James Gold

University of Maryland, Baltimore | UMB · Maryland Psychiatric Research Center (MPRC)

Diminished social motivation is a core feature of schizophrenia that might reflect disturbances in social reward processing. It is not known whether these disturbances reflect anticipatory (“wanting”) and/or consummatory (“liking”) pleasure deficits. The primary aim of this study was to examine social versus nonsocial reward processing during these...

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 t...

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this s...

Self-report questionnaires have been developed to efficiently assess psychosis risk and vulnerability. Despite this, the validity of these questionnaires for assessing specific positive symptoms in those at clinical high risk for psychosis (CHR) is unclear. Positive symptoms have largely been treated as a uniform construct in this critical populati...

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this s...

Background and hypothesis: Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CH...

Objective: Difficulties in social cognition are common in individuals with schizophrenia (SZ) and are not ameliorated by antipsychotic treatment. Intranasal oxytocin (OT) administration has been explored as a potential intervention to improve social cognition; however, results are inconsistent, suggesting potential individual difference variables...

Background and hypothesis: Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs. Study design: Here we induce hallucinated tones by associating tones with the presentation of a visual cue....

Sedentary behavior contributes to a shortened life expectancy in individuals with schizophrenia-spectrum disorders (SSDs), highlighting the need for effective interventions to improve health. This study examined whether reduced ecological momentary assessment (EMA) measures of sedentary activities were observed in individuals with SSDs who particip...

Objective: Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods to characterize the patterns of symptom clustering and how clusters relate to one another.Methods: We analyzed publicly-available data from 153 particip...

Objectives: Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare...

Recent evidence suggests that the aberrant signaling of salience is associated with psychotic illness. Salience, however, can take many forms in task environments. For example, salience may refer to any of the following: (1) the valence of an outcome, (2) outcomes that are unexpected, called reward prediction errors (PEs), or (3) cues associated wi...

Identifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception...

Importance Recent accounts suggest that delusions and hallucinations may result from alterations in how prior knowledge is integrated with new information, but experimental evidence supporting this idea has been complex and inconsistent. Evidence from a simpler perceptual task would make clear whether psychotic symptoms are associated with overreli...

Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs. Here we induce hallucinated tones by associating tones with the presentation of a visual cue. We find that people with schizophrenia who...

Although people with schizophrenia (PSZ) exhibit robust and reliable deficits in working memory (WM) capacity, the neural processes that give rise to this impairment remain poorly understood. One reason for this lack of clarity is that most studies employ a single neural recording modality—each with strengths and weaknesses—with few examples of int...

Although schizophrenia is classically thought to involve impaired attentional filtering, people with schizophrenia (PSZ) exhibit a more intense and more exclusive attentional focus than healthy control subjects (HCS) in many tasks. To resolve this contradiction, this functional magnetic resonance imaging study tested the impact of attentional contr...

Schizophrenia is widely thought to involve elevated distractibility, which may reflect a general impairment in top-down inhibitory processes. Schizophrenia also appears to involve increased priming of previously performed actions. Here, we used a highly refined eye-tracking paradigm that makes it possible to concurrently assess distractibility, inh...

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in indivi...

The article by Catalan and colleagues¹ provides an updated meta-analysis of neuropsychological impairment in individuals considered to be at clinical high risk for psychosis (CHR-P). The authors summarize the extensive literature addressing the CHR-P impairments compared with healthy controls, as well as the smaller literature contrasting impairmen...

Background Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g. psychosis in bipolar disorder vs schiz...

Background: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizo...

We hypothesized that cerebral white matter deficits in schizophrenia (SZ) are driven in part by accelerated white matter aging and are associated with cognitive deficits. We used a machine learning model to predict individual age from diffusion tensor imaging features and calculated the delta age (Δage) as the difference between predicted and chron...

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 contras...

A growing body of research has suggested that people with schizophrenia (SZ) exhibit altered patterns of functional and anatomical brain connectivity. For example, many previous resting state functional connectivity (rsFC) studies have shown that, compared to healthy controls (HC), people with SZ demonstrate hyperconnectivity between subregions of...

Early detection and intervention with young people at clinical high risk (CHR) for psychosis is critical for prevention efforts focused on altering the trajectory of psychosis. Early CHR research largely focused on validating clinical interviews for detecting at-risk individuals; however, this approach has limitations related to: (1) specificity (i...

People with schizophrenia often experience attentional impairments that hinder learning during psychological interventions. Attention shaping is a behavioral technique that improves attentiveness in this population. Because reinforcement learning (RL) is thought to be the mechanism by which attention shaping operates, we investigated if preshaping...

Background Motivational deficits in people with psychosis may be a result of impairments in reinforcement learning (RL). Therefore, behavioral paradigms that can accurately measure these impairments and their change over time are essential. Methods We examined the reliability and replicability of 2 RL paradigms (1 implicit and 1 explicit, each wit...

Background Schizophrenia spectrum disorders (SSDs) feature social cognitive deficits, though their neural basis remains unclear. Social cognitive performance may relate to neural circuit activation patterns more than diagnosis, which would have important prognostic and therapeutic implications. The present study aimed to determine how functional co...

Computational neuroscience models propose that working memory (WM) involves recurrent excitatory feedback loops that maintain firing over time along with lateral inhibition that prevents the spreading of activity to other feature values. In behavioral paradigms, this lateral inhibition appears to cause a repulsion of WM representations away from ea...

We hypothesized that cerebral white matter deficits in schizophrenia (SZ) are driven in part by accelerated white matter aging and are associated with cognitive deficits. We used machine learning model to predict individual age from diffusion tensor imaging features and calculated the delta age (Δage) as the difference between predicted and chronol...

Background Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning mea...

Background: Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. Methods: Thirty-nine...

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...

Research suggests that early identification and intervention with individuals at clinical high risk (CHR) for psychosis may be able to improve the course of illness. The first generation of studies suggested that the identification of CHR through the use of specialized interviews evaluating attenuated psychosis symptoms is a promising strategy for...

Schizophrenia is associated with a number of deficits in decision-making, but the scope, nature, and cause of these deficits are not completely understood. Here we focus on a particular type of decision, known as the explore/ exploit dilemma, in which people must choose between exploiting options that yield relatively known rewards and exploring mo...

The current study examined whether subgroups of individuals with schizophrenia could be identified based on their profiles of trait positive and negative emotional experience, and whether those subgroups differed in their symptom presentation and functional outcome. Participants included 192 outpatients diagnosed with schizophrenia or schizoaffecti...

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 informa...

Cognitive deficits are characteristic of schizophrenia but their etiology is not understood. Previous studies show an association between viral exposures and cognitive impairment. This meta-analysis was undertaken to determine the relationship of herpes simplex virus type 1 (HSV-1) exposure and cognitive functioning in schizophrenia. A systematic s...

Early intervention in psychotic spectrum disorders is critical for maximizing key clinical outcomes. While there is some evidence for the utility of intervention during the prodromal phase of the illness, efficacy of interventions is difficult to assess without appropriate risk stratification. This will require biomarkers that robustly help to iden...

Background We have found that measures of reinforcement learning (RL) performance correlate with negative symptoms severity in adult schizophrenia patients as well as in adolescents and young adults seeking psychiatric services. Most of these tasks assess reinforcement learning in stable environments, however. In unstable, or volatile environments,...

Background Previous research shows that trait emotion is more affected than state emotion in schizophrenia. This literature is also somewhat inconsistent, particularly in terms of specific links between affective traits and clinical symptoms. The current study examined whether subgroups of trait emotional experience predict symptom presentation and...

Background Cognitive control mechanisms enable an individual to regulate, coordinate, and sequence thoughts and actions to obtain desired outcomes. A theory of control specialization posits that proactive control is necessary for anticipatory planning and goal maintenance and recruits sustained lateral prefrontal activity, whereas reactive control,...

Background Impairments in spatial working memory (sWM) have been well-documented in schizophrenia. Here we provide a comprehensive test of a microcircuit model of WM performance in schizophrenia, which predicts enhanced effects of increasing delay duration and distractors based on a hypothesized imbalance of excitatory and inhibitory processes. Me...

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 pres...

A frequent finding when studying substrates of working memory (WM) deficits in people with schizophrenia (PSZ) is task-induced hyperactivation relative to healthy control subjects (HCS) when WM load is low. Hyperactivation accompanying similar performance is commonly attributed to cognitive deficits rendering relatively easy operations more resourc...

Multivariate pattern classification (decoding) methods are commonly employed to study mechanisms of neurocognitive processing in typical individuals, where they can be used to quantify the information that is present in single-participant neural signals. These decoding methods are also potentially valuable in determining how the representation of i...

Prior studies examining the impact of oxytocin on negative symptoms in schizophrenia have yielded mixed results. The current study explored whether oxytocin can improve more proximal indicators of social affiliation as indicated by changes in behavior, language and subjective indices of social affiliation among individuals with schizophrenia spectr...

Schizophrenia is a complex mental illness characterized by positive and negative symptoms. Antipsychotic medications are the main treatment for this condition; however, many patients have only a partial response. All currently available antipsychotics involve modulation of the dopamine system, although the underlying pathophysiology of this illness...

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamical...

Network analysis was used to examine how densely interconnected individual negative symptom domains are, whether some domains are more central than others, and whether sex influenced network structure. Participants included outpatients with schizophrenia (SZ; n = 201), a bipolar disorder (BD; n = 46) clinical comparison group, and healthy controls...

Despite rapidly growing knowledge of the clinical high-risk (CHR) state for psychosis, the vast majority of case-control studies have relied on healthy volunteers as a reference point for drawing inferences about the CHR construct. Researchers have long recognized that results generated from this design are limited by significant interpretive conce...

Abstract Depressive symptoms are highly prevalent in psychotic populations and result in significant functional impairment. Limited knowledge of whether depressive symptoms are invariant across stages of illness curtails our ability to understand how these relate to illness progression. Clarifying the latent structure of depressive symptoms across...

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is...

In February 2019 a workshop was convened at the Banbury Centre at Cold Spring Harbor, NY. The purpose of the meeting was to identify key developments required in the practice and infrastructure of computational psychiatry research to accelerate its ability to address real world clinical problems in the near future. This report provides a summary of...

Finger tapping is sensitive to motor slowing and emerging symptoms in individuals at clinical high risk for psychosis (CHR). A sensitive, computerized finger tapping task would be beneficial in early psychosis screening batteries. The study included 41 CHR and 32 healthy volunteers, who completed a computerized finger tapping task and clinical inte...

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamical...

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 propo...

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) — a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were p...