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Papers by James Gold

Research paper thumbnail of Detecting reliable cognitive change in individual patients with the MATRICS Consensus Cognitive Battery

Schizophrenia research, 2014

Clinicians often need to evaluate the treatment response of an individual person and to know that... more Clinicians often need to evaluate the treatment response of an individual person and to know that observed change is true improvement or worsening beyond usual week-to-week changes. This paper gives clinicians tools to evaluate individual changes on the MATRICS Consensus Cognitive Battery (MCCB). We compare three different approaches: a descriptive analysis of MCCB test-retest performance with no intervention, a reliable change index (RCI) approach controlling for average practice effects, and a regression approach. Data were gathered as part of the MATRICS PASS study (Nuechterlein et al., 2008). A total of 159 people with schizophrenia completed the MCCB at baseline and 4weeks later. Data were analyzed using an RCI and a regression formula establishing confidence intervals. The RCI and regression approaches agree within one point when baseline values are close to the sample mean. However, the regression approach offers more accurate limits for expected change at the tails of the di...

Research paper thumbnail of The Hyperfocusing Hypothesis: A New Account of Cognitive Dysfunction in Schizophrenia

Schizophrenia Bulletin, Jul 18, 2019

Impairments in basic cognitive processes such as attention and working memory are commonly observ... more Impairments in basic cognitive processes such as attention and working memory are commonly observed in people with schizophrenia and are predictive of long-term outcome. In this review, we describe a new theory-the hyperfocusing hypothesis-which provides a unified account of many aspects of impaired cognition in schizophrenia. This hypothesis proposes that schizophrenia involves an abnormally narrow but intense focusing of processing resources. This hyperfocusing impairs the ability of people with schizophrenia to distribute attention among multiple locations, decreases the number of representations that can simultaneously be maintained in working memory, and causes attention to be abnormally captured by irrelevant inputs that share features with active representations. Evidence supporting the hyperfocusing hypothesis comes from a variety of laboratory tasks and from both behavioral and electrophysiological measures of processing. In many of these tasks, people with schizophrenia exhibit supranormal effects of task manipulations, which cannot be explained by a generalized cognitive deficit or by nonspecific factors such as reduced motivation or poor task comprehension. In addition, the degree of hyperfocusing in these tasks is often correlated with the degree of impairment in measures of broad cognitive function, which are known to be related to long-term outcome. Thus, the mechanisms underlying hyperfocusing may be a good target for new treatments targeting cognitive deficits in schizophrenia.

Research paper thumbnail of Spatial recall performance: Differential landmark bias in schizophrenia

Journal of Vision, Aug 31, 2017

Research paper thumbnail of Retention of Value Representations Across Time in People With Schizophrenia and Healthy Control Subjects

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Apr 1, 2021

Background:The current study aimed to further etiological understanding of the psychological mech... more Background:The current study aimed to further etiological understanding of the psychological mechanisms underlying negative symptoms in people with schizophrenia. Specifically, we tested whether negative symptom severity is associated with reduced retention of reward-related information over time, and thus a degraded ability to utilize such information to guide future action selection.Methods:44 patients with a diagnosis of schizophrenia or schizoaffective disorder and 28 healthy volunteers performed a probabilistic reinforcement-learning task involving stimulus pairs in which choices resulted in reward or in loss avoidance. Following training, participants indicated their valuation of learned stimuli in a test/transfer phase. The test/transfer phase was administered immediately following training and one-week later. Percent retention was defined as accuracy at weeklong delay divided by accuracy at immediate delay.Results:Both healthy controls and people with schizophrenia showed similarly robust retention of reinforcement learning over a one-week delay interval. However, in the schizophrenia group, negative symptom severity was associated with reduced retention of information regarding the value of actions across a weeklong interval. This pattern was particularly notable for stimuli associated with reward compared to loss avoidance.Conclusions:Our results show that, although individuals with schizophrenia may initially learn about rewarding aspects of their environment, such learning decays at a more rapid rate in patients with severe negative symptoms. Thus, previously learned reward-related information may be more difficult to access to guide future decision-making and to motivate action selection.

Research paper thumbnail of Transdiagnostic Predictors of Everyday Functioning: Examining the Relationships of Depression and Reinforcement Learning

Schizophrenia Bulletin, Jun 29, 2023

Background and Hypothesis Impairments in function (ie, the ability to independently accomplish da... more 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 (βs = 0.18–0.42), and negative/positive reinforcement learning (β = −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 (β = 0.34), and the negative association between positive symptoms and self-reported social acceptability was stronger for BD than for SZ (β = 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.

Research paper thumbnail of All or nothing belief updating in patients with schizophrenia reduces precision and flexibility of beliefs

Brain, Jan 12, 2021

Schizophrenia is characterized by abnormal perceptions and beliefs, but the computational mechani... more Schizophrenia is characterized by abnormal perceptions and beliefs, but the computational mechanisms through which these abnormalities emerge remain unclear. One prominent hypothesis asserts that such abnormalities result from overly precise representations of prior knowledge, which in turn lead beliefs to become insensitive to feedback. In contrast, another prominent hypothesis asserts that such abnormalities result from a tendency to interpret prediction errors as indicating meaningful change, leading to the assignment of aberrant salience to noisy or misleading information. Here we examine behaviour of patients and control subjects in a behavioural paradigm capable of adjudicating between these competing hypotheses and characterizing belief updates directly on individual trials. We show that patients are more prone to completely ignoring new information and perseverating on previous responses, but when they do update, tend to do so completely. This updating strategy limits the integration of information over time, reducing both the flexibility and precision of beliefs and provides a potential explanation for how patients could simultaneously show over-sensitivity and under-sensitivity to feedback in different paradigms.

Research paper thumbnail of Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Mar 1, 2018

Background-The current study was designed to test the hypothesis that motivational deficits in sc... more Background-The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of lossavoidance in the brain, leading to reduced ability to form adaptive representations of expected value. Methods-We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 controls, in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial-types with different expected values (Expected Gain-Non-monetary, e.g.), and between outcomes with the same prediction error valence but different experienced values (Gain-Loss-avoidance outcome, Miss-Loss outcome, e.g.). Results-Both whole-brain and regions-of-interest analyses revealed that schizophrenia patients showed reduced differentiation between Gain and Loss-avoidance outcomes in dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. Furthermore, we observed significant correlations between [Gain-Loss-avoidance outcome] contrasts in ventral

Research paper thumbnail of Relieving the Burden: Identifying Diminishing Returns to Create More Efficient Tasks

Background: If well-constructed, efficient measures of cognition have the potential to increase v... more Background: If well-constructed, efficient measures of cognition have the potential to increase validity, while decreasing research burden and costs for participants and assessors with little loss of reliability. There is the possibility that long and difficult measures create even noisier data for people with serious mental illness compared to the general population. In this study, we aim to assess the extent to which working memory and reinforcement learning tasks can be made more efficient.Methods: Participants included 185 people with serious mental illness and 75 controls. Internal consistency (Cronbach’s , Item-Total Correlations, and/or Spearman-Brown Prophecy Correlations) and test-retest reliability (Intraclass Correlations) were calculated for increasing subsets of trials on each task to assess the point at which reliability reached acceptable and good levels or reached diminishing returns.Results: Generally, the tasks had met acceptable internal consistency values by the time only half of the values had been included and either good reliability or diminishing returns by the time two-thirds of the task trials were considered. This was largely similar for test-retest on the working memory tasks, but acceptable test-retest reliability was mostly never achieved on the reinforcement learning tasks.Conclusions: Overall, each of the working memory and reinforcement learning tasks can be made 25-50% more efficient without significant loss of psychometric integrity. However, there may be limitations on the utility of some of the tasks due to acceptable test-retest reliability never being achieved.

Research paper thumbnail of 206. The Impact of Reward History on Allocation of Spatial Attention in Schizophrenia

Schizophrenia Bulletin, Mar 1, 2017

Background: Dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and ... more Background: Dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and its putative prodrome, the clinical high risk state (CHR). Striatal DA results from the activity of midbrain DA neurons projecting mainly from the substantia nigra (SN). Elevated stress-induced DA release in SCZ and CHR was observed in the striatum, however whether it is also elevated in the SN is unclear. The current study aims to determine whether nigral DA release in response to a validated stress task is altered in CHR and in antipsychotic-naive SCZ. Further, we explore how DA release in the SN and striatum might be related. Methods: 24 CHR subjects, 9 antipsychotic-naive SCZ and 25 healthy volunteers (HV) underwent two positron emission tomography (PET) scans using the DA D2/3 agonist radiotracer, [11C]-(+)-PHNO, which allows simultaneous investigations of DA in the SN and striatum. Psychosocial stress-induced DA release was estimated as the percentage differences in BPND (%[11C]-(+)-PHNO displacement) between stress and sensorymotor control sessions. Results: We observed a significant group by sessions interaction on [11C]-(+)-PHNO BPND in the SN (F = 6.896, P = .002). The SCZ showed a 25.90% [11C]-(+)-PHNO binding change change in nigral [11C]-(+)-PHNO displacement, while HV showed-10.94% and CHR exhibited an intermediate response [11C]-(+)-PHNO binding change (−1.13%). Only among the CHR subjects, we found a positive trend of association between [11C]-(+)-PHNO binding changes displacement in the SN and the whole striatum (r = .382, P = .072). Conclusion: Our findings suggest a sensitized nigral DA response to stress in antipsychotic-naive SCZ. The unique trend association between nigral and striatal [11C]-(+)-PHNO binding changes, and a differential nigrostriatal DA pathway in CHR, which may suggest a stage specific biomarker warrants further investigation to confirm.

Research paper thumbnail of Effects of clozapine on cognition in patients with schizophrenia

Schizophrenia Research, May 1, 1991

Research paper thumbnail of Increased influence of a previously attended feature in people with schizophrenia

Journal of Abnormal Psychology, Apr 1, 2020

Everyday functioning requires the appropriate allocation of visual attention, which is achieved t... more Everyday functioning requires the appropriate allocation of visual attention, which is achieved through multiple mechanisms of attentional guidance. Traditional theories have focused on top-down and bottom-up factors, but implicit learning from recent experience ("selection history") also has a substantial impact on attentional allocation. The present experiment examined the influence of intertrial priming on attentional guidance in people with schizophrenia and matched control subjects. Participants searched for a color pop-out target, which switched randomly between a red target among blue distractors and a blue target among red distractors. We found that performance on the current trial was more influenced by the previous-trial target color in people with schizophrenia than in control subjects. Moreover, this implicit priming effect was greater in individuals with lower working memory capacity (as measured in a separate task). These results suggest that intertrial priming has an exaggerated impact on attentional guidance in people with schizophrenia and that this is associated with other aspects of impaired cognition. Overall, these results are consistent with the hyperfocusing hypothesis, which proposes that a single underlying attentional abnormality may explain a range of atypical effects across perception, attention, and cognition in schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Research paper thumbnail of Antisaccade Deficits in Schizophrenia Can Be Driven by Attentional Relevance of the Stimuli

Schizophrenia Bulletin, Aug 7, 2020

The antisaccade task is considered a test of cognitive control because it creates a conflict betw... more The antisaccade task is considered a test of cognitive control because it creates a conflict between the strong bottom-up signal produced by the cue and the top-down goal of shifting gaze to the opposite side of the display. Antisaccade deficits in schizophrenia are thought to reflect impaired top-down inhibition of the prepotent bottom-up response to the cue. However, the cue is also a highly taskrelevant stimulus that must be covertly attended to determine where to shift gaze. We tested the hypothesis that difficulty in overcoming the attentional relevance of the cue, rather than its bottom-up salience, is key in producing impaired performance in people with schizophrenia (PSZ). We implemented 3 versions of the antisaccade task in which we varied the bottom-up salience of the cue while holding its attentional relevance constant. We found that difficulty in performing a given antisaccade taskrelative to a prosaccade version using the same stimuliwas largely independent of the cue's bottom-up salience. The magnitude of impairment in PSZ relative to control subjects was also independent of bottom-up salience. The greatest impairment was observed in a version where the cue lacked bottom-up salience advantage over other locations. These results indicate that the antisaccade deficit in PSZ does not reflect an impairment in overcoming bottom-up salience of the cue, but PSZ are instead impaired at overcoming its attentional relevance. This deficit may still indicate an underlying inhibitory control impairment but could also reflect a hyperfocusing of attentional resources on the cue.

Research paper thumbnail of 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 schizophr... more Background and Hypotheses: Auditory verbal hallucinations (AVH) are central features of schizophrenia. 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 schizophrenia such as delusional beliefs, cognitive impairment, and negative symptoms. Study design: We recruited 76 people with a DSM-V diagnosis of schizophrenia/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 two 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.

Research paper thumbnail of Impaired expected value computations coupled with overreliance on prediction error learning in schizophrenia

bioRxiv (Cold Spring Harbor Laboratory), Dec 22, 2017

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

Schizophrenia Bulletin Open

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few st... more 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. Amon...

Research paper thumbnail of F9. Reduced Uncertainty-Driven Exploration and Associated Neural Reward-Related Signals Relate to Motivational Deficit Severity

Schizophrenia Bulletin, 2019

Poster Session II S257 Results: Body weight, waist circumference and fasting insulin levels were ... more Poster Session II S257 Results: Body weight, waist circumference and fasting insulin levels were similar between patients on olanzapine or risperidone. Plasma IGFBP-2 levels were also not different between the two groups (173 ± 15 vs 199 ± 16 ng/mL, respectively). As expected, IGFBP-2 concentrations were negatively correlated with BMI, waist circumference, insulin sensitivity, and plasma triglyceride levels in the entire cohort. However, the proportion of schizophrenic patients with a hypertriglyceridemia and large waist circumference ranged from 43% for olanzapine and 12% for risperidone users with IGFBP-2 levels lower than 220 ng/mL, compared to 8% and 0%, respectively for patients with plasma IGFBP-2 above this threshold (p = 0.0178). Discussion: Our findings suggest that circulating levels of IGFBP-2 may underlie the inter-variability on metabolic risk in schizophrenic patients using SGAs. Longitudinal studies are required to evaluate whether IGFBP-2 levels can predict the development of a hypertriglyceridemic waist phenotype in this population.

Research paper thumbnail of Latent Profiles of Cognitive Control, Episodic Memory, and Visual Perception Across Psychiatric Disorders Reveal a Dimensional Structure

Schizophrenia Bulletin, 2019

Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocogn... more Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocognitive phenotype than mood disorders such as bipolar disorder, considerable between-subject heterogeneity exists in the phenotypic presentation of these deficits across mental illnesses. Indeed, it is unclear whether the processes that underlie cognitive dysfunction in these disorders are unique to each disease or represent a common neurobiological process that varies in severity. Here we used latent profile analysis (LPA) across 3 distinct cognitive domains (cognitive control, episodic memory, and visual integration; using data from the CNTRACS consortium) to identify distinct profiles of patients across psychotic illnesses. LPA was performed on a sample of 223 psychosis patients (59 with Type I bipolar disorder, 88 with SZ, and 76 with schizoaffective disorder). Seventy-three healthy control participants were included for comparison but were not included in sample LPA. Three latent prof...

Research paper thumbnail of Cross-diagnostic analysis of cognitive control in mental illness: Insights from the CNTRACS consortium

Schizophrenia Research, 2019

Background: In recent years, psychiatry research has increasingly focused on understanding mental... more Background: In recent years, psychiatry research has increasingly focused on understanding mental illnesses from a cross-diagnostic, dimensional perspective in order to better align their neurocognitive features with underlying neurobiological mechanisms. In this multi-site study, we examined two measures of cognitive control (d-prime context and lapsing rate) during the Dot Probe Expectancy (DPX) version of the AX-Continuous Performance Task in patients with either schizophrenia (SZ), schizoaffective disorder (SZ-A), or Type I bipolar disorder (BD) as well as healthy control (HC) subjects. We hypothesized significantly lower d-prime context and higher lapsing rate in SZ and SZ-A patients and intermediate levels in BD patients relative to HC. Methods: 72 HC, 84 SZ, 77 SZ-A, and 58 BD patients (ages 18-56) were included in the final study sample. Results: Significant main effects of diagnosis were observed on d-prime context (F(3,279) = 9.59, p b 0.001) and lapsing (F(3,279) = 8.08, p b 0.001). A priori linear contrasts suggesting intermediate dysfunction in BD patients were significant (p b 0.001), although post-hoc tests showed the BD group was only significantly different from HC on d-prime context. Group results for d-prime context remained significant after covarying for lapsing rate. Primary behavioral measures were associated with mania and disorganization symptoms as well as everyday functioning. Conclusions: These findings suggest a continuum of dysfunction in cognitive control (particularly d-prime context) across diagnostic categories in psychiatric illness. These results further suggest that lapsing and d-prime context, while related, make unique contributions towards explaining deficits in cognitive control in these disorders.

Research paper thumbnail of Impaired expected value computations in schizophrenia are associated with a reduced ability to integrate reward probability and magnitude of recent outcomes

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2018

Background: Motivational deficits in people with schizophrenia (PSZ) are associated with an inabi... more Background: Motivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on "value-less" stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits. Methods: Healthy volunteers (n=38) and PSZ (n=49) completed a learning paradigm consisting of four stimulus pairs. Reward magnitude (3/2/1/0 points) and probability (90%/80%/20%/10%) determined each stimulus' EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value. Results: PSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability*magnitude) between two competing stimuli increased. Using a previously-validated computational hybrid model, PSZ relied less on EV ("Q-learning") and more on stimulus-response learning ("actor-critic"), which correlated with SANS motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability.

Research paper thumbnail of Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2017

BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in s... more BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-lossavoidance outcome, miss-loss outcome). RESULTS: Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS: These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.

Research paper thumbnail of Detecting reliable cognitive change in individual patients with the MATRICS Consensus Cognitive Battery

Schizophrenia research, 2014

Clinicians often need to evaluate the treatment response of an individual person and to know that... more Clinicians often need to evaluate the treatment response of an individual person and to know that observed change is true improvement or worsening beyond usual week-to-week changes. This paper gives clinicians tools to evaluate individual changes on the MATRICS Consensus Cognitive Battery (MCCB). We compare three different approaches: a descriptive analysis of MCCB test-retest performance with no intervention, a reliable change index (RCI) approach controlling for average practice effects, and a regression approach. Data were gathered as part of the MATRICS PASS study (Nuechterlein et al., 2008). A total of 159 people with schizophrenia completed the MCCB at baseline and 4weeks later. Data were analyzed using an RCI and a regression formula establishing confidence intervals. The RCI and regression approaches agree within one point when baseline values are close to the sample mean. However, the regression approach offers more accurate limits for expected change at the tails of the di...

Research paper thumbnail of The Hyperfocusing Hypothesis: A New Account of Cognitive Dysfunction in Schizophrenia

Schizophrenia Bulletin, Jul 18, 2019

Impairments in basic cognitive processes such as attention and working memory are commonly observ... more Impairments in basic cognitive processes such as attention and working memory are commonly observed in people with schizophrenia and are predictive of long-term outcome. In this review, we describe a new theory-the hyperfocusing hypothesis-which provides a unified account of many aspects of impaired cognition in schizophrenia. This hypothesis proposes that schizophrenia involves an abnormally narrow but intense focusing of processing resources. This hyperfocusing impairs the ability of people with schizophrenia to distribute attention among multiple locations, decreases the number of representations that can simultaneously be maintained in working memory, and causes attention to be abnormally captured by irrelevant inputs that share features with active representations. Evidence supporting the hyperfocusing hypothesis comes from a variety of laboratory tasks and from both behavioral and electrophysiological measures of processing. In many of these tasks, people with schizophrenia exhibit supranormal effects of task manipulations, which cannot be explained by a generalized cognitive deficit or by nonspecific factors such as reduced motivation or poor task comprehension. In addition, the degree of hyperfocusing in these tasks is often correlated with the degree of impairment in measures of broad cognitive function, which are known to be related to long-term outcome. Thus, the mechanisms underlying hyperfocusing may be a good target for new treatments targeting cognitive deficits in schizophrenia.

Research paper thumbnail of Spatial recall performance: Differential landmark bias in schizophrenia

Journal of Vision, Aug 31, 2017

Research paper thumbnail of Retention of Value Representations Across Time in People With Schizophrenia and Healthy Control Subjects

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Apr 1, 2021

Background:The current study aimed to further etiological understanding of the psychological mech... more Background:The current study aimed to further etiological understanding of the psychological mechanisms underlying negative symptoms in people with schizophrenia. Specifically, we tested whether negative symptom severity is associated with reduced retention of reward-related information over time, and thus a degraded ability to utilize such information to guide future action selection.Methods:44 patients with a diagnosis of schizophrenia or schizoaffective disorder and 28 healthy volunteers performed a probabilistic reinforcement-learning task involving stimulus pairs in which choices resulted in reward or in loss avoidance. Following training, participants indicated their valuation of learned stimuli in a test/transfer phase. The test/transfer phase was administered immediately following training and one-week later. Percent retention was defined as accuracy at weeklong delay divided by accuracy at immediate delay.Results:Both healthy controls and people with schizophrenia showed similarly robust retention of reinforcement learning over a one-week delay interval. However, in the schizophrenia group, negative symptom severity was associated with reduced retention of information regarding the value of actions across a weeklong interval. This pattern was particularly notable for stimuli associated with reward compared to loss avoidance.Conclusions:Our results show that, although individuals with schizophrenia may initially learn about rewarding aspects of their environment, such learning decays at a more rapid rate in patients with severe negative symptoms. Thus, previously learned reward-related information may be more difficult to access to guide future decision-making and to motivate action selection.

Research paper thumbnail of Transdiagnostic Predictors of Everyday Functioning: Examining the Relationships of Depression and Reinforcement Learning

Schizophrenia Bulletin, Jun 29, 2023

Background and Hypothesis Impairments in function (ie, the ability to independently accomplish da... more 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 (βs = 0.18–0.42), and negative/positive reinforcement learning (β = −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 (β = 0.34), and the negative association between positive symptoms and self-reported social acceptability was stronger for BD than for SZ (β = 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.

Research paper thumbnail of All or nothing belief updating in patients with schizophrenia reduces precision and flexibility of beliefs

Brain, Jan 12, 2021

Schizophrenia is characterized by abnormal perceptions and beliefs, but the computational mechani... more Schizophrenia is characterized by abnormal perceptions and beliefs, but the computational mechanisms through which these abnormalities emerge remain unclear. One prominent hypothesis asserts that such abnormalities result from overly precise representations of prior knowledge, which in turn lead beliefs to become insensitive to feedback. In contrast, another prominent hypothesis asserts that such abnormalities result from a tendency to interpret prediction errors as indicating meaningful change, leading to the assignment of aberrant salience to noisy or misleading information. Here we examine behaviour of patients and control subjects in a behavioural paradigm capable of adjudicating between these competing hypotheses and characterizing belief updates directly on individual trials. We show that patients are more prone to completely ignoring new information and perseverating on previous responses, but when they do update, tend to do so completely. This updating strategy limits the integration of information over time, reducing both the flexibility and precision of beliefs and provides a potential explanation for how patients could simultaneously show over-sensitivity and under-sensitivity to feedback in different paradigms.

Research paper thumbnail of Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Mar 1, 2018

Background-The current study was designed to test the hypothesis that motivational deficits in sc... more Background-The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of lossavoidance in the brain, leading to reduced ability to form adaptive representations of expected value. Methods-We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 controls, in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial-types with different expected values (Expected Gain-Non-monetary, e.g.), and between outcomes with the same prediction error valence but different experienced values (Gain-Loss-avoidance outcome, Miss-Loss outcome, e.g.). Results-Both whole-brain and regions-of-interest analyses revealed that schizophrenia patients showed reduced differentiation between Gain and Loss-avoidance outcomes in dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. Furthermore, we observed significant correlations between [Gain-Loss-avoidance outcome] contrasts in ventral

Research paper thumbnail of Relieving the Burden: Identifying Diminishing Returns to Create More Efficient Tasks

Background: If well-constructed, efficient measures of cognition have the potential to increase v... more Background: If well-constructed, efficient measures of cognition have the potential to increase validity, while decreasing research burden and costs for participants and assessors with little loss of reliability. There is the possibility that long and difficult measures create even noisier data for people with serious mental illness compared to the general population. In this study, we aim to assess the extent to which working memory and reinforcement learning tasks can be made more efficient.Methods: Participants included 185 people with serious mental illness and 75 controls. Internal consistency (Cronbach’s , Item-Total Correlations, and/or Spearman-Brown Prophecy Correlations) and test-retest reliability (Intraclass Correlations) were calculated for increasing subsets of trials on each task to assess the point at which reliability reached acceptable and good levels or reached diminishing returns.Results: Generally, the tasks had met acceptable internal consistency values by the time only half of the values had been included and either good reliability or diminishing returns by the time two-thirds of the task trials were considered. This was largely similar for test-retest on the working memory tasks, but acceptable test-retest reliability was mostly never achieved on the reinforcement learning tasks.Conclusions: Overall, each of the working memory and reinforcement learning tasks can be made 25-50% more efficient without significant loss of psychometric integrity. However, there may be limitations on the utility of some of the tasks due to acceptable test-retest reliability never being achieved.

Research paper thumbnail of 206. The Impact of Reward History on Allocation of Spatial Attention in Schizophrenia

Schizophrenia Bulletin, Mar 1, 2017

Background: Dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and ... more Background: Dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and its putative prodrome, the clinical high risk state (CHR). Striatal DA results from the activity of midbrain DA neurons projecting mainly from the substantia nigra (SN). Elevated stress-induced DA release in SCZ and CHR was observed in the striatum, however whether it is also elevated in the SN is unclear. The current study aims to determine whether nigral DA release in response to a validated stress task is altered in CHR and in antipsychotic-naive SCZ. Further, we explore how DA release in the SN and striatum might be related. Methods: 24 CHR subjects, 9 antipsychotic-naive SCZ and 25 healthy volunteers (HV) underwent two positron emission tomography (PET) scans using the DA D2/3 agonist radiotracer, [11C]-(+)-PHNO, which allows simultaneous investigations of DA in the SN and striatum. Psychosocial stress-induced DA release was estimated as the percentage differences in BPND (%[11C]-(+)-PHNO displacement) between stress and sensorymotor control sessions. Results: We observed a significant group by sessions interaction on [11C]-(+)-PHNO BPND in the SN (F = 6.896, P = .002). The SCZ showed a 25.90% [11C]-(+)-PHNO binding change change in nigral [11C]-(+)-PHNO displacement, while HV showed-10.94% and CHR exhibited an intermediate response [11C]-(+)-PHNO binding change (−1.13%). Only among the CHR subjects, we found a positive trend of association between [11C]-(+)-PHNO binding changes displacement in the SN and the whole striatum (r = .382, P = .072). Conclusion: Our findings suggest a sensitized nigral DA response to stress in antipsychotic-naive SCZ. The unique trend association between nigral and striatal [11C]-(+)-PHNO binding changes, and a differential nigrostriatal DA pathway in CHR, which may suggest a stage specific biomarker warrants further investigation to confirm.

Research paper thumbnail of Effects of clozapine on cognition in patients with schizophrenia

Schizophrenia Research, May 1, 1991

Research paper thumbnail of Increased influence of a previously attended feature in people with schizophrenia

Journal of Abnormal Psychology, Apr 1, 2020

Everyday functioning requires the appropriate allocation of visual attention, which is achieved t... more Everyday functioning requires the appropriate allocation of visual attention, which is achieved through multiple mechanisms of attentional guidance. Traditional theories have focused on top-down and bottom-up factors, but implicit learning from recent experience ("selection history") also has a substantial impact on attentional allocation. The present experiment examined the influence of intertrial priming on attentional guidance in people with schizophrenia and matched control subjects. Participants searched for a color pop-out target, which switched randomly between a red target among blue distractors and a blue target among red distractors. We found that performance on the current trial was more influenced by the previous-trial target color in people with schizophrenia than in control subjects. Moreover, this implicit priming effect was greater in individuals with lower working memory capacity (as measured in a separate task). These results suggest that intertrial priming has an exaggerated impact on attentional guidance in people with schizophrenia and that this is associated with other aspects of impaired cognition. Overall, these results are consistent with the hyperfocusing hypothesis, which proposes that a single underlying attentional abnormality may explain a range of atypical effects across perception, attention, and cognition in schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Research paper thumbnail of Antisaccade Deficits in Schizophrenia Can Be Driven by Attentional Relevance of the Stimuli

Schizophrenia Bulletin, Aug 7, 2020

The antisaccade task is considered a test of cognitive control because it creates a conflict betw... more The antisaccade task is considered a test of cognitive control because it creates a conflict between the strong bottom-up signal produced by the cue and the top-down goal of shifting gaze to the opposite side of the display. Antisaccade deficits in schizophrenia are thought to reflect impaired top-down inhibition of the prepotent bottom-up response to the cue. However, the cue is also a highly taskrelevant stimulus that must be covertly attended to determine where to shift gaze. We tested the hypothesis that difficulty in overcoming the attentional relevance of the cue, rather than its bottom-up salience, is key in producing impaired performance in people with schizophrenia (PSZ). We implemented 3 versions of the antisaccade task in which we varied the bottom-up salience of the cue while holding its attentional relevance constant. We found that difficulty in performing a given antisaccade taskrelative to a prosaccade version using the same stimuliwas largely independent of the cue's bottom-up salience. The magnitude of impairment in PSZ relative to control subjects was also independent of bottom-up salience. The greatest impairment was observed in a version where the cue lacked bottom-up salience advantage over other locations. These results indicate that the antisaccade deficit in PSZ does not reflect an impairment in overcoming bottom-up salience of the cue, but PSZ are instead impaired at overcoming its attentional relevance. This deficit may still indicate an underlying inhibitory control impairment but could also reflect a hyperfocusing of attentional resources on the cue.

Research paper thumbnail of 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 schizophr... more Background and Hypotheses: Auditory verbal hallucinations (AVH) are central features of schizophrenia. 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 schizophrenia such as delusional beliefs, cognitive impairment, and negative symptoms. Study design: We recruited 76 people with a DSM-V diagnosis of schizophrenia/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 two 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.

Research paper thumbnail of Impaired expected value computations coupled with overreliance on prediction error learning in schizophrenia

bioRxiv (Cold Spring Harbor Laboratory), Dec 22, 2017

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

Schizophrenia Bulletin Open

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few st... more 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. Amon...

Research paper thumbnail of F9. Reduced Uncertainty-Driven Exploration and Associated Neural Reward-Related Signals Relate to Motivational Deficit Severity

Schizophrenia Bulletin, 2019

Poster Session II S257 Results: Body weight, waist circumference and fasting insulin levels were ... more Poster Session II S257 Results: Body weight, waist circumference and fasting insulin levels were similar between patients on olanzapine or risperidone. Plasma IGFBP-2 levels were also not different between the two groups (173 ± 15 vs 199 ± 16 ng/mL, respectively). As expected, IGFBP-2 concentrations were negatively correlated with BMI, waist circumference, insulin sensitivity, and plasma triglyceride levels in the entire cohort. However, the proportion of schizophrenic patients with a hypertriglyceridemia and large waist circumference ranged from 43% for olanzapine and 12% for risperidone users with IGFBP-2 levels lower than 220 ng/mL, compared to 8% and 0%, respectively for patients with plasma IGFBP-2 above this threshold (p = 0.0178). Discussion: Our findings suggest that circulating levels of IGFBP-2 may underlie the inter-variability on metabolic risk in schizophrenic patients using SGAs. Longitudinal studies are required to evaluate whether IGFBP-2 levels can predict the development of a hypertriglyceridemic waist phenotype in this population.

Research paper thumbnail of Latent Profiles of Cognitive Control, Episodic Memory, and Visual Perception Across Psychiatric Disorders Reveal a Dimensional Structure

Schizophrenia Bulletin, 2019

Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocogn... more Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocognitive phenotype than mood disorders such as bipolar disorder, considerable between-subject heterogeneity exists in the phenotypic presentation of these deficits across mental illnesses. Indeed, it is unclear whether the processes that underlie cognitive dysfunction in these disorders are unique to each disease or represent a common neurobiological process that varies in severity. Here we used latent profile analysis (LPA) across 3 distinct cognitive domains (cognitive control, episodic memory, and visual integration; using data from the CNTRACS consortium) to identify distinct profiles of patients across psychotic illnesses. LPA was performed on a sample of 223 psychosis patients (59 with Type I bipolar disorder, 88 with SZ, and 76 with schizoaffective disorder). Seventy-three healthy control participants were included for comparison but were not included in sample LPA. Three latent prof...

Research paper thumbnail of Cross-diagnostic analysis of cognitive control in mental illness: Insights from the CNTRACS consortium

Schizophrenia Research, 2019

Background: In recent years, psychiatry research has increasingly focused on understanding mental... more Background: In recent years, psychiatry research has increasingly focused on understanding mental illnesses from a cross-diagnostic, dimensional perspective in order to better align their neurocognitive features with underlying neurobiological mechanisms. In this multi-site study, we examined two measures of cognitive control (d-prime context and lapsing rate) during the Dot Probe Expectancy (DPX) version of the AX-Continuous Performance Task in patients with either schizophrenia (SZ), schizoaffective disorder (SZ-A), or Type I bipolar disorder (BD) as well as healthy control (HC) subjects. We hypothesized significantly lower d-prime context and higher lapsing rate in SZ and SZ-A patients and intermediate levels in BD patients relative to HC. Methods: 72 HC, 84 SZ, 77 SZ-A, and 58 BD patients (ages 18-56) were included in the final study sample. Results: Significant main effects of diagnosis were observed on d-prime context (F(3,279) = 9.59, p b 0.001) and lapsing (F(3,279) = 8.08, p b 0.001). A priori linear contrasts suggesting intermediate dysfunction in BD patients were significant (p b 0.001), although post-hoc tests showed the BD group was only significantly different from HC on d-prime context. Group results for d-prime context remained significant after covarying for lapsing rate. Primary behavioral measures were associated with mania and disorganization symptoms as well as everyday functioning. Conclusions: These findings suggest a continuum of dysfunction in cognitive control (particularly d-prime context) across diagnostic categories in psychiatric illness. These results further suggest that lapsing and d-prime context, while related, make unique contributions towards explaining deficits in cognitive control in these disorders.

Research paper thumbnail of Impaired expected value computations in schizophrenia are associated with a reduced ability to integrate reward probability and magnitude of recent outcomes

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2018

Background: Motivational deficits in people with schizophrenia (PSZ) are associated with an inabi... more Background: Motivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on "value-less" stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits. Methods: Healthy volunteers (n=38) and PSZ (n=49) completed a learning paradigm consisting of four stimulus pairs. Reward magnitude (3/2/1/0 points) and probability (90%/80%/20%/10%) determined each stimulus' EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value. Results: PSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability*magnitude) between two competing stimuli increased. Using a previously-validated computational hybrid model, PSZ relied less on EV ("Q-learning") and more on stimulus-response learning ("actor-critic"), which correlated with SANS motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability.

Research paper thumbnail of Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2017

BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in s... more BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-lossavoidance outcome, miss-loss outcome). RESULTS: Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS: These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.