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Compromised white matter has been reported in schizophrenia; however, few studies have investigated neurochemical abnormalities underlying microstructural differences. N-acetylaspartate (NAA) is used to synthesize myelin and is often reduced in persons with schizophrenia (PSZ) and their unaffected first-degree relatives (REL). Low levels of NAA could affect white matter by preventing the synthesis or repair of myelin. We used magnetic resonance spectroscopy and diffusion tensor imaging to investigate the relationship between NAA and white matter integrity in PSZ. REL were included to examine whether putative relationships are associated with symptom expression or illness liability. 52 controls, 23 REL and 25 PSZ underwent 7T proton magnetic resonance spectroscopy and/or 3T diffusion tensor imaging. NAA in the visual cortex and basal ganglia were measured and compared across groups. Diffusivity measures were compared across groups using tract-based spatial statistics and related to NAA concentrations. Visual cortex NAA was significantly reduced in PSZ compared to controls. White matter integrity did not differ between groups. Reduced cortical and subcortical NAA were associated with diffusivity measures of poor white matter microstructure. These data suggest that levels of neural NAA may be related to white matter integrity similarly across individuals with schizophrenia, those at genetic risk, and controls.

Schizophrenia research has traditionally focused almost exclusively on how the brain interprets the outside world. However, our internal bodily milieu is also central to how we interpret the world and construct our reality: signals from within the body are critical for not only basic survival, but also a wide range of brain functions from basic perception, emotion, and motivation, to sense of self. In this article, we propose that interoception-the processing of bodily signals-may have implications for a wide range of clinical symptoms in schizophrenia and may thus provide key insights into illness mechanisms. We start with an overview of interoception pathways. Then we provide a review of direct and indirect findings in various interoceptive systems in schizophrenia and interpret these findings in the context of computational frameworks that model interoception as hierarchical Bayesian inference. Finally, we propose a conceptual model of how altered interoceptive inference may contribute to specific schizophrenia symptoms-negative symptoms in particular-and suggest directions for future research, including potential new avenues of treatment.

Interoception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also many cognitive processes, especially motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but few studies have explored their potential neural underpinning. The current study aims to investigate the anatomical connectivity of a previously identified interoception network in individuals with schizophrenia, and the relationship between structural connectivity in this network and both emotional functioning and clinical symptoms. Thirty-five participants with schizophrenia (SZ) and 36 healthy control participants (HC) underwent diffusion tensor imaging (DTI) and performed tasks measuring emotional functioning. Probabilistic tractography was used to identify white matter tracts connecting key hubs in an interoception network (rostral and caudal anterior cingulate cortex, ventral anterior insula, dorsal mid and posterior insula, and amygdala). Microstructural integrity of these tracts was compared across groups and correlated with measures of emotional functioning and symptom severity. Compared with HC, SZ exhibited altered structural connectivity in the interoception network, specifically between the amygdala and the insular cortex. In HC, the structural connectivity of the network was significantly correlated with emotion recognition, supporting a link between the interoception network and emotional functioning. However, this correlation was much weaker in SZ, suggesting less involvement of this network. These findings suggest that altered interoception may have implications for illness mechanisms of schizophrenia, especially in relation to emotional deficits.

Much of past research has been dedicated to refining the operationalization and correlates of the broader autism phenotype (BAP) and less on how the BAP differs by socio-demographic characteristics, like age-particularly after midlife. This gap is important because other nonclinical trait-like characteristics (e.g., personality) have shown considerable age differences, leading to work assessing the malleability of psychological characteristics and improving outcomes for individuals and their significant others. In the current study, we examined cross-sectional age differences in the BAP in a large sample of adults ranging in age from 18 to 85. We recruited a sample of 2966 adults ranging in age from 18 to 85 (Mage = 36.53, SD = 12.61; 58.9% Female; 1.1% with an ASD diagnosis) recruited from an online survey service. We found that total BAP scores were higher in younger adults and lower among older adults. These differences were particularly true for pragmatic language difficulties, with this component of the BAP showing the most dramatic age differences. Aloofness showed similar negative associations with age, albeit much smaller. Rigidity was not significantly associated with age. The results are consistent with other research showing an abatement of symptoms among individuals with autism spectrum disorders (ASDs) across early life and theories predicting changes in other psychological characteristics (e.g., personality). The results are discussed in the context of the malleability of ASD and BAP traits across life, the clinical implications of these changes, and the origins and consequences for lifespan differences in BAP. LAY SUMMARY: Little is known about how subclinical autistic-like traits among middle-aged and older adults compare to younger adults. We found that these subclinical traits were highest in young adults and lowest in older adults. Knowing how these traits differ by age can provide researchers and clinicians with a sense of how much these traits might change across life, if the traits might be sensitive to interventions, and when in development it might be best to intervene.

Schizophrenia has been studied from the perspective of cognitive- or reward-related impairments, yet it cannot be wholly related to one or the other process and corresponding neural circuits. We posit a comprehensive circuit-based model proposing that dysfunctional interactions between the brain’s cognitive and reward circuits underlie schizophrenia. The model is underpinned by how the relationship between glutamatergic and dopaminergic dysfunction in schizophrenia drives interactions between cognition and reward circuits. We argue that this interaction is synergistic: that is, deficits of cognition and reward processing interact, and this interaction is a core feature of schizophrenia. In adopting this position, we undertake a focused review of animal physiology and human clinical data, and in proposing this synergistic model, we highlight dopaminergic afferents from the ventral tegmental area to nucleus accumbens (mesolimbic circuit) and frontal cortex (mesocortical circuit). We then expand on the role of glutamatergic inputs to these dopamine circuits, and dopaminergic modulation of critical excitatory pathways, with attention given to the role of glutamatergic hippocampal outputs onto nucleus accumbens. Finally, we present evidence for how in schizophrenia, dysfunction in the mesolimbic and mesocortical circuits, and their corresponding glutamatergic inputs gives rise to clinical and cognitive phenotypes, and is associated with positive and negative symptom dimensions. The synthesis attempted here provides an impetus for a conceptual shift that links cognitive and motivational aspects of schizophrenia and which can lead to treatment approaches that seek to harmonize network interactions between the brain’s cognition and reward circuits with ameliorative effects in each behavioral domain.

Epidemiological studies have described higher rates of psychotic disorder diagnoses in transgender, as compared to cisgender, individuals. With the exception of this work and a small number of published case studies, however, there has been little consideration of gender diversity in psychosis research or clinical care. In this paper, we will review and critically evaluate the limited literature on gender diversity and clinical psychosis and articulate the critical need for more work in this field, more specifically on the following areas and how they bear on clinical care: 1) diagnostic biases; 2) how chronic non-affirmation and bias, gender dysphoria, and other gender minority stressors may operate as trauma and can contribute to clinically significant psychotic symptoms; 3) the potential impact of gender-affirming care, such as hormone therapies, on mental health and barriers for receiving such care in transgender and nonbinary individuals; and 4) culturally-sensitive and gender-affirming approaches for addressing psychosis. Finally, we consider ways in which researchers may engage in ethical, gender-affirming, and accurate approaches to better address gender identity in psychosis research. We hope that such research will aid in the creation of clinical guidelines for understanding, diagnosing, and treating psychosis in gender diverse individuals.

Corollary discharge (CD) signals are motor-related signals that exert an influence on sensory processing. They allow mobile organisms to predict the sensory consequences of their imminent actions. Among the many functions of CD is to provide a means by which we can distinguish sensory experiences caused by our own actions from those with external causes. In this way, they contribute to a subjective sense of agency. A disruption in the sense of agency is central to many of the clinical symptoms of schizophrenia, and abnormalities in CD signaling have been theorized to underpin particularly those agency-related psychotic symptoms of the illness. Characterizing abnormal CD associated with eye movements in schizophrenia and their resulting influence on visual processing and subsequent action plans may have advantages over other sensory and motor systems. That is because the most robust psychophysiological and neurophysiological data regarding the dynamics and influence of CD as well as the neural circuitry implicated in CD generation and transmission comes from the study of eye movements in humans and non-human primates. In this paper, we review studies of oculomotor CD signaling in the schizophrenia spectrum and possible neurobiological correlates of CD disturbances. We conclude by speculating upon the ways in which oculomotor CD dysfunction, specifically, may invoke specific experiences, clinical symptoms and cognitive impairments. These speculations lay the groundwork for empirical study, and we conclude by outlining potentially fruitful research directions.

Psychosis-a cardinal symptom of schizophrenia-has been associated with a failure to appropriately create or use stored regularities about past states of the world to guide the interpretation of incoming information, which leads to abnormal perceptions and beliefs. The visual system provides a test bed for investigating the role of prior experience and prediction, as accumulated knowledge of the world informs our current perception. More specifically, the strength of visual aftereffects, illusory percepts that arise after prolonged viewing of a visual stimulus, can serve as a valuable measure of the influence of prior experience on current visual processing. In this paper, we review findings from a largely older body of work on visual aftereffects in schizophrenia, attempt to reconcile discrepant findings, highlight the role of antipsychotic medication, consider mechanistic interpretations for behavioral effects, and propose directions for future research.

Abnormalities in synaptic plasticity are argued to underlie the neural dysconnectivity observed in schizophrenia. One way to measure synaptic plasticity is through sensory adaptation, whereby sensory neurons exhibit reduced sensitivity after sustained stimulus exposure. Evidence for decreased adaptation in individuals with schizophrenia is currently inconclusive, possibly due to heterogeneity in clinical and medication status across samples. Here we circumvent these confounds by examining whether altered adaptation is represented sub-clinically in the general population. To test this we used three paradigms from visual perception research that provide a precise and non-invasive index of adaptation in the visual system. Two paradigms involve a class of illusory percepts termed visual aftereffects. The third relies on a visual phenomenon termed binocular rivalry, where incompatible stimuli are presented to the two eyes and observers alternate between perceiving exclusively one stimulus or a combination of the two (i.e. mixed perception). We analyzed the strength and dynamics of visual adaptation in these paradigms, in relation to schizotypy. Our results showed that increased schizotypal traits were related to reduced orientation, but not luminance, aftereffect strength (Exp. 1). Further, increased schizotypy was related to a greater proportion of mixed perception during binocular rivalry (Exp. 1 and 2). Given that visual adaption is well understood at cellular and computational levels, our data suggest that short-term plasticity in the visual system can provide important information about the disease mechanisms of schizophrenia.

Perception is not the passive registration of incoming sensory data. Rather, it involves some analysis by synthesis, based on past experiences and context. One adaptive consequence of this arrangement is imagination—the ability to richly simulate sensory experiences, interrogate and manipulate those simulations, in service of action and decision making. In this paper, we will discuss one possible cost of this adaptation, namely hallucinations—perceptions without sensory stimulation, which characterize serious mental illnesses like schizophrenia, but which also occur in neurological illnesses, and—crucially for the present piece—are common also in the non-treatment-seeking population. We will draw upon a framework for imagination that distinguishes voluntary from non-voluntary experiences and explore the extent to which the varieties and features of hallucinations map onto this distinction, with a focus on auditory-verbal hallucinations (AVHs)—colloquially, hearing voices. We will propose that sense of agency for the act of imagining is key to meaningfully dissecting different forms and features of AVHs, and we will outline the neural, cognitive and phenomenological sequelae of this sense. We will conclude that a compelling unifying framework for action, perception and belief—predictive processing—can incorporate observations regarding sense of agency, imagination and hallucination. This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.

Symptoms of schizophrenia have been explained as a failure to appropriately apply past environmental regularities to the interpretation of incoming sensory information, thus leading to abnormal perceptions and beliefs. Here we use the visual system as a test bed for investigating how prior experience shapes perception in individuals with schizophrenia. Specifically, we use visual aftereffects, illusory percepts resulting from prior exposure to visual input, to measure the influence of prior events on current processing. At a neural level, visual aftereffects arise due to attenuation in the responses of neurons that code the features of the prior stimulus (neuronal adaptation) and subsequent disinhibition of neurons signaling activity at the opposite end of the feature dimension. In the current study, we measured tilt aftereffects and negative afterimages, two types of aftereffects that reflect, respectively, adaptation of cortical orientation-coding neurons and adaptation of subcortical and retinal luminance-coding cells in persons with schizophrenia (PSZ; n=36) and demographically-matched healthy controls (HC; n=22). We observed stronger tilt aftereffects in PSZ compared to HC, but no difference in negative afterimages. Stronger tilt aftereffects were related to more severe negative symptoms. These data suggest over-sensitivity to recent regularities at cortical, but not subcortical, levels in schizophrenia, which is in line with a growing literature that predictive processes in schizophrenia are altered at multiple cortical levels. More broadly, the results underscore the value of aftereffect paradigms as a tool for the quantitative examination of canonical computations whose dysfunction may underpin symptom genesis in schizophrenia.

Social dysfunction is an intractable problem in a wide spectrum of psychiatric illnesses, undermining patients’ capacities for employment, independent living, and maintaining meaningful relationships. Identifying common markers of social impairment across disorders and understanding their mechanisms are prerequisites to developing targeted neurobiological treatments that can be applied productively across diagnoses and illness stages to improve functional outcome. This project focuses on eye gaze perception, the ability to accurately and efficiently discriminate others’ gaze direction, as a potential biomarker of social functioning that cuts across psychiatric diagnoses. This premise builds on both the monkey and human literatures showing gaze perception as a basic building block supporting higher-level social communication and social development, and reports of abnormal gaze perception in multiple psychiatric conditions accompanied by prominent social dysfunction (e.g., psychosis-spectrum disorders, autism-spectrum disorders, social phobia). A large sample (n = 225) of adolescent and young adult (age 14–30) psychiatric patients (regardless of diagnosis) with various degrees of impaired social functioning, and demographically-matched healthy controls (n = 75) will be recruited for this study. Participant’s psychiatric phenotypes, cognition, social cognition, and community functioning will be dimensionally characterized. Eye gaze perception will be assessed using a psychophysical task, and two metrics (precision, self-referential bias) that respectively tap into gaze perception disturbances at the visual perceptual and interpretation levels, independent of general deficits, will be derived using hierarchical Bayesian modeling. A subset of the participants (150 psychiatric patients, 75 controls) will additionally undergo multimodal fMRI to determine the functional and structural brain network features of altered gaze perception. The specific aims of this project are three-fold: (1) Determine the generality of gaze perception disturbances in psychiatric patients with prominent social dysfunction; (2) Map behavioral indices of gaze perception disturbances to dimensions of psychiatric phenotypes and core functional domains; and (3) Identify the neural correlates of altered gaze perception in psychiatric patients with social dysfunction. Successfully completing these specific aims will identify the specific basic deficits, clinical profile, and underlying neural circuits associated with social dysfunction that can be used to guide targeted, personalized treatments, thus advancing NIMH’s Strategic Objective 1 (describe neural circuits associated with mental illnesses and map the connectomes for mental illnesses) and Objective 3 (develop new treatments based on discoveries in neuroscience and behavioral science).

The ability to form associations between stimuli and commit those associations to memory is a cornerstone of human cognition. Dopamine and noradrenaline are neuromodulators that are critically implicated in a range of cognitive functions, including learning and memory. Eye blink rate (EBR) and pupil diameter have been shown to index dopaminergic and noradrenergic activity. Here, we examined how these ocular measures relate to accuracy during a paired-associate learning task where participants learned consistent object-location associations over eight trials. We recorded EBR, pupil diameter, and visual scanning behavior in a largely young adult sample (N=73). We examined these ocular metrics in terms of between and within participant mean centered effects using linear mixed effects modeling. In the encoding and delay epochs, we found that increased accuracy was related to increased EBR relative to the individual’s own average rate within the respective epoch across the eight trials. Additionally, increased between participant mean centered EBR showed decreased accuracy in pre-trial fixation, encoding, and retrieval epochs, indicating that blinking more relative to others during these epochs was related to poorer recall. These effects of EBR on accuracy were observed even after controlling for the extent of visual scanning, which, during the delay epoch, also conferred a beneficial effect on recall accuracy. Finally, we found no effect of pupil diameter on accuracy. These results provide novel evidence supporting the utility of ocular metrics in illuminating cognitive and neurobiological mechanisms of paired associate learning.

Study ObjectivesCoordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.MethodsIn 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.ResultsN=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (pConclusionThe implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.FundingSupported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

Corollary discharge (CD) signals are "copies" of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.

Psychosis - an impaired contact with reality - is a hallmark of schizophrenia. Many psychotic symptoms are associated with disruptions in agency - the sense that 'I' cause my actions. A failure to predict sensory consequences of one's own actions may underlie agency disturbances. Such predictions rely on corollary discharge (CD) signals, 'copies' of movement commands sent to sensory regions prior to action execution. Here, we make a case that the oculomotor system is a promising model for understanding CD in psychosis, building on advances in our understanding of the behavioral and neurophysiological correlates of CD associated with eye movements. In this opinion article, we provide an overview of recent evidence for disturbed oculomotor CD in schizophrenia, potentially linking bizarre and disturbing psychotic experiences with basic physiological processes.

Highlights • Thalamo-prefrontal structural connectivity reduced in persons with schizophrenia. • Similar reduction in thalamo-prefrontal connectivity in healthy siblings. • Thalamo-motor structural connectivity increased in persons with schizophrenia. • No alterations in thalamo-motor structural connectivity in healthy siblings., Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors.

The ability to form associations between stimuli and commit those associations to memory is a cornerstone of human cognition. Dopamine and noradrenaline are critical neuromodulators implicated in a range of cognitive functions, including learning and memory. Eye blink rate (EBR) and pupil diameter have been shown to index dopaminergic and noradrenergic activity. Here, we examined how these ocular measures relate to accuracy in a paired-associate learning task where participants (N = 73) learned consistent object-location associations over eight trials consisting of pre-trial fixation, encoding, delay, and retrieval epochs. In order to examine how within-subject changes and between-subject changes in ocular metrics related to accuracy, we mean centered individual metric values on each trial based on within-person and across-subject means for each epoch. Within-participant variation in EBR was positively related to accuracy in both encoding and delay epochs: faster EBR within the individual predicted better retrieval. Differences in EBR across participants was negatively related to accuracy in the encoding epoch and in early trials of the pre-trial fixation: faster EBR, relative to other subjects, predicted poorer retrieval. Visual scanning behavior in pre-trial fixation and delay epochs was also positively related to accuracy in early trials: more scanning predicted better retrieval. We found no relationship between pupil diameter and accuracy. These results provide novel evidence supporting the utility of ocular metrics in illuminating cognitive and neurobiological mechanisms of paired-associate learning.

The present study examined longitudinal associations between family member perceived burden and clinical correlates to understand potential covariation in change over time in the context of first-episode schizophrenia in the RAISE-ETP study (N = 282). Across 24 months, family burden, patient quality of life, and positive symptoms improved. Findings from the present study suggest covariation in change over time in quality of life and family burden. As patient quality of life improved, family burden decreased. However, initial levels of quality of life were not significantly associated with changes in family burden and vice versa. Initial levels of positive symptoms were significantly associated with initial levels of family burden. These findings have treatment implications by suggesting the potential for interventions aimed at improving quality of life to have a spillover effect on family burden, or alternatively, that reducing perceived family burden may improve patient quality of life.

By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals—“copies” of motor signals sent to sensory areas—permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD–FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD–FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD–FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients.SIGNIFICANCE STATEMENTPeople with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.

Fast cancellation or switching of action plans is a critical cognitive function. Rapid signal transmission is key for quickly executing and inhibiting responses, and the structural integrity of connections between brain regions plays a crucial role in signal transmission speed. In this study, we used the search-step task, which has been used in nonhuman primates to measure dynamic alteration of saccade plans, in combination with functional and diffusion-weighted MRI. Functional MRI results were used to identify brain regions involved in the reactive control of gaze. Probabilistic tractography was used to identify white matter pathways connecting these structures, and the integrity of these connections, as indicated by fractional anisotropy (FA), was correlated with search-step task performance. Average FA from tracts between the right frontal eye field (FEF) and both right supplementary eye field (SEF) and the dorsal striatum were associated with faster saccade execution. Average FA of connections between the dorsal striatum and both right SEF and right inferior frontal cortex (IFC) as well as between SEF and IFC predicted the speed of inhibition. These relationships were largely behaviorally specific, despite the correlation between saccade execution and inhibition. Average FA of connections between the IFC and both SEF and the dorsal striatum specifically predicted the speed of inhibition, and connections between the FEF and SEF specifically predicted the speed of execution. In addition, these relationships were anatomically specific; correlations were observed after controlling for global FA. These data suggest that networks supporting saccade initiation and inhibition are at least partly dissociable. Hum Brain Mapp 37:2811-2822, 2016. © 2016 Wiley Periodicals, Inc.

Executive control is the ability to flexibly control behavior and is frequently studied with saccadic eye movements. Contrary to frontal oculomotor areas, the role of the superior parietal lobe (SPL) in the executive control of saccades remains unknown. To explore the role of SPL networks in saccade control, we performed a saccadic search-step task while acquiring functional magnetic resonance imaging data for 41 participants. Psychophysiological interaction analyses assessed task-related differences in the effective connectivity of SPL with other brain regions during the inhibition and redirection of saccades. Results indicate an increased coupling of SPL with frontal, posterior, and striatal oculomotor areas for redirected saccades versus visually guided saccades. Saccade inhibition versus unsuccessful inhibition revealed an increased coupling of SPL with dorsolateral prefrontal cortex and anterior cingulate cortex. We discuss how these findings relate to ongoing debates about the implementation of executive control and conclude that early attentional control and rapid updating of saccade goals are important signals for executive control.

Highlights • Rapid control of planned gaze shift impaired in individuals with schizophrenia (SZ). • Current study aimed to investigate neural basis of these impairments. • SZ less efficient at inhibiting gaze shift, which was related to employment. • SZ showed altered activation in oculomotor control network during task performance. • Effective connectivity and its modulation by inhibitory demands altered in SZ., Rapid inhibition or modification of actions is a crucial cognitive ability, which is impaired in persons with schizophrenia (SZP). Primate neurophysiology studies have identified a network of brain regions that subserves control over gaze. Here, we examine effective connectivity within this oculomotor control network in SZP and healthy controls (HC). During fMRI, participants performed a stop-signal task variant in which they were instructed to saccade to a visual target (no-step trials) unless a second target appeared (redirect trials); on redirect trials, participants were instructed to inhibit the planned saccade and redirect to the new target. We compared functional responses on redirect trials to no-step trials and used dynamic causal modelling (DCM) to examine group differences in network effective connectivity. Behaviorally, SZP were less efficient at inhibiting, which was related to their employment status. Compared to HC, they showed a smaller difference in activity between redirect trials and no-step trials in frontal eye fields (FEF), supplementary eye fields (SEF), inferior frontal cortex (IFC), thalamus, and caudate. DCM analyses revealed widespread group differences in effective connectivity across the task, including different patterns of self-inhibition in many nodes in SZP. Group differences in how effective connectivity was modulated on redirect trials revealed differences between the FEF and SEF, between the SEF and IFC, between the superior colliculus and the thalamus, and self-inhibition within the FEF and caudate. These results provide insight into the neural mechanisms of inefficient inhibitory control in individuals with schizophrenia.

Impairments in cognitive control-the ability to exert control over thoughts and actions and respond flexibly to the environment-are well-documented in schizophrenia. However, the degree to which experimental task performance reflects true cognitive control impairments or more general alterations in effort, arousal and/or task preparedness is unclear. Pupillary responses can provide insight into these latter factors, as the pupil dilates with degree of cognitive effort and response preparation. In the current study, 16 medicated outpatients with schizophrenia (SZP) and 18 healthy controls performed a task that measures the ability to reactively inhibit and modify a planned action-the double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their eye movement plan. Applying a race model of performance, we have previously shown that SZP require more time to inhibit a planned action. In the current analysis, we measured pupil dilation associated with task preparation and found that SZP had a shallower increase in pupil size prior to the onset of the trial. Additionally, reduced magnitude of the pupil response was associated with negative symptom severity in patients. Based on primate neurophysiology and cognitive neuroscience work, we suggest that this blunted pupillary response may reflect abnormalities in a general orienting response or reduced motivational significance of a cue signifying the onset of a preparatory period and that these abnormalities might share an autonomic basis with negative symptoms.

The objective of the present study was to compare two components of executive functioning, response monitoring and inhibition, in bipolar disorder (BP) and schizophrenia (SZ). The saccadic countermanding task is a translational paradigm optimized for detecting subtle abnormalities in response monitoring and response inhibition. We have previously reported countermanding performance abnormalities in SZ, but the degree to which these impairments are shared by other psychotic disorders is unknown. 18 BP, 17 SZ, and 16 demographically matched healthy controls (HC) participated in a saccadic countermanding task. Performance on the countermanding task is approximated as a race between movement generation and inhibition processes; this model provides an estimate of the time needed to cancel a planned movement. Response monitoring was assessed by the reaction time (RT) adjustments based on trial history. Like SZ patients, BP patients needed more time to cancel a planned movement. The two patient groups had equivalent inhibition efficiency. On trial history-based RT adjustments, however, we found a trend towards exaggerated trial history-based slowing in SZ compared to BP. Findings have implications for understanding the neurobiology of cognitive control, for defining the etiological overlap between schizophrenia and bipolar disorder, and for developing pharmacological treatments of cognitive impairments.

Objectives Deficits in social cognition predict poor functional outcome in severe mental illnesses such as schizophrenia and autism. However, research findings on social cognition in bipolar disorder (BD) are sparse and inconsistent. This study aimed to characterize a critical social cognitive process-eye gaze perception-and examine its functional correlates in BD to inform psychopathological mechanisms. Methods Thirty participants with BD, 37 healthy controls (HC), and 46 psychiatric controls with schizophrenia (SZ) completed an eye-contact perception task. They viewed faces with varying gaze directions, head orientations, and emotion, and made eye-contact judgments. Psychophysics methods were used to estimate perception thresholds and the slope of the perception curve, which were then compared between the groups and correlated with clinical and functional measures using Bayesian inference. Results Compared with HC, patients with BD over-perceived eye contact when gaze direction was ambiguous, and this self-referential bias was similar to that in SZ. Patients with BD had lower thresholds (i.e., needed weaker eye-contact signal to start perceiving gaze as self-directed) but a similar slope compared with HC. Regression analyses showed that steeper slope predicted better socio-emotional functioning in HC and SZ, but not in BD. Conclusions The psychopathology of social dysfunction was fundamentally different between BD and SZ in this modest sample. Eye gaze perception in BD was characterized by a self-referential bias but preserved perceptual sensitivity, the latter of which distinguished BD from SZ. The relationship between gaze perception and broader socio-emotional functioning in SZ and HC was absent in BD.

Background The N -methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. Methods Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. Results Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia. Conclusions Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives.

Rapid and reactive control of movement is essential in a dynamic environment and is disrupted in several neuropsychiatric disorders. Nonhuman primate neurophysiology studies have made significant contributions to our understanding of how saccadic eye movements can be rapidly inhibited, changed, and monitored. These results highlight a frontostriatal network involved in gaze control and provide a strong basis for understanding how cognitive control of action is implemented in the human brain. The goal of the present study was to bridge human and nonhuman primate studies by investigating reactive control of eye movements during fMRI using a task that has been used in neurophysiology studies: the search-step task. This task requires a speeded response to a visual target (no-step trial). On a minority (40%) of trials, the target jumps to a new location and participants are instructed to inhibit the initially planned saccade and redirect gaze toward the new location (redirect trial). Compared with no-step trials, greater activation in a frontal oculomotor network, including frontal and supplementary eye fields (SEFs), and the striatum was observed during correctly executed redirect trials. Individual differences in stopping efficiency were related to striatal activation. Further, greater activation in SEF was in a region anterior to that activated during visually guided saccades and scaled positively with error magnitude, suggesting a prominent role in response monitoring. Combined, these data lend new evidence for a role of the striatum in reactive saccade control and further clarify the role of SEF in action inhibition and performance monitoring.

The Schizophrenia International Research Society held its first scientific conference in Venice, Italy, June 21 to 25th, 2008. A wide range of controversial topics were presented in overlapping and plenary oral sessions. These included new genetic studies, controversies about early detection of schizophrenia and the prodrome, treatment issues, clinical characteristics, cognition, neuropathology and neurophysiology, other etiological considerations, substance abuse co-morbidity, and animal models for investigating disease etiology and for use as targets in drug studies. Young investigators in the field were awarded travel grants to participate in the congress and one of their roles was to summarize the oral sessions and subsequent discussions. The reports that follow are the culmination of this work produced by 30 young investigators who attended the congress. It is hoped that these summaries will be useful synopses of what actually occurred at the congress for those who did not attend each session or were unable to be present. The abstracts of all presentations, as submitted by the authors a few months prior, were previously published as supplement 2 to volume 102/1-3, June 2008.

Background: A subjective sense of agency over actions is thought to arise from a match between the predicted and actual sensory consequences of a movement command. A failure to appropriately generate or utilize such predictions is argued to give rise to the agency disturbances that characterize psychosis. A likely mechanism of such predictions are corollary discharge (CD) signals—“copies” of motor signals that, rather than being sent to the muscles, are sent to sensory areas. The most robust behavioral paradigms for studying CD as well as the only neurophysiological evidence for CD signals in primates have come from the oculomotor system, making it an ideal translational framework in which to investigate CD and, in turn, the mechanisms of agency disturbances in psychosis.

Background Cognitive control deficits are pervasive in individuals with schizophrenia (SZ) and are reliable predictors of functional outcome, but the specificity of these deficits and their underlying neural mechanisms have not been fully elucidated. The objective of the present study was to determine the nature of response inhibition and response monitoring deficits in SZ and their relationship to symptoms and social and occupational functioning with a behavioral paradigm that provides a translational approach to investigating cognitive control. Methods Seventeen patients with SZ and 16 demographically matched healthy control subjects participated in a saccadic countermanding task. Performance on this task is approximated as a race between movement generation and inhibition processes; this race model provides an estimate of the time needed to cancel a planned movement. Response monitoring can be assessed by reaction time adjustments on the basis of trial history. Results Saccadic reaction time was normal, but patients required more time to inhibit a planned saccade. The latency of the inhibitory process was associated with the severity of negative symptoms and poorer occupational functioning. Both groups slowed down significantly after correctly cancelled and erroneously noncancelled stop signal trials, but patients slowed down more than control subjects after correctly inhibited saccades. Conclusions These results suggest that SZ is associated with a difficulty in inhibiting planned movements and an inflated response adjustment effect after inhibiting a saccade. Furthermore, behavioral results are consistent with potential abnormalities in frontal and supplementary eye fields in patients with SZ.

Working memory (WM) impairment is a core feature of schizophrenia (SZ), but the integrity of the various components of WM is unclear. After encoding, mental representations must be maintained in WM during the delay period. In addition to maintenance, manipulation of internal representation can occur in WM. It has been argued that manipulation of items in WM is more impaired than simple maintenance in SZ, but direct empirical data to support this claim have been mixed. Discrepant findings among studies might be explained by task parameters, specifically the degree to which the manipulation task places demands on encoding and maintenance processes. The present study set out to examine these components of WM in patients with SZ (n = 20) and demographically matched healthy controls (n = 19) using a spatial delayed response task (DRT) to measure maintenance processes and 2 mental rotation tasks (allocentric and egocentric) with no delay period or restriction on encoding time to measure manipulation processes. Consistent with previous findings, patients were impaired on the spatial DRT. However, patients performed equally well on the egocentric mental rotation task and were more accurate than controls on the allocentric mental rotation task as the required degree of rotation increased. These results indicated impaired maintenance and spared manipulation of representations in WM and suggest a pocket of cognitive function that might be enhanced in SZ.

Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research.

To perform well on any challenging task, it is necessary to evaluate your performance so that you can learn from errors. Recent theoretical and experimental work suggests that the neural sequellae of error commission in a dorsal anterior cingulate circuit index a type of contingency- or reinforcement-based learning, while activation in a rostral anterior cingulate circuit reflects appraisal of the affective or motivational significance of errors. Patients with schizophrenia show rigid, perseverative behaviour that is not optimally responsive to outcome. Findings of reduced anterior cingulate cortex (ACC) activity during error commission in schizophrenia suggest that difficulties in evaluating and modifying behaviour in response to errors may contribute to behavioural rigidity. Using event-related functional MRI and an antisaccade paradigm with concurrent monitoring of eye position, the present study examined error-related activation and its relation to task performance in the anatomic components of two ACC circuits that are theorized to make distinct contributions to error processing. Eighteen chronic-medicated schizophrenia patients and 15 healthy controls participated. Compared to controls, patients showed increased antisaccade error rates and decreased error-related activation in the reinforcement learning network--dorsal ACC, striatum and brainstem (possibly substantia nigra)--and also in the affective appraisal network--rostral ACC, insula and amygdala. These reductions remained when the effects of antipsychotic medication dose and error rate were statistically controlled. Activation in these networks was inversely related to error rate in both patient and control groups, but the slope of this relation was shallower in patients (i.e. across participants with schizophrenia, decrements in error rate were associated with smaller decrements in activation). This indicates that the blunted neural response to errors in schizophrenia was not simply a reflection of more frequent errors. Our findings demonstrate a blunted response to error commission that is associated with worse performance in two ACC circuits in schizophrenia. In the dACC circuit, the blunted response may reflect deficient modification of prepotent stimulus-response mappings in response to errors, and in the rACC network it may reflect diminished concern regarding behavioural outcomes. However, despite these deficits and in the absence of external feedback regarding errors, patients corrected their errors as frequently as controls suggesting intact error recognition and ability to institute corrective action. Impairments in evaluating and learning from errors in schizophrenia may contribute to behaviour that is rigid and perseverative rather than optimally guided by outcomes, and may compromise performance across a wide range of tasks.

Fast cancellation or switching of action plans is a critical cognitive function. Rapid signal transmission is key for quickly executing and inhibiting responses, and the structural integrity of connections between brain regions plays a crucial role in signal transmission speed. In this study, we used the search‐step task, which has been used in nonhuman primates to measure dynamic alteration of saccade plans, in combination with functional and diffusion‐weighted MRI. Functional MRI results were used to identify brain regions involved in the reactive control of gaze. Probabilistic tractography was used to identify white matter pathways connecting these structures, and the integrity of these connections, as indicated by fractional anisotropy (FA), was correlated with search‐step task performance. Average FA from tracts between the right frontal eye field (FEF) and both right supplementary eye field (SEF) and the dorsal striatum were associated with faster saccade execution. Average FA of connections between the dorsal striatum and both right SEF and right inferior frontal cortex (IFC) as well as between SEF and IFC predicted the speed of inhibition. These relationships were largely behaviorally specific, despite the correlation between saccade execution and inhibition. Average FA of connections between the IFC and both SEF and the dorsal striatum specifically predicted the speed of inhibition, and connections between the FEF and SEF specifically predicted the speed of execution. In addition, these relationships were anatomically specific; correlations were observed after controlling for global FA. These data suggest that networks supporting saccade initiation and inhibition are at least partly dissociable. Hum Brain Mapp 37:2811–2822, 2016. © 2016 Wiley Periodicals, Inc.

Disruptions in corollary discharge (CD), motor signals that send information to sensory areas and allow for prediction of sensory states, are argued to underlie the perceived loss of agency in schizophrenia. Behavioral and neurophysiological evidence for CD in primates comes largely from the saccadic double-step task, which requires participants to make two visually triggered saccadic eye movements in brief succession. Healthy individuals use CD to anticipate the change in eye position resulting from the first saccade when preparing the second saccade. In the current study with human participants, schizophrenia patients and healthy controls of both sexes performed a modified double-step task. Most trials required a saccade to a single visual target (T1). On a subset of trials, a second target (T2) was flashed shortly following T1. Subjects were instructed to look directly at T2. Healthy individuals also use CD to make rapid, corrective responses following erroneous saccades to T1. To assess CD in schizophrenia, we examined the following on error trials: (1) frequency and latency of corrective saccades, and (2) mislocalization of the corrective (second) saccade in the direction predicted by a failure to use CD to account for the first eye movement. Consistent with disrupted CD, patients made fewer and slower error corrections. Importantly, the corrective saccade vector angle was biased in a manner consistent with disrupted CD. These results provide novel and clear evidence for dysfunctional CD in the oculomotor system in patients with schizophrenia. Based on neurophysiology work, these disturbances might have their basis in medial thalamus dysfunction. SIGNIFICANCE STATEMENT According to the World Health Organization, acute schizophrenia carries more disability weight than any other disease, but its etiology remains unknown. One promising theory of schizophrenia highlights alterations in a sense of self, in which self-generated thoughts or actions are attributed externally. Disruptions in corollary discharge (CD), motor signals sent to sensory areas that allow for the prediction of impending sensations, are proposed to underlie these symptoms. Direct physiological evidence, however, is limited. In nonhuman primates, inactivation of mediodorsal thalamic neurons disrupts CD associated with eye movements. Using the same task, we show similar impairments in schizophrenia patients, consistent with disrupted CD. These findings allow us to link clinical phenomenology to primate neurophysiology and interpret findings within a biological framework.

The anterior cingulate cortex (ACC) participates in both performance optimization and evaluation, with dissociable contributions from dorsal (dACC) and rostral (rACC) regions. Deactivation in rACC and other default-mode regions is important for performance optimization, whereas increased rACC and dACC activation contributes to performance evaluation. Errors activate both rACC and dACC. We propose that this activation reflects differential error-related involvement of rACC and dACC during both performance optimization and evaluation, and that these two processes can be distinguished by the timing of their occurrence within a trial. We compared correct and error antisaccade trials. We expected errors to correlate with an early failure of rACC deactivation and increased activation of both rACC and dACC later in the trial. Eighteen healthy subjects performed a series of prosaccade and antisaccade trials during event-related functional MRI. We estimated the hemodynamic responses for error and correct antisaccades using a finite impulse-response model. We examined ACC activity by comparing error and correct antisaccades with a fixation baseline and error to correct antisaccades directly. Compared with correct antisaccades, errors were characterized by an early bilateral failure of deactivation of rACC and other default-mode regions. This difference was significant in rACC. Errors also were associated with increased activity in both rACC and dACC later in the trial. These results show that accurate performance involves deactivation of the rACC and other default mode regions and suggest that both rACC and dACC contribute to the evaluation of error responses.

Background: Cognitive control impairments are linked to functional outcome in schizophrenia. The goal of the current study was to investigate precise abnormalities in two aspects of cognitive control: reactively changing a prepared response, and monitoring performance and adjusting behavior accordingly. We adapted an oculomotor task from neurophysiological studies of the cellular basis of cognitive control in nonhuman primates. Methods: 16 medicated outpatients with schizophrenia (SZ) and 18 demographically-matched healthy controls performed the modified double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their response. A race model provided an estimate of the time needed to cancel a planned movement. Response monitoring was assessed by measuring reaction time (RT) adjustments based on trial history. Results: SZ patients had normal visually-guided saccadic RTs but required more time to switch the response to the new target location. Additionally, the estimated latency of inhibition was longer in patients and related to employment. Finally, although both groups slowed down on trials that required inhibiting and changing a response, patients showed exaggerated performance-based adjustments in RTs, which was correlated with positive symptom severity. Conclusions: SZ patients have impairments in rapidly inhibiting eye movements and show idiosyncratic response monitoring. These results are consistent with functional abnormalities in a network involving cortical oculomotor regions, the superior colliculus, and basal ganglia, as described in neurophysiological studies of non-human primates using an identical paradigm, and provide a translational bridge for understanding cognitive symptoms of SZ.