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.

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.

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.

Intact hemisphere and corpus callosum compensate for visuomotor functions after early visual cortex damage.

Unilateral damage to the primary visual cortex (V1) leads to clinical blindness in the opposite visual hemifield, yet nonconscious ability to transform unseen visual input into motor output can be retained, a condition known as "blindsight." Here we combined psychophysics, functional magnetic resonance imaging, and tractography to investigate the functional and structural properties that enable the developing brain to partly overcome the effects of early V1 lesion in one blindsight patient. Visual stimuli appeared in either the intact or blind hemifield and simple responses were given with either the left or right hand, thereby creating conditions where visual input and motor output involve the same or opposite hemisphere. When the V1-damaged hemisphere was challenged by incoming visual stimuli, or controlled manual responses to these unseen stimuli, the corpus callosum (CC) dynamically recruited areas in the visual dorsal stream and premotor cortex of the intact hemisphere to compensate for altered visuomotor functions. These compensatory changes in functional brain activity were paralleled by increased connections in posterior regions of the CC, where fibers connecting homologous areas of the parietal cortex course.

The Dorsomedial Prefrontal Cortex Plays a Causal Role in Integrating Social Impressions from Faces and Verbal Descriptions.

Several neuroimaging studies point to a key role of the dorsomedial prefrontal cortex (dmPFC) in the formation of socially relevant impressions. In 3 different experiments, participants were required to form socially relevant impressions about other individuals on the basis of text descriptions of their social behaviors, and to decide whether a face alone, a trait adjective (e.g., "selfish"), or a face presented with a trait adjective was consistent or inconsistent with the impression they had formed. Before deciding whether the target stimulus matched the impression they had previously formed, participants received transcranial magnetic stimulation (TMS) over the dmPFC, the inferior frontal gyrus (IFG, also implicated in social impression formation), or over a control site (vertex). Results from the 3 experiments converged in showing that interfering with dmPFC activity significantly delayed participants in responding whether a face-adjective pair was consistent with the impression they had formed. No effects of TMS were observed following stimulation of the IFG or when evaluations had to be made on faces or trait adjectives presented alone. Our findings critically extend previous neuroimaging evidence by indicating a causal role of the dmPFC in creating coherent impressions based on the integration of face and verbal description of social behaviors.

Neural bases of the non-conscious perception of emotional signals.

Many emotional stimuli are processed without being consciously perceived. Recent evidence indicates that subcortical structures have a substantial role in this processing. These structures are part of a phylogenetically ancient pathway that has specific functional properties and that interacts with cortical processes. There is now increasing evidence that non-consciously perceived emotional stimuli induce distinct neurophysiological changes and influence behaviour towards the consciously perceived world. Understanding the neural bases of the non-conscious perception of emotional signals will clarify the phylogenetic continuity of emotion systems across species and the integration of cortical and subcortical activity in the human brain.

From affective blindsight to emotional consciousness.

Following destruction or denervation of the primary visual cortex (V1) cortical blindness ensues. Affective blindsight refers to the uncanny ability of such patients to respond correctly, or above chance level, to visual emotional expressions presented to their blind fields. Fifteen years after its original discovery, affective blindsight still fascinates neuroscientists and philosophers alike, as it offers a unique window on the vestigial properties of our visual system that, though present in the intact brain, tend to be unnoticed or even actively inhibited by conscious processes. Here we review available studies on affective blindsight with the intent to clarify its functional properties, neural bases and theoretical implications. Evidence converges on the role of subcortical structures of old evolutionary origin such as the superior colliculus, the pulvinar and the amygdala in mediating affective blindsight and nonconscious perception of emotions. We conclude that approaching consciousness, and its absence, from the vantage point of emotion processing may uncover important relations between the two phenomena, as consciousness may have evolved as an evolutionary specialization to interact with others and become aware of their social and emotional expressions.

Amygdala activation for eye contact despite complete cortical blindness.

Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the amygdala response to eye contact does not require an intact primary visual cortex.

Cortico-subcortical visual, somatosensory, and motor activations for perceiving dynamic whole-body emotional expressions with and without striate cortex (V1).

Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception.

Dissociation between goal-directed and discrete response localization in a patient with bilateral cortical blindness.

We investigated localization performance of simple targets in patient TN, who suffered bilateral damage of his primary visual cortex and shows complete cortical blindness. Using a two-alternative forced-choice paradigm, TN was asked to guess the position of left-right targets with goal-directed and discrete manual responses. The results indicate a clear dissociation between goal-directed and discrete responses. TN pointed toward the correct target location in approximately 75% of the trials but was at chance level with discrete responses. This indicates that the residual ability to localize an unseen stimulus depends critically on the possibility to translate a visual signal into a goal-directed motor output at least in certain forms of blindsight.

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.

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.

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.

Spatiotemporal profiles of visual processing with and without primary visual cortex.

The spatiotemporal profiles of visual processing are normally distributed in two temporal phases, each lasting about 100 ms. Within each phase, cortical processing begins in V1 and traverses the visual cortical hierarchy. However, the causal role of V1 in starting each of these two phases is unknown. Here we used magnetoencephalography to study the spatiotemporal profiles of visual processing and the causal contribution of V1 in three neurologically intact participants and in a rare patient (GY) with unilateral destruction of V1, in whom residual visual functions mediated by the extra-geniculostriate pathways have been reported. In healthy subjects, visual processing in the first 200 ms post-stimulus onset proceeded in the two usual phases. Normally perceived stimuli in the left hemifield of GY elicited a spatiotemporal profile in the intact right hemisphere that closely matched that of healthy subjects. However, stimuli presented in the cortically blind hemifield produced no detectable response during the first phase of processing, indicating that the responses in extrastriate visual areas during this phase are determined by the feedforward progression of activity initiated in V1. The first responses occurred during the second processing phase, in the ipsilesional high-level visual areas. The activity then spread forward toward higher-level areas and backward toward lower-level areas. However, in contrast to responses in the intact hemisphere, the back-propagated activity in the early visual cortex did not exhibit the classic retinotopic organization and did not have well-defined response peaks.

Unseen facial and bodily expressions trigger fast emotional reactions.

The spontaneous tendency to synchronize our facial expressions with those of others is often termed emotional contagion. It is unclear, however, whether emotional contagion depends on visual awareness of the eliciting stimulus and which processes underlie the unfolding of expressive reactions in the observer. It has been suggested either that emotional contagion is driven by motor imitation (i.e., mimicry), or that it is one observable aspect of the emotional state arising when we see the corresponding emotion in others. Emotional contagion reactions to different classes of consciously seen and "unseen" stimuli were compared by presenting pictures of facial or bodily expressions either to the intact or blind visual field of two patients with unilateral destruction of the visual cortex and ensuing phenomenal blindness. Facial reactions were recorded using electromyography, and arousal responses were measured with pupil dilatation. Passive exposure to unseen expressions evoked faster facial reactions and higher arousal compared with seen stimuli, therefore indicating that emotional contagion occurs also when the triggering stimulus cannot be consciously perceived because of cortical blindness. Furthermore, stimuli that are very different in their visual characteristics, such as facial and bodily gestures, induced highly similar expressive responses. This shows that the patients did not simply imitate the motor pattern observed in the stimuli, but resonated to their affective meaning. Emotional contagion thus represents an instance of truly affective reactions that may be mediated by visual pathways of old evolutionary origin bypassing cortical vision while still providing a cornerstone for emotion communication and affect sharing.

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'.

The recognition of facial emotions in spinocerebellar ataxia patients.

Patients with cerebellar lesions present some affective and cognitive disorders, defining a peculiar pattern of cognitive impairment, so-called cerebellar cognitive affective syndrome. This pattern has been confirmed in many genotypes of spinocerebellar ataxias (SCA), a group of genetically defined pathologies characterized by the degeneration of the cerebellum and its connections. Recently, in SCA patients, some authors focused the interest on social cognition evidencing an impairment of theory of mind and basic emotion recognition by verbal material. The recognition of emotions in faces is an essential component of social cognition; therefore, we assessed this ability in SCA patients, expanding the study from the basic verbal emotions to the basic and social visual emotion recognition. We assessed facial emotion recognition using two basic and social emotion tasks in a group of SCA patients together with a complete clinical and neuropsychological evaluation. We compared results with the performance of a control group. We demonstrated a significant difference between patients and controls both in basic and social emotion recognition, although we found a specific impairment only for social emotions. The deficit was not correlated to clinical and demographic features. The cognitive and psychological profile did not explain the impairment in emotion recognition. This result supports the hypothesis that the impairment in social emotion recognition could be specifically related to a defect in the corticocerebellar network.

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.