Schizophrenia (SCZ) is a neurodevelopmental disorder characterized by positive symptoms (hallucinations and delusions), negative symptoms (anhedonia, social withdrawal) and marked cognitive deficits (memory, executive function, and attention). Current mainstays of treatment, including medications and psychotherapy, do not adequately address cognitive symptoms, which are essential for everyday functioning. However, recent advances in computational neurobiology have rekindled interest in neurofeedback (NF), a form of self-regulation or neuromodulation, in potentially alleviating cognitive symptoms in patients with SCZ. Therefore, we conducted a systematic review of the literature for NF studies in SCZ to identify lessons learned and to identify steps to move the field forward. Our findings reveal that NF studies to date consist mostly of case studies and small sample, single-group studies. Despite few randomized clinical trials, the results suggest that NF is feasible and that it leads to measurable changes in brain function. These findings indicate early proof-of-concept data that needs to be followed up by larger, randomized clinical trials, testing the efficacy of NF compared to well thought out placebos. We hope that such an undertaking by the field will lead to innovative solutions that address refractory symptoms and improve everyday functioning in patients with SCZ.

The aging population of the world is increasing at an unprecedented rate which is expected to lead to a corresponding unparalleled increase in age related diseases. Of particular concern are the large number of older adults expected to develop Alzheimers disease (AD), which will require extraordinary local, national and worldwide healthcare resources. In this context, innovative interventions are needed urgently to delay AD onset and thereby give our healthcare systems time to prepare and provide meaningful care to our aging populations. This focused review discusses the crucial role of frontal gamma oscillations as a therapeutic target to delay or ameliorate cognitive decline in AD. Frontal gamma oscillations, including from prefrontal cortical areas, serve as a biomarker for working memory and other cognitive functions, and their impairment is observed before clinical symptoms manifest. This review evaluates evidence from animal models and human subjects to highlight the correlation between gamma wave abnormalities and cognitive deterioration. Furthermore, the review summarizes 11 clinical studies using neuromodulation techniques designed to stimulate gamma oscillations in mild cognitive impairment (MCI) and AD patients, including transcranial electrical stimulation, transcranial magnetic stimulation, and rhythmic sensory stimulation. These interventions have shown promise in mitigating early-stage cognitive decline, as evidenced by improved performance on memory tests, increased gamma oscillatory responses, and some have even shown reduced brain atrophy. These early studies suggest that treatments that strengthen frontal gamma oscillatory responses through neuromodulation are a promising approach to delay cognitive decline, that may serve as an adjunct to other therapies or as a standalone treatment in some populations.

Schizophrenia (SCZ) is a neurodevelopmental disorder characterized by positive symptoms (hallucinations and delusions), negative symptoms (anhedonia, social withdrawal) and marked cognitive deficits (memory, executive function, and attention). Current mainstays of treatment, including medications and psychotherapy, do not adequately address cognitive symptoms, which are essential for everyday functioning. However, recent advances in computational neurobiology have rekindled interest in neurofeedback (NF), a form of self-regulation or neuromodulation, in potentially alleviating cognitive symptoms in patients with SCZ. Therefore, we conducted a systematic review of the literature for NF studies in SCZ to identify lessons learned and to identify steps to move the field forward. Our findings reveal that NF studies to date consist mostly of case studies and small sample, single-group studies. Despite few randomized clinical trials, the results suggest that NF is feasible and that it leads to measurable changes in brain function. These findings indicate early proof-of-concept data that needs to be followed up by larger, randomized clinical trials, testing the efficacy of NF compared to well thought out placebos. We hope that such an undertaking by the field will lead to innovative solutions that address refractory symptoms and improve everyday functioning in patients with SCZ.

Schizophrenia is a debilitating mental disorder that is associated with cognitive deficits. Impairments in cognition occur early in the course of illness and are associated with poor functional outcome, but have been difficult to treat with conventional treatments. Recent studies have implicated abnormal neural network dynamics and impaired connectivity in frontal brain regions as possible causes of cognitive deficits. For example, high-frequency, dorsal-lateral prefrontal oscillatory activity in the gamma range (30-50 Hz) is associated with impaired working memory in individuals with schizophrenia.In light of these findings, it may be possible to use EEG neurofeedback (EEG-NFB) to train individuals with schizophrenia to enhance frontal gamma activity to improve working memory and cognition. In a single-group, proof-of-concept study, 31 individuals with schizophrenia received 12 weeks of twice weekly EEG-NFB to enhance frontal gamma band response. EEG-NFB was well-tolerated, associated with increased gamma training threshold, and significant increases in frontal gamma power during an n-back working memory task. Additionally, EEG-NFB was associated with significant improvements in n-back performance and working memory, speed of processing, and reasoning and problem solving on neuropsychological tests. Change in gamma power was associated with change in cognition. Significant improvements in psychiatric symptoms were also found. These encouraging findings suggest EEG-NFB targeting frontal gamma activity may provide a novel effective approach to cognitive remediation in schizophrenia, although placebo-controlled trials are needed to assess the effects of non-treatment related factors.

Post-Traumatic Stress Disorder (PTSD) is not solely a psychiatric disorder; it also includes significant medical morbidity. Although there is evidence of increased risk of metabolic syndrome (MetS) in PTSD, the interpretation of previous studies is confounded by inclusion of people on antipsychotic medications, which independently cause increased MetS. In this study we investigated whether Veterans with PTSD not treated with antipsychotic medications (n=115) demonstrate increased MetS compared to an age-comparable group of people from the U.S. National Health and Nutrition Examination Survey (NHNES; n=1005). Using standardized criteria (abnormal values in 3 out of the 5 domains of obesity, hypertension, high density lipoprotein, triglyceride and fasting glucose concentrations) we compared the prevalence of MetS across groups. Relative to the NHNES group, a significantly higher proportion of the Veteran PTSD group met criteria for MetS (26.9% vs. 41.7%) with a higher proportion of abnormal values in four out of five MetS domains (excepting glucose). Our results suggest that the elevation of MetS associated with PTSD cannot be fully explained by iatrogenic effects of antipsychotic medication. We suggest that extra attention be devoted to the clinical management of metabolic risk factors for morbidity in patients with PTSD.