Reduced Auditory Mismatch Negativity Reflects Impaired Deviance Detection in Schizophrenia
The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify...
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Published in | Schizophrenia bulletin Vol. 46; no. 4; pp. 937 - 946 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
08.07.2020
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Abstract | The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia (N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a “many-standards paradigm” that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders. |
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AbstractList | The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia (N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a “many-standards paradigm” that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders. The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia ( N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a “many-standards paradigm” that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders. The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia (N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a "many-standards paradigm" that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders.The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia (N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a "many-standards paradigm" that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders. |
Author | Tada, Mariko Usui, Kaori Fujioka, Mao Koshiyama, Daisuke Kasai, Kiyoto Araki, Tsuyoshi Kirihara, Kenji Nagai, Tatsuya |
AuthorAffiliation | 3 Department of Psychiatry, Kawamuro Memorial Hospital , Niigata, Japan 1 Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan 2 The International Research Center for Neurointelligence (WPI-IRCN) at The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo , Tokyo, Japan |
AuthorAffiliation_xml | – name: 3 Department of Psychiatry, Kawamuro Memorial Hospital , Niigata, Japan – name: 1 Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan – name: 2 The International Research Center for Neurointelligence (WPI-IRCN) at The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo , Tokyo, Japan |
Author_xml | – sequence: 1 givenname: Daisuke surname: Koshiyama fullname: Koshiyama, Daisuke organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 2 givenname: Kenji surname: Kirihara fullname: Kirihara, Kenji organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 3 givenname: Mariko surname: Tada fullname: Tada, Mariko organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 4 givenname: Tatsuya surname: Nagai fullname: Nagai, Tatsuya organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 5 givenname: Mao surname: Fujioka fullname: Fujioka, Mao organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 6 givenname: Kaori surname: Usui fullname: Usui, Kaori organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 7 givenname: Tsuyoshi surname: Araki fullname: Araki, Tsuyoshi organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 8 givenname: Kiyoto surname: Kasai fullname: Kasai, Kiyoto email: kasaik-tky@umin.net organization: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan |
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SubjectTerms | Adaptation, Physiological - physiology Adult Auditory Perception - physiology Biomarkers Electroencephalography Evoked Potentials, Auditory - physiology Female Humans Male Perceptual Disorders - etiology Perceptual Disorders - physiopathology Regular Schizophrenia Schizophrenia - complications Schizophrenia - physiopathology Young Adult |
Title | Reduced Auditory Mismatch Negativity Reflects Impaired Deviance Detection in Schizophrenia |
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