***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives . Abnormalities of oscillatory gamma activity are supposed to reflect a core pathophysiological mechanism underlying cognitive disturbances in schizophrenia . The auditory evoked gamma-b and response ( aeGBR ) is known to be reduced across all stages of the disease . The present study aim ed to eluci date alterations of an aeGBR-specific network mediated by gamma oscillations in the high-risk state of psychosis ( HRP ) by means of functional magnetic resonance imaging ( fMRI ) informed by electroencephalography ( EEG ) . Methods . EEG and fMRI were simultaneously recorded from 27 HRP individuals and 26 healthy controls ( HC ) during performance of a cognitively dem and ing auditory reaction task . We used single trial coupling of the aeGBR with the corresponding blood oxygen level depending response ( EEG-informed fMRI ) . Results . A gamma-b and –specific network was significantly lower active in HRP subjects compared with HC ( r and om effects analysis , P < .01 , Bonferroni-corrected for multiple comparisons ) accompanied by a worse task performance . This network involved the bilateral auditory cortices , the thalamus and frontal brain regions including the anterior cingulate cortex , as well as the bilateral dorsolateral prefrontal cortex . Conclusions . For the first time we report a reduced activation of an aeGBR-specific network in HRP subjects brought forward by EEG-informed fMRI . Because the HRP reflects the clinical risk for conversion to psychotic disorders including schizophrenia and the aeGBR has repeatedly been shown to be altered in patients with schizophrenia the results of our study point towards a potential applicability of aeGBR disturbances as a marker for the prediction of transition of HRP subjects to schizophrenia Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems The North American Prodrome Longitudinal Study ( NAPLS ) is a consortium of eight programs focusing on the psychosis prodrome . Funded by the National Institute of Mental Health ( NIMH ) , the sites are located at Emory University , Harvard University , University of Calgary , UCLA , UCSD , University of North Carolina Chapel Hill , Yale University , and Zucker Hillside Hospital . Although the programs initially developed independently , they previously collaborated to combine their historical data sets and to produce a series of analyses on predictors of psychosis in one of the largest sample s of longitudinally followed prodromal subjects worldwide . This led to the development of a five year prospect i ve study " Predictors and Mechanisms of Conversion to Psychosis " , ( also known as NAPLS-2 ) with three major aims : ( 1 ) to prospect ively test the prediction algorithm developed in NAPLS-1 , ( 2 ) to investigate the neuroanatomical , neurophysiological , neurocognitive , and neurohormonal factors that may contribute to the development of psychosis , and ( 3 ) to develop a repository of DNA , RNA , and plasma from participants meeting diagnostic criteria for a clinical high risk ( CHR ) state and from demographically similar healthy subjects . Funded by NIMH in 2008 , NAPLS-2 will generate the largest CHR for psychosis sample with 720 CHR and 240 healthy comparison subjects , and thus will provide statistical power and scientific scope that can not be duplicated by any single site study . This paper describes the overall methodology of the NAPLS-2 project and reports on the ascertainment and demographics at the midway point of the study with ( 360 CHR ) and 180 controls BACKGROUND Disturbed functional connectivity is assumed to underlie neurocognitive deficits in patients with schizophrenia . As neurocognitive deficits are already present in the high-risk state , identification of the neural networks involved in this core feature of schizophrenia is essential to our underst and ing of the disorder . Resting-state studies enable such investigations , while at the same time avoiding the known confounder of impaired task performance in patients . The aim of the present study was to investigate EEG resting-state connectivity in high-risk individuals ( HR ) compared to first episode patients with schizophrenia ( SZ ) and to healthy controls ( HC ) , and its association with cognitive deficits . METHODS 64-channel resting-state EEG recordings ( eyes closed ) were obtained for 28 HR , 19 stable SZ , and 23 HC , matched for age , education , and parental education . The imaginary coherence-based multivariate interaction measure ( MIM ) was used as a measure of connectivity across 80 cortical regions and six frequency b and s. Mean connectivity at each region was compared across groups using the non-parametric r and omization approach . Additionally , the network-based statistic was applied to identify affected networks in patients . RESULTS SZ displayed increased theta-b and resting-state MIM connectivity across midline , sensorimotor , orbitofrontal regions and the left temporoparietal junction . HR displayed intermediate theta-b and connectivity patterns that did not differ from either SZ or HC . Mean theta-b and connectivity within the above network partially mediated verbal memory deficits in SZ and HR . CONCLUSIONS Aberrant theta-b and connectivity may represent a trait characteristic of schizophrenia associated with neurocognitive deficits . As such , it might constitute a promising target for novel treatment applications BACKGROUND Schizophrenia has long been suggested to represent a disorder with prominent neural dysconnectivity . Gamma-b and oscillations are highly relevant in this context , due both to their proposed involvement in neuronal synchronization and to their association with neurotransmitter systems relevant for schizophrenia . Several task-related studies have confirmed reduced power and synchronization of gamma-b and oscillations in schizophrenia , but it has been suggested that these findings might not apply to the resting state . The present study aim ed to investigate resting-state gamma-b and connectivity in patients with schizophrenia . METHODS Sixty-four channel resting-state electroencephalography ( eyes closed ) was recorded in 22 patients with first-episode schizophrenia and 22 healthy controls matched for age and gender . Orthogonalized power envelope correlation was used as a measure of connectivity across 80 cortical regions at 40 Hz . Mean connectivity at each region was compared across groups using the nonparametric r and omization approach . Additionally , the network-based statistic was applied to identify affected networks in patients . RESULTS Patients displayed increased mean functional gamma-b and connectivity compared to controls in the left rol and ic operculum . Network-based analyses indicated increased connectivity in patients within a strongly lateralized network consisting mainly of left inferior frontal/orbitofrontal , lateral and medial temporal , and inferior parietal areas . Within this network , gamma-b and connectivity was higher in patients with low positive and disorganization symptom levels . CONCLUSIONS The present study provides a link between resting-state gamma-b and connectivity and the core symptoms of schizophrenia . The observed findings are different than those reported by task-related studies , suggesting that resting-state studies might reveal new aspects in the pathophysiology of schizophrenia OBJECTIVES We hypothesized that an oscillatory abnormality that is consistently observed across various testing paradigms may index an elementary neuronal abnormality marking schizophrenia risk . METHODS Compared neural oscillations in resting EEG and sensory gating conditions in schizophrenia patients ( n=128 ) , their first-degree relatives ( n=80 ) , and controls ( n=110 ) and calculated phenotypic and /or genetic correlation of the abnormal measure across these conditions . RESULTS Using a uniform , single trial analytical approach , we identified two prominent oscillatory characteristics in schizophrenia : ( 1 ) augmented neural oscillatory power was pervasive in medicated schizophrenia patients in most frequencies , most prominent in the theta-alpha range ( 4 - 11 Hz ) across the two paradigms ( all p<0.007 ) ; and ( 2 ) their first-degree relatives shared significantly augmented oscillatory energy in theta-alpha frequency in resting ( p=0.002 ) and insufficient suppression of theta-alpha in sensory gating ( p=0.01 ) compared with normal controls . Heritability estimates for theta-alpha related measures for resting and gating conditions ranged from 0.44 to 0.49 ( p<0.03 ) . The theta-alpha measures were correlated genetically with each other ( RhoG=0.82±0.43 ; p<0.05 ) . CONCLUSIONS Augmented theta-alpha rhythm may be an elementary neurophysiological problem associated with genetic liability of schizophrenia . SIGNIFICANCE This finding helps to refine key electrophysiologic biomarkers for genetic and clinical studies of schizophrenia Significance In vitro and modeling studies have indicated that GABAergic signaling underlies gamma oscillations . It would be valuable to measure this correlation between GABA and gamma oscillations in the human brain , and a recent study [ Muthukumaraswamy SD , et al. ( 2009 ) Proc Natl Acad Sci USA 106(20):8356–8361 ] indicated that this is possible , using magnetoencephalography and magnetic resonance spectroscopy . If true , such a correlation would make the gamma peak frequency a useful surrogate marker of cortical excitability for studies investigating clinical population s and /or the effects of pharmacological agents . However , magnetic resonance spectroscopy does not measure synaptic GABA specifically , and the results from the current study ( n = 50 ) indicate that GABA , as measured with magnetic resonance spectroscopy , does not correlate with gamma peak frequency . Gamma b and oscillations arise in neuronal networks of interconnected GABAergic interneurons and excitatory pyramidal cells . A previous study found a correlation between visual  gamma peak frequency  , as measured with magnetoencephalography , and resting GABA levels , as measured with magnetic resonance spectroscopy ( MRS ) , in 12 healthy volunteers . If true , this would allow studies in clinical population s testing modulation of this relationship , but this finding has not been replicated . We addressed this important question by measuring gamma oscillations and GABA , as well as glutamate , in 50 healthy volunteers .  Visual gamma activity was evoked using an established gratings paradigm , and we applied a beamformer spatial filtering technique to extract source -reconstructed gamma peak frequency and amplitude from the occipital lobe . We determined gamma peak frequency and amplitude from the location with maximal activation and from the location of the MRS voxel to assess the relationship of GABA with gamma . Gamma peak frequency was estimated from the highest value of the raw spectra and by a Gaussian fit to the spectra . MRS data were acquired from occipital cortex . We did not replicate the previously found correlation between gamma peak frequency and GABA concentration . Calculation of a Bayes factor provided strong evidence in favor of the null hypothesis . We also did not find a correlation between gamma activity and glutamate or between gamma and the ratio of GABA/glutamate . Our results suggest that cortical gamma oscillations do not have a consistent , demonstrable relationship to excitatory/inhibitory network activity as proxied by MRS measurements of GABA and glutamate 
    Output:
    
HighlightsGamma oscillations are synchronised by parvalbumin positive interneurons .
Gamma b and responses to tasks were reduced in psychosis and at risk population s .