The orbitofrontal cortex: A goal-directed cognitive map framework for social and non-social behaviors.

The orbitofrontal cortex (OFC) is regarded as one of the core brain areas in a variety of value-based behaviors. Over the past two decades, tremendous knowledge about the OFC function was gained from studying the behaviors of single subjects. As a result, our previous understanding of the OFC's function of encoding decision variables, such as the value and identity of choices, has evolved to the idea that the OFC encodes a more complex representation of the task space as a cognitive map. Accumulating evidence also indicates that the OFC importantly contributes to behaviors in social contexts, especially those involved in cooperative interactions. However, it remains elusive how exactly OFC neurons contribute to social functions and how non-social and social behaviors are related to one another in the computations performed by OFC neurons. In this review, we aim to provide an integrated view of the OFC function across both social and non-social behavioral contexts. We propose that seemingly complex functions of the OFC may be explained by its role in providing a goal-directed cognitive map to guide a wide array of adaptive reward-based behaviors in both social and non-social domains.

Non-uniform contextual interactions in the visual cortex place fundamental limits on spatial vision.

A prevailing assumption in our understanding of how neurons in the primary visual cortex (V1) integrate contextual information is that such processes are spatially uniform. Conversely, perceptual phenomena such as visual crowding, the impaired ability to accurately recognize a target stimulus among distractors, suggest that interactions among stimuli are distinctly non-uniform. Prior studies have shown flankers at specific spatial geometries exert differential effects on target perception. To resolve this discrepancy, we investigated how flanker geometry impacted the representation of a target stimulus in the laminar microcircuits of V1. Our study reveals flanker location differentially impairs stimulus representation in excitatory neurons in the superficial and input layers of V1 by tuned suppression and untuned facilitation of orientation responses. Mechanistically, this effect can be explained by asymmetrical spatial kernels in a normalization model of cortical activity. Strikingly, these non-uniform modulations of neural representation mirror perceptual anisotropies. These results establish the non-uniform spatial integration of information in the earliest stages of cortical processing as a fundamental limitation of spatial vision.

Brain-state mediated modulation of inter-laminar dependencies in visual cortex.

Spatial attention is a quintessential example of adaptive information processing in the brain and is critical for recognizing behaviorally relevant objects in a cluttered environment. Object recognition is mediated by neural encoding along the ventral visual hierarchy. How the deployment of spatial attention aids these hierarchical computations is unclear. Prior studies point to two distinct mechanisms: an improvement in the efficacy of information directed from one encoding stage to another, and/or a suppression of shared information within encoding stages. To test these proposals, it is crucial to estimate the attentional modulation of unique information flow across and shared information within the encoding stages of the visual hierarchy. We investigated this in the multi-stage laminar network of visual area V4, an area strongly modulated by attention. Using network-based dependency estimation from multivariate data, we quantified the modulation of inter-layer information flow during a change detection task and found that deployment of attention indeed strengthened unique dependencies between the input and superficial layers. Using the partial information decomposition framework, we estimated the modulation of shared dependencies and found that they are reduced specifically in the putative excitatory subpopulations within a layer. Surprisingly, we found a strengthening of unique dependencies within the laminar populations, a finding not previously predicted. Crucially, these modulation patterns were also observed during successful behavioral outcomes (hits) that are thought to be mediated by endogenous brain state fluctuations, and not by experimentally imposed attentive states. Finally, phases of endogenous fluctuations that were optimal for 'hits' were associated with reduced neural excitability. A reduction in neural excitability, potentially mediated by diminished shared inputs, suggests a novel mechanism for enhancing unique information transmission during optimal states. By decomposing the modulation of multivariate information, and combined with prior theoretical work, our results suggest common computations of optimal sensory states that are attained by either task demands or endogenous fluctuations.

Brain-state mediated modulation of inter-laminar dependencies in visual cortex.

Spatial attention is critical for recognizing behaviorally relevant objects in a cluttered environment. How the deployment of spatial attention aids the hierarchical computations of object recognition remains unclear. We investigated this in the laminar cortical network of visual area V4, an area strongly modulated by attention. We found that deployment of attention strengthened unique dependencies in neural activity across cortical layers. On the other hand, shared dependencies were reduced within the excitatory population of a layer. Surprisingly, attention strengthened unique dependencies within a laminar population. Crucially, these modulation patterns were also observed during successful behavioral outcomes that are thought to be mediated by internal brain state fluctuations. Successful behavioral outcomes were also associated with phases of reduced neural excitability, suggesting a mechanism for enhanced information transfer during optimal states. Our results suggest common computation goals of optimal sensory states that are attained by either task demands or internal fluctuations.

Automated 3D analysis of social head-gaze behaviors in freely moving marmosets.

Social communication relies on the ability to perceive and interpret the direction of others' attention, which is commonly conveyed through head orientation and gaze direction in both humans and non-human primates. However, traditional social gaze experiments in non-human primates require restraining head movements, which significantly limit their natural behavioral repertoire. Here, we developed a novel framework for accurately tracking facial features and three-dimensional head gaze orientations of multiple freely moving common marmosets (Callithrix jacchus). To accurately track the facial features of marmoset dyads in an arena, we adapted computer vision tools using deep learning networks combined with triangulation algorithms applied to the detected facial features to generate dynamic geometric facial frames in 3D space, overcoming common occlusion challenges. Furthermore, we constructed a virtual cone, oriented perpendicular to the facial frame, to model the head gaze directions. Using this framework, we were able to detect different types of interactive social gaze events, including partner-directed gaze and jointly-directed gaze to a shared spatial location. We observed clear effects of sex and familiarity on both interpersonal distance and gaze dynamics in marmoset dyads. Unfamiliar pairs exhibited more stereotyped patterns of arena occupancy, more sustained levels of social gaze across inter-animal distance, and increased gaze monitoring. On the other hand, familiar pairs exhibited higher levels of joint gazes. Moreover, males displayed significantly elevated levels of gazes toward females' faces and the surrounding regions irrespective of familiarity. Our study lays the groundwork for a rigorous quantification of primate behaviors in naturalistic settings.

Development of a Marmoset Apparatus for Automated Pulling (MarmoAAP) to Study Cooperative Behaviors.

In recent years, the field of neuroscience has increasingly recognized the importance of studying animal behaviors in naturalistic environments to gain deeper insights into ethologically relevant behavioral processes and neural mechanisms. The common marmoset (Callithrix jacchus), due to its small size, prosocial nature, and genetic proximity to humans, has emerged as a pivotal model toward this effort. However, traditional research methodologies often fail to fully capture the nuances of marmoset social interactions and cooperative behaviors. To address this critical gap, we developed the Marmoset Apparatus for Automated Pulling (MarmoAAP), a novel behavioral apparatus designed for studying cooperative behaviors in common marmosets. MarmoAAP addresses the limitations of traditional behavioral research methods by enabling high-throughput, detailed behavior outputs that can be integrated with video and audio recordings, allowing for more nuanced and comprehensive analyses even in a naturalistic setting. We also highlight the flexibility of MarmoAAP in task parameter manipulation which accommodates a wide range of behaviors and individual animal capabilities. Furthermore, MarmoAAP provides a platform to perform investigations of neural activity underlying naturalistic social behaviors. MarmoAAP is a versatile and robust tool for advancing our understanding of primate behavior and related cognitive processes. This new apparatus bridges the gap between ethologically relevant animal behavior studies and neural investigations, paving the way for future research in cognitive and social neuroscience using marmosets as a model organism.

WIDESPREAD RECEPTIVE FIELD REMAPPING IN EARLY VISUAL CORTEX.

Our eyes are in constant motion, yet we perceive the visual world as being stable. Predictive remapping of receptive fields is thought to be one of the critical mechanisms for enforcing perceptual stability during eye movements. While receptive field remapping has been identified in several cortical areas, the spatiotemporal dynamics of remapping, and its consequences on the tuning properties of neurons, remain poorly understood. Here, we tracked remapping receptive fields in hundreds of neurons from visual Area V2 while subjects performed a cued saccade task. We found that remapping was far more widespread in Area V2 than previously reported and can be found in neurons from all recorded neural populations in the laminar cortical circuit. Surprisingly, neurons undergoing remapping exhibit sensitivity to two punctate locations in visual space. Remapping is also accompanied by a transient sharpening of orientation tuning. Taken together, these results shed light on the spatiotemporal dynamics of remapping and its ubiquitous prevalence in the early visual cortex, and force us to revise current models of perceptual stability.

Laminar compartmentalization of attention modulation in area V4 aligns with the demands of visual processing hierarchy in the cortex.

Attention selectively enhances neural responses to low contrast stimuli in visual area V4, a critical hub that sends projections both up and down the visual hierarchy. Veridical encoding of contrast information is a key computation in early visual areas, while later stages encoding higher level features benefit from improved sensitivity to low contrast. How area V4 meets these distinct information processing demands in the attentive state is unknown. We found that attentional modulation in V4 is cortical layer and cell-class specific. Putative excitatory neurons in the superficial layers show enhanced boosting of low contrast information, while those of deep layers exhibit contrast-independent scaling. Computational modeling suggested the extent of spatial integration of inhibitory neurons as the mechanism behind such laminar differences. Considering that superficial neurons are known to project to higher areas and deep layers to early visual areas, our findings suggest that the interactions between attention and contrast in V4 are compartmentalized, in alignment with the demands of the visual processing hierarchy.

Laminar mechanisms of saccadic suppression in primate visual cortex.

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

Efficient integration across spatial frequencies for letter identification in foveal and peripheral vision.

Objects in natural scenes are spatially broadband; in contrast, feature detectors in the early stages of visual processing are narrowly tuned in spatial frequency. Earlier studies of feature integration using gratings suggested that integration across spatial frequencies is suboptimal. Here we re-examined this conclusion using a letter identification task at the fovea and at 10 deg in the lower visual field. We found that integration across narrow-band (1-octave) spatial frequency components of letter stimuli is optimal in the fovea. Surprisingly, this optimality is preserved in the periphery, even though feature integration is known to be deficient in the periphery from studies of other form-vision tasks such as crowding. A model that is otherwise a white-noise ideal observer except for a limited spatial resolution defined by the human contrast sensitivity function and using internal templates slightly wider in bandwidth than the stimuli is able to account for the human data. Our findings suggest that deficiency in feature integration found in peripheral vision is not across spatial frequencies.

The nature of letter crowding as revealed by first- and second-order classification images.

Visual crowding refers to the marked inability to identify an otherwise perfectly identifiable object when it is flanked by other objects. Crowding places a significant limit on form vision in the visual periphery; its mechanism is, however, unknown. Building on the method of signal-clamped classification images (Tjan & Nandy, 2006), we developed a series of first- and second-order classification-image techniques to investigate the nature of crowding without presupposing any model of crowding. Using an "o" versus "x" letter-identification task, we found that (1) crowding significantly reduced the contrast of first-order classification images, although it did not alter the shape of the classification images; (2) response errors during crowding were strongly correlated with the spatial structures of the flankers that resembled those of the erroneously perceived targets; (3) crowding had no systematic effect on intrinsic spatial uncertainty of an observer nor did it suppress feature detection; and (4) analysis of the second-order classification images revealed that crowding reduced the amount of valid features used by the visual system and, at the same time, increased the amount of invalid features used. Our findings strongly support the feature-mislocalization or source-confusion hypothesis as one of the proximal contributors of crowding. Our data also agree with the inappropriate feature-integration account with the requirement that feature integration be a competitive process. However, the feature-masking account and a front-end version of the spatial attention account of crowding are not supported by our data.

Laminar Organization of Attentional Modulation in Macaque Visual Area V4.

Attention is critical to perception, serving to select behaviorally relevant information for privileged processing. To understand the neural mechanisms of attention, we must discern how attentional modulation varies by cell type and across cortical layers. Here, we test whether attention acts non-selectively across cortical layers or whether it engages the laminar circuit in specific and selective ways. We find layer- and cell-class-specific differences in several different forms of attentional modulation in area V4. Broad-spiking neurons in the superficial layers exhibit attention-mediated increases in firing rate and decreases in variability. Spike count correlations are highest in the input layer and attention serves to reduce these correlations. Superficial and input layer neurons exhibit attention-dependent decreases in low-frequency (<10 Hz) coherence, but deep layer neurons exhibit increases in coherence in the beta and gamma frequency ranges. Our study provides a template for attention-mediated laminar information processing that might be applicable across sensory modalities.

Classification images with uncertainty.

Classification image and other similar noise-driven linear methods have found increasingly wider applications in revealing psychophysical receptive field structures or perceptual templates. These techniques are relatively easy to deploy, and the results are simple to interpret. However, being a linear technique, the utility of the classification-image method is believed to be limited. Uncertainty about the target stimuli on the part of an observer will result in a classification image that is the superposition of all possible templates for all the possible signals. In the context of a well-established uncertainty model, which pools the outputs of a large set of linear frontends with a max operator, we show analytically, in simulations, and with human experiments that the effect of intrinsic uncertainty can be limited or even eliminated by presenting a signal at a relatively high contrast in a classification-image experiment. We further argue that the subimages from different stimulus-response categories should not be combined, as is conventionally done. We show that when the signal contrast is high, the subimages from the error trials contain a clear high-contrast image that is negatively correlated with the perceptual template associated with the presented signal, relatively unaffected by uncertainty. The subimages also contain a "haze" that is of a much lower contrast and is positively correlated with the superposition of all the templates associated with the erroneous response. In the case of spatial uncertainty, we show that the spatial extent of the uncertainty can be estimated from the classification subimages. We link intrinsic uncertainty to invariance and suggest that this signal-clamped classification-image method will find general applications in uncovering the underlying representations of high-level neural and psychophysical mechanisms.

Neurons in Macaque Area V4 Are Tuned for Complex Spatio-Temporal Patterns.

To deepen our understanding of object recognition, it is critical to understand the nature of transformations that occur in intermediate stages of processing in the ventral visual pathway, such as area V4. Neurons in V4 are selective to local features of global shape, such as extended contours. Previously, we found that V4 neurons selective for curved elements exhibit a high degree of spatial variation in their preference. If spatial variation in curvature selectivity was also marked by distinct temporal response patterns at different spatial locations, then it might be possible to untangle this information in subsequent processing based on temporal responses. Indeed, we find that V4 neurons whose receptive fields exhibit intricate selectivity also show variation in their temporal responses across locations. A computational model that decodes stimulus identity based on population responses benefits from using this temporal information, suggesting that it could provide a multiplexed code for spatio-temporal features.

Rapid and persistent adaptability of human oculomotor control in response to simulated central vision loss.

The central region of the human retina, the fovea, provides high-acuity vision. The oculomotor system continually brings targets of interest into the fovea via ballistic eye movements (saccades). Thus, the fovea serves both as the locus for fixations and as the oculomotor reference for saccades. This highly automated process of foveation is functionally critical to vision and is observed from infancy. How would the oculomotor system adjust to a loss of foveal vision (central scotoma)? Clinical observations of patients with central vision loss suggest a lengthy adjustment period, but the nature and dynamics of this adjustment remain unclear. Here, we demonstrate that the oculomotor system can spontaneously and rapidly adopt a peripheral locus for fixation and can rereference saccades to this locus in normally sighted individuals whose central vision is blocked by an artificial scotoma. Once developed, the fixation locus is retained over weeks in the absence of the simulated scotoma. Our data reveal a basic guiding principle of the oculomotor system that prefers control simplicity over optimality. We demonstrate the importance of a visible scotoma on the speed of the adjustment and suggest a possible rehabilitation regimen for patients with central vision loss.

Crowding during restricted and free viewing.

Crowding impairs the perception of form in peripheral vision. It is likely to be a key limiting factor of form vision in patients without central vision. Crowding has been extensively studied in normally sighted individuals, typically with a stimulus duration of a few hundred milliseconds to avoid eye movements. These restricted testing conditions do not reflect the natural behavior of a patient with central field loss. Could unlimited stimulus duration and unrestricted eye movements change the properties of crowding in any fundamental way? We studied letter identification in the peripheral vision of normally sighted observers in three conditions: (i) a fixation condition with a brief stimulus presentation of 250 ms, (ii) another fixation condition but with an unlimited viewing time, and (iii) an unrestricted eye movement condition with an artificial central scotoma and an unlimited viewing time. In all conditions, contrast thresholds were measured as a function of target-to-flanker spacing, from which we estimated the spatial extent of crowding in terms of critical spacing. We found that presentation duration beyond 250 ms had little effect on critical spacing with stable gaze. With unrestricted eye movements and a simulated central scotoma, we found a large variability in critical spacing across observers, but more importantly, the variability in critical spacing was well correlated with the variability in target eccentricity. Our results assure that the large body of findings on crowding made with briefly presented stimuli remains relevant to conditions where viewing time is unconstrained. Our results further suggest that impaired oculomotor control associated with central vision loss can confound peripheral form vision beyond the limits imposed by crowding.

The fine structure of shape tuning in area V4.

Previous studies have shown that neurons in area V4 are involved in the processing of shapes of intermediate complexity and are sensitive to curvature. These studies also suggest that curvature-tuned neurons are position invariant. We sought to examine the mechanisms that endow V4 neurons with these properties. Consistent with previous studies, we found that response rank order to the most- and least-preferred stimuli was preserved throughout the receptive field. However, a fine-grained analysis of shape tuning revealed a surprising result: V4 neurons tuned to highly curved shapes exhibit very limited translation invariance. At a fine spatial scale, these neurons exhibit local variation in orientation. In contrast, neurons that prefer straight contours exhibit spatially invariant orientation-tuning and homogenous fine-scale orientation maps. Both of these patterns are consistent with a simple orientation-pooling model, with tuning for straight or curved shapes resulting, respectively, from pooling of homogenous or heterogeneous orientation signals inherited from early visual areas.

Saccade-confounded image statistics explain visual crowding.

Processing of shape information in human peripheral visual fields is impeded beyond what can be expected by poor spatial resolution. Visual crowding, the inability to identify objects in clutter, has been shown to be the primary factor limiting shape perception in peripheral vision. Despite the well-documented effects of crowding, its underlying causes remain poorly understood. Given that spatial attention both facilitates learning of image statistics and directs saccadic eye movements, we propose that the acquisition of image statistics in peripheral visual fields is confounded by eye-movement artifacts. Specifically, the image statistics acquired under a peripherally deployed spotlight of attention are systematically biased by saccade-induced image displacements. These erroneously represented image statistics lead to inappropriate contextual interactions in the periphery and cause crowding.

The angry brain: neural correlates of anger, angry rumination, and aggressive personality.

Very little is known about the neural circuitry guiding anger, angry rumination, and aggressive personality. In the present fMRI experiment, participants were insulted and induced to ruminate. Activity in the dorsal anterior cingulate cortex was positively related to self-reported feelings of anger and individual differences in general aggression. Activity in the medial prefrontal cortex was related to self-reported rumination and individual differences in displaced aggression. Increased activation in the hippocampus, insula, and cingulate cortex following the provocation predicted subsequent self-reported rumination. These findings increase our understanding of the neural processes associated with the risk for aggressive behavior by specifying neural regions that mediate the subjective experience of anger and angry rumination as well as the neural pathways linked to different types of aggressive behavior.