RESEARCH

Solving visual correspondence between the two eyes via domain-based population encoding in NHPs

Stereoscopic vision depends on correct matching of corresponding features between the two eyes. It is unclear where the brain solves this binocular correspondence problem. Although our visual system is able to make correct global matches, there are many possible false matches between any two images. Here, we use optical imaging data of binocular disparity response in the visual cortex of awake and anesthetized monkeys to demonstrate that the second visual cortical area (V2) is the first cortical stage that correctly discards false matches and robustly encodes correct matches. Our findings indicate that a key transformation for achieving depth perception lies in early stages of extrastriate visual cortex and is achieved by population coding.

Functional architecture matters in the formation of perception.

Elimination of false matches is a multistep process. V2 is an important step in the process. We show that by integrating disparity domain neuron responses with similar preferred disparity but across different preferences of other visual features (including spatial scale, receptive field size, and phase disparity, based on previously published data), our model preserves responses to correct matching and greatly attenuates responses to false matching. We extend the energy model to a population levelto account for our findings in V2. We start with neurons similar to previously described single-neuron responses: Each neuron is responsive to both correct and to false  matches as predicted by the energy model. Based on an estimate of 110,000 neurons per cubic millimeter of cortical tissue and the average size of a V2 disparity cluster of 3.5 mm3  for 10–15 different disparities within that cluster, each would integrate on the order of 30,000 neurons. We further estimated the number of neurons needed in the population to achieve a result that predicts the percept. To do this, we defined the “perceptual index” for different numbers of neurons in the population model. A perceptual index value of 100 indicates complete discarding of false matches and is close to the subject’s depth percept, while a value of 0 indicates no attenuation to false matches. By examining a range of populations from 2 neurons to 100,000 neurons, the ability to discard false matching increases: the more neurons included, the lower the response to false matching. With as few as 250 neurons, the amplitude of response to false matches is reduced by 91%. A disparity domain with 30,000 neurons, according to our model, eliminates 97% of false matches. An additional layer of pooling inputs from multiple V2 neurons within one disparity domain could further reduce aRDS response among single neurons in V4 and inferior temporal cortex. These simulations illustrate that V2 can respond to correct matches and reject false ones by pooling over the population. The greater the numbers pooled, the better the performance. By pooling over a population of neurons with similar disparity preference, binocular correspondence for depth percept can be established.

Focal infrared neural stimulation with high-field functional MRI: A rapid way to map mesoscale brain

We have developed a way to map brain-wide networks using focal pulsed infrared neural stimulation in ultrahigh-field magnetic resonance imaging (MRI). The patterns of connections revealed are similar to those of connections previously mapped with anatomical tract tracing methods. These include connections between cortex and subcortical locations and long-range cortico-cortical connections. Studies of local cortical connections reveal columnar-sized laminar activation, consistent with feed-forward and feedback projection signatures. This method is broadly applicable and can be applied to multiple areas of the brain in different species and across different MRI platforms. Systematic point-by-point application of this method may lead to fundamental advances in our understanding of brain connectomes.

Layer-specific BOLD activation in awake monkey V1 revealed by ultra-high spatial resolution fMRI

The laminar structure of the cortex has previously been explored both in non-human primates and human subjects using high-resolution functional magnetic resonance imaging (fMRI). However, whether the spatial specificity of the blood-oxygenation-level-dependent (BOLD) fMRI is sufficiently high to reveal lamina specific organization in the cortex reliably is still unclear. In this study we demonstrate for the first time the detection of such layer-specific activation in awake monkeys at the spatial resolution of 200 × 200 × 1000 μm3 in a ultra-high field MR scanner. Results collected in trained monkeys are high in contrast-to-noise ratio and low in motion artifacts. Isolation of laminar activation was aided by choosing the optimal slice orientation and thickness using a novel pial vein pattern analysis derived from optical imaging. We found that the percent change of GE-BOLD signal is the highest at a depth corresponding to layer IV. Changes in the middle layers (layer IV) were 30% greater than changes in the top layers (layers I-III), and 32% greater than the bottom layers (layers V/VI). The laminar distribution of BOLD signal correlates well with neural activity reported in the literature. Our results suggest that the high intrinsic spatial resolution of GE-BOLD signal is sufficient for mapping sub-millimeter functional structures in awakemonkeys. This degree of spatial specificity will be useful for mapping both laminar activations and columnar structures in the cerebral cortex.

Functional magnetic resonance imaging of awake monkeys

Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using ultra-high field fMRI, we have developed acquisition and analysis procedures to improve image quality with encouraging results. We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 μm to less than 80 μm, a displacement close to that observed in anesthetized monkeys scanned in a horizontal scanner. Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise-ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil. In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain.

Identification of cortical lamination in awake monkeys by high resolution magnetic resonance imaging

Brodmann divided the neocortex into 47 different cortical areas based on histological differences in laminar myeloarchitectonic and cytoarchitectonic defined structure. The ability to do so in vivo with anatomical magnetic resonance(MR) methods in awake subjects would be extremely advantageous for many functional studies. However, due to the limitations of spatial resolution and contrast, this has been difficult to achieve in awake subjects. Here, we report that by using a combination of MR microscopy and novel contrast effects, cortical layers can be delineated in the visual cortex of awake subjects (nonhuman primates) at a ultra-high field MR scanner. We obtained data from 30-min acquisitions at voxel size of 62.5 × 62.5 × 1000 μm3 (4 nl). Both the phase and magnitude components of the T(2)*-weighted image were used to generate laminar profiles which are believed to reflect variations in myelin and local cell density content across cortical depth. Based on this, we were able to identify six layers characteristic of the striate cortex (V1). These were the stripe of Kaes-Bechterew (in layer II/III), the stripe of Gennari (in layer IV), the inner band of Baillarger (in layer V), as well as three sub-layers within layer IV (IVa, IVb, and IVc). Furthermore, we found that the laminar structure of two extrastriate visual cortex (V2, V4) can also be detected. Following the tradition of Brodmann, this significant improvement in cortical laminar visualization should make it possible to discriminate cortical regions in awake subjects corresponding to differences in myeloarchitecture and cytoarchitecture.

A rapid topographic mapping and eye alignment method using optical imaging in Macaque visual cortex

In optical imaging experiments, it is often advantageous to map the field of view and to converge the eyes without electrophysiological recording. This occurs when limited space precludes placement of an electrode or in chronic opticalchambers in which one may not want to introduce an electrode each session or for determining eye position in studies of ocular disparity response in visual cortex of anesthetized animals. For these purposes, we have developed a spot imagingmethod that can be conducted rapidly and repeatedly throughout an experiment. Using small 0.2 degrees -0.5 degrees spots, the extent of the imaged field of view is mapped by imaging cortical response to single spots, placed at different positions in either the horizontal or vertical axes. By shifting the relative positions of two spots, one presented to each eye, eye convergence can be assessed to within 0.1 degrees resolution. Once appropriate eye alignmentis determined, stimuli for further optical imaging procedures  can then be confidently placed. This procedure can be quickly repeated throughout the experiment to ensure maintained eye alignment.

A map for horizontal disparity in monkey V2

The perception of visual depth is determined by integration of spatial disparities of inputs from the two eyes. Single cells in visual cortex of monkeys are known to respond to specific binocular disparities; however, little is known about their functional organization. We now show, using intrinsic signal optical imaging and single-unit physiology, that, in the thick stripe compartments of the second visual area (V2), there is a clustered organization of Near cells and Far cells, and moreover, there are topographic maps for Near to Far disparities within V2. Our findings suggest that maps for visual disparity are calculated in V2, and demonstrate parallels in functional organization between the thin, pale, and thick stripes of V2.

Stimulation of non-classical receptive field enhances orientation selectivity.

We have investigated how the nonclassical receptive field (nCRF) affects dynamic orientation selectivity of cells in the primary visual cortex (V1) in anaesthetized and paralysed cats using the reverse correlation method. We found that tuning to the orientation of the test stimulus depends on the size of the stimulation area. A significant sharpening of orientation tuning was induced by nCRF stimulation, with the magnitude of the effect increasing with the size of stimulation. The effect of the nCRF on the temporal dynamics of orientation tuning was also investigated by examining the tuning over a range of delays from stimulus onset. We found small but detectable changes in both the preferred orientation and the bandwidth of tuning over time when the classical receptive field (CRF) was stimulated alone. Stimulation in nCRF significantly increased the magnitude of these temporal changes. Thus, nCRF stimulation not only enhances the overall orientation selectivity, but also enriches the temporal dynamics of cortical neurones, which may increase the computational power of the visual cortex in information processing.