion with an eye movement to a ring that surrounded the motion stimulus. Marmosets and humans exhibited similar trade-offs in speed versus accuracy: errors were larger and reaction times were longer as the strength of the motion signal was reduced. Reverse correlation on the temporal fluctuations in motion direction revealed that both species exhibited short integration windows; however, marmosets had substantially less nondecision time than humans. Our results provide the first quantification of motion perception in the marmoset and demonstrate several advantages to using analog estimation tasks.

Mechanisms of Feature Selectivity and Invariance in Primary Visual Cortex.

Visual object identification requires both selectivity for specific visual features that are important to the object's identity and invariance to feature manipulations. For example, a hand can be shifted in position, rotated, or contracted but still be recognized as a hand. How are the competing requirements of selectivity and invariance built into the early stages of visual processing? Typically, cells in the primary visual cortex are classified as either simple or complex. They both show selectivity for edge-orientation but complex cells develop invariance to edge position within the receptive field (spatial phase). Using a data-driven model that extracts the spatial structures and nonlinearities associated with neuronal computation, we quantitatively describe the balance between selectivity and invariance in complex cells. Phase invariance is frequently partial, while invariance to orientation and spatial frequency are more extensive than expected. The invariance arises due to two independent factors: (1) the structure and number of filters and (2) the form of nonlinearities that act upon the filter outputs. Both vary more than previously considered, so primary visual cortex forms an elaborate set of generic feature sensitivities, providing the foundation for more sophisticated object processing.

Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons.

Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.

A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.

Contrast-dependent phase sensitivity in V1 but not V2 of macaque visual cortex.

Some neurons in early visual cortex are highly selective for the position of oriented edges in their receptive fields (simple cells), whereas others are largely position insensitive (complex cells). These characteristics are reflected in their sensitivity to the spatial phase of moving sine-wave gratings: simple cell responses oscillate at the fundamental frequency of the stimulus, whereas this is less so for complex cells. In primates, when assessed at high stimulus contrast, simple cells and complex cells are roughly equally represented in the first visual cortical area, V1, whereas in the second visual area, V2, the majority of cells are complex. Recent evidence has shown that phase sensitivity of complex cells is contrast dependent. This has led to speculation that reduced contrast may lead to changes in the spatial structure of receptive fields, perhaps due to changes in how feedforward and recurrent signals interact. Given the substantial interconnections between V1 and V2 and recent evidence for the emergence of unique functional capacity in V2, we assess the relationship between contrast and phase sensitivity in the two brain regions. We show that a substantial proportion of complex cells in macaque V1 exhibit significant increases in phase sensitivity at low contrast, whereas this is rarely observed in V2. Our results support a degree of hierarchical processing from V1 to V2 with the differences possibly relating to the fact that V1 combines both subcortical and cortical input, whereas V2 receives input purely from cortical circuits.

Contrast and response gain control depend on cortical map architecture.

Visual cortical neurons are sensitive to visual stimulus contrast and most cells adapt their sensitivity to the prevailing visual environment. Specifically, they match the steepest region of their contrast response function to the prevailing contrast (contrast gain control), and reduce spike rates to limit saturation (response gain control). Most neurons are also tuned for stimulus orientation, and neurons with similar orientation preference are clustered together into iso-orientation zones arranged around pinwheels, i.e. points where all orientations are represented. Here we investigated the relationship between the contrast adaptation properties of neurons and their location relative to pinwheels in the orientation preference map. We measured orientation preference maps in cat cortex using optical intrinsic signal imaging. We then characterized the contrast adaptation properties of single neurons located close to pinwheels, in iso-orientation zones, and at regions in between. We found little evidence of differential contrast sensitivity of neurons adapted to zero contrast. However, after adaptation to their preferred orientation at high contrast, changes in both contrast and response gain were greater for neurons near pinwheels compared with other map regions. Therefore, in the adapted state, which is probably typical during natural viewing, there is a spatial map of contrast sensitivity that is associated with the orientation preference map. This differential adaptation revealed a new dimension of cortical functional organization, linking the contrast adaptation of cells with the orientation preference of their nearest neighbours.

Stripe-rearing changes multiple aspects of the structure of primary visual cortex.

An important example of brain plasticity is the change in the structure of the orientation map in mammalian primary visual cortex in response to a visual environment consisting of stripes of one orientation. In principle there are many different ways in which the structure of a normal map could change to accommodate increased preference for one orientation. However, until now these changes have been characterised only by the relative sizes of the areas of primary visual cortex representing different orientations. Here we extend to the stripe-reared case a recently proposed Bayesian method for reconstructing orientation maps from intrinsic signal optical imaging data. We first formulated a suitable prior for the stripe-reared case, and developed an efficient method for maximising the marginal likelihood of the model in order to determine the optimal parameters. We then applied this to a set of orientation maps from normal and stripe-reared cats. This analysis revealed that several parameters of overall map structure, specifically the difference between wavelength, scaling and mean of the two vector components of maps, changed in response to stripe-rearing, which together give a more nuanced assessment of the effect of rearing condition on map structure than previous measures. Overall this work expands our understanding of the effects of the environment on brain structure.

Virtual Reality Assisted Motor Imagery for Early Post-Stroke Recovery: A Review.

Stroke is a serious neurological disease that may lead to long-term disabilities and even death for stroke patients worldwide. The acute period, ( ≤ 1 mo post-stroke), is crucial for rehabilitation but the current standard clinical practice may be ineffective for patients with severe motor impairment, since most rehabilitation programs involve physical movement. Imagined movement - the so-called motor imagery (MI) - has been shown to activate motor areas of the brain without physical movement. MI therefore offers an opportunity for early rehabilitation of stroke patients. MI, however, is not widely employed in clinical practice due to a lack of evidence-based research. Here, we review MI-based approaches to rehabilitation of stroke patients and immersive virtual reality (VR) technologies to potentially assist MI and thus, promote recovery of motor function.

Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis.

Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

Orientation pinwheels in primary visual cortex of a highly visual marsupial.

Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and-pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.

Liquid-Crystal Display (LCD) of achromatic, mean-modulated flicker in clinical assessment and experimental studies of visual systems.

Achromatic, mean-modulated flicker-wherein luminance increments and decrements of equal magnitude are applied, over time, to a test field-is commonly used in both clinical assessment of vision and experimental studies of visual systems. However, presenting flicker on computer-controlled displays is problematic; displays typically introduce luminance artifacts at high flicker frequency or contrast, potentially interfering with the validity of findings. Here, we present a battery of tests used to weigh the relative merits of two displays for presenting achromatic, mean-modulated flicker. These tests revealed marked differences between a new high-performance liquid-crystal display (LCD; EIZO ColorEdge CG247X) and a new consumer-grade LCD (Dell U2415b), despite displays' vendor-supplied specifications being almost identical. We measured displayed luminance using a spot meter and a linearized photodiode. We derived several measures, including spatial uniformity, the effect of viewing angle, response times, Fourier amplitude spectra, and cycle-averaged luminance. We presented paired luminance pulses to quantify the displays' nonlinear dynamics. The CG247X showed relatively good spatial uniformity (e.g., at moderate luminance, standard deviation 2.8% versus U2415b's 5.3%). Fourier transformation of nominally static test patches revealed spectra free of artifacts, with the exception of a frame response. The CG247X's rise and fall times depended on both the luminance from which, and to which, it responded, as is to be generally expected from LCDs. Despite this nonlinear behaviour, we were able to define a contrast and frequency range wherein the CG247X appeared largely artifact-free; the relationship between nominal luminance and displayed luminance was accurately modelled using a causal, linear time-invariant system. This range included contrasts up to 80%, and flicker frequencies up to 30 Hz. This battery of tests should prove useful to others conducting clinical assessment of vision and experimental studies of visual systems.

Complex cell receptive fields: evidence for a hierarchical mechanism.

Simple cells in the primary visual cortex have segregated ON and OFF subregions in their receptive fields, while complex cells have overlapping ON and OFF subregions. These two cell types form the extremes at each end of a continuum of receptive field types. Hubel and Wiesel in 1962 suggested a hierarchical scheme of processing whereby spatially offset simple cells drive complex cells. Simple and complex cells are often classified by their responses to moving sine wave gratings: simple cells have oscillatory responses while complex cells produce unmodulated responses. Here, using moving gratings as stimuli, we show that a significant number of cells that display low levels of response modulation at high contrasts demonstrate high levels of response modulation at low contrasts. Most often a drifting low contrast grating generates a large phasic response at the fundamental frequency of the grating (F(1)) and a smaller but significant phasic response that is approximately 180 deg out-of-phase with the F(1) component. We present several models capable of capturing the effects of stimulus contrast on complex cell responses. The model that best reproduces our experimental results is a variation of the classical hierarchical model. In our model several spatially offset simple cells provide input to a complex cell, with each simple cell exhibiting a different contrast response function. At low contrasts only one of these simple cells is sufficiently excited to reveal its receptive field properties. As contrast is increased additional spatially offset simple cells with higher contrast thresholds add their responses to the overall spiking activity.

Saccadic modulation of neural responses: possible roles in saccadic suppression, enhancement, and time compression.

Humans use saccadic eye movements to make frequent gaze changes, yet the associated full-field image motion is not perceived. The theory of saccadic suppression has been proposed to account for this phenomenon, but it is not clear whether suppression originates from a retinal signal at saccade onset or from the brain before saccade onset. Perceptually, visual sensitivity is reduced before saccades and enhanced afterward. Over the same time period, the perception of time is compressed and even inverted. We explore the origins and neural basis of these effects by recording from neurons in the dorsal medial superior temporal area (MSTd) of alert macaque monkeys. Neuronal responses to flashed presentations of a textured pattern presented at random times relative to saccades exhibit a stereotypical pattern of modulation. Response amplitudes are strongly suppressed for flashes presented up to 90 ms before saccades. Immediately after the suppression, there is a period of 200-450 ms in which flashes generate enhanced response amplitudes. Our results show that (1) MSTd is not directly suppressed, rather suppression is inherited from earlier visual areas; (2) early suppression of the visual system must be of extra-retinal origin; (3) postsaccadic enhancement of neural activity occurs in MSTd; and (4) the enhanced responses have reduced latencies. As a whole, these observations reveal response properties that could account for perceptual observations relating to presaccadic suppression, postsaccadic enhancement and time compression.

Contrast-dependent phase sensitivity in area MT of macaque visual cortex.

In primate visual cortex (V1), about half the neurons are sensitive to the spatial phases of grating stimuli and generate highly modulated responses to drifting gratings (simple cells). The remaining cells show far less phase sensitivity and relatively unmodulated responses to moving gratings (complex cells). In the second visual area (V2) and the motion processing area MT (or V5), the majority of cells have unmodulated responses to drifting gratings - they are phase invariant. At just-detectable contrasts, 44% of V1 complex cells show highly modulated responses, but this contrast-dependent phase sensitivity is found in only 7% of V2 complex cells. We recorded from 149 cells in macaque MT - 142 classed as complex cells at high contrast. Approximately 14% (20/142) of MT complex cells showed significantly modulated responses to drifting gratings at just-detectable contrasts. A general feature of MT cells is that they can be divided into pattern and component selective types, but we found no correlation between this classification and contrast-dependent phase sensitivity. Phase sensitivity in MT is discussed in relation to MT's input structure.

Comparison of contrast-dependent phase sensitivity in primary visual cortex of mouse, cat and macaque.

Neurones in the primary visual cortex (V1) are classified into simple and complex types. Simple cells are phase-sensitive, that is, they modulate their responses according to the position and brightness polarity of edges in their receptive fields. Complex cells are phase invariant, that is, they respond to edges in their receptive fields regardless of location or brightness polarity. Simple and complex cells are quantified by the degree of sensitivity to the spatial phases of drifting sinusoidal gratings. Some V1 complex cells become more phase-sensitive at low contrasts. Here we use a standardized analysis method for data derived from grating stimuli developed for macaques to reanalyse data previously collected from cats, and also collect and analyse the responses of 73 mouse V1 neurons. The analysis provides the first consistent comparative study of contrast-dependent phase sensitivity in V1 of mouse, cat and macaque monkey.

Synaptic Basis for Contrast-Dependent Shifts in Functional Identity in Mouse V1.

A central transformation that occurs within mammalian visual cortex is the change from linear, polarity-sensitive responses to nonlinear, polarity-insensitive responses. These neurons are classically labelled as either simple or complex, respectively, on the basis of their response linearity (Skottun et al., 1991). While the difference between cell classes is clear when the stimulus strength is high, reducing stimulus strength diminishes the differences between the cell types and causes some complex cells to respond as simple cells (Crowder et al., 2007; van Kleef et al., 2010; Hietanen et al., 2013). To understand the synaptic basis for this shift in behavior, we used in vivo whole-cell recordings while systematically shifting stimulus contrast. We find systematic shifts in the degree of complex cell responses in mouse primary visual cortex (V1) at the subthreshold level, demonstrating that synaptic inputs change in concert with the shifts in response linearity and that the change in response linearity is not simply due to the threshold nonlinearity. These shifts are consistent with a visual cortex model in which the recurrent amplification acts as a critical component in the generation of complex cell responses (Chance et al., 1999).

Psychophysical measurement of marmoset acuity and myopia.

The common marmoset has attracted increasing interest as a model for visual neuroscience. A measurement of fundamental importance to ensure the validity of visual studies is spatial acuity. The marmoset has excellent acuity that has been reported at the fovea to be nearly half that of the human (Ordy and Samorajski []: Vision Res 8:1205-1225), a value that is consistent with them having similar photoreceptor densities combined with their smaller eye size (Troilo et al. []: Vision Res 33:1301-1310). Of interest, the marmoset exhibits a higher proportion of cones than rods in peripheral vision than human or macaque, which in principle could endow them with better peripheral acuity depending on how those signals are pooled in subsequent processing. Here, we introduce a simple behavioral paradigm to measure acuity and then test how acuity in the marmoset scales with eccentricity. We trained subjects to fixate a central point and detect a peripheral Gabor by making a saccade to its location. First, we found that accurate assessment of acuity required correction for myopia in all adult subjects. This is an important point because marmosets raised in laboratory conditions often have mild to severe myopia (Graham and Judge []: Vision Res 39:177-187), a finding that we confirm, and that would limit their utility for studies of vision if uncorrected. With corrected vision, we found that their acuity scales with eccentricity similar to that of humans and macaques, having roughly half the value of the human and with no clear departure for higher acuity in the periphery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 300-313, 2017.

Long-term sensorimotor adaptation in the ocular following system of primates.

The sudden movement of a wide-field image leads to a reflexive eye tracking response referred to as short-latency ocular following. If the image motion occurs soon after a saccade the initial speed of the ocular following is enhanced, a phenomenon known as post-saccadic enhancement. We show in macaque monkeys that repeated exposure to the same stimulus regime over a period of months leads to progressive increases in the initial speeds of ocular following. The improvement in tracking speed occurs for ocular following with and without a prior saccade. As a result of the improvement in ocular following speeds, the influence of post-saccadic enhancement wanes with increasing levels of training. The improvement in ocular following speed following repeated exposure to the same oculomotor task represents a novel form of sensori-motor learning in the context of a reflexive movement.

Prediction of cortical responses to simultaneous electrical stimulation of the retina.

OBJECTIVE: Simultaneous electrical stimulation of multiple electrodes has shown promise in diversifying the responses that can be elicited by retinal prostheses compared to interleaved single electrode stimulation. However, the effects of interactions between electrodes are not well understood and clinical trials with simultaneous stimulation have produced inconsistent results. We investigated the effects of multiple electrode stimulation of the retina by developing a model of cortical responses to retinal stimulation. APPROACH: Electrical stimuli consisting of temporally sparse, biphasic current pulses, with amplitudes sampled from a bi-dimensional Gaussian distribution, were simultaneously delivered to the retina across a 42-channel electrode array implanted in the suprachoroidal space of anesthetized cats. Visual cortex activity was recorded using penetrating microelectrode arrays. These data were used to identify a linear-nonlinear model of cortical responses to retinal stimulation. The ability of the model to generalize was tested by predicting responses to non-white patterned stimuli. MAIN RESULTS: The model accurately predicted two cortical activity measures: multi-unit neural responses and evoked potential responses to white noise stimuli. The model also provides information about electrical receptive fields, including the relative effects of each stimulating electrode on every recording site. SIGNIFICANCE: We have demonstrated a simple model that accurately describes cortical responses to simultaneous stimulation of a suprachoroidal retinal prosthesis. Overall, our results demonstrate that cortical responses to simultaneous multi-electrode stimulation of the retina are repeatable and predictable, and that interactions between electrodes during simultaneous stimulation are predominantly linear. The model shows promise for determining optimal stimulation paradigms for exploiting interactions between electrodes to shape neural activity, thereby improving outcomes for patients with retinal prostheses.