There is growing recognition that neural oscillations are important in a wide range of perceptual and cognitive functions. One of the key issues in electrophysiological studies of schizophrenia is whether high or low frequency oscillations, or both, are related to schizophrenia because many brain functions are modulated with frequency specificities. Many recent electrophysiological studies of schizophrenia have focused on high frequency oscillations at gamma band and in general support gamma band dysfunction in schizophrenia. We discuss the concept that gamma oscillation abnormalities in schizophrenia often occur in the background of oscillation abnormalities of lower frequencies. The review discusses the basic neurobiology for the emergence of oscillations of all frequency bands in association with networks of inhibitory interneurons and the convergence and divergence of such mechanisms in generating high vs low frequency oscillations. We then review the literature of oscillatory frequency abnormalities identified in each frequency band in schizophrenia. By describing some of the key functional roles exerted by gamma, low frequencies, and their cross-frequency coupling, we conceptualize that even isolated alterations in gamma or low frequency oscillations may impact the interactions of high and low frequency bands that are involved in key cognitive functions. The review concludes that studying the full spectrum and the interaction of gamma and low frequency oscillations may be critical for deciphering the complex electrophysiological abnormalities observed in schizophrenia patients.Key words: oscillation/schizophrenia/gamma/theta Overview Neural oscillations are electrical activities of the brain measurable at different frequencies. They are typically described as low frequency bands at delta (<4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) to high frequencies at gamma band that spans from roughly gamma (30-80 Hz) to high gamma (>80 Hz). These oscillatory activities can be obtained at many levels, ranging from single cell to local field potentials in animals, to large-scale synchronized activities in human scalp. Patients with schizophrenia exhibit impaired neural oscillatory activities during sensory and cognitive tasks. One of the oldest but also reemerging debates in electrophysiology is what is the key frequency relevant to the pathophysiology of schizophrenia, given that abnormalities of neural oscillations are found essentially in all frequency bands in schizophrenia patients. Research into the specificity of frequency abnormality, if found, could provide key biological markers linking disease mechanism to the clinical dysfunctions in schizophrenia.Many known brain functions are associated with electrical activities at specific frequencies. Recent event-related potential (ERP) studies of schizophrenia have focused on gamma band because of its critical role in cognitive functions 1 and in general support gamma band reduction in schizophrenia. 2,3 In comparison, earlier electroencephalographic ...

Background Systems level modeling of fMRI data has demonstrated dysfunction of several large-scale brain networks in schizophrenia. Anomalies across multiple functional networks associated with schizophrenia could be due to diffuse pathology across multiple networks or alternatively, dysfunction at a converging control(s) common to these networks. The right anterior insula has been shown to modulate activity in the central executive and default mode networks in healthy individuals. We tested the hypothesis that right anterior insula modulation of central executive and default mode networks is disrupted in schizophrenia and is associated with cognitive deficits. Methods In 44 patients with schizophrenia and 44 healthy controls, we used seed-based resting state functional connectivity fMRI analysis to examine connectivity between right insular subregions and central executive/default mode network regions. We also performed two directed connectivity analyses of resting state data: Granger analysis and confirmatory structural equation modeling. Between-group differences in path coefficients were used to evaluate anterior insula modulation of central executive and default mode networks. Cognitive performance was assessed using the rapid visual information processing task, a test of sustained attention. Results Using multiple connectivity techniques, we found compelling, corroborative evidence of disruption of right anterior insula modulation of central executive and default mode networks in patients with schizophrenia. The strength of right anterior insula modulation of these networks predicted cognitive performance. Conclusions Individuals with schizophrenia have impaired right anterior insula modulation of large-scale brain networks. The right anterior insula may be an emergent pathophysiological gateway in schizophrenia.

BACKGROUND The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit–hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.)