Inhibition of the P50 cerebral evoked response to repeated auditory stimuli: Results from the Consortium on Genetics of Schizophrenia
ABSTRACT Inhibition of the P50 evoked electroencephalographic response to the second of paired auditory stimuli has been frequently examined as a neurophysiological deficit in schizophrenia. The Consortium on the Genetics of Schizophrenia (COGS), a 7-site study funded by the National Institute of Mental Health, examined this endophenotype in recordings from 181 probands with schizophrenia, 429 of their first degree relatives, and 333 community comparison control subjects. Most probands were treated with second generation antipsychotic medications. Highly significant differences in P50 inhibition, measured as either the ratio of amplitudes or their difference in response to the two stimuli, were found between the probands and the community comparison sample. There were no differences between the COGS sites for these findings. For the ratio parameter, an admixture analysis found that nearly 40% of the relatives demonstrated deficiencies in P50 inhibition that are comparable to the deficit found in the probands. These results indicate that P50 auditory evoked potentials can be recorded across multiple sites and reliably demonstrate a physiological abnormality in schizophrenia. The appearance of the physiological abnormality in a substantial proportion of clinically unaffected first degree relatives is consistent with the hypothesis that deficits in cerebral inhibition are a familial neurobiological risk factor for the illness.
- SourceAvailable from: Susan Mahaffey
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- "The P50 potential, as established in human and animal studies, is generated by the PPN and is manifested at the vertex  . These sensory gating deficits demonstrate a lack of inhibition of responses to repetitive stimuli, which have been found in patients with schizophrenia and in some clinically unaffected first-degree relatives . Gamma oscillations appear to participate in sensory perception , problem solving, and memory      , and coherence at these frequencies may occur at cortical or thalamocortical levels  . "
ABSTRACT: Schizophrenia is characterized by major sleep/wake disturbances including increased vigilance and arousal, decreased slow wave sleep, and increased REM sleep drive. Other arousal-related symptoms include sensory gating deficits as exemplified by decreased habituation of the blink reflex. There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease. Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia.Sleep Science 05/2015; 17. DOI:10.1016/j.slsci.2015.04.003
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- "For each participant, we computed the final P50 ratio by dividing the trough-to-peak amplitude value for the averaged second click by the corresponding trough-to-peak amplitude value for the averaged first click (Cadenhead et al., 2000; Chang et al., 2012; Olincy et al., 2010). A participant who demonstrates selective sensory gating would manifest a smaller P50 response to the second click, and thus a smaller Click 2/Click 1 ratio, typically less than 1.0. "
ABSTRACT: Creativity has previously been linked with atypical attention, but it is not clear what aspects of attention, or what types of creativity are associated. Here we investigated specific neural markers of a very early form of attention, namely sensory gating, indexed by the P50 ERP, and how it relates to two measures of creativity: divergent thinking and real-world creative achievement. Data from 84 participants revealed that divergent thinking (assessed with the Torrance Test of Creative Thinking) was associated with selective sensory gating, whereas real-world creative achievement was associated with “leaky” sensory gating, both in zero-order correlations and when controlling for academic test scores in a regression. Thus both creativity measures related to sensory gating, but in opposite directions. Additionally, divergent thinking and real-world creative achievement did not interact in predicting P50 sensory gating, suggesting that these two creativity measures orthogonally relate to P50 sensory gating. Finally, the ERP effect was specific to the P50 – neither divergent thinking nor creative achievement were related to later components, such as the N100 and P200. Overall results suggest that leaky sensory gating may help people integrate ideas that are outside of focus of attention, leading to creativity in the real world; whereas divergent thinking, measured by divergent thinking tests which emphasize numerous responses within a limited time, may require selective sensory processing more than previously thought.Neuropsychologia 01/2015; 69. DOI:10.1016/j.neuropsychologia.2015.01.034 · 3.45 Impact Factor
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- "They all also showed poorer performance in SZ probands than in HCS. Performance in non-psychotic relatives varied, however, for both the cognitive and psychophysiological endophenotypes (Horan et al., 2008; Turetsky et al., 2008; Olincy et al., 2010; Radant et al., 2010). "
ABSTRACT: The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. Copyright © 2014. Published by Elsevier B.V.Schizophrenia Research 12/2014; 163(1-3). DOI:10.1016/j.schres.2014.10.029 · 4.43 Impact Factor