Rapid processing of threatening faces in the amygdala of nonhuman primates: subcortical inputs and dual roles.

A subcortical pathway through the superior colliculus and pulvinar has been proposed to provide the amygdala with rapid but coarse visual information about emotional faces. However, evidence for short-latency, facial expression-discriminating responses from individual amygdala neurons is lacking; even if such a response exists, how it might contribute to stimulus detection is unclear. Also, no definitive anatomical evidence is available for the assumed pathway. Here we showed that ensemble responses of amygdala neurons in monkeys carried robust information about open-mouthed, presumably threatening, faces within 50 ms after stimulus onset. This short-latency signal was not found in the visual cortex, suggesting a subcortical origin. Temporal analysis revealed that the early response contained excitatory and suppressive components. The excitatory component may be useful for sending rapid signals downstream, while the sharpening of the rising phase of later-arriving inputs (presumably from the cortex) by the suppressive component might improve the processing of facial expressions over time. Injection of a retrograde trans-synaptic tracer into the amygdala revealed presumed monosynaptic labeling in the pulvinar and disynaptic labeling in the superior colliculus, including the retinorecipient layers. We suggest that the early amygdala responses originating from the colliculo-pulvino-amygdalar pathway play dual roles in threat detection.

Microstructural properties of the vertical occipital fasciculus explain the variability in human stereoacuity.

Stereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies have reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity and, in the same participants, we analyzed the microstructural properties of visual white matter tracts on the basis of two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the behavioral-structural relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.

Mapping stimulus feature selectivity in macaque V1 by two-photon Ca2+ imaging: Encoding-model analysis of fluorescence responses to natural movies.

In vivo calcium (Ca2+) imaging using two-photon microscopy allows activity to be monitored simultaneously from hundreds of individual neurons within a local population. While this allows us to gain important insights into how cortical neurons represent sensory information, factors such as photo-bleaching of the Ca2+ indicator limit imaging duration (and thus the numbers of stimuli that can be tested), which in turn hampers the full characterization of neuronal response properties. Here, we demonstrate that using an encoding model combined with presentation of natural movies results in detailed characterization of receptive field (RF) properties despite the relatively short time for data collection. During presentation of natural movie clips to macaque monkeys, we recorded fluorescence signals from primary visual cortex (V1) neurons that had been loaded with a Ca2+ indicator. For each recorded neuron, we constructed an encoding model that comprised an array of motion-energy filters that tiled over the RFs. We optimized the weight of each filter's output so that the linear sum of the outputs across the filters mimicked the neuron's Ca2+-signal responses. These models were able to predict the neural responses to a different set of natural movies with a significant degree of accuracy. Moreover, the orientation tunings of neurons simulated by the model were highly correlated with those experimentally obtained when grating stimuli were presented to the monkeys. The model predictions were also consistent with what is known about spatial frequency tunings, the structure of excitatory subfields of RFs (i.e., classical RFs), and functional maps for these RF properties in V1. Further analysis revealed a new aspect of V1 functional architecture; the extent and distribution of suppressive RF subfields varied among nearby neurons, while those for excitatory subfields were shared. Thus, applying our encoding-model analysis to two-photon Ca2+ imaging of neuronal responses to natural movies provides a reliable and efficient means of analyzing a wide range of RF properties in multiple neurons imaged in a local region.

Cortical and subcortical responses to biological motion.

Using fMRI and multivariate analyses we sought to understand the neural representations of articulated body shape and local kinematics in biological motion. We show that in addition to a cortical network that includes areas identified previously for biological motion perception, including the posterior superior temporal sulcus, inferior frontal gyrus, and ventral body areas, the ventral lateral nucleus, a presumably motoric thalamic area is sensitive to both form and kinematic information in biological motion. Our findings suggest that biological motion perception is not achieved as an end-point of segregated cortical form and motion networks as often suggested, but instead involves earlier parts in the visual system including a subcortical network.

Postnatal Development of Intrinsic Horizontal Axons in Macaque Inferior Temporal and Primary Visual Cortices.

Two distinct areas along the ventral visual stream of monkeys, the primary visual (V1) and inferior temporal (TE) cortices, exhibit different projection patterns of intrinsic horizontal axons with patchy terminal fields in adult animals. The differences between the patches in these 2 areas may reflect differences in cortical representation and processing of visual information. We studied the postnatal development of patches by injecting an anterograde tracer into TE and V1 in monkeys of various ages. At 1 week of age, labeled patches with distribution patterns reminiscent of those in adults were already present in both areas. The labeling intensity of patches decayed exponentially with projection distance in monkeys of all ages in both areas, but this trend was far less evident in TE. The number and extent of patches gradually decreased with age in V1, but not in TE. In V1, axonal and bouton densities increased postnatally only in patches with short projection distances, whereas in TE this density change occurred in patches with various projection distances. Thus, patches with area-specific distribution patterns are formed early in life, and area-specific postnatal developmental processes shape the connectivity of patches into adulthood.

Similarity in Neuronal Firing Regimes across Mammalian Species.

UNLABELLED: The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT: By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.

A relative frame of reference underlies reversed depth perception in anticorrelated random-dot stereograms.

Binocular disparity is represented by interocular cross-correlation of visual images in the striate and some extrastriate cortices. This correlation-based representation produces reversed depth perception in a binocularly anticorrelated random-dot stereogram (aRDS) when it is accompanied by an adjacent correlated RDS (cRDS). Removal of the cRDS or spatial separation between the aRDS and cRDS abolishes reversed depth perception. However, how an immediate plane supports reversed depth perception is unclear. One possible explanation is that the correlation-based representation generates reversed depth based on the relative disparity between the aRDS and cRDS rather than the absolute disparity of the aRDS. Here, we psychophysically tested this hypothesis. We found that participants perceived reversed depth in an aRDS with zero absolute disparity when it was surrounded by a cRDS with nonzero absolute disparity (i.e., nonzero relative disparity), suggesting a role of relative disparity on the depth reversal. In addition, manipulation of the absolute disparities of the central aRDS and surrounding cRDS caused depth perception to reverse with respect to the depth of the surround. Further, depth reversal persisted after swapping the locations of the two RDSs. A model of relative-disparity encoding explains all these results. We conclude that reversed depth perception in aRDSs occurs in a relative frame of reference and suggest that the visual system contains correlation-based representation that encodes relative disparity.

Computation of Object Size in Visual Cortical Area V4 as a Neural Basis for Size Constancy.

Even when we view an object from different distances, so that the size of its projection onto the retina varies, we perceive its size to be relatively unchanged. In this perceptual phenomenon known as size constancy, the brain uses both distance and retinal image size to estimate the size of an object. Given that binocular disparity, the small positional difference between the retinal images in the two eyes, is a powerful visual cue for distance, we examined how it affects neuronal tuning to retinal image size in visual cortical area V4 of macaque monkeys. Depending on the imposed binocular disparity of a circular patch embedded in random dot stereograms, most neurons adjusted their preferred size in a manner consistent with size constancy. They preferred larger retinal image sizes when stimuli were stereoscopically presented nearer and preferred smaller retinal image sizes when stimuli were presented farther away. This disparity-dependent shift of preferred image size was not affected by the vergence angle, a cue for the fixation distance, suggesting that different V4 neurons compute object size for different fixation distances rather than that individual neurons adjust the shift based on vergence. This interpretation was supported by a simple circuit model, which could simulate the shift of preferred image size without any information about the fixation distance. We suggest that a population of V4 neurons encodes the actual size of objects, rather than simply the size of their retinal images, and that these neurons thereby contribute to size constancy. SIGNIFICANCE STATEMENT: We perceive the size of an object to be relatively stable despite changes in the size of its retinal image that accompany changes in viewing distance. This phenomenon, called size constancy, is accomplished by combining retinal image size and distance information in our brain. We demonstrate that a large population of V4 neurons changes their size tuning depending on the perceived distance of a visual stimulus derived from binocular disparity. They prefer larger or smaller retinal image sizes when stimuli are stereoscopically presented nearer or farther away, respectively. This property makes V4 neurons suitable for encoding the actual size of objects, not simply the retinal image sizes, and providing a possible mechanism for perceptual size constancy.

Pooled, but not single-neuron, responses in macaque V4 represent a solution to the stereo correspondence problem.

Binocular disparity is an important cue for depth perception. To correctly represent disparity, neurons must find corresponding visual features between the left- and right-eye images. The visual pathway ascending from V1 to inferior temporal cortex solves the correspondence problem. An intermediate area, V4, has been proposed to be a critical stage in the correspondence process. However, the distinction between V1 and V4 is unclear, because accumulating evidence suggests that the process begins within V1. In this article, we report that the pooled responses in macaque V4, but not responses of individual neurons, represent a solution to the correspondence problem. We recorded single-unit responses of V4 neurons to random-dot stereograms of varying degrees of anticorrelation. To achieve gradual anticorrelation, we reversed the contrast of an increasing proportion of dots as in our previous psychophysical studies, which predicted that the neural correlates of the solution to correspondence problem should gradually eliminate their disparity modulation as the level of anticorrelation increases. Inconsistent with this prediction, the tuning amplitudes of individual V4 neurons quickly decreased to a nonzero baseline with small anticorrelation. By contrast, the shapes of individual tuning curves changed more gradually so that the amplitude of population-pooled responses gradually decreased toward zero over the entire range of graded anticorrelation. We explain these results by combining multiple energy-model subunits. From a comparison with the population-pooled responses in V1, we suggest that disparity representation in V4 is distinctly advanced from that in V1. Population readout of V4 responses provides disparity information consistent with the correspondence solution.

Relationship between the local structure of orientation map and the strength of orientation tuning of neurons in monkey V1: a 2-photon calcium imaging study.

A majority of neurons in the monkey primary visual cortex (V1) are tuned to stimulus orientations. Preferred orientations and tuning strengths vary among V1 neurons. The preferred orientation of neurons gradually changes across the cortex with occasional failures of this organization. How V1 neurons are arranged by the strength of orientation tuning and whether neuronal arrangement for tuning strength relates to orientation preference maps remains controversial. In this study, we performed in vivo two-photon calcium imaging in macaque V1 to examine the local spatial organization of orientation tuning at the level of single cells. We recorded fluorescence signals from individual neurons loaded with a calcium-sensitive dye in layer 2 and the uppermost tier of layer 3. The strength of orientation tuning was shared by nearby neurons, and changed across the cortex. The neurons with similar tuning strength were distributed across at least the entire thickness of layer 2. The tuning strength was weaker in regions where neurons exhibited heterogeneous preferred orientations, as compared with regions where neurons shared similar orientation preferences. Nearby direction-selective neurons often shared their preferred directions, although only a few neurons were direction selective in the layers examined. Thus, the orientation tuning strength of V1 neurons is partially predictable from the local structure of orientation map. The weaker orientation tuning we found in regions with heterogeneous orientation preferences suggests that orientation-independent interactions among local populations of V1 neurons play a critical role in determining their orientation tuning.

Neural activity in cortical area V4 underlies fine disparity discrimination.

Primates are capable of discriminating depth with remarkable precision using binocular disparity. Neurons in area V4 are selective for relative disparity, which is the crucial visual cue for discrimination of fine disparity. Here, we investigated the contribution of V4 neurons to fine disparity discrimination. Monkeys discriminated whether the center disk of a dynamic random-dot stereogram was in front of or behind its surrounding annulus. We first behaviorally tested the reference frame of the disparity representation used for performing this task. After learning the task with a set of surround disparities, the monkey generalized its responses to untrained surround disparities, indicating that the perceptual decisions were generated from a disparity representation in a relative frame of reference. We then recorded single-unit responses from V4 while the monkeys performed the task. On average, neuronal thresholds were higher than the behavioral thresholds. The most sensitive neurons reached thresholds as low as the psychophysical thresholds. For subthreshold disparities, the monkeys made frequent errors. The variable decisions were predictable from the fluctuation in the neuronal responses. The predictions were based on a decision model in which each V4 neuron transmits the evidence for the disparity it prefers. We finally altered the disparity representation artificially by means of microstimulation to V4. The decisions were systematically biased when microstimulation boosted the V4 responses. The bias was toward the direction predicted from the decision model. We suggest that disparity signals carried by V4 neurons underlie precise discrimination of fine stereoscopic depth.

A formyl peptide substituted with a conformationally constrained phenylalanine residue evokes a selective immune response in human neutrophils.

Formyl-Met-Leu-Phe-OH (fMLP) binds to formyl peptide receptors, FPR1 and FPR2, and evokes migration and superoxide anion production in human neutrophils. To obtain a more effective and selective ligand, fMLP analogs in which the Phe residue was substituted with four isomers of cyclopropanephenylalanine were synthesized. While Z-isomer peptides induced both migration and superoxide anion production, E-isomer peptides elicited only chemotaxis. Homologous receptor desensitization experiments revealed that E-isomer peptides bound to FPR2. Although a selective agonist of chemotaxis also binds to FPR2 without increasing intracellular calcium concentration, E-isomer peptide elevated the concentration to the same level as fMLP. Understanding of mechanisms responsible for the selectivity of the reported selective agonists and ∇Phe-substituted analogs should prove useful for revealing the relationship between receptor-ligand interactions and biological responses of human neutrophils.

Temporal channels and disparity representations in stereoscopic depth perception.

Stereoscopic depth perception is supported by a combination of correlation-based and match-based representations of binocular disparity. It also relies on both transient and sustained temporal channels of the visual system. Previous studies suggest that the relative contribution of the correlation-based representation (over the match-based representation) and the transient channel (over the sustained channel) to depth perception increases with the disparity magnitude. The mechanisms of the correlation-based and match-based representations may receive preferential inputs from the transient and sustained channels, respectively. We examined near/far discrimination by observers using random-dot stereograms refreshed at various rates. The relative contribution of the two representations was inferred by changing the fraction of dots that were contrast reversed between the two eyes. Both representations contributed to depth discrimination over the tested range of refresh rates. As the rate increased, the correlation-based representation increased its contribution to near/far discrimination. Another experiment revealed that the match-based representation was constructed by exploiting the variability in correlation-based disparity signals. Thus, the relative weight of the transient over sustained channel differs between the two representations. The correlation-based representation dominates depth perception with dynamic inputs. The match-based representation, which may be a nonlinear refinement of the correlation-based representation, exerts more influence on depth perception with slower inputs.

Analysis of convolutional neural networks reveals the computational properties essential for subcortical processing of facial expression.

Perception of facial expression is crucial for primate social interactions. This visual information is processed through the ventral cortical pathway and the subcortical pathway. However, the subcortical pathway exhibits inaccurate processing, and the responsible architectural and physiological properties remain unclear. To investigate this, we constructed and examined convolutional neural networks with three key properties of the subcortical pathway: a shallow layer architecture, concentric receptive fields at the initial processing stage, and a greater degree of spatial pooling. These neural networks achieved modest accuracy in classifying facial expressions. By replacing these properties, individually or in combination, with corresponding cortical features, performance gradually improved. Similar to amygdala neurons, some units in the final processing layer exhibited sensitivity to retina-based spatial frequencies (SFs), while others were sensitive to object-based SFs. Replacement of any of these properties affected the coordinates of the SF encoding. Therefore, all three properties limit the accuracy of facial expression information and are essential for determining the SF representation coordinate. These findings characterize the role of the subcortical computational processes in facial expression recognition.

Neuronal Population Activity in Macaque Visual Cortices Dynamically Changes through Repeated Fixations in Active Free Viewing.

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys (Macaca fuscata): the primary and secondary visual cortices (V1, V2) and the inferotemporal cortex (IT). We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a smaller number of spikes, thereby allowing for discrimination between individual objects with smaller energy.

A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain.

Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel vector of which capsid was composed of capsid proteins derived from both of the AAV serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for AAV1 vector) and neuron specificity (for AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.

Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

Effects of vorticity on solitary waves.

The vorticity effect on solitary wave profiles has not been solved experimentally; previous studies theoretically and numerically showed that when a solitary wave progressed in the positive direction, the effective wavelength of a solitary wave with positive vorticity increased. Using laboratory experiments and fully nonlinear numerical simulations, we here show that the effective wavelength is extended more when positive vorticity is given to a progressive wave in the positive direction. We further show that the total energy increases with increasing positive vorticity, demonstrating that a wave with positive vorticity propagates with less attenuation and lasts longer than a solitary wave with no vorticity. We anticipate that our outcomes will provide a starting point for more sophisticated methods to investigate the effect of vorticity on solitary waves in laboratory experiments and numerical simulations.

Convolutional neural networks reveal differences in action units of facial expressions between face image databases developed in different countries.

Cultural similarities and differences in facial expressions have been a controversial issue in the field of facial communications. A key step in addressing the debate regarding the cultural dependency of emotional expression (and perception) is to characterize the visual features of specific facial expressions in individual cultures. Here we developed an image analysis framework for this purpose using convolutional neural networks (CNNs) that through training learned visual features critical for classification. We analyzed photographs of facial expressions derived from two databases, each developed in a different country (Sweden and Japan), in which corresponding emotion labels were available. While the CNNs reached high rates of correct results that were far above chance after training with each database, they showed many misclassifications when they analyzed faces from the database that was not used for training. These results suggest that facial features useful for classifying facial expressions differed between the databases. The selectivity of computational units in the CNNs to action units (AUs) of the face varied across the facial expressions. Importantly, the AU selectivity often differed drastically between the CNNs trained with the different databases. Similarity and dissimilarity of these tuning profiles partly explained the pattern of misclassifications, suggesting that the AUs are important for characterizing the facial features and differ between the two countries. The AU tuning profiles, especially those reduced by principal component analysis, are compact summaries useful for comparisons across different databases, and thus might advance our understanding of universality vs. specificity of facial expressions across cultures.