Mismatch negativity and clinical trajectories in psychotic disorders: Five-year stability and predictive utility.

BACKGROUND: Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear. METHOD: We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning. RESULTS: MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (ß = 0.19), everyday functioning (ß = -0.13), and illness severity (ß = -0.12) at follow-up. Meanwhile, initial IQ (ß = -0.24), negative symptoms (ß = 0.23), and illness severity (ß = -0.16) were significant predictors of worsening MMN amplitude five years later. CONCLUSIONS: These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.

Dynamic interplay between life events and course of psychotic disorders: 10-year longitudinal study following first admission.

BACKGROUND: Life events (LEs) are a risk factor for first onset and relapse of psychotic disorders. However, the impact of LEs on specific symptoms - namely reality distortion, disorganization, negative symptoms, depression, and mania - remains unclear. Moreover, the differential effects of negative v. positive LEs are poorly understood. METHODS: The present study utilizes an epidemiologic cohort of patients (N = 428) ascertained at first-admission for psychosis and followed for a decade thereafter. Symptoms were assessed at 6-, 24-, 48-, and 120-month follow-ups. RESULTS: We examined symptom change within-person and found that negative events in the previous 6 months predicted an increase in reality distortion (ß = 0.07), disorganized (ß = 0.07), manic (ß = 0.08), and depressive symptoms (ß = 0.06), and a decrease in negative symptoms (ß = -0.08). Conversely, positive LEs predicted fewer reality distortion (ß = -0.04), disorganized (ß = -0.04), and negative (ß = -0.13) symptoms, and were unrelated to mood symptoms. A between-person approach to the same hypotheses confirmed that negative LEs predicted change in all symptoms, while positive LEs predicted change only in negative symptoms. In contrast, symptoms rarely predicted future LEs. CONCLUSIONS: These findings confirm that LEs have an effect on symptoms, and thus contribute to the burden of psychotic disorders. That LEs increase positive symptoms and decrease negative symptoms suggest at least two different mechanisms underlying the relationship between LEs and symptoms. Our findings underscore the need for increased symptom monitoring following negative LEs, as symptoms may worsen during that time.

They're watching you: the impact of social evaluation and anxiety on threat-related perceptual decision-making.

In day-to-day social interactions, we frequently use cues and contextual knowledge to make perceptual decisions regarding the presence or absence of threat in facial expressions. Such perceptual decisions are often made in socially evaluative contexts. However, the influence of such contexts on perceptual discrimination of threatening and neutral expressions has not been examined empirically. Furthermore, it is unclear how individual differences in anxiety interact with socially evaluative contexts to influence threat-related perceptual decision-making. In the present study, participants completed a 2-alternative forced choice perceptual decision-making task in which they used threatening and neutral cues to discriminate between threatening and neutral faces while being socially evaluated by purported peers or not. Perceptual sensitivity and reaction time were measured. Individual differences in state anxiety were assessed immediately after the task. In the presence of social evaluation, higher state anxiety was associated with worse perceptual sensitivity, i.e., worse discrimination of threatening and neutral faces. These findings suggest that individual differences in anxiety interact with social evaluation to impair the use of threatening cues to discriminate between threatening and neutral expressions. Such impairment in perceptual decision-making may contribute to maladaptive social behavior that often accompanies evaluative social contexts.

Intrinsic neural circuitry of depression in adolescent females.

BACKGROUND: Adolescence is characterized by affective and cognitive changes that increase vulnerability to depression, especially in females. Neurodevelopmental models attribute adolescent depression to abnormal responses in amygdala, striatum, and prefrontal cortex (PFC). We examined whether the strength of functional brain networks involving these regions predicts depression symptoms in adolescent females. METHODS: In this longitudinal study, we recorded resting-state functional connectivity (RSFC) in 174 adolescent females. Using a cross-validation strategy, we related RSFC profiles that included (a) a network consisting of amygdala, striatum, and PFC (within-circuit model), (b) connectivity of this network to the whole brain (extended-circuit model), and (c) a network consisting of the entire brain (whole-brain model) to depression symptoms assessed concurrently and 18 months later. RESULTS: In testing subsets, the within-circuit RSFC profiles were associated with depression symptoms concurrently and 18 months later, while the extended-circuit and whole-brain model did not explain any additional variance in depression symptoms. Connectivity related to anterior cingulate and ventromedial prefrontal cortex contributed most to the association. CONCLUSIONS: Our results demonstrate that RSFC-based brain networks that include amygdala, striatum, and PFC are stable neural signatures of concurrent and future depression symptoms, representing a significant step toward identifying the neural mechanism of depression in adolescence.

Memory for dangers past: threat contexts produce more consistent learning than do non-threatening contexts.

In earlier work we showed that individuals learn the spatial regularities within contexts and use this knowledge to guide detection of threatening targets embedded in these contexts. While it is highly adaptive for humans to use contextual learning to detect threats, it is equally adaptive for individuals to flexibly readjust behaviour when contexts once associated with threatening stimuli begin to be associated with benign stimuli, and vice versa. Here, we presented face targets varying in salience (threatening or non-threatening) in new or old spatial configurations (contexts) and changed the target salience (threatening to non-threatening and vice versa) halfway through the experiment to examine if contextual learning changes with the change in target salience. Detection of threatening targets was faster in old than new configurations and this learning persisted even after the target changed to non-threatening. However, the same pattern was not seen when the targets changed from non-threatening to threatening. Overall, our findings show that threat detection is driven not only by stimulus properties as theorised traditionally but also by the learning of contexts in which threatening stimuli appear, highlighting the importance of top-down factors in threat detection. Further, learning of contexts associated with threatening targets is robust and speeds detection of non-threatening targets subsequently presented in the same context.

Here Comes Trouble: Prestimulus Brain Activity Predicts Enhanced Perception of Threat.

Research on the perceptual prioritization of threatening stimuli has focused primarily on the physical characteristics and evolutionary salience of these stimuli. However, perceptual decision-making is strongly influenced by prestimulus factors such as goals, expectations, and prior knowledge. Using both event-related potentials and functional magnetic resonance imaging, we test the hypothesis that prior threat-related information and related increases in prestimulus brain activity play a key role in subsequent threat-related perceptual decision-making. After viewing threatening and neutral cues, participants detected perceptually degraded threatening and neutral faces presented at individually predetermined perceptual thresholds in a perceptual decision-making task. Compared with neutral cues, threat cues resulted in (1) improved perceptual sensitivity and faster detection of target stimuli; (2) increased late positive potential (LPP) and superior temporal sulcus (STS) activity, both of which are measures of emotional face processing; and (3) increased amygdala activity for subsequently presented threatening versus and neutral faces. Importantly, threat cue-related LPP and STS activity predicted subsequent improvement in the speed and precision of perceptual decisions specifically for threatening faces. Present findings establish the importance of top-down factors and prestimulus neural processing in understanding how the perceptual system prioritizes threatening information.

Context learning for threat detection.

It is hypothesised that threatening stimuli are detected better due to their salience or physical properties. However, these stimuli are typically embedded in a rich context, motivating the question whether threat detection is facilitated via learning of contexts in which threat stimuli appear. To address this question, we presented threatening face targets in new or old spatial configurations consisting of schematic faces and found that detection of threatening targets was faster in old configurations. This indicates that individuals are able to learn regularities within visual contexts and use this contextual information to guide detection of threatening targets. Next, we presented threatening and non-threatening face targets embedded in new or old spatial configurations. Detection of threatening targets was facilitated in old configurations, and this effect was reversed for non-threatening targets. Present findings show that detection of threatening targets is driven not only by stimulus properties as theorised traditionally but also by learning of contexts in which threatening stimuli appear. Further, results show that context learning for threatening targets obstructs context learning for non-threatening targets. Overall, in addition to typically emphasised bottom-up factors, our findings highlight the importance of top-down factors such as context and learning in detection of salient, threatening stimuli.

Human Amygdala Represents the Complete Spectrum of Subjective Valence.

Although the amygdala is a major locus for hedonic processing, how it encodes valence information is poorly understood. Given the hedonic potency of odor stimuli and the amygdala's anatomical proximity to the peripheral olfactory system, we combined high-resolution fMRI with pattern-based multivariate techniques to examine how valence information is encoded in the amygdala. Ten human subjects underwent fMRI scanning while smelling 9 odorants that systematically varied in perceived valence. Representational similarity analyses showed that amygdala codes the entire dimension of valence, ranging from pleasantness to unpleasantness. This unidimensional representation significantly correlated with self-reported valence ratings but not with intensity ratings. Furthermore, within-trial valence representations evolved over time, prioritizing earlier differentiation of unpleasant stimuli. Together, these findings underscore the idea that both spatial and temporal features uniquely encode pleasant and unpleasant odor valence in the amygdala. The availability of a unidimensional valence code in the amygdala, distributed in both space and time, would create greater flexibility in determining the pleasantness or unpleasantness of stimuli, providing a mechanism by which expectation, context, attention, and learning could influence affective boundaries for guiding behavior. SIGNIFICANCE STATEMENT: Our findings elucidate the mechanisms of affective processing in the amygdala by demonstrating that this brain region represents the entire valence dimension from pleasant to unpleasant. An important implication of this unidimensional valence code is that pleasant and unpleasant valence cannot coexist in the amygdale because overlap of fMRI ensemble patterns for these two valence extremes obscures their unique content. This functional architecture, whereby subjective valence maps onto a pattern continuum between pleasant and unpleasant poles, offers a robust mechanism by which context, expectation, and experience could alter the set-point for valence-based behavior. Finally, identification of spatial and temporal differentiation of valence in amygdala may shed new insights into individual differences in emotional responding, with potential relevance for affective disorders.

Understanding anxiety through uncertainty quantification.

Uncertainty has been a central concept in psychological theories of anxiety. However, this concept has been plagued by divergent connotations and operationalizations. The lack of consensus hinders the current search for cognitive and biological mechanisms of anxiety, jeopardizes theory creation and comparison, and restrains translation of basic research into improved diagnoses and interventions. Drawing upon uncertainty decomposition in Bayesian Decision Theory, we propose a well-defined conceptual structure of uncertainty in cognitive and clinical sciences, with a focus on anxiety. We discuss how this conceptual structure provides clarity and can be naturally applied to existing frameworks of psychopathology research. Furthermore, it allows formal quantification of various types of uncertainty that can benefit both research and clinical practice in the era of computational psychiatry.

Knowledge of Threat Biases Perceptual Decision Making in Anxiety: Evidence From Signal Detection Theory and Drift Diffusion Modeling.

Background: Threat biases are considered key factors in the development and maintenance of anxiety. However, these biases are poorly operationalized and remain unquantified. Furthermore, it is unclear whether and how prior knowledge of threat and its uncertainty induce these biases and how they manifest in anxiety. Method: Participants (n = 55) used prestimulus cues to decide whether the subsequently presented stimuli were threatening or neutral. The cues either provided no information about the probability (high uncertainty) or indicated high probability (low uncertainty) of encountering threatening or neutral targets. We used signal detection theory and hierarchical drift diffusion modeling to quantify bias. Results: High-uncertainty threat cues improved discrimination of subsequent threatening and neutral stimuli more than neutral cues. However, anxiety was associated with worse discrimination of threatening versus neutral stimuli following high-uncertainty threat cues. Using hierarchical drift diffusion modeling, we found that threat cues biased decision making not only by shifting the starting point of evidence accumulation toward the threat decision but also by increasing the efficiency with which sensory evidence was accumulated for both threat-related and neutral decisions. However, higher anxiety was associated with a greater shift of starting point toward the threat decision but not with the efficiency of evidence accumulation. Conclusions: Using computational modeling, these results highlight the biases by which knowledge regarding uncertain threat improves perceptual decision making but impairs it in case of anxiety.

Hallucination-Proneness is Associated With a Decrease in Robust Averaging of Perceptual Evidence.

BACKGROUND AND HYPOTHESIS: Hallucinations are characterized by disturbances in perceptual decision-making about environmental stimuli. When integrating across multiple stimuli to form a perceptual decision, typical observers engage in "robust averaging" by down-weighting extreme perceptual evidence, akin to a statistician excluding outlying data. Furthermore, observers adapt to contexts with more unreliable evidence by increasing this down-weighting strategy. Here, we test the hypothesis that hallucination-prone individuals (n = 38 high vs n = 91 low) would show a decrease in this robust averaging and diminished sensitivity to changes in evidence variance. STUDY DESIGN: We used a multielement perceptual averaging task to elicit dichotomous judgments about the "average color" (red/blue) of an array of stimuli in trials with varied strength (mean) and reliability (variance) of decision-relevant perceptual evidence. We fitted computational models to task behavior, with a focus on a log-posterior-ratio (LPR) model which integrates evidence as a function of the log odds of each perceptual option and produces a robust averaging effect. STUDY RESULTS: Hallucination-prone individuals demonstrated less robust averaging, seeming to weigh inlying and outlying extreme or untrustworthy evidence more equally. Furthermore, the model that integrated evidence as a function of the LPR of the two perceptual options and produced robust averaging showed poorer fit for the group prone to hallucinations. Finally, the weighting strategy in hallucination-prone individuals remained insensitive to evidence variance. CONCLUSIONS: Our findings provide empirical support for theoretical proposals regarding evidence integration aberrations in psychosis and alterations in the perceptual systems that track statistical regularities in environmental stimuli.

Emotional distractors can enhance attention.

The deleterious effects of emotional distractors on attention have been well demonstrated. However, it is unclear whether emotional distractors inevitably disrupt task-relevant attention. In the research reported here, the impact of the valence and arousal of distracting emotional stimuli and individual differences in anxiety on task-relevant processing were examined using multilevel modeling. Consistent with prior literature, results showed that high-arousal negative distractors, compared with positive and neutral distractors, were associated with poorer task-relevant attention. However, low-arousal negative distractors were associated with better task-relevant performance than were positive and neutral distractors. Furthermore, these effects were accentuated by individual differences in worry. These findings challenge assumptions that distraction and worry must be minimized for augmented attentional performance. Overall, these results emphasize the importance of taking into account emotional dimensions of arousal and valence as well as individual differences in anxiety when examining attention in the presence of emotional distractors.

What Do We Know About Threat-Related Perceptual Decision Making?

The ability to make rapid and precise decisions regarding the presence or absence of threats in our environment is critical for our survival. While threatening stimuli may be detected more accurately and faster due to the "bottom-up" salience of their features, in the real-world, these stimuli are often encountered in familiar environments in which "top-down" cues signal their arrival. There has been significant progress in our understanding of the mechanisms by which we make perceptual decisions regarding relatively routine stimuli; however, the mechanisms of threat-related perceptual decision-making remain unclear. In this paper, we discuss the psychological, computational, and neural mechanisms by which information from threatening stimuli is integrated with our prior knowledge from cues and surrounding contexts to guide perceptual decision-making.

Linking the past to the future by predictive processing: Implications for psychopathology.

Most theories of psychopathology have focused on etiology at a specific level (e.g., genetic, neurobiological, psychological, or environmental) to explain specific symptoms or disorders. A few biopsychosocial theories have provided explanations that attempt to integrate different levels and disorders to some extent. However, these theories lack a framework in which different levels of analysis are integrated and thus do not explain the mechanism by which etiological factors interact and perturb neurobiology which in turn leads to psychopathology. We propose that predictive processing (PP), which originated in theoretical neurobiology literature, may provide a conceptually parsimonious and biologically plausible framework to achieve such integration. In PP, the human brain can be cast as implementing a generative model whose task is to minimize the surprise of sensory evidence by inferring its causes and actively controlling future sensory signals via action. This account offers a unifying model of perception, action, and emotion implicated in psychopathology. Furthermore, we show that PP can explain how different factors or levels result in psychopathology via updates of the generative model (the depth of the PP framework). Finally, we demonstrate the transdiagnostic appeal of PP by showing how perturbations within this framework can explain a broad range of psychopathology (the breadth of the PP framework), with a focus on bridging well-established psychosocial theories of psychopathology and PP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Is threat detection Black and White? Race effects in threat-related perceptual decision-making.

There is a vast literature base indicating that people respond differently to Black and White individuals based on differential perceptions of threat. As facial affect is a fundamental way that individuals communicate their emotional state, studies have examined differences in how Black and White threatening facial expressions are perceived. However, perceptual decisions regarding threatening and neutral stimuli often occur in familiar contexts or in environments where explicit cues indicate the presence or absence of threat. Furthermore, these decisions often occur in "noisy" (i.e., ambiguous) environments where the quality of sensory evidence is poor, requiring us to rely on perceptual "sets" or expectations to interpret such evidence. Therefore, in the present study we used a two-alternative perceptual decision-making task in which participants used threatening and neutral cue-elicited perceptual sets to discriminate between subsequently presented threatening and neutral Black and White faces. Threatening cues led to a greater tendency to decide that both Black and White faces were threatening, as well as faster and greater discriminability between threatening and neutral Black and White faces. However, race-related differences revealed that, following both cue types, discriminability between threatening and neutral Black faces was worse compared to White faces. Therefore, using a paradigm that is ecologically valid, our findings highlight the importance of examining basic aspects of visual perception to understand race-related differences in threat-related perceptual decision-making. Furthermore, these findings emphasize the importance of anticipatory top-down factors when making perceptual decisions about the presence or absence of threat in faces of different races. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Threat and uncertainty in the face of perceptual decision-making in anxiety.

Anxiety is defined as an anticipatory response to uncertain, future threats. It is unknown how anticipatory information regarding uncertainty about upcoming threatening and neutral stimuli impacts attention and perception in anxiety. Individuals with and without anxiety disorders performed two perceptual decision-making tasks in which they used threat or neutral prestimulus cues to discriminate between subsequent threatening and neutral faces. In one task, cues provided no probability information (high uncertainty). In the other, cues indicated a high probability of encountering threatening or neutral faces (low uncertainty). Under high uncertainty only, anxious apprehension was associated with worse discrimination between threatening versus neutral faces after threat cues. Additionally, anxious arousal was associated with worse discrimination after neutral cues in individuals with anxiety disorders. These findings will advance the field by spurring the development of more comprehensive and ecologically valid models in which anticipatory top-down factors influence threat perception in anxiety. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association of attention and memory biases for negative stimuli with post-traumatic stress disorder symptoms.

Cognitive models have highlighted the role of attentional and memory biases towards negatively-valenced emotional stimuli in the maintenance of post-traumatic stress disorder (PTSD). However, previous research has focused mainly on attentional biases towards distracting (task-irrelevant) negative stimuli. Furthermore, attentional and memory biases have been examined in isolation and the links between them remain underexplored. We manipulated attention during encoding of trauma-unrelated negative and neutral words and examined the differential relationship of their encoding and recall with PTSD symptoms. Responders to the World Trade Center disaster (N = 392) performed tasks in which they read negative and neutral words and reported the color of another set of such words. Subsequently, participants used word stems to aid retrieval of words shown earlier. PTSD symptoms were associated with slower response times for negative versus neutral words in the word-reading task (r = 0.170) but not color-naming task. Furthermore, greater PTSD symptom severity was associated with more accurate recall of negative versus neutral words, irrespective of whether words were encoded during word-reading or color-naming tasks (F = 4.11, p = 0.044, ηp2 = 0.018). Our results show that PTSD symptoms in a trauma-exposed population are related to encoding of trauma-unrelated negative versus neutral stimuli only when attention was voluntarily directed towards the emotional aspects of the stimuli and to subsequent recall of negative stimuli, irrespective of attention during encoding.

Pleasant and unpleasant odor identification ability is associated with distinct dimensions of negative symptoms transdiagnostically in psychotic disorders.

Negative symptoms are among the greatest sources of functional impairment for individuals with schizophrenia, yet their mechanisms remain poorly understood. Olfactory impairment is associated with negative symptoms. The processing of pleasant olfactory stimuli is subserved by reward-related neural circuitry while unpleasant olfactory processing is subserved by emotion-related neural circuitry, suggesting that these two odor dimensions may offer a window into differential mechanisms of negative symptoms. We examined whether pleasant and unpleasant odor identification bears differential relationships with avolition and inexpressivity dimensions of negative symptoms, whether these relationships are transdiagnostic, and whether pleasant and unpleasant odor processing also relate differently to other domains of functioning in a sample of individuals diagnosed with schizophrenia (N = 54), other psychotic disorders (N = 65), and never-psychotic adults (N = 160). Hierarchical regressions showed that pleasant odor identification was uniquely associated with avolition, while unpleasant odor identification was uniquely associated with inexpressivity. These relationships were largely transdiagnostic across groups. Additionally, pleasant and unpleasant odor identification displayed signs of specificity with other functional and cognitive measures. These results align with past work suggesting dissociable pathomechanisms of negative symptoms and provide a potential avenue for future work using valence-specific olfactory dysfunction as a semi-objective and low-cost marker for understanding and predicting the severity of specific negative symptom profiles.

Structural Connectivity Between Rostral Anterior Cingulate Cortex and Amygdala Predicts First Onset of Depressive Disorders in Adolescence.

BACKGROUND: Adolescent-onset depressive disorders (DDs) are associated with deficits in the regulation of negative affect across modalities (self-report, behavioral paradigms, and neuroimaging), which may manifest prior to first-onset DDs. Whether the neurocircuitry governing emotional regulation predates DDs is unclear. This study tested whether a critical pathway for emotion regulation (rostral anterior cingulate cortex-amygdala structural connectivity) predicts first-onset DDs in adolescent females. METHODS: Diffusion tensor imaging data were acquired on adolescent females (n = 212) without a history of DDs and the cohort was reassessed for first-onset DDs over the next 27 months. RESULTS: A total of 26 girls developed first onsets of DDs in the 27 months after imaging. Multivariate logistic regression showed that lower weighted average fractional anisotropy of uncinate fasciculus tracts between the rostral anterior cingulate cortex and amygdala prospectively predicted first onset of DDs (adjusted odds ratio = 0.44, p = .005), above and beyond established risk factors including baseline depression symptom severity, history of anxiety disorders, parental history of depression, parental education, and age. CONCLUSIONS: This study provides evidence for the first time showing that aberrant structural connectivity between the rostral anterior cingulate cortex and amygdala prospectively predates first onset of DDs in adolescent females. These results highlight the importance of a well-established neural circuit implicated in the regulation of negative affect as a likely etiological factor and a promising target for intervention and prevention of DDs.

Amygdala connectivity during emotional face perception in psychotic disorders.

Emotional face perception (EFP) deficits have been identified as a significant feature of psychotic disorders and are associated with symptoms and real-world functioning in these disorders. The amygdala is frequently implicated in EFP and bears extensive structural connectivity with other brain regions supporting EFP. Amygdala functional connectivity during attentional control of implicitly processed emotional faces in psychotic disorders is well examined. However, it is unclear whether amygdala functional connectivity while explicitly processing emotional faces contributes to EFP deficits in psychotic disorders. Further, it is unclear whether these connectivity differences are associated with symptoms or functioning and if these relationships are transdiagnostic across psychotic disorders. We used functional magnetic resonance imaging (fMRI) and seed-based functional connectivity analyses to examine connectivity of amygdala to other regions of the face processing network during an EFP task. The sample consisted of 55 cases with psychotic disorders and 29 participants with no history of psychosis (NP). Results indicated that, compared to NP, cases showed worse accuracy, greater inferior frontal gyrus (IFG) activation, and greater amygdala-insula connectivity while matching emotional and neutral faces. Additionally, worse accuracy, greater IFG activation, greater amygdala-insula and amygdala-IFG connectivity during emotional vs. neutral faces was associated with worse negative symptoms and greater deficits in social and global functioning in cases. Importantly, these relationships transcended diagnostic categories, and applied across psychotic disorders. The present study presents compelling evidence relating alterations in amygdala functional connectivity during explicit EFP with clinical and functioning deficits seen across psychotic disorders.