A core component of psychological therapy causes adaptive changes in computational learning mechanisms.

BACKGROUND: Cognitive distancing is an emotion regulation strategy commonly used in psychological treatment of various mental health disorders, but its therapeutic mechanisms are unknown. METHODS: 935 participants completed an online reinforcement learning task involving choices between pairs of symbols with differing reward contingencies. Half (49.1%) of the sample was randomised to a cognitive self-distancing intervention and were trained to regulate or 'take a step back' from their emotional response to feedback throughout. Established computational (Q-learning) models were then fit to individuals' choices to derive reinforcement learning parameters capturing clarity of choice values (inverse temperature) and their sensitivity to positive and negative feedback (learning rates). RESULTS: Cognitive distancing improved task performance, including when participants were later tested on novel combinations of symbols without feedback. Group differences in computational model-derived parameters revealed that cognitive distancing resulted in clearer representations of option values (estimated 0.17 higher inverse temperatures). Simultaneously, distancing caused increased sensitivity to negative feedback (estimated 19% higher loss learning rates). Exploratory analyses suggested this resulted from an evolving shift in strategy by distanced participants: initially, choices were more determined by expected value differences between symbols, but as the task progressed, they became more sensitive to negative feedback, with evidence for a difference strongest by the end of training. CONCLUSIONS: Adaptive effects on the computations that underlie learning from reward and loss may explain the therapeutic benefits of cognitive distancing. Over time and with practice, cognitive distancing may improve symptoms of mental health disorders by promoting more effective engagement with negative information.

A Neuroanatomical Substrate Linking Perceptual Stability to Cognitive Rigidity in Autism.

Overly stable visual perception seen in individuals with autism spectrum disorder (ASD) is related to higher-order core symptoms of the condition. However, the neural basis by which these seemingly different symptoms are simultaneously observed in individuals with ASD remains unclear. Here, we aimed to identify such a neuroanatomical substrate linking perceptual stability to autistic cognitive rigidity, a part of core restricted, repetitive behaviors (RRBs). First, using a bistable visual perception test, we measured the perceptual stability of 22 high-functioning adults with ASD and 22 age-, IQ-, and sex-matched typically developing human individuals and confirmed overstable visual perception in autism. Next, using a spontaneous task-switching (TS) test, we showed that the individuals with ASD were more likely to repeat the same task voluntarily and spontaneously, and such rigid TS behavior was associated with the severity of their RRB symptoms. We then compared these perceptual and cognitive behaviors and found a significant correlation between them for individuals with ASD. Finally, we found that this behavioral link was supported by a smaller gray matter volume (GMV) of the posterior superior parietal lobule (pSPL) in individuals with ASD. Moreover, this smaller GMV in the pSPL was also associated with the RRB symptoms and replicated in two independent datasets. Our findings suggest that the pSPL could be one of the neuroanatomical mediators of cognitive and perceptual inflexibility in autism, which could help a unified biological understanding of the mechanisms underpinning diverse symptoms of this developmental disorder.SIGNIFICANCE STATEMENT Behavioral studies show perceptual overstability in autism spectrum disorder (ASD). However, the neural mechanisms by which such sensory symptoms can coexist and often correlate with seemingly separate core symptoms remain unknown. Here, we have identified such a key neuroanatomical substrate. We have revealed that overstable sensory perception of individuals with ASD is linked with their cognitive rigidity, a part of core restricted, repetitive behavior symptoms, and such a behavioral link is underpinned by a smaller gray matter volume in the posterior superior parietal lobule in autism. These findings uncover a key neuroanatomical mediator of autistic perceptual and cognitive inflexibility and would ignite future studies on how the core symptoms of ASD interact with its unique sensory perception.

Perception and Processing of Faces in the Human Brain Is Tuned to Typical Feature Locations.

UNLABELLED: Faces are salient social stimuli whose features attract a stereotypical pattern of fixations. The implications of this gaze behavior for perception and brain activity are largely unknown. Here, we characterize and quantify a retinotopic bias implied by typical gaze behavior toward faces, which leads to eyes and mouth appearing most often in the upper and lower visual field, respectively. We found that the adult human visual system is tuned to these contingencies. In two recognition experiments, recognition performance for isolated face parts was better when they were presented at typical, rather than reversed, visual field locations. The recognition cost of reversed locations was equal to ∼60% of that for whole face inversion in the same sample. Similarly, an fMRI experiment showed that patterns of activity evoked by eye and mouth stimuli in the right inferior occipital gyrus could be separated with significantly higher accuracy when these features were presented at typical, rather than reversed, visual field locations. Our findings demonstrate that human face perception is determined not only by the local position of features within a face context, but by whether features appear at the typical retinotopic location given normal gaze behavior. Such location sensitivity may reflect fine-tuning of category-specific visual processing to retinal input statistics. Our findings further suggest that retinotopic heterogeneity might play a role for face inversion effects and for the understanding of conditions affecting gaze behavior toward faces, such as autism spectrum disorders and congenital prosopagnosia. SIGNIFICANCE STATEMENT: Faces attract our attention and trigger stereotypical patterns of visual fixations, concentrating on inner features, like eyes and mouth. Here we show that the visual system represents face features better when they are shown at retinal positions where they typically fall during natural vision. When facial features were shown at typical (rather than reversed) visual field locations, they were discriminated better by humans and could be decoded with higher accuracy from brain activity patterns in the right occipital face area. This suggests that brain representations of face features do not cover the visual field uniformly. It may help us understand the well-known face-inversion effect and conditions affecting gaze behavior toward faces, such as prosopagnosia and autism spectrum disorders.

The habenula encodes negative motivational value associated with primary punishment in humans.

Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.

A meta-analysis of cognitive flexibility in autism spectrum disorder.

Cognitive flexibility is a fundamental process that underlies adaptive behaviour in response to environmental change. Studies examining the profile of cognitive flexibility in autism spectrum disorder (ASD) have reported inconsistent findings. To address whether difficulties with cognitive flexibility are characteristic of autism, we conducted a random-effects meta-analysis and employed subgroup analyses and meta-regression to assess the impact of relevant moderator variables such as task, outcomes, and age. Fifty-nine studies were included and comprised of 2122 autistic individuals without intellectual disabilities and 2036 neurotypical controls, with an age range of 4 to 85 years. The results showed that autistic individuals have greater difficulties with cognitive flexibility, with an overall statistically significant small to moderate effect size. Subgroup analyses revealed a significant difference between task outcomes, with perseverative errors obtaining the largest effect size. In summary, the present meta-analysis highlights the existence of cognitive flexibility difficulties in autistic people, in the absence of learning disabilities, but also that this profile is characterised by substantial heterogeneity. Potential contributing factors are discussed.

Defining the habenula in human neuroimaging studies.

Recently there has been renewed interest in the habenula; a pair of small, highly evolutionarily conserved epithalamic nuclei adjacent to the medial dorsal (MD) nucleus of the thalamus. The habenula has been implicated in a range of behaviours including sleep, stress and pain, and studies in non-human primates have suggested a potentially important role in reinforcement processing, putatively via its effects on monoaminergic neurotransmission. Over the last decade, an increasing number of neuroimaging studies have reported functional responses in the human habenula using functional magnetic resonance imaging (fMRI). However, standard fMRI analysis approaches face several challenges in isolating signal from this structure because of its relatively small size, around 30 mm(3) in volume. In this paper we offer a set of guidelines for locating and manually tracing the habenula in humans using high-resolution T1-weighted structural images. We also offer recommendations for appropriate pre-processing and analysis of high-resolution functional magnetic resonance imaging (fMRI) data such that signal from the habenula can be accurately resolved from that in surrounding structures.

Transdiagnostic computations of uncertainty: towards a new lens on intolerance of uncertainty.

People radically differ in how they cope with uncertainty. Clinical researchers describe a dispositional characteristic known as "intolerance of uncertainty", a tendency to find uncertainty aversive, reported to be elevated across psychiatric and neurodevelopmental conditions. Concurrently, recent research in computational psychiatry has leveraged theoretical work to characterise individual differences in uncertainty processing. Under this framework, differences in how people estimate different forms of uncertainty can contribute to mental health difficulties. In this review, we briefly outline the concept of intolerance of uncertainty within its clinical context, and we argue that the mechanisms underlying this construct may be further elucidated through modelling how individuals make inferences about uncertainty. We will review the evidence linking psychopathology to different computationally specified forms of uncertainty and consider how these findings might suggest distinct mechanistic routes towards intolerance of uncertainty. We also discuss the implications of this computational approach for behavioural and pharmacological interventions, as well as the importance of different cognitive domains and subjective experiences in studying uncertainty processing.

Uncertainty as a driver of the youth mental health crisis.

Mental health problems in young people have been on the rise for over a decade, with that trend accelerating during the pandemic. This review proposes that the catalyst effect of the pandemic offers insights into a key driver of increases in youth depression and anxiety: greater uncertainty. Uncertainty about many aspects of everyday life, including social connections, education, job security and health, increased during the pandemic, and this coincided with increasing rates of depression and anxiety. Lab-based developmental cognitive and clinical neuroscience research on tolerance of uncertainty and adolescent mental health shows that when adolescents fail to show age-typical tolerance of uncertainty, they are at greater risk of mental health problems. Avenues for future research to understand and promote tolerance of uncertainty in adolescents are proposed.

Changes in "top-down" connectivity underlie repetition suppression in the ventral visual pathway.

Repetition of the same stimulus leads to a reduction in neural activity known as repetition suppression (RS). In functional magnetic resonance imaging (fMRI), RS is found for multiple object categories. One proposal is that RS reflects locally based "within-region" changes, such as neural fatigue. Thus, if a given region shows RS across changes in stimulus size or view, then it is inferred to hold size- or view-invariant representations. An alternative hypothesis characterizes RS as a consequence of "top-down" between-region modulation. Differentiating between these accounts is central to the correct interpretation of fMRI RS data. It is also unknown whether the same mechanisms underlie RS to identical stimuli and RS across changes in stimulus size or view. Using fMRI, we investigated RS within a body-sensitive network in human visual cortex comprising the extrastriate body area (EBA) and the fusiform body area (FBA). Both regions showed RS to identical images of the same body that was unaffected by changes in body size or view. Dynamic causal modeling demonstrated that changes in backward, top-down (FBA-to-EBA) effective connectivity play a critical role in RS. Furthermore, only repetition of the identical image showed additional changes in forward connectivity (EBA-to-FBA). These results suggest that RS is driven by changes in top-down modulation, whereas the contribution of "feedforward" changes in connectivity is dependent on the precise nature of the repetition. Our results challenge previous interpretations regarding the underlying nature of neural representations made using fMRI RS paradigms.

Perceptual decision-making in autism as assessed by "spot the difference" visual cognition tasks.

Discriminating between similar figures proves to be a remarkably demanding task due to the limited capacity of our visual cognitive processes. Here we examine how perceptual inference and decision-making are modulated by differences arising from neurodiversity. A large sample of autistic (n = 140) and typical (n = 147) participants completed two forced choice similarity judgement tasks online. Each task consisted of "match" (identical figures) and "mismatch" (subtle differences between figures) conditions. Signal detection theory analyses indicated a response bias by the autism group during conditions of uncertainty. More specifically, autistic participants were more likely to choose the "mismatch" option, thus leading to more hits on the "mismatch" condition, but also more false alarms on the "match" condition. These results suggest differences in response strategies during perceptual decision-making in autism.

A real head turner: horizontal and vertical head directions are multichannel coded.

Head direction is a salient cue to the focus of other people's attention. Electrophysiology in macaques has shown head-selective cells in the superior temporal sulcus that are mostly tuned to different directions (up, down, left, right, front, back, etc.). However, there has been no systematic investigation into the visual representation of head direction in both the horizontal (left-right) and vertical (up-down) planes in humans. We addressed whether the coding of head direction is best accounted for by a multichannel system, with distinct pools of cells (or channels) tuned to different head views (i.e., left, right, direct, up, and down), or an opponent-coding system with two broadly tuned pools of cells responding to two extremes (i.e., left-right and up-down) and "direct" represented as the equilibrium state in the system. In a series of four experiments, we carried out two adaptation procedures for which multichannel and opponent coding predict distinct outcomes. The results support multichannel coding of head direction in both the vertical and horizontal axes.

Disrupted Dorsal Mid-Insula Activation During Interoception Across Psychiatric Disorders.

OBJECTIVE: Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While altered neural activation during interoception in specific psychiatric disorders has been reported in many studies, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences. METHODS: The authors conducted a meta-analysis of neuroimaging studies comparing patients with psychiatric disorders with healthy control subjects to identify brain regions exhibiting convergent disrupted activation during interoception. Bibliographic, neuroimaging, and preprint databases through May 2020 were searched. A total of 306 foci from 33 studies were extracted, which included 610 control subjects and 626 patients with schizophrenia, bipolar or unipolar depression, posttraumatic stress disorder, anxiety, eating disorders, or substance use disorders. Data were pooled using a random-effects model implemented by the activation likelihood estimation algorithm. The preregistered primary outcome was the neuroanatomical location of the convergence of peak voxel coordinates. RESULTS: Convergent disrupted activation specific to the left dorsal mid-insula was found (Z=4.47, peak coordinates: -36, -2, 14; volume: 928 mm3). Studies directly contributing to the cluster included patients with bipolar disorder, anxiety, major depression, anorexia, and schizophrenia, assessed with task probes including pain, hunger, and interoceptive attention. A series of conjunction analyses against extant meta-analytic data sets revealed that this mid-insula cluster was anatomically distinct from brain regions involved in affective processing and from regions altered by psychological or pharmacological interventions for affective disorders. CONCLUSIONS: These results reveal transdiagnostic, domain-general differences in interoceptive processing in the left dorsal mid-insula. Disrupted mid-insular activation may represent a neural marker of psychopathology and a putative target for novel interventions.

The effect of uncertainty on prediction error in the action perception loop.

Among all their sensations, agents need to distinguish between those caused by themselves and those caused by external causes. The ability to infer agency is particularly challenging under conditions of uncertainty. Within the predictive processing framework, this should happen through active control of prediction error that closes the action-perception loop. Here we use a novel, temporally-sensitive, behavioural proxy for prediction error to show that it is minimised most quickly when volatility is high and when participants report agency, regardless of the accuracy of the judgement. We demonstrate broad effects of uncertainty on accuracy of agency judgements, movement, policy selection, and hypothesis switching. Measuring autism traits, we find differences in policy selection, sensitivity to uncertainty and hypothesis switching despite no difference in overall accuracy.

The Computational, Pharmacological, and Physiological Determinants of Sensory Learning under Uncertainty.

The ability to represent and respond to uncertainty is fundamental to human cognition and decision-making. Noradrenaline (NA) is hypothesized to play a key role in coordinating the sensory, learning, and physiological states necessary to adapt to a changing world, but direct evidence for this is lacking in humans. Here, we tested the effects of attenuating noradrenergic neurotransmission on learning under uncertainty. We probed the effects of the ß-adrenergic receptor antagonist propranolol (40 mg) using a between-subjects, double-blind, placebo-controlled design. Participants performed a probabilistic associative learning task, and we employed a hierarchical learning model to formally quantify prediction errors about cue-outcome contingencies and changes in these associations over time (volatility). Both unexpectedness and noise slowed down reaction times, but propranolol augmented the interaction between these main effects such that behavior was influenced more by prior expectations when uncertainty was high. Computationally, this was driven by a reduction in learning rates, with people slower to update their beliefs in the face of new information. Attenuating the global effects of NA also eliminated the phasic effects of prediction error and volatility on pupil size, consistent with slower belief updating. Finally, estimates of environmental volatility were predicted by baseline cardiac measures in all participants. Our results demonstrate that NA underpins behavioral and computational responses to uncertainty. These findings have important implications for understanding the impact of uncertainty on human biology and cognition.

About turn: the visual representation of human body orientation revealed by adaptation.

Body orientation provides an important cue to other individuals' focus of attention, particularly when one is viewing them at a distance. Single-cell recording in macaques has identified cells in the superior temporal sulcus that show a view-selective response to particular body orientations. Whether similar separable coding is found in humans is not known, and there is currently no functional account of the visual representation of seen body orientation. This study addressed this issue using visual adaptation. Experiment 1 demonstrated distinct channels that code left- and right-oriented bodies. Experiment 2 investigated whether the visual representation of body orientation is best accounted for by an opponent-coding system, which has been shown to account for the visual representation of facial identity, or by a multichannel system, which provides the optimal account of coding line orientation and direction of motion. Our results provide evidence for multichannel coding of seen body orientation, with separate channels (or neuronal populations) selectively tuned to different body directions.

Cultural effects on computational metrics of spatial and temporal context.

The concept of "prediction error" - the difference between what occurred and was expected - is key to understanding the cognitive processes of human decision making. Expectations have to be learned so the concept of prediction error critically depends on context, specifically the temporal context of probabilistically related events and their changes across time (i.e. volatility). While past research suggests context differently affects some cognitive processes in East Asian and Western individuals, it is currently unknown whether this extends to computationally-grounded measures of learning and prediction error. Here we compared Chinese and British nationals in an associative learning task that quantifies behavioural effects of prediction error, and-through a hierarchical Bayesian learning model-also captures how individuals learn about probabilistic relationships and their volatility. For comparison, we also administered a psychophysical task, the tilt illusion, to assess cultural differences in susceptibility to spatial context. We found no cultural differences in the effect of spatial context on perception. In the domain of temporal context there was no effect of culture on sensitivity to prediction error, or learning about volatility, but some suggestion that Chinese individuals may learn more readily about probabilistic relationships.

Adaptation of social and non-social cues to direction in adults with autism spectrum disorder and neurotypical adults with autistic traits.

Perceptual constancy strongly relies on adaptive gain control mechanisms, which shift perception as a function of recent sensory history. Here we examined the extent to which individual differences in magnitude of adaptation aftereffects for social and non-social directional cues are related to autistic traits and sensory sensitivity in healthy participants (Experiment 1); and also whether adaptation for social and non-social directional cues is differentially impacted in adults with Autism Spectrum Disorder (ASD) relative to neurotypical (NT) controls (Experiment 2). In Experiment 1, individuals with lower susceptibility to adaptation aftereffects, i.e. more 'veridical' perception, showed higher levels of autistic traits across social and non-social stimuli. Furthermore, adaptation aftereffects were predictive of sensory sensitivity. In Experiment 2, only adaptation to eye-gaze was diminished in adults with ASD, and this was related to difficulties categorizing eye-gaze direction at baseline. Autism Diagnostic Observation Schedule (ADOS) scores negatively predicted lower adaptation for social (head and eye-gaze direction) but not non-social (chair) stimuli. These results suggest that the relationship between adaptation and the broad socio-cognitive processing style captured by 'autistic traits' may be relatively domain-general, but in adults with ASD diminished adaptation is only apparent where processing is most severely impacted, such as the perception of social attention cues.

Autistic adults show preserved normalisation of sensory responses in gaze processing.

Progress in our understanding of autism spectrum disorder (ASD) has recently been sought by characterising how systematic differences in canonical neural computations employed across the sensory cortex might contribute to clinical symptoms in diverse sensory, cognitive, and social domains. A key proposal is that ASD is characterised by reduced divisive normalisation of sensory responses. This provides a bridge between genetic and molecular evidence for an increased ratio of cortical excitation to inhibition in ASD and the functional characteristics of sensory coding that are relevant for understanding perception and behaviour. Here we tested this hypothesis in the context of gaze processing (i.e., the perception of other people's direction of gaze), a domain with direct relevance to the core diagnostic features of ASD. We show that reduced divisive normalisation in gaze processing is associated with specific predictions regarding the psychophysical effects of sensory adaptation to gaze direction, and test these predictions in adults with ASD. We report compelling evidence that both divisive normalisation and sensory adaptation occur robustly in adults with ASD in the context of gaze processing. These results have important theoretical implications for defining the types of divisive computations that are likely to be intact or compromised in this condition (e.g., relating to local vs distal control of cortical gain). These results are also a strong testament to the typical sensory coding of gaze direction in ASD, despite the atypical responses to others' gaze that are a hallmark feature of this diagnosis.

Adults with autism overestimate the volatility of the sensory environment.

Insistence on sameness and intolerance of change are among the diagnostic criteria for autism spectrum disorder (ASD), but little research has addressed how people with ASD represent and respond to environmental change. Here, behavioral and pupillometric measurements indicated that adults with ASD are less surprised than neurotypical adults when their expectations are violated, and decreased surprise is predictive of greater symptom severity. A hierarchical Bayesian model of learning suggested that in ASD, a tendency to overlearn about volatility in the face of environmental change drives a corresponding reduction in learning about probabilistically aberrant events, thus putatively rendering these events less surprising. Participant-specific modeled estimates of surprise about environmental conditions were linked to pupil size in the ASD group, thus suggesting heightened noradrenergic responsivity in line with compromised neural gain. This study offers insights into the behavioral, algorithmic and physiological mechanisms underlying responses to environmental volatility in ASD.