Different learning aberrations relate to delusion-like beliefs with different contents.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control, or that events in the world have specific personal meaning. We compare learning on two different cognitive tasks, probabilistic reversal learning (PRL) and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that Clinical High-Risk status alone does not result in different behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioral data to explore how latent parameters vary within individuals between tasks, and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which - given the transdiagnostic status of paranoia - may have differential utility in predicting psychosis.

Assessing Trial-by-Trial Electrophysiological and Behavioral Markers of Attentional Control and Sensory Precision in Psychotic and Mood Disorders.

BACKGROUND AND HYPOTHESIS: The current study investigated the extent to which changes in attentional control contribute to performance on a visual perceptual discrimination task, on a trial-by-trial basis in a transdiagnostic clinical sample. STUDY DESIGN: Participants with schizophrenia (SZ; N = 58), bipolar disorder (N = 42), major depression disorder (N = 51), and psychiatrically healthy controls (N = 92) completed a visual perception task in which stimuli appeared briefly. The design allowed us to estimate the lapse rate and the precision of perceptual representations of the stimuli. Electroencephalograms (EEG) were recorded to examine pre-stimulus activity in the alpha band (8-13 Hz), overall and in relation to behavior performance on the task. STUDY RESULTS: We found that the attention lapse rate was elevated in the SZ group compared with all other groups. We also observed group differences in pre-stimulus alpha activity, with control participants showing the highest levels of pre-stimulus alpha when averaging across trials. However, trial-by-trial analyses showed within-participant fluctuations in pre-stimulus alpha activity significantly predicted the likelihood of making an error, in all groups. Interestingly, our analysis demonstrated that aperiodic contributions to the EEG signal (which affect power estimates across frequency bands) serve as a significant predictor of behavior as well. CONCLUSIONS: These results confirm the elevated attention lapse rate that has been observed in SZ, validate pre-stimulus EEG markers of attentional control and their use as a predictor of behavior on a trial-by-trial basis, and suggest that aperiodic contributions to the EEG signal are an important target for further research in this area, in addition to alpha-band activity.

A Transdiagnostic Study of Effort-Cost Decision-Making in Psychotic and Mood Disorders.

BACKGROUND: Research suggests that effort-cost decision-making (ECDM), the estimation of work required to obtain reward, may be a relevant framework for understanding motivational impairment in psychotic and mood pathology. Specifically, research has suggested that people with psychotic and mood pathology experience effort as more costly than controls, and thus pursue effortful goals less frequently. This study examined ECDM across psychotic and mood pathology. HYPOTHESIS: We hypothesized that patient groups would show reduced willingness to expend effort compared to controls. STUDY DESIGN: People with schizophrenia (N = 33), schizoaffective disorder (N = 28), bipolar disorder (N = 39), major depressive disorder (N = 40), and controls (N = 70) completed a physical ECDM task. Participants decided between completing a low-effort or high-effort option for small or larger rewards, respectively. Reward magnitude, reward probability, and effort magnitude varied trial-by-trial. Data were analyzed using standard and hierarchical logistic regression analyses to assess the subject-specific contribution of various factors to choice. Negative symptoms were measured with a clinician-rated interview. STUDY RESULTS: There was a significant effect of group, driven by reduced choice of high-effort options in schizophrenia. Hierarchical logistic regression revealed that reduced choice of high-effort options in schizophrenia was driven by weaker contributions of probability information. Use of reward information was inversely associated with motivational impairment in schizophrenia. Surprisingly, individuals with major depressive disorder and bipolar disorder did not differ from controls. CONCLUSIONS: Our results provide support for ECDM deficits in schizophrenia. Additionally, differences between groups in ECDM suggest a seemingly similar behavioral phenotype, reduced motivation, could arise from disparate mechanisms.

Comparing a Computerized Digit Symbol Test to a Pen-and-Paper Classic.

Background and Hypothesis: Processing speed dysfunction is a core feature of psychosis and predictive of conversion in individuals at clinical high risk (CHR) for psychosis. Although traditionally measured with pen-and-paper tasks, computerized digit symbol tasks are needed to meet the increasing demand for remote assessments. Therefore we: (1) assessed the relationship between traditional and computerized processing speed measurements; (2) compared effect sizes of impairment for progressive and persistent subgroups of CHR individuals on these tasks; and (3) explored causes contributing to task performance differences. Study Design: Participants included 92 CHR individuals and 60 healthy controls who completed clinical interviews, the Brief Assessment of Cognition in Schizophrenia Symbol Coding test, the computerized TestMyBrain Digit Symbol Matching Test, a finger-tapping task, and a self-reported motor abilities measure. Correlations, Hedges' g, and linear models were utilized, respectively, to achieve the above aims. Study Results: Task performance was strongly correlated (r = 0.505). A similar degree of impairment was seen between progressive (g = -0.541) and persistent (g = -0.417) groups on the paper version. The computerized task uniquely identified impairment for progressive individuals (g = -477), as the persistent group performed similarly to controls (g = -0.184). Motor abilities were related to the computerized version, but the paper version was more related to symptoms and psychosis risk level. Conclusions: The paper symbol coding task measures impairment throughout the CHR state, while the computerized version only identifies impairment in those with worsening symptomatology. These results may be reflective of sensitivity differences, an artifact of existing subgroups, or evidence of mechanistic differences.

Qualitatively Different Delay-Dependent Working Memory Distortions in People With Schizophrenia and Healthy Control Participants.

BACKGROUND: Impairments in working memory (WM) have been well documented in people with schizophrenia (PSZ). However, these quantitative WM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed response task to explore a qualitative difference in WM dynamics between PSZ and healthy control participants (HCs). More specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous trial targets (serial dependence). We tested the hypothesis that WM representations would drift toward the previous trial target in HCs but away from the previous trial target in PSZ. METHODS: We assessed serial dependence in PSZ (n = 31) and HCs (n = 25) using orientation as the to-be-remembered feature and memory delays lasting from 0 to 8 seconds. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a delay period of varying length. RESULTS: Consistent with prior studies, we found that current trial memory representations were less precise in PSZ than in HCs. We also found that WM for the current trial orientation drifted toward the previous trial orientation in HCs (representational attraction) but drifted away from the previous trial orientation in PSZ (representational repulsion). CONCLUSIONS: These results demonstrate a qualitative difference in WM dynamics between PSZ and HCs that cannot be easily explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCs in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.

Sustained attention deficits in schizophrenia: Effect of memory load on the Identical Pairs Continuous Performance Test.

Background: Sustained attention and vigilance impairments are well documented in people with schizophrenia (PSZ). The processes implicated in this impairment remain unclear. Here we investigated whether vigilance performance varied as a function of working memory load, and also examined the role of attentional lapsing that might arise from a loss of task set resulting in mind wandering. Method: We examined Continuous Performance Test Identical Pairs (CPT-IP) data from a cumulative sample of 247 (PSZ) and 238 healthy control (HC) participants collected over a series of studies. Results: PSZ performed more poorly that HC across conditions with signal/noise discrimination (d') decreasing with increasing working memory load across both groups However, there was a significant interaction of group and load suggesting that performance of PSZ was more negatively impacted by increasing load. We also found that PSZ has a significantly higher rate of attention lapsing than did HC. Discussion: Our results suggest that difficulties maintaining task set and working memory limitations are implicated in the impairments observed on the Identical Pairs CPT. Difficulties with task set maintenance appear to explain the majority of between-group variance, with a more subtle impact of increasing working memory load.

Phenomenological and Cognitive Features Associated With Auditory Hallucinations in Clinical and Nonclinical Voice Hearers.

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVH) are central features of schizophrenia (SZ). However, AVH also occur in a small percentage of the general population who do not have a need for care, termed nonclinical voice hearers (NCVH). We sought to determine the degree to which the experience of AVH was similar in NCVH and in people with schizophrenia (PSZ) and evaluate the degree to which NCVH shared other features of SZ such as delusional beliefs, cognitive impairment, and negative symptoms. STUDY DESIGN: We recruited 76 people with a DSM-V diagnosis of SZ/schizoaffective disorder (PSZ; 49 with current AVH, 27 without), 48 NCVH, and 51 healthy controls. Participants received a broad battery of clinician-administered and self-report symptom assessments and a focused cognitive assessment. STUDY RESULTS: The AVH of NCVH and PSZ shared very similar sensory features. NCVH experienced less distress, had greater control over their AVH, and, unlike PSZ, rarely heard 2 voices speaking to each other. NCVH demonstrated a wide range of deeply held unusual beliefs, but reported less paranoia, and fewer first-rank symptoms such as passivity and alterations in self-experience. NCVH showed no evidence of cognitive deficits or negative symptoms. CONCLUSIONS: The AVH in NCVH and PSZ demonstrate important similarities as well as clear differences. Specific features, rather than the presence, of AVH appear to determine the need for care. NCVH do not share the cognitive and motivational deficits seen in PSZ. These results suggest that AVH and unusual beliefs can be separated from the broader phenotype of SZ.

Transdiagnostic Predictors of Everyday Functioning: Examining the Relationships of Depression and Reinforcement Learning.

BACKGROUND AND HYPOTHESIS: Impairments in function (ie, the ability to independently accomplish daily tasks) have been established in psychotic disorders. Identifying factors that contribute to these deficits is essential to developing effective interventions. The current study had several goals: examine potential differential relationships across domains of neurocognition, assess whether reinforcement learning is related to function, identify if predictors of function are transdiagnostic, determine whether depression and positive symptoms contribute to function, and to explore whether the modality of assessment impacts observed relationships. STUDY DESIGN: Data from 274 participants were examined with schizophrenia/schizoaffective disorder (SZ; n = 195) and bipolar disorder (BD; n = 79). To reduce dimensionality, a PCA was completed on neurocognitive tasks which resulted in 3 components. These components and clinical interview data were used to investigate predictors of functional domains across measures of function (self- and informant-report SLOF and UPSA). RESULTS: Two components, working memory/processing speed/episodic memory (ßs = 0.18-0.42), and negative/positive reinforcement learning (ß = -0.04), predicted different functional domains. Predictors of function were largely transdiagnostic with two exceptions: reinforcement learning had a positive association with self-reported interpersonal relationships for SZ and a negative association for BD (ß = 0.34), and the negative association between positive symptoms and self-reported social acceptability was stronger for BD than for SZ (ß = 0.93). Depression robustly predicted self-reported but not informant-reported function, and anhedonia predicted all domains of informant-reported function. CONCLUSIONS: These findings imply that reinforcement learning may differentially relate to function across disorders, traditional domains of neurocognition can be effective transdiagnostic targets for interventions, and positive symptoms and depression play a critical role in self-perceived functional impairments.

Qualitatively different delay-dependent working memory distortions in people with schizophrenia and healthy control subjects.

Background: Impairments in working memory(WM) have been well-documented in people with schizophrenia(PSZ). However, these quantitative WM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed-response task to explore a qualitative difference in WM dynamics between PSZ and healthy control subjects(HCS). Specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous-trial targets(serial dependence). We tested the hypothesis that WM representations drift toward the previous-trial target in HCS but away from the previous-trial target in PSZ. Methods: We assessed serial dependence in PSZ(N=31) and HCS(N=25), using orientation as the to-be-remembered feature and memory delays from 0 to 8s. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a varying delay period. Results: Consistent with prior studies, we found that current-trial memory representations were less precise in PSZ than in HCS. We also found that WM for the current-trial orientation drifted toward the previous-trial orientation in HCS(representational attraction) but drifted away from the previous-trial orientation in PSZ(representational repulsion). Conclusions: These results demonstrate a qualitative difference in WM dynamics between PSZ and HCS that cannot easily be explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results, because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCS in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.

Multivariate Associations Among White Matter, Neurocognition, and Social Cognition Across Individuals With Schizophrenia Spectrum Disorders and Healthy Controls.

BACKGROUND AND HYPOTHESIS: Neurocognitive and social cognitive abilities are important contributors to functional outcomes in schizophrenia spectrum disorders (SSDs). An unanswered question of considerable interest is whether neurocognitive and social cognitive deficits arise from overlapping or distinct white matter impairment(s). STUDY DESIGN: We sought to fill this gap, by harnessing a large sample of individuals from the multi-center Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) dataset, unique in its collection of advanced diffusion imaging and an extensive battery of cognitive assessments. We applied canonical correlation analysis to estimates of white matter microstructure, and cognitive performance, across people with and without an SSD. STUDY RESULTS: Our results established that white matter circuitry is dimensionally and strongly related to both neurocognition and social cognition, and that microstructure of the uncinate fasciculus and the rostral body of the corpus callosum may assume a "privileged role" subserving both. Further, we found that participant-wise estimates of white matter microstructure, weighted by cognitive performance, were largely consistent with participants' categorical diagnosis, and predictive of (cross-sectional) functional outcomes. CONCLUSIONS: The demonstrated strength of the relationship between white matter circuitry and neurocognition and social cognition underscores the potential for using relationships among these variables to identify biomarkers of functioning, with potential prognostic and therapeutic implications.

Self-reported Gesture Interpretation and Performance Deficits in Individuals at Clinical High Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Deficits in performing and interpreting communicative nonverbal behaviors, such as gesture, have been linked to varied psychopathology and dysfunction. Some evidence suggests that individuals at risk for psychosis have deficits in gesture interpretation and performance; however, individuals with internalizing disorders (eg, depression) may have similar deficits. No previous studies have examined whether gesture deficits in performance and interpretation are specific to those at risk for psychosis. Additionally, the underlying mechanisms (eg, cognition) and consequences (eg, functioning) of these deficits are poorly understood. STUDY DESIGN: This study examined self-reported gesture interpretation (SRGI) and performance (SRGP) in those at clinical high risk for psychosis (CHR; N = 88), those with internalizing disorders (INT; N = 51), and healthy controls (HC; N = 53). Participants completed questionnaires, clinical interviews, and neurocognitive tasks. STUDY RESULTS: Results indicated that the CHR group was characterized by significantly lower SRGI scores than the HC or INT groups (d = 0.41); there were no differences among groups in SRGP. Within CHR participants, greater deficits in SRGP were associated with lower verbal learning and memory (r = -.33), but not general intelligence or processing speed. Furthermore, gesture deficits were associated with higher cross-sectional risk for conversion to a full psychotic disorder in the CHR group. CONCLUSIONS: Overall, these findings suggest that specific subdomains of gesture may reflect unique vulnerability for psychosis, self-report may be a viable assessment tool in understanding these phenomena, and gesture dysfunction may signal risk for transition to psychosis.

The reliability and validity of the revised Green et al. paranoid thoughts scale in individuals at clinical high-risk for psychosis.

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.

Using dimensionality-reduction techniques to understand the organization of psychotic symptoms in persistent psychotic illness and first episode psychosis.

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophrenia or schizoaffective disorder (fBIRN Data Repository and the Consortium for Neuropsychiatric Phenomics), as well as 636 first-episode psychosis (FEP) participants from the Prevention and Early Intervention Program for Psychosis (PEPP-Montreal). In all participants, the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were collected. Multidimensional scaling (MDS) combined with cluster analysis was applied to SAPS and SANS scores across these two groups of participants. MDS revealed relationships between items of SAPS and SANS. Our application of cluster analysis to these results identified: 1 cluster of disorganization symptoms, 2 clusters of hallucinations/delusions, and 2 SANS clusters (asocial and apathy, speech and affect). Those reality distortion items which were furthest from auditory hallucinations had very weak to no relationship with hallucination severity. Despite being at an earlier stage of illness, symptoms in FEP presentations were similarly organized. While hallucinations and delusions commonly co-occur, we found that their specific themes and content sometimes travel together and sometimes do not. This has important implications, not only for treatment, but also for research-particularly efforts to understand the neurocomputational and pathophysiological mechanism underlying delusions and hallucinations.

Studying Healthy Psychosislike Experiences to Improve Illness Prediction.

Importance: Distinguishing delusions and hallucinations from unusual beliefs and experiences has proven challenging. Observations: The advent of neural network and generative modeling approaches to big data offers a challenge and an opportunity; healthy individuals with unusual beliefs and experiences who are not ill may raise false alarms and serve as adversarial examples to such networks. Conclusions and Relevance: Explicitly training predictive models with adversarial examples should provide clearer focus on the features most relevant to casehood, which will empower clinical research and ultimately diagnosis and treatment.

Comparing the functional neuroanatomy of proactive and reactive control between patients with schizophrenia and healthy controls.

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Attention in Schizophrenia.

Attention is clearly a core area of cognitive dysfunction in schizophrenia, but the concept of "attention" is complex and multifaceted. This chapter focuses on three different aspects of attentional function that are of particular interest in schizophrenia. First, we discuss the evidence that schizophrenia involves a reduction in global alertness, leading to an inward focusing of attention and a neglect of external stimuli and tasks. Second, we discuss the control of attention, the set of processes that allow general goals to be translated into shifts of attention toward task-relevant information. When a goal is adequately represented, people with schizophrenia often show no deficit in using the goal to direct attention in the visual modality unless challenged by stimuli that strongly activate the magnocellular processing pathway. Finally, we discuss the implementation of selection, the processes that boost relevant information and suppress distractors once attention has been directed to a given source of information. Although early evidence indicated an impairment in selection, more recent evidence indicating that people with schizophrenia actually focus their attention more narrowly and more intensely that healthy individuals (hyperfocusing). However, this hyperfocused attention may be directed toward goal-irrelevant information, creating the appearance of impaired attentional filtering.

Working Memory in People with Schizophrenia.

Working memory (WM) refers to the ability to maintain a small number of representations in an activated, easily accessible state for a short period of time in the service of ongoing cognitive processing and behavior. Because WM is a resource critical for multiple forms of complex cognition and executive control of behavior, it is of central interest in the study of disorders such as schizophrenia that involve a broad compromise of cognitive function and in the regulation of goal-directed behavior. There is now robust evidence that WM impairment is characteristic of people with schizophrenia. The impairment includes both elementary storage capacity as well as more complex forms of WM that involve the manipulation and updating of WM representations. These impairments appear to underlie a substantial portion of the generalized cognitive deficit in schizophrenia. Neuroimaging studies have implicated widespread abnormalities in the broad neural system that subserves WM performance, consistent with the evidence of broad cognitive impairment seen in PSZ.

Cognitive [Computational] Neuroscience Test Reliability and Clinical Applications for Serious Mental Illness (CNTRaCS) Consortium: Progress and Future Directions.

The development of treatments for impaired cognition in schizophrenia has been characterized as the most important challenge facing psychiatry at the beginning of the twenty-first century. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) project was designed to build on the potential benefits of using tasks and tools from cognitive neuroscience to better understanding and treat cognitive impairments in psychosis. These benefits include: (1) the use of fine-grained tasks that measure discrete cognitive processes; (2) the ability to design tasks that distinguish between specific cognitive domain deficits and poor performance due to generalized deficits resulting from sedation, low motivation, poor test taking skills, etc.; and (3) the ability to link cognitive deficits to specific neural systems, using animal models, neuropsychology, and functional imaging. CNTRICS convened a series of meetings to identify paradigms from cognitive neuroscience that maximize these benefits and identified the steps need for translation into use in clinical populations. The Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRaCS) Consortium was developed to help carry out these steps. CNTRaCS consists of investigators at five different sites across the country with diverse expertise relevant to a wide range of the cognitive systems identified as critical as part of CNTRICs. This work reports on the progress and current directions in the evaluation and optimization carried out by CNTRaCS of the tasks identified as part of the original CNTRICs process, as well as subsequent extensions into the Positive Valence systems domain of Research Domain Criteria (RDoC). We also describe the current focus of CNTRaCS, which involves taking a computational psychiatry approach to measuring cognitive and motivational function across the spectrum of psychosis. Specifically, the current iteration of CNTRaCS is using computational modeling to isolate parameters reflecting potentially more specific cognitive and visual processes that may provide greater interpretability in understanding shared and distinct impairments across psychiatric disorders.

Gamma-band entrainment abnormalities in schizophrenia: Modality-specific or cortex-wide impairment?

A growing body of literature suggests that cognitive impairment in people with schizophrenia (PSZ) results from disrupted cortical excitatory/inhibitory (E-I) balance, which may be linked to gamma entrainment and can be measured noninvasively using electroencephalography (EEG). However, it is not yet known the degree to which these entrainment abnormalities covary within subjects across sensory modalities. Furthermore, the degree to which cross-modal gamma entrainment reflects variation in biological processes associated with cognitive performance remains unclear. We used EEG to measure entrainment to repetitive auditory and visual stimulation at beta (20 Hz) and gamma (30 and 40 Hz) frequencies in PSZ (n = 78) and healthy control subjects (HCS; n = 80). Three indices were measured for each frequency and modality: event-related spectral perturbation (ERSP), intertrial coherence (ITC), and phase-lag angle (PLA). Cognition and symptom severity were also assessed. We found little evidence that gamma entrainment covaried across sensory modalities. PSZ exhibited a modest correlation between modalities at 40 Hz for ERSP and ITC measures (r = 0.23-0.24); however, no other significant correlations between modalities emerged for either HCS or PSZ. Both univariate and multivariate analyses revealed that (a) the pattern of entrainment abnormalities in PSZ differed across modalities, and (b) modality rather than frequency band was the main source of variance. Finally, we observed a significant association between cognition and gamma entrainment in the auditory domain only in HCS. Gamma-band EEG entrainment does not reflect a unitary transcortical mechanism but is instead modality specific. To the extent that entrainment reflects the integrity of cortical E-I balance, the deficits observed in PSZ appear to be modality specific and not consistently associated with cognitive impairment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Linking Salience Signaling With Early Adversity and Affective Distress in Individuals at Clinical High Risk for Psychosis: Results From an Event-Related fMRI Study.

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few studies have examined the intersection of stress exposure and affective distress with prediction error (PE) signals among youth at clinical high-risk (CHR). Here, 26 individuals at CHR and 19 healthy volunteers (HVs) completed a monetary incentive delay task in conjunction with fMRI. We compared these groups on the amplitudes of neural responses to surprising outcomes-PEs without respect to their valence-across the whole brain and in two regions of interest, the anterior insula and amygdala. We then examined relations of these signals to the severity of depression, anxiety, and trauma histories in the CHR group. Relative to HV, youth at CHR presented with aberrant PE-evoked activation of the temporoparietal junction and weaker deactivation of the precentral gyrus, posterior insula, and associative striatum. No between-group differences were observed in the amygdala or anterior insula. Among youth at CHR, greater trauma histories were correlated with stronger PE-evoked amygdala activation. No associations were found between affective symptoms and the neural responses to PE. Our results suggest that unvalenced PE signals may provide unique information about the neurobiology of CHR syndromes and that early adversity exposure may contribute to neurobiological heterogeneity in this group. Longitudinal studies of young people with a range of risk syndromes are needed to further disentangle the contributions of distinct aspects of salience signaling to the development of psychopathology.