The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model.

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma.

Sensory eye dominance plasticity in the human adult visual cortex.

Sensory eye dominance occurs when the visual cortex weighs one eye's data more heavily than those of the other. Encouragingly, mechanisms underlying sensory eye dominance in human adults retain a certain degree of plasticity. Notably, perceptual training using dichoptically presented motion signal-noise stimuli has been shown to elicit changes in sensory eye dominance both in visually impaired and normal observers. However, the neural mechanisms underlying these learning-driven improvements are not well understood. Here, we measured changes in fMRI responses before and after a five-day visual training protocol to determine the neuroplastic changes along the visual cascade. Fifty visually normal observers received training on a dichoptic or binocular variant of a signal-in-noise (left-right) motion discrimination task over five consecutive days. We show significant shifts in sensory eye dominance following training, but only for those who received dichoptic training. Pattern analysis of fMRI responses revealed that responses of V1 and hMT+ predicted sensory eye dominance for both groups, but only before training. After dichoptic (but not binocular) visual training, responses of V1 changed significantly, and were no longer able to predict sensory eye dominance. Our data suggest that perceptual training-driven changes in eye dominance are driven by a reweighting of the two eyes' data in the primary visual cortex. These findings may provide insight into developing region-targeted rehabilitative paradigms for the visually impaired, particularly those with severe binocular imbalance.

Life Detection From Biological Motion.

Life motion, the active movements of people and other animals, contains a wealth of information that is potentially accessible to the visual system of an observer. Biological-motion point-light displays have been widely used to study both the information contained in life motion stimuli and the visual mechanisms that make use of it. Biological motion conveys motion-mediated dynamic shape, which in turn can be used for identification and recognition of the agent, but it also contains local visual invariants that humans and other animals use as a general detection system that signals the presence of other agents in the visual environment. Here, we review recent research on behavioral, neurophysiological, and genetic aspects of this life-detection system and discuss its functional significance in the light of earlier hypotheses.

Context-based modulations of 3D vision are expertise dependent.

An object's identity can influence depth-position judgments. The mechanistic underpinnings underlying this phenomenon are largely unknown. Here, we asked whether context-dependent modulations of stereoscopic depth perception are expertise dependent. In 2 experiments, we tested whether training that attaches meaning (i.e. classification labels) to otherwise novel, stereoscopically presented objects changes observers' sensitivity for judging their depth position. In Experiment 1, observers were randomly assigned to 3 groups: a Greeble-classification training group, an orientation-discrimination training group, or a no-training group, and were tested on their stereoscopic depth sensitivity before and after training. In Experiment 2, participants were tested before and after training while fMRI responses were concurrently imaged. Behaviorally, stereoscopic performance was significantly better following Greeble-classification (but not orientation-discrimination, or no-) training. Using the fMRI data, we trained support vector machines to predict whether the data were from the pre- or post-training sessions. Results indicated that classification accuracies in V4 were higher for the Greeble-classification group as compared with the orientation-discrimination group for which accuracies were at chance level. Furthermore, classification accuracies in V4 were negatively correlated with response times for Greeble identification. We speculate that V4 is implicated in an expertise-dependent, object-tuning manner that allows it to better guide stereoscopic depth retrieval.

Neural Correlates of Sensory Eye Dominance in Human Visual White Matter Tracts.

A significant proportion of the human neurotypical population exhibits some degree of sensory eye dominance (SED), referring to the brain's preferential processing of one eye's input versus another. The neural substrates underlying this functional imbalance are not well known. Here, we investigated the relationship between visual white matter tract properties and SED in the human neurotypical population. Observers' performance on two commonly used dichoptic tasks were used to index SED, along with performance on a third task to address a functional implication of binocular imbalance: stereovision. We show that diffusivity metrics of the optic radiations (ORs) well predict behavioral SED metrics. We found no relationship between SED and stereosensitivity. Our data suggest that SED is not simply reflected by gray matter structural and functional alterations, as often suggested, but relates, at least in part to the microstructural properties of thalamocortical white matter.

Uncovering the Locus of Object-Context-Based Modulations in Depth Processing Using Repetitive Transcranial Magnetic Stimulation.

Neural responses of dorsal visual area V7 and lateral occipital complex (LOC) have been shown to correlate with changes in behavioral metrics of depth sensitivity observed as a function of object context, although it is unclear as to whether the behavioral manifestation results from an alteration of early depth-specific responses in V7 or arises as a result of alterations of object-level representations at LOC that subsequently feed back to affect disparity readouts in dorsal cortex. Here, we used online transcranial magnetic stimulation (TMS) to examine the roles of these two areas in giving rise to context-disparity interactions. Stimuli were disparity-defined geometric objects rendered as random-dot stereograms, presented in geometrically plausible and implausible variations. Observers' sensitivity to depth (depth discrimination) or object identity (plausibility discrimination) was indexed while receiving repetitive TMS at one of the two sites of interest (V7, LOC) along with a control site (Cz). TMS over LOC produced results no different from TMS over baseline Cz (and prior no-TMS behavioral work). That is, depth sensitivity was higher for implausible versus plausible objects. Strikingly, TMS over V7 abolished differences in depth sensitivity for implausible versus plausible objects. V7 serves as a key locus in bringing stereosensitivity changes because of object context, perhaps by reweighing stereoscopic data en route to informing object-motoric interactions.

Amygdala-pons connectivity is hyperactive and associated with symptom severity in depression.

Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinically depressed people demonstrate hyperactive amygdala-pons connectivity. Furthermore, this connectivity is related to depression symptom severity and is a significant indicator of depression. We speculate that visual sad information reinforces depressed mood and stimulates the pons, strengthening the amygdala-pons connectivity. The relationship between this connectivity and depressive symptom severity suggests that guiding one's visual attention and processing of sad information may benefit mood regulation.

Sound-modulations of visual motion perception implicate the cortico-vestibular brain.

A widely used example of the intricate (yet poorly understood) intertwining of multisensory signals in the brain is the audiovisual bounce inducing effect (ABE). This effect presents two identical objects moving along the azimuth with uniform motion and towards opposite directions. The perceptual interpretation of the motion is ambiguous and is modulated if a transient (sound) is presented in coincidence with the point of overlap of the two objects' motion trajectories. This phenomenon has long been written-off to simple attentional or decision-making mechanisms, although the neurological underpinnings for the effect are not well understood. Using behavioural metrics concurrently with event-related fMRI, we show that sound-induced modulations of motion perception can be further modulated by changing motion dynamics of the visual targets. The phenomenon engages the posterior parietal cortex and the parieto-insular-vestibular cortical complex, with a close correspondence of activity in these regions with behaviour. These findings suggest that the insular cortex is engaged in deriving a probabilistic perceptual solution through the integration of multisensory data.

Dichoptic Perceptual Training and Sensory Eye Dominance Plasticity in Normal Vision.

Purpose: We introduce a set of dichoptic training tasks that differ in terms of (1) the presence of external noise and (2) the visual feature implicated (motion, orientation), examining the generality of training effects between the different training and test cues and their capacity for driving changes in sensory eye dominance and stereoscopic depth perception. Methods: We randomly assigned 116 normal-sighted observers to five groups (four training groups and one no training group). All groups completed both pre- and posttests, during which they were tested on dichoptic motion and orientation tasks under noisy and noise-free conditions, as well as a binocular phase combination task and two depth tasks to index sensory eye dominance and binocular function. Training groups received visual training on one of the four dichoptic tasks over 3 consecutive days. Results: Training under noise-free conditions supported generalization of learning to noise-free tasks involving an untrained feature. By contrast, there was a symmetric learning transfer between the signal-noise and no-noise tasks within the same visual feature. Further, training on all tasks reduced sensory eye dominance but did not improve depth perception. Conclusions: Training-driven changes in sensory eye balance do not depend on the stimulus feature or whether the training entails the presence of external noise. We conjecture that dichoptic visual training acts to balance interocular suppression before or at the site of binocular combination.

Modulations of depth responses in the human brain by object context: Does biological relevance matter?

Depth sensitivity has been shown to be modulated by object context (plausibility). It is possible that it is behavioural relevance rather than object plausibility per se which drives this effect. Here, we manipulated the biological relevance of objects (face or a non-face) and tested whether object relevance affects behavioural sensitivity and neural responses to depth-position. In a first experiment, we presented human observers with disparity-defined faces and non-faces, and observers were asked to judge the depth position of the target under signal-noise and clear (fine) task conditions. In the second experiment, we concurrently measured behavioural and fMRI responses to depth. We found that behavioural performance varied across stimulus conditions such that they were significantly worse for the upright face than the inverted face and the random shape in the SNR task, but worse for the random shape than the upright face in the feature task. Pattern analysis of fMRI responses revealed that activity of FFA was distinctly different during depth judgments of the upright face versus the other two stimuli, with its responses (and to a stronger extent, those of V3) appearing functionally-relevant to behavioural performance. We speculate that FFA is not only involved in object analysis, but exerts considerable influence on stereoscopic mechanisms as early as in V3 based on a broader appreciation of the stimulus' behavioural relevance.Significance StatementWe asked how disparity sensitivity is modulated by object (biological) relevance using behavioural and neuroimaging paradigms. We show that behavioural sensitivity to depth-position changes in biological (face) vs non-biological (random surface) contexts, and that these changes are task-dependent. Imaging results highlight a potentially key role of the fusiform region for governing the modulation of stereo encoding by object relevance. These findings highlight powerful interactions between object recognition mechanisms and stereoencoding, such that the utility of disparity information may be up/down weighed depending on the biological relevance of the object.

Spatiotemporal dynamics of responses to biological motion in the human brain.

We sought to understand the spatiotemporal characteristics of biological motion perception. We presented observers with biological motion walkers that differed in terms of form coherence or kinematics (i.e., the presence or absence of natural acceleration). Participants were asked to discriminate the facing direction of the stimuli while their magnetoencephalographic responses were concurrently imaged. We found that two univariate response components can be observed around ~200 msec and ~650 msec post-stimulus onset, each engaging lateral-occipital and parietal cortex prior to temporal and frontal cortex. Moreover, while univariate responses show biological motion form-specificity only after 300 msec, multivariate patterns specific to form can be well discriminated from those for local cues as early as 100 msec after stimulus onset. By finally examining the representational similarity of fMRI and MEG patterned responses, we show that early responses to biological motion are most likely sourced to occipital cortex while later responses likely originate from extrastriate body areas.

The human posterior cingulate and the stress-response benefits of viewing green urban landscapes.

The mechanistic and neural bases of why green environments drive positive mental health outcomes remain poorly understood. We show that viewing green urban landscapes that vary in terms of green-space density elicits corresponding changes in the activity of the human ventral posterior cingulate cortex that is correlated to behavioural stress-related responses. We further show that cingulate responses are engaged early in the processing cascade, influencing attentional and executive regions in a predominantly feedforward manner. Our data suggest a key role for this region in regulating (nature) dose-dependent changes in stress responses, potentially through its extensive connections to the prefrontal and hippocampal regions which in turn project towards the neuroendocrine system. As the posterior cingulate cortex is implicated in a variety of neurological diseases and disorders, these findings raise a therapeutic potential for natural environmental exposure, highlighting green-cover as a modifiable element that links to changes in limbic responses, and has health consequences for practitioners and city-planners alike.

Positive affect is inversely related to the salience and emotion network's connectivity.

Increasing evidence has shown that positive affect enhances many aspects of daily functioning. Yet, how dispositional positive affect is represented in the intrinsic brain networks remains unclear. Here, we used resting-state functional Magnetic Resonance Imaging to test how trait positive and negative affect of an individual were associated with the intrinsic connectivity of brain regions within the salience and emotion network and the default mode network in 70 healthy young adults. We observed that positive affect was negatively associated with connectivity within the salience and emotion network, particularly with the bidirectional connections spanning the left anterior insula and left nucleus accumbens. For connections between the salience and emotion network and the rest of the brain, we observed that positive affect was negatively related to the connectivity between the right amygdala and the right middle temporal gyrus. Affect-based modulations of connectivity were specific to positive affect and to the salience and emotion network. Our findings highlight the critical role of salience and emotion network in the neural relations of positive affect, and lay the groundwork for future studies on modeling the connectivity of salience and emotion network to predict mental well-being.

The pontine-driven somatic gaze tract contributes to affective processing in humans.

The relevance of subcortical structures for affective processing is not fully understood. Inspired by the gerbil retino-raphe pathway that has been shown to regulate affective behavior and previous human work showing that the pontine region is important for processing emotion, we asked whether well-established tracts in humans traveling between the eye and the brain stem contribute to functions beyond their conventionally understood roles. Here we report neuroimaging findings showing that optic chiasm-brain stem diffusivity predict responses reflecting perceived arousal and valence. Analyses of subsequent task-evoked connectivity further revealed that visual affective processing implicates the brain stem, particularly the pontine region at an early stage of the cascade, projecting to cortico-limbic regions in a feedforward manner. The optimal model implies that all intrinsic connections between the regions of interest are unidirectional and outwards from the pontine region. These findings suggest that affective processing implicates regions outside the cortico-limbic network. The involvement of a phylogenetically older locus in the pons that has consequences in oculomotor control may imply adaptive consequences of affect detection.

Human Depth Sensitivity Is Affected by Object Plausibility.

Using behavioral and fMRI paradigms, we asked how the physical plausibility of complex 3-D objects, as defined by the object's congruence with 3-D Euclidean geometry, affects behavioral thresholds and neural responses to depth information. Stimuli were disparity-defined geometric objects rendered as random dot stereograms, presented in plausible and implausible variations. In the behavior experiment, observers were asked to complete (1) a noise-based depth task that involved judging the depth position of a target embedded in noise and (2) a fine depth judgment task that involved discriminating the nearer of two consecutively presented targets. Interestingly, results indicated greater behavioral sensitivities of depth judgments for implausible versus plausible objects across both tasks. In the fMRI experiment, we measured fMRI responses concurrently with behavioral depth responses. Although univariate responses for depth judgments were largely similar across cortex regardless of object plausibility, multivariate representations for plausible and implausible objects were notably distinguishable along depth-relevant intermediate regions V3 and V3A, in addition to object-relevant LOC. Our data indicate significant modulations of both behavioral judgments of and neural responses to depth by object context. We conjecture that disparity mechanisms interact dynamically with the object recognition problem in the visual system such that disparity computations are adjusted based on object familiarity.

Biological motion perception is differentially predicted by Autistic trait domains.

We tested the relationship between biological motion perception and the Autism-Spectrum Quotient. In three experiments, we indexed observers' performance on a classic left-right discrimination task in which participants were asked to report the facing direction of walkers containing solely structural or kinematics information, a motion discrimination task in which participants were asked to indicate the apparent motion of a (non-biological) random-dot stimulus, and a novel naturalness discrimination task. In the naturalness discrimination task, we systematically manipulated the degree of natural acceleration contained in the stimulus by parametrically morphing between a fully veridical stimulus and one where acceleration was removed. Participants were asked to discriminate the more natural stimulus (i.e., acceleration-containing stimulus) from the constant velocity stimulus. Although we found no reliable associations between overall AQ scores nor subdomain scores with performance on the direction-related tasks, we found a robust association between performance on the biological motion naturalness task and attention switching domain scores. Our findings suggest that understanding the relationship between the Autism Spectrum and perception is a far more intricate problem than previously suggested. While it has been shown that the AQ can be used as a proxy to tap into perceptual endophenotypes in Autism, the eventual diagnostic value of the perceptual task depends on the task's consideration of biological content and demands.

Color contrast adaptation: fMRI fails to predict behavioral adaptation.

fMRI-adaptation is a valuable tool for inferring the selectivity of neural responses. Here we use it in human color vision to test the selectivity of responses to S-cone opponent (blue-yellow), L/M-cone opponent (red-green), and achromatic (Ach) contrast across nine regions of interest in visual cortex. We measure psychophysical adaptation, using comparable stimuli to the fMRI-adaptation, and find significant selective adaptation for all three stimulus types, implying separable visual responses to each. For fMRI-adaptation, we find robust adaptation but, surprisingly, much less selectivity due to high levels of cross-stimulus adaptation in all conditions. For all BY and Ach test/adaptor pairs, selectivity is absent across all ROIs. For RG/Ach stimulus pairs, this paradigm has previously shown selectivity for RG in ventral areas and for Ach in dorsal areas. For chromatic stimulus pairs (RG/BY), we find a trend for selectivity in ventral areas. In conclusion, we find an overall lack of correspondence between BOLD and behavioral adaptation suggesting they reflect different aspects of the underlying neural processes. For example, raised cross-stimulus adaptation in fMRI may reflect adaptation of the broadly-tuned normalization pool. Finally, we also identify a longer-timescale adaptation (1h) in both BOLD and behavioral data. This is greater for chromatic than achromatic contrast. The longer-timescale BOLD effect was more evident in the higher ventral areas than in V1, consistent with increasing windows of temporal integration for higher-order areas.

Attentional advantages in video-game experts are not related to perceptual tendencies.

Previous studies have suggested that extensive action video gaming may enhance perceptual and attentional capacities. Here, we probed whether attentional differences between video-game experts and non-experts hold when attention is selectively directed at global or local structures. We measured performance on a modified attentional-blink task using hierarchically structured stimuli that consisted of global and local elements. Stimuli carried congruent or incongruent information. In two experiments, we asked observers to direct their attention globally (Experiment 1) or locally (Experiment 2). In each RSVP trial, observers were asked to identify the identity of an initial target (T1), and detect the presence or absence of a second target (T2). Experts showed a markedly attenuated attentional blink, as quantified by higher T2 detection sensitivity, relative to non-experts, in both global and local tasks. Notably, experts and non-experts were comparably affected by stimulus congruency. We speculate that the observed visuo-attentional advantage is unlikely to be related to mere differences perceptual tendencies (i.e., greater global precedence), which has been previously associated with diminished attentional blink.