Targeting Human Glucocorticoid Receptors in Fear Learning: A Multiscale Integrated Approach to Study Functional Connectivity.

Fear extinction is a phenomenon that involves a gradual reduction in conditioned fear responses through repeated exposure to fear-inducing cues. Functional brain connectivity assessments, such as functional magnetic resonance imaging (fMRI), provide valuable insights into how brain regions communicate during these processes. Stress, a ubiquitous aspect of life, influences fear learning and extinction by changing the activity of the amygdala, prefrontal cortex, and hippocampus, leading to enhanced fear responses and/or impaired extinction. Glucocorticoid receptors (GRs) are key to the stress response and show a dual function in fear regulation: while they enhance the consolidation of fear memories, they also facilitate extinction. Accordingly, GR dysregulation is associated with anxiety and mood disorders. Recent advancements in cognitive neuroscience underscore the need for a comprehensive understanding that integrates perspectives from the molecular, cellular, and systems levels. In particular, neuropharmacology provides valuable insights into neurotransmitter and receptor systems, aiding the investigation of mechanisms underlying fear regulation and potential therapeutic targets. A notable player in this context is cortisol, a key stress hormone, which significantly influences both fear memory reconsolidation and extinction processes. Gaining a thorough understanding of these intricate interactions has implications in terms of addressing psychiatric disorders related to stress. This review sheds light on the complex interactions between cognitive processes, emotions, and their neural bases. In this endeavor, our aim is to reshape the comprehension of fear, stress, and their implications for emotional well-being, ultimately aiding in the development of therapeutic interventions.

Increasing associative plasticity in temporo-occipital back-projections improves visual perception of emotions.

The posterior superior temporal sulcus (pSTS) is a critical node in a network specialized for perceiving emotional facial expressions that is reciprocally connected with early visual cortices (V1/V2). Current models of perceptual decision-making increasingly assign relevance to recursive processing for visual recognition. However, it is unknown whether inducing plasticity into reentrant connections from pSTS to V1/V2 impacts emotion perception. Using a combination of electrophysiological and neurostimulation methods, we demonstrate that strengthening the connectivity from pSTS to V1/V2 selectively increases the ability to perceive facial expressions associated with emotions. This behavior is associated with increased electrophysiological activity in both these brain regions, particularly in V1/V2, and depends on specific temporal parameters of stimulation that follow Hebbian principles. Therefore, we provide evidence that pSTS-to-V1/V2 back-projections are instrumental to perception of emotion from facial stimuli and functionally malleable via manipulation of associative plasticity.

Implicit Selective Attention: The Role of the Mesencephalic-basal Ganglia System.

The ability of the brain to recognize and orient attention to relevant stimuli appearing in the visual field is highlighted by a tuning process, which involves modulating the early visual system by both cortical and subcortical brain areas. Selective attention is coordinated not only by the output of stimulus-based saliency maps but is also influenced by top-down cognitive factors, such as internal states, goals, or previous experiences. The basal ganglia system plays a key role in implicitly modulating the underlying mechanisms of selective attention, favouring the formation and maintenance of implicit sensory-motor memories that are capable of automatically modifying the output of priority maps in sensory-motor structures of the midbrain, such as the superior colliculus. The article presents an overview of the recent literature outlining the crucial contribution of several subcortical structures to the processing of different sources of salient stimuli. In detail, we will focus on how the mesencephalic-basal ganglia closed loops contribute to implicitly addressing and modulating selective attention to prioritized stimuli. We conclude by discussing implicit behavioural responses observed in clinical populations in which awareness is compromised at some level. Implicit (emergent) awareness in clinical conditions that can be accompanied by manifest anosognosic symptomatology (i.e., hemiplegia) or involving abnormal conscious processing of visual information (i.e., unilateral spatial neglect and blind sight) represents interesting neurocognitive "test cases" for inferences about mesencephalic-basal ganglia closed-loops involvement in the formation of implicit sensory-motor memories.

Convolutional neural networks for vision neuroscience: significance, developments, and outstanding issues.

Convolutional Neural Networks (CNN) are a class of machine learning models predominately used in computer vision tasks and can achieve human-like performance through learning from experience. Their striking similarities to the structural and functional principles of the primate visual system allow for comparisons between these artificial networks and their biological counterparts, enabling exploration of how visual functions and neural representations may emerge in the real brain from a limited set of computational principles. After considering the basic features of CNNs, we discuss the opportunities and challenges of endorsing CNNs as in silico models of the primate visual system. Specifically, we highlight several emerging notions about the anatomical and physiological properties of the visual system that still need to be systematically integrated into current CNN models. These tenets include the implementation of parallel processing pathways from the early stages of retinal input and the reconsideration of several assumptions concerning the serial progression of information flow. We suggest design choices and architectural constraints that could facilitate a closer alignment with biology provide causal evidence of the predictive link between the artificial and biological visual systems. Adopting this principled perspective could potentially lead to new research questions and applications of CNNs beyond modeling object recognition.

GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.

BACKGROUND: Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). METHODS: We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants' residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. RESULTS: Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level-dependent signal change in this motion-sensitive region. CONCLUSIONS: Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level-dependent signal changes-in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined.

A deep neural network model of the primate superior colliculus for emotion recognition.

Although sensory processing is pivotal to nearly every theory of emotion, the evaluation of the visual input as 'emotional' (e.g. a smile as signalling happiness) has been traditionally assumed to take place in supramodal 'limbic' brain regions. Accordingly, subcortical structures of ancient evolutionary origin that receive direct input from the retina, such as the superior colliculus (SC), are traditionally conceptualized as passive relay centres. However, mounting evidence suggests that the SC is endowed with the necessary infrastructure and computational capabilities for the innate recognition and initial categorization of emotionally salient features from retinal information. Here, we built a neurobiologically inspired convolutional deep neural network (DNN) model that approximates physiological, anatomical and connectional properties of the retino-collicular circuit. This enabled us to characterize and isolate the initial computations and discriminations that the DNN model of the SC can perform on facial expressions, based uniquely on the information it directly receives from the virtual retina. Trained to discriminate facial expressions of basic emotions, our model matches human error patterns and above chance, yet suboptimal, classification accuracy analogous to that reported in patients with V1 damage, who rely on retino-collicular pathways for non-conscious vision of emotional attributes. When presented with gratings of different spatial frequencies and orientations never 'seen' before, the SC model exhibits spontaneous tuning to low spatial frequencies and reduced orientation discrimination, as can be expected from the prevalence of the magnocellular (M) over parvocellular (P) projections. Likewise, face manipulation that biases processing towards the M or P pathway affects expression recognition in the SC model accordingly, an effect that dovetails with variations of activity in the human SC purposely measured with ultra-high field functional magnetic resonance imaging. Lastly, the DNN generates saliency maps and extracts visual features, demonstrating that certain face parts, like the mouth or the eyes, provide higher discriminative information than other parts as a function of emotional expressions like happiness and sadness. The present findings support the contention that the SC possesses the necessary infrastructure to analyse the visual features that define facial emotional stimuli also without additional processing stages in the visual cortex or in 'limbic' areas. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

A subcortical network for implicit visuo-spatial attention: Implications for Parkinson's Disease.

Recent studies in humans and animal models suggest a primary role of the basal ganglia in the extraction of stimulus-value regularities, then exploited to orient attentional shift and build up sensorimotor memories. The tail of the caudate and the posterior putamen both receive early visual input from the superficial layers of the superior colliculus, thus forming a closed-loop. We portend that the functional value of this circuit is to manage the selection of visual stimuli in a rapid and automatic way, once sensory-motor associations are formed and stored in the posterior striatum. In Parkinson's Disease, the nigrostriatal dopamine depletion starts and tends to be more pronounced in the posterior putamen. Thus, at least some aspect of the visuospatial attention deficits observed since the early stages of the disease could be the behavioral consequences of a cognitive system that has lost the ability to translate high-level processing in stable sensorimotor memories.

Functional neuroanatomy of racial categorization from visual perception: A meta-analytic study.

We effortlessly sort people into different racial groups from their visual appearance and implicitly generate racial bias affecting cognition and behavior. As these mental activities provide the proximate mechanisms for social behaviours, it becomes essential to understand the neural activity underlying differences between own-race and other-race visual categorization. Yet intrinsic limitations of individual neuroimaging studies, owing to reduced sample size, inclusion of multiple races, and interactions between races in the participants and in the displayed visual stimuli, dampens generalizability of results. In the present meta-analytic study, we applied multimodal techniques to partly overcome these hurdles, and we investigated the entire functional neuroimaging literature on race categorization, therefore including more than 2000 Black, White and Asian participants. Our data-driven approach shows that own- and other-race visual categorization involves partly segregated neural networks, with distinct connectivity and functional profiles, and defined hierarchical organization. Categorization of own-race mainly engages areas related to cognitive components of empathy and mentalizing, such as the medial prefrontal cortex and the inferior frontal gyrus. These areas are functionally co-activated with cortical structures involved in auto-biographical memories and social knowledge. Conversely, other-race categorization recruits areas implicated in, and functionally connected with, visuo-attentive processing, like the fusiform gyrus and the inferior parietal lobule, and areas engaged in affective functions, like the amygdala. These results contribute to a better definition of the neural networks involved in the visual parcelling of social categories based on race, and help to situate these processes within a common neural space.

Changes in peri-calcarine cortical thickness in blindsight.

Blindsight is the ability of patients with primary visual cortex (V1) damage to process information in their clinically blind visual field in the absence of conscious awareness. In addition to those with localized V1 lesions, some patients exhibiting this phenomenon have had a cerebral hemisphere removed or disconnected from the rest of the brain for the treatment of drug-resistant epilepsy (hemispherectomy). Research into the underlying neural substrates of blindsight has long implicated the intact visual cortex in maintaining residual vision and supporting visuo-guided responses to stimuli presented ipsilaterally within the blind visual field while operating outside the geniculo-striate pathway. A recent study demonstrated functional reorganization in the dorsal visual areas of the intact hemisphere, thereby supporting its compensatory role in non-conscious vision. In this study, we used cortical thickness analysis to examine anatomical differences in the visual cortex of the intact hemisphere of three subjects with varying degrees of cortical damage and well documented blindsight: two with a right hemispherectomy (complete and partial), and one with a left V1 lesion. T1-weighted MRI data were obtained for the subjects while control data were chosen from publicly available NKI-dataset to match closely the acquisition parameters of our blindsight cases. Our results show significant increases in cortical thickness in the visual cortex of all blindsight subjects compared to healthy controls, irrespective of age-onset, etiology, and extent of the damage. Our findings add to accumulating evidence from behavioral, functional imaging, and tractography studies of cerebral compensation and reorganization.

The neuroethology of spontaneous mimicry and emotional contagion in human and non-human animals.

Spontaneous mimicry appears fundamental to emotional perception and contagion, especially when it involves facial emotional expressions. Here we cover recent evidence on spontaneous mimicry from ethology, psychology and neuroscience, in non-human and human animals. We first consider how mimicry unfolds in non-human animals (particularly primates) and how it relates to emotional contagion. We focus on two forms of mimicry-related phenomena: facial mimicry and yawn contagion, which are largely conserved across mammals and useful to draw evolutionary scenarios. Next, we expand on the psychological evidence from humans that bears on current theoretical debates and also informs non-human animal research. Finally, we cover the neural bases of facial mimicry and yawn contagion. We move beyond the perception/expression/experience trichotomy and from the correlational to the causal evidence that links facial mimicry to emotional contagion by presenting evidence from neuroimaging, direct manipulation, neuro-stimulation and lesion studies. In conclusion, this review proposes a bottom-up, multidisciplinary approach to the study of spontaneous mimicry that accounts for the evolutionary continuity linking non-human and human animals.

Towards a comparative science of emotion: Affect and consciousness in humans and animals.

The componential view of human emotion recognises that affective states comprise conscious, behavioural, physiological, neural and cognitive elements. Although many animals display bodily and behavioural changes consistent with the occurrence of affective states similar to those seen in humans, the question of whether and in which species these are accompanied by conscious experiences remains controversial. Finding scientifically valid methods for investigating markers for the subjective component of affect in both humans and animals is central to developing a comparative understanding of the processes and mechanisms of affect and its evolution and distribution across taxonomic groups, to our understanding of animal welfare, and to the development of animal models of affective disorders. Here, contemporary evidence indicating potential markers of conscious processing in animals is reviewed, with a view to extending this search to include markers of conscious affective processing. We do this by combining animal-focused approaches with investigations of the components of conscious and non-conscious emotional processing in humans, and neuropsychological research into the structure and functions of conscious emotions.

Toward an integrative science of social vision in intergroup bias.

Social neuroscience is unveiling how the brain coordinates the construal of social categories and the generation of intergroup biases from facial perception. Recent evidence indicates that social categorization is more sensitive and malleable to elemental facial features than previously assumed. At the same time, perception of social categories can be crafted by top-down factors, including prior knowledge, motivations, and social expectations. In this review, we summarize extant wisdom and propose a model that goes beyond traditional accounts that have conceived stereotypes and prejudices as the end result of "reading out" social categories in the face, and have assumed a hierarchical brain organization. Our model proposes recursive and dynamic interactions amid distant brain regions. Accordingly, the reciprocal exchange of sensory evidence and predictions biases and "explains away" visual input in face perception regions until a compromise is achieved and social perception stabilizes. Ideally, this effort would contribute to shape a research field at the interface between neural and social sciences, which is often referred to as social vision.

Emotion Recognition in Low-Spatial Frequencies Is Partly Preserved following Traumatic Brain Injury.

After a Traumatic Brain Injury (TBI), emotion recognition is typically impaired. This is commonly attributed to widespread multifocal damage in cortical areas involved in emotion processing as well as to Diffuse Axonal Injury (DAI). However, current models suggest that emotional recognition is subserved by a distributed network cantered on the amygdala, which involves both cortical and subcortical structures. While the cortical system is preferentially tuned to process high spatial frequencies, the subcortical networks are more sensitive to low-spatial frequencies. The aim of this study was to evaluate whether emotion perception from low-spatial frequencies underpinning the subcortical system is relatively preserved in TBI patients. We tested a group of 14 subjects with severe TBI and 20 matched healthy controls. Each participant was asked to recognize the emotion expressed by each stimulus that consisted of happy and fearful faces, filtered for their low and high spatial frequencies components. Results in TBI patients' performances showed that low-spatial frequency expressions were recognized with higher accuracy and faster reaction times when compared to high spatial frequency stimuli. On the contrary, healthy controls did not show any effect in the two conditions, neither for response accuracy nor for reaction times. The outcomes of this study indicate that emotion perception from low-spatial frequencies is relatively preserved in TBI, thereby suggesting spare of functioning in the subcortical system in mediating emotion recognition.

Functional reorganization of population receptive fields in a hemispherectomy patient with blindsight.

Blindsight refers to the ability of some patients with destruction of the primary visual cortex (V1) to respond to stimuli presented in their clinically blind visual field despite lack of visual awareness. Here we tested a rare and well-known patient with blindsight following hemispherectomy, DR, who has had the entire cortex in the right hemisphere removed, and in whom the right superior colliculus is the only post-chiasmatic visual structure remaining intact. Compared to more traditional cases of blindsight after damage confined to V1, the study of blindsight in hemispherectomy has offered the invaluable opportunity to examine directly two outstanding questions: the contribution of the intact hemisphere to visual processing without awareness, and the nature of plastic and compensatory changes in these remaining contralesional visual areas. Population receptive field (pRF) mapping was used to define retinotopic maps, delineate the boundaries between the visual areas, examine changes in the sizes of receptive field centres within each visual area, and their variability as a function of eccentricity. Aside from the dorsal visual areas showing blurred borders between V2d and V3d, not otherwise detected with perimetric mapping, the retinotopic maps of DR did not differ substantially from those of three matched healthy controls. Interestingly, those dorsal compartments showed a significant increase in the RF sizes toward values typical of higher-order processing cortices, while no differences were observed in the corresponding ventral visual areas. Findings showed that whereas receptive field sizes at foveal and parafoveal eccentricities (≤ 4°) were not measurably altered, the pRF size increased by ~ 270% at 4-6° of eccentricity, and the size difference reached ~ 300% between 8° and 10°. We interpret these findings to suggest that an increase in pRF sizes could be indicative of cerebral plasticity involving the retinotopic reorganization of the dorsal visual areas.

Functional neuroanatomy of blindsight revealed by activation likelihood estimation meta-analysis.

Blindsight, the residual abilities of patients with cortical blindness to respond proficiently to stimuli they do not consciously acknowledge, offers a unique opportunity to study the functional and anatomical mechanisms sustaining visual awareness. Over decades, the phenomenon has been documented in a wide number of different patients, across independent laboratories, and for a variety of tasks and stimulus properties. Nevertheless, the functional neuroanatomy of blindsight remains elusive and alternative proposals have been put forth. To tackle this issue from a novel perspective, we performed a quantitative Activation Likelihood Estimation (ALE) meta-analysis on the neuroimaging literature available on blindsight. Significant activity was reported in subcortical structures, such as the superior colliculus, pulvinar and amygdala, as well as in cortical extrastriate areas along the dorsal and ventral visual stream. This data-driven functional network collectively defines the extant neural fingerprint of blindsight. To further characterize the unique combination of segregation and integration in brain networks engaged in blindsight, we measured the relationship between active areas and experimental features in the original studies, their clustering and hierarchical organization. Results support a network-based organization in the functional neuroanatomy of blindsight, which likely reflects the intersection of different stimulus properties and behavioural tasks examined. We suggest that the conceptualization of blindsight as a constellation of multiple nonconscious visual abilities is better apt as a summary of present-day wisdom, thereby mirroring the variety of existing V1-independent pathway and their different functional roles.

Classical paintings may trigger pain and pleasure in the gendered brain.

The human body is the most common object of pictorial representation in western art and its representations trigger a vast range of experiences from pain to pleasure. The goal of this study was to investigate brain activity triggered by paintings of male and female body images exemplifying conditions associated with pleasure or pain. Our findings show participant-general as well as gender specific brain activity for either the pain or the pleasure conditions. Although our participants were fully aware that they were viewing artworks, the inferior parietal lobule - known for its role in the perception of emotional body images - and the somatosensory cortex related to touch were selectively active for female body paintings in all participants in the pleasure conditions. As regards gender we observed that the sight of female bodies activated the subgenual anterior cingulate cortex in males, an area known to subserve autonomic arousal. In contrast, in females the sight of the male body activated reward and control related parts of the dorsal anterior cingulate cortex. This study supports the notion that some basic evolutionary processes operate when we view body images, also when they are cultural heritage paintings far removed from daily experience.