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Optimal working memory (WM), the mental ability to internally maintain and manipulate task-relevant information, requires coordinated activity of dorsal-lateral prefrontal cortical (DLPFC) neurons. More specifically, during delay periods of tasks with WM features, DLPFC microcircuits generate persistent, stimulus-specific higher-frequency (e.g., gamma) activity. This activity largely depends on recurrent connections between parvalbumin positive inhibitory interneurons and pyramidal neurons in more superficial DLPFC layers. Due to the size and organization of pyramidal neurons (especially apical dendrites), local field potentials generated by DLPFC microcircuits are strong enough to pass outside the skull and can be detected using electroencephalography (EEG). Since patients with schizophrenia (SCZ) exhibit both DLPFC and WM abnormalities, EEG markers of DLPFC microcircuit activity during WM may serve as effective biomarkers or treatment targets. In this review, we summarize converging evidence from primate and human studies for a critical role of DLPFC microcircuit activity during WM and in the pathophysiology of SCZ. We also present a meta-analysis of studies available in PubMed specifically comparing frontal gamma activity between participants with SCZ and healthy controls, to determine whether frontal gamma activity may be a valid biomarker or treatment target for patients with SCZ. We summarize the complex cognitive and neurophysiologic processes contributing to neural oscillations during tasks with WM features, and how such complexity has stalled the development of neurophysiologic biomarkers and treatment targets. Finally, we summarize promising results from early reports using neuromodulation to target DLPFC neural activity and improve cognitive function in participants with SCZ, including a study from our team demonstrating that gamma-EEG neurofeedback increases frontal gamma power and WM performance in participants with SCZ. From the evidence discussed in this review, we believe the emerging field of neuromodulation, which includes extrinsic (electrical or magnetic stimulation) and intrinsic (EEG neurofeedback) modalities, will, in the coming decade, provide promising treatment options targeting specific neurophysiologic properties of specific brain areas to improve cognitive and behavioral health for patients with SCZ., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.) more...

Patients with schizophrenia (SCZ) exhibit working memory (WM) deficits that are associated with deficient dorsal-lateral prefrontal cortical activity, including decreased frontal gamma power. We thus hypothesized that training SCZ patients to increase frontal gamma activity would improve their WM performance. We administered electroencephalographic (EEG) neurofeedback (NFB) to 31 participants with SCZ for 12 weeks (24 sessions), which provides real-time visual and auditory feedback related to frontal gamma activity. The EEG-NFB training significantly improved EEG markers of optimal working memory, e.g., frontal P3 amplitude and gamma power. Based on these promising results, we developed a novel, EEGLAB/MATLAB-based brain-computer interface (BCI) that delivers F3-F4 gamma coherence NFB with a dynamic threshold to SCZ patients randomized in a double-blind, placebo-controlled clinical trial. The BCI significantly increased F3-F4 gamma coherence after 12 weeks (24 sessions) of training, according to data from the first 12 subjects ( n=6 /group) who completed gamma- or placebo-NFB training. more...

Psychosocial interventions for serious mental illness are resource intensive and poorly accessible. Brief interventions (eg, single session) that are augmented by follow-on automated mobile health intervention may expand treatment access. This was a randomized single-blind controlled trial with 255 individuals diagnosed with schizophrenia or bipolar disorder. Participants were randomized to one of three conditions: CBT2go, which combined one individual session of cognitive behavioral therapy with automated thought challenging/adaptive behavior delivered through mobile devices; Self-Monitoring (SM), which combined single-session illness psychoeducation with self-monitoring of symptoms; and treatment-as-usual (TAU). Participants were assessed at baseline, 6 weeks (midpoint), 12 weeks (posttreatment), and 24 weeks (follow-up) with our primary outcome global psychopathology (Brief Psychiatric Rating Scale-expanded version [BPRS-24]), and secondary outcomes community functioning (Specific Level of Function; SLOF) and defeatist performance beliefs (DPBs). We also collected data on adverse events. Outcome analyses on the primary outcome, BPRS Total score, indicated a significant time (0-24 wk) by group interaction with significant but modest improvement comparing two active conditions (CBT2go and SM) relative to TAU. Effects of CBT2go were not different from SM. There was a significant time × group interaction with better SLOF scores in CBT2go across 24 weeks, but not in SM. There were no time-by-group effects on DPBs. DPBs decreased in the CBT2go condition but not in SM. These results indicated that single intervention augmented by mobile intervention was feasible and associated with small yet sustained effects on global psychopathology and, when inclusive of CBT, community function compared with usual care., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...

Neurocognitive and theory of mind deficits, dysfunctional attitudes, and negative symptoms have all been linked to poor functioning in schizophrenia, but interactions among these factors have not been extensively examined. We investigated whether dysfunctional attitudes (e.g., defeatist performance beliefs and social disinterest attitudes) moderated associations between neurocognition and theory of mind and poor everyday functioning and social competence in 146 participants with schizophrenia. We examined whether cognitive deficits are more likely to influence functioning in participants with more severe dysfunctional attitudes. Social disinterest, but not defeatist performance, attitudes were found to moderate associations between cognitive deficits and social competence but not everyday functioning, such that neurocognition and theory of mind deficits were only associated with poorer social competence in participants with more severe social disinterest attitudes. In contrast, no significant moderation effects were found for defeatist performance beliefs. Findings indicate that deficits in abilities were less likely to impact social competence in participants with greater interest in socializing. It may be that greater motivation for socializing engenders increased practice and engagement in social interactions, which then leads to greater social competence despite poor cognitive abilities. Treatments that target social disinterest attitudes may lead to greater social competence and engagement., (Copyright © 2018 Elsevier B.V. All rights reserved.) more...

Despite the increasing attention to social appraisals in suicide risk, the interpersonal correlates of suicidal thoughts and behavior in schizophrenia are not well understood. Ecological momentary assessment could reveal whether dysfunctional social appraisals and behavior are evident in people with schizophrenia with suicidal ideation. A total of 93 outpatients with diagnoses of schizophrenia with (n=18, 19%) and without (N=75; 81%) suicidal ideation participated in one week of intensive daily monitoring via mobile devices, generating real-time reports on the quantity of social interactions and appraisals about them, as well as information concerning concurrent affect and symptoms. The presence of suicidal ideation was not associated with the quantity of social interactions or time spent alone, but it was associated with the anticipation of being alone as well as greater negative and lower positive affect when alone. Despite this aversive experience of being alone, people with suicidal ideation reported negative appraisals about the value of recent and potential social interactions. These findings suggest that suicidal ideation in schizophrenia may not be associated with the quantity of social interactions, but with negative expectations about the quality of social interactions coupled with an aversive experience of being alone. Cognitive therapy interventions that address negative expectations and pleasure about social interactions, especially when alone, may reduce suicidal ideation., (Copyright © 2016. Published by Elsevier B.V.) more...

Problems in real-world functioning are pervasive in schizophrenia and much recent effort has been devoted to uncovering factors which contribute to poor functioning. The goal of this study was to examine the role of four such factors: social cognition (theory of mind), neurocognition, negative symptoms, and functional capacity (social competence). 178 individuals with schizophrenia or schizoaffective disorder completed measures of theory of mind, neurocognition, negative symptoms, social competence, and self-reported functioning. Path models sought to determine the relationships among these variables. Theory of mind as indexed by the Hinting Task partially mediated the relationship between neurocognition and social competence, and negative symptoms and social competence demonstrated significant direct paths with self-reported functioning. Study results suggest theory of mind serves as an important mediator in addition to previously investigated social cognitive domains of emotional and social perception. The current study also highlights the need to determine variables which mediate the relationship between functional capacity and real-world functioning., (Copyright © 2010 Elsevier B.V. All rights reserved.) more...