Inhibition of the P50 cerebral evoked response to repeated auditory stimuli: results from the Consortium on Genetics of Schizophrenia.

Department of Psychiatry, Veterans Affairs Denver Medical Center VISN 19 MIRECC, CO 80045, USA.
Schizophrenia Research (Impact Factor: 4.43). 04/2010; 119(1-3):175-82. DOI: 10.1016/j.schres.2010.03.004
Source: PubMed

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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sensory gating disturbances in schizophrenia are often described as an inability to filter redundant sensory stimuli that typically manifest as inability to gate neuronal responses related to the P50 wave, characterizing a decreased ability of the brain to inhibit various responses to insignificant stimuli. It implicates various deficits of perceptual and attentional functions, and this inability to inhibit, or "gate", irrelevant sensory inputs leads to sensory and information overload that also may result in neuronal hyperexcitability related to disturbances of habituation mechanisms. These findings seem to be particularly important in the context of modern electrophysiological and neuroimaging data suggesting that the filtering deficits in schizophrenia are likely related to deficits in the integrity of connections between various brain areas. As a consequence, this brain disintegration produces disconnection of information, disrupted binding, and disintegration of consciousness that in terms of modern neuroscience could connect original Bleuler's concept of "split mind" with research of neural information integration.
    Neuropsychiatric Disease and Treatment 01/2014; 10:1309-15. · 2.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with schizophrenia have been hypothesized to have a functional impairment in filtering irrelevant sensory information, which may result in positive symptoms such as hallucinations or delusions. Many evidences suggest that abnormalities in the event-related brain potentials (ERPs), resting state electroencephalography (EEG) and synchronized oscillatory activity of neurons may reflect core pathophysiological mechanisms of schizophrenia. Abnormalities in amplitude and latency of the ERPs reflecting aberrations in gating and difficulties in the detection of changes in auditory stimuli, as well as defects in stimuli evaluation and integration of information are common in patients with schizophrenia. This chapter highlights the findings of electrophysiological studies in schizophrenia dealing with early sensory perception and attention, automatic sensory detection of stimuli changes and cognitive evaluation and integration of information, relevant to the pathophysiological mechanisms underpinning hallucinations and delusions. Results of electrophysiological studies investigating the neural correlates of positive symptoms suggest aberrant intrinsic organization of functional brain networks.
    Current topics in behavioral neurosciences. 06/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neural habituation, the decrease in brain response to repeated stimulation, is a basic form of learning. There is strong evidence for behavioral and physiological habituation deficits in schizophrenia, and one previous study found reduced neural habituation within the hippocampus. However, it is unknown whether neural habituation deficits are specific to faces and limited to the hippocampus. Here we studied habituation of several brain regions in schizophrenia, using both face and object stimuli. Post-scan memory measures were administered to test for a link between hippocampal habituation and memory performance. During an fMRI scan, 23 patients with schizophrenia and 21 control subjects viewed blocks of a repeated neutral face or neutral object, and blocks of different neutral faces and neutral objects. Habituation in the hippocampus, primary visual cortex and fusiform face area (FFA) was compared between groups. Memory for faces, words, and word pairs was assessed after the scan. Patients showed reduced habituation to faces in the hippocampus and primary visual cortex, but not the FFA. Healthy control subjects exhibited a pattern of hippocampal discrimination that distinguished between repeated and different images for both faces and objects, and schizophrenia patients did not. Hippocampal discrimination was positively correlated with memory for word pairs. Patients with schizophrenia showed reduced habituation of the hippocampus and visual cortex, and a lack of neural discrimination between old and new images in the hippocampus. Hippocampal discrimination correlated with memory performance, suggesting reduced habituation may contribute to the memory deficits commonly observed in schizophrenia.
    Schizophrenia Research 11/2013; · 4.43 Impact Factor