Search

There is a growing literature on brain activity in the nonpsychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients' relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients' relatives. The diversity of findings in studies of patients' relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged. [ABSTRACT FROM AUTHOR]

This commentary to the capstone paper by Keshavan and colleagues reflects on the history of this project and the challenging nature of curating and establishing facts. While a number of approaches exist, none of them in-and-of-themselves are without drawbacks. A combination of techniques may provide the most satisfying results. We emphasize the importance of determining what facts are specific to the disorder - a particularly challenging endeavor - and the usefulness of various ways of quantifying these facts. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex disorder that is diagnosed mainly with clinical observation and evaluation. Recent studies suggest that many people with schizophrenia have abnormalities in the function of the N-methyl-d-aspartate receptor (NMDAR). The retina is part of the central nervous system and expresses the NMDAR, raising the possibility of the early detection of NMDAR-related schizophrenia by detecting differences in retinal function. As a first-step, we used two non-invasive outpatient tests of retinal function, the photopic negative response (PhNR) of the light-adapted flash-electroretinogram (PhNR-fERG) and the pattern ERG (PERG), to test individuals with schizophrenia and controls to determine if there were measurable differences between the two populations. The PhNR-fERG showed that males with schizophrenia had a significant increase in the variability of the overall response, which was not seen in the females with schizophrenia. Additionally at the brightest flash strength, there were significant increases in the PhNR amplitude in people with schizophrenia that were maximal in controls. Our results show measurable dysfunction of retinal ganglion cells (RGCs) in schizophrenia using the PhNR-fERG, with a good deal of variability in the retinal responses of people with schizophrenia. The PhNR-fERG holds promise as a method to identify individuals more at risk for developing schizophrenia, and may help understand heterogeneity in etiology and response to treatment. [ABSTRACT FROM AUTHOR]

Abstract: Patients with schizophrenia frequently demonstrate hypofrontality in tasks that require executive processing; however questions still remain as to whether prefrontal cortex dysfunctions are specific to schizophrenia, or a general feature of major psychopathology. Context processing is conceptualized as an executive function associated with attention and working memory processes. Impairment in the ability of patients with schizophrenia to represent and maintain context information has been previously reported in a number of studies. To examine the question of the specificity of a context processing deficit to schizophrenia, we used functional MRI and an expectancy AX continuous performance task designed to assess context processing in a group of healthy controls (n =9), depressed patient controls (n =10), and patients with schizophrenia (n =7). The behavioral performance was consistent with a context processing deficit in patients with schizophrenia, but not those with depression. The imaging data replicate previous results in showing abnormal activity in the right middle frontal gyrus (BA9) in schizophrenia patients related to context processing. [Copyright &y& Elsevier]

Background: Executive dysfunction such as inattention or forgetfulness can lead to disruptions in a person's daily functioning and quality of life., Objective/hypothesis: This triple-blinded randomized clinical trial assessed the efficacy of bifrontal (over the forehead) transcranial direct current stimulation (tDCS) concurrent with cognitive training to improve cognitive performance in a healthy sample., Methods: Fifty-eight participants were randomly assigned to one of three stimulation conditions (2 mA left anode-right cathode, 2 mA right anode-left cathode, or sham), which was administered with cognitive training tasks 3x/week over 12 weeks with assessments at baseline, midpoint (6 weeks), and post-training (12 weeks). We assessed cognitive performance, functional connectivity, and the influence of individual differences in training advancement., Results: Forty participants completed training. We found that at midpoint and post, all groups improved significantly on overall cognitive performance. The left anode group's attention & vigilance score improved significantly at post, but the other two groups did not. Greater attention training advancement predicted attention improvement by post, most notably in the left anode group. Finally, within-network connectivity decreased in the control network and increased in the somatomotor network across all groups., Conclusions: These results suggest that, given cognitive training, the left anode montage is more effective at improving attention than the right anode montage and sham. Future research may focus on the application of the left anode montage during cognitive training to assess its effectiveness in improving cognition in neuropsychiatric disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lim is Chief Scientific Officer of and holds equity in Omnikog, which is developing platforms for delivering transcranial electrical stimulation. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies., (Copyright © 2024. Published by Elsevier Inc.)

Background: Major barriers to addressing SARS-CoV-2 vaccine hesitancy include limited knowledge of what causes delay/refusal of SARS-CoV-2 vaccination and limited ability to predict who will remain unvaccinated over significant time periods despite vaccine availability. The present study begins to address these barriers by developing a machine learning model that prospectively predicts who will persist in not vaccinating against SARS-CoV-2., Method: Unvaccinated individuals (n = 325) who completed a baseline survey were followed over the six-month period when vaccines against SARS-CoV-2 were first widely available (April-October 2021). A random forest model was used to predict who would remain unvaccinated against SARS-CoV-2 from their baseline measures, including demographic information (e.g., age), medical history (e.g., of influenza vaccination), Health-Belief Model constructs (e.g., perceived vaccine dangerousness), conspiracist ideation, and task-based metrics of vulnerability to conspiracist ideation (e.g., tendency toward illusory pattern perception)., Results: The resulting model significantly predicted vaccination status (AUC-PR = 0.77, 95%CI [0.56 0.90]). At the optimal probability threshold determined by the Generalized Threshold Shifting Protocol, the model was moderately precise (0.83) when identifying individuals who remained unvaccinated (n = 80), and had a very low rate (0.04) of false-positives (incorrectly suggesting that individuals remained unvaccinated). Permutational importance tests suggested that baseline SARS-CoV-2 vaccine intentions conveyed the most information about future SARS-CoV-2 vaccination status. Conspiracist ideation was the second most informative predictor, suggesting that misinformation influences vaccination behavior. Other important predictors included perceived vaccine dangerousness, as expected under the Health Belief Model, and influenza vaccination history., Conclusions: The model we developed can accurately and prospectively identify individuals who remain unvaccinated against SARS-CoV-2. It could therefore facilitate empirically-informed allocation of interventions that encourage vaccine uptake. The predictive value of conspiracist ideation, perceived vaccine dangerousness, and vaccine intentions in our model is consistent with potential causal relations between these variables and SARS-CoV-2 vaccine uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

BACKGR1OUND: Widespread vaccine hesitancy and refusal complicate containment of the SARS-CoV-2 pandemic. Extant research indicates that biased reasoning and conspiracist ideation discourage vaccination. However, causal pathways from these constructs to vaccine hesitancy and refusal remain underspecified, impeding efforts to intervene and increase vaccine uptake., Method: 554 participants who denied prior SARS-CoV-2 vaccination completed self-report measures of SARS-CoV-2 vaccine intentions, conspiracist ideation, and constructs from the Health Belief Model of medical decision-making (such as perceived vaccine dangerousness) along with tasks measuring reasoning biases (such as those concerning data gathering behavior). Cutting-edge machine learning algorithms (Greedy Fast Causal Inference) and psychometric network analysis were used to elucidate causal pathways to (and from) vaccine intentions., Results: Results indicated that a bias toward reduced data gathering during reasoning may cause paranoia, increasing the perceived dangerousness of vaccines and thereby reducing willingness to vaccinate. Existing interventions that target data gathering and paranoia therefore hold promise for encouraging vaccination. Additionally, reduced willingness to vaccinate was identified as a likely cause of belief in conspiracy theories, subverting the common assumption that the opposite causal relation exists. Finally, perceived severity of SARS-CoV-2 infection and perceived vaccine dangerousness (but not effectiveness) were potential direct causes of willingness to vaccinate, providing partial support for the Health Belief Model's applicability to SARS-CoV-2 vaccine decisions., Conclusions: These insights significantly advance our understanding of the underpinnings of vaccine intentions and should scaffold efforts to prepare more effective interventions on hesitancy for deployment during future pandemics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A number of studies have found that hypersexuality is associated with a high propensity for sexual excitation. In comparison, less is known about the relationship between hypersexuality and sexual arousal at the state level. Also, previous research has revealed a relationship between hypersexuality and negative mood. However, the possibility that sexual response might not be as negatively impacted by negative mood in hypersexual individuals has, as yet, not been tested., Aim: The purpose of this study was to investigate sexual responsivity and the effects of negative mood on sexual arousal in hypersexual men who have sex with men (MSM)., Methods: A total of 211 MSM were assigned to a hypersexuality (N = 81) or a control (N = 130) group using an interview patterned with a semi-structured Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders format. Participants filled out questionnaires and were shown neutral, sexual, and anxiety- and sadness-inducing films., Outcomes: Changes in penile circumference and self-reported sexual arousal were the primary outcomes analyzed in this study., Results: Controlling for age and HIV status, no differences were found in genital response between hypersexual and non-hypersexual men. Also, the 2 groups did not differ in subjective sexual arousal. Moreover, no effects of negative mood were found. Time series clustering analyses revealed 3 groups-low responders and slow and fast high responders. Sexual excitation, but not sexual compulsivity or pornography use, predicted cluster membership., Clinical Translation: Hypersexual MSM may benefit more from an exploration of motivational and behavioral, as compared to psychophysiological, mechanisms underlying possible links between (negative) mood and sexual behavior., Strengths & Limitations: Strengths of the study include its sample size, making it one of the larger psychophysiological sex studies; the use of clinical interviews for group assignment; the inclusion of genital response measures; and the application of time series clustering to examine differences among participants. Limitations include possible sample heterogeneity and the reliance on researcher-selected stimuli., Conclusion: Given the lack of any effects of negative mood on sexual response in hypersexual MSM, future studies could explore in more depth possible motivational and behavioral effects, including, for example, the impact of negative mood on the tendency to seek out sex as a form of distraction or for validation or emotional support. Janssen E, Prause N, Romine RS, et al. Sexual Responsivity and the Effects of Negative Mood on Sexual Arousal in Hypersexual Men Who Have Sex With Men (MSM). J Sex Med 2020;17:1751-1760., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Although item response models have grown in popularity in many areas of educational and psychological assessment, there are relatively few applications of these models in experimental psychopathology. In this article, we explore the use of item response models in the context of a computerized cognitive task designed to assess visual working memory capacity in people with psychosis as well as healthy adults. We begin our discussion by describing how item response theory can be used to evaluate and improve unidimensional cognitive assessment tasks in various examinee populations. We then suggest how computerized adaptive testing can be used to improve the efficiency of cognitive task administration. Finally, we explore how these ideas might be extended to multidimensional item response models that better represent the complex response processes underlying task performance in psychopathological populations., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

The change detection task is a common method for assessing the storage capacity of working memory, but estimates of memory capacity from this task can be distorted by lapses of attention. When combined with appropriate mathematical models, some versions of the change detection task make it possible to separately estimate working memory and the probability of attentional lapses. In principle, these models should allow researchers to isolate the effects of experimental manipulations, group differences, and individual differences on working memory capacity and on the rate of attentional lapses. However, the present research found that two variants of a widely accepted model of the change detection task are not mathematically identified.

Introduction: Hypersexuality has been conceptualized as sexual addiction, compulsivity, and impulsivity, among others, in the absence of strong empirical data in support of any specific conceptualization., Aim: To investigate personality factors and behavioral mechanisms that are relevant to hypersexuality in men who have sex with men., Methods: A sample of 242 men who have sex with men was recruited from various sites in a moderate-size mid-western city. Participants were assigned to a hypersexuality group or a control group using an interview similar to the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Self-report inventories were administered that measured the broad personality constructs of positive emotionality, negative emotionality, and constraint and more narrow constructs related to sexual behavioral control, behavioral activation, behavioral inhibition, sexual excitation, sexual inhibition, impulsivity, attention-deficit/hyperactivity disorder, and sexual behavior., Main Outcome Measures: Hierarchical logistic regression was used to determine the relation between these personality and behavioral variables and group membership., Results: A hierarchical logistic regression controlling for age showed a significant positive relation between hypersexuality and negative emotionality and a negative relation with constraint. None of the behavioral mechanism variables entered this equation. However, a hierarchical multiple regression analysis predicting sexual behavioral control indicated that lack of such control was positively related to sexual excitation and sexual inhibition owing to the threat of performance failure and negatively related to sexual inhibition owing to the threat of performance consequences and general behavioral inhibition, Conclusion: Hypersexuality was found to be related to two broad personality factors that are characterized by emotional reactivity, risk taking, and impulsivity. The associated lack of sexual behavior control is influenced by sexual excitatory and inhibitory mechanisms, but not by general behavioral activation and inhibitory mechanisms., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Visual perceptual organization impairments in schizophrenia (SCZ) are well established, but their neurobiological bases are not. The current study used the previously validated Jittered Orientation Visual Integration (JOVI) task, along with fMRI, to examine the neural basis of contour integration (CI), and its impairment in SCZ. CI is an aspect of perceptual organization in which multiple distinct oriented elements are grouped into a single continuous boundary or shape., Methods: On the JOVI, five levels of orientational jitter were added to non-contiguous closed contour elements embedded in background noise to progressively increase the difficulty in perceiving contour elements as left- or right-pointing ovals. Multi-site fMRI data were analyzed for 56 healthy control subjects and 47 people with SCZ., Results: SCZ patients demonstrated poorer CI, and this was associated with increased activation in regions involved in global shape processing and visual attention, namely the lateral occipital complex and superior parietal lobules. There were no brain regions where controls demonstrated more activation than patients., Conclusions: CI impairment in this sample of outpatients with SCZ was related to excessive activation in regions associated with object processing and allocation of visual-spatial attention. There was no evidence for basic impairments in contour element linking in the fMRI data. The latter may be limited to poor outcome patients, where more extensive structural and functional changes in the occipital lobe have been observed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this manuscript, we present connectivity cluster analysis (CoCA), a novel computational framework that takes advantage of structure of the brain networks to magnify reproducible signals and quash noise. Resting state functional Magnetic Resonance Imaging (fMRI) data that is used in estimating functional brain networks is often noisy, leading to reduced power and inconsistent findings across independent studies. There is a need for techniques that can unearth signals in noisy datasets, while addressing redundancy in the functional connections that are used for testing association. CoCA is a data driven approach that addresses the problems of redundancy and noise by first finding groups of region pairs that behave in a cohesive way across the subjects. These cohesive sets of functional connections are further tested for association with the disease. CoCA is applied in the context of patients with schizophrenia, a disorder characterized as a disconnectivity syndrome. Our results suggest that CoCA can find reproducible sets of functional connections that behave cohesively. Applying this technique, we found that the connectivity clusters joining thalamus to parietal, temporal, and visuoparietal regions are highly discriminative of schizophrenia patients as well as reproducible using retest data and replicable in an independent confirmatory sample., (© 2014 Wiley Periodicals, Inc.)

Neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics.

The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative highlighted a contour integration test as a promising index of visual integration impairment because of its well-established psychometric properties; its prior validation in healthy adults, patients, and nonhuman primates; and its potential sensitivity to treatment effects. In this multisite study, our goals were to validate the task on the largest subject sample to date, clarify the task conditions and number of trials that best discriminate patients from controls, and determine whether this discrimination can occur in standard clinical trial settings. For our task, subjects briefly observed a field of disconnected, oriented elements and attempted to decide whether a subset of those elements formed a leftward- or rightward-pointing shape. Difficulty depended on the amount of orientational jitter that was added to the shape's elements. Two versions of this Jittered Orientation Visual Integration task (JOVI) were examined. Study 1 did not reveal between-group differences in threshold (ie, the jitter magnitude needed to reach a performance level of ∼80%), but this likely owed to the wide sampling distribution of jitter levels and resulting floor/ceiling effects in many conditions. Study 2 incorporated a narrower range of difficulty levels and revealed lower thresholds (worse performance) among patients (p < .001). This group difference remained even when only the first half of the trials was analyzed (p = .001). Thus, the JOVI-2 provides a brief, sensitive measure of visual integration deficits in schizophrenia. Neural implications and potential future applications of the JOVI are discussed.

In this article, we describe results of the 5th Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia meeting which identified candidate imaging biomarkers for used in measuring neural activity associated with specific component processes of cognition that are targeted for treatment development in schizophrenia and other disorders. This manuscript describes the process by which measures related to executive control were selected, along with the specific measures recommended for further development. Two paradigms were recommended for measurement of the cognitive and neural mechanisms underlying 2 core component processes of executive control, rule generation and selection, and dynamic adjustments of Control. The 2 paradigms are the AX continuous performance task task (letter and dot forms), implemented as an functional magnetic resonance imaging (fMRI) paradigm to engage neural systems supporting rule generation and selection, and the switching Stroop task, implemented as either fMRI or electroencephalography that may be used as a measure of both rule generation and selection as well as dynamic adjustment in control. A detailed description of each paradigm, together with a review of the relevant literature related to their cognitive and neural validity and measurement properties is provided. These 2 paradigms are recommended for further development, including further validation at the cognitive and neural level and optimization with respect to subject tolerability, psychometric, and neurometric features.

The goal of the current project was to further develop a measure of gain control--the Contrast-Contrast Effect (CCE)--for use in clinical studies of schizophrenia. The CCE is based on an illusion in which presenting a medium contrast patch surrounded by a high-contrast patch induces individuals to perceive that center patch as having lower contrast than when the patch is presented in isolation. Thus, in the CCE, impaired gain control should lead to more accurate perceptions of the center patch. We tested 132 individuals with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder and 130 demographically similar healthy controls. The results indicated that the CCE effect can be obtained with standard equipment, simplified scoring, and a short interstimulus interval (100 ms), revealing a robust suppression of perceived contrast of the center patch when surrounded by a high-contrast annulus. Furthermore, we found a significant reduction in the effect of the high-contrast surround among individuals with schizophrenia, though the effect size was smaller than original reported by Dakin. However, when we eliminated subjects who performed poorly on "catch" trials that controlled for off-task performance, the reduced surround effect among patients was no longer significant in the main analyses. Importantly, this suggests that at least part of the reduced surround effect (if not all) in schizophrenia could be attributable to impaired attentional mechanisms that contribute to off-task performance. Additional analyses suggested that the length of the task could be shortened without losing power to detect surround effects in healthy individuals.

Cognitive training is increasingly used in the treatment of schizophrenia, but it remains unknown how this training affects functional neuroanatomy. Practice on specific cognitive tasks generally leads to automaticity and decreased prefrontal cortical activity, yet broad-based cognitive training programs may avoid automaticity and increase prefrontal cortex (PFC) activity. This study used quasi-randomized, placebo-control design and pre/post neuroimaging to examine functional plasticity associated with attention and working memory-focused cognitive training in patients with schizophrenia. Twenty-one participants with schizophrenia or schizoaffective disorder split into two demographically and performance matched groups (nine scanned per group) and nine control participants were tested 6-8 weeks apart. Compared with both patient controls and healthy controls, patients receiving cognitive training increased activation significantly more in attention and working memory networks, including dorsolateral prefrontal cortex, anterior cingulate and frontopolar cortex. The extent to which activity increased in a subset of these regions predicted performance improvements. Although this study was not designed to speak to the efficacy of cognitive training as a treatment, it is the first study to show that such training can increase the ability of patients to activate the PFC regions subserving attention and working memory.

The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) was focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of working memory, the 2 constructs of interest were goal maintenance and interference control. CNTRICS received 3 task nominations for each of these constructs, and the breakout group for working memory evaluated the degree to which each of these tasks met prespecified criteria. For goal maintenance, the breakout group for working memory recommended the AX-Continuous Performance Task/Dot Pattern Expectancy task for translation for use in clinical trial contexts in schizophrenia research. For interference control, the breakout group recommended the recent probes and operation/symmetry span tasks for translation for use in clinical trials. This article describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development.

Objective: The dorsolateral prefrontal cortex and the anterior cingulate cortex are critical components of the brain circuitry underlying executive control. The objective of this study was to investigate control-related dorsolateral prefrontal cortex functioning and conflict-related anterior cingulate cortex functioning in a group of never medicated first-episode schizophrenia patients to determine whether both regions show dysfunction at illness onset. A second objective was to assess short-term effects of atypical antipsychotic medication on dorsolateral prefrontal cortex and anterior cingulate cortex functioning., Method: First-episode schizophrenia patients (N=23) and healthy comparison subjects (N=24) underwent event-related fMRI and performed a cognitive task designed to functionally dissociate the two regions. Four weeks after initiation of pharmacotherapy for patients, a subset of 11 patients and 16 comparison subjects underwent a repeat assessment., Results: At baseline, patients exhibited hypoactivation in the dorsolateral prefrontal cortex and anterior cingulate cortex. After 4 weeks of antipsychotic treatment, the patients demonstrated improved functioning in the anterior cingulate cortex but not in the dorsolateral prefrontal cortex., Conclusions: These findings confirm the presence of dorsolateral prefrontal cortex dysfunction early in the course of schizophrenia and suggest that anterior cingulate cortex functioning may be altered at illness onset as well. Results also suggest that anterior cingulate cortex functioning may be especially sensitive to remedial antipsychotic treatment effects. These findings are consistent with an emerging literature documenting short-term benefits of atypical antipsychotic medication for the neural circuitry underlying cognitive deficits in schizophrenia.

Background: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing., Methods: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test., Results: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands., Conclusions: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.