PMID- 33603682 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240402 IS - 1664-0640 (Print) IS - 1664-0640 (Electronic) IS - 1664-0640 (Linking) VI - 11 DP - 2020 TI - Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia. PG - 629144 LID - 10.3389/fpsyt.2020.629144 [doi] LID - 629144 AB - Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types. CI - Copyright (c) 2021 Sehatpour, Avissar, Kantrowitz, Corcoran, De Baun, Patel, Girgis, Brucato, Lopez-Calderon, Silipo, Dias, Martinez and Javitt. FAU - Sehatpour, Pejman AU - Sehatpour P AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. FAU - Avissar, Michael AU - Avissar M AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. FAU - Kantrowitz, Joshua T AU - Kantrowitz JT AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. FAU - Corcoran, Cheryl M AU - Corcoran CM AD - Icahn School of Medicine at Mt. Sinai, New York, NY, United States. FAU - De Baun, Heloise M AU - De Baun HM AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. FAU - Patel, Gaurav H AU - Patel GH AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. FAU - Girgis, Ragy R AU - Girgis RR AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. FAU - Brucato, Gary AU - Brucato G AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. FAU - Lopez-Calderon, Javier AU - Lopez-Calderon J AD - Centro de Investigaciones Medicas, Escuela de Medicina, Universidad de Talca, Talca, Chile. FAU - Silipo, Gail AU - Silipo G AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. FAU - Dias, Elisa AU - Dias E AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. FAU - Martinez, Antigona AU - Martinez A AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. FAU - Javitt, Daniel C AU - Javitt DC AD - College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, New York, NY, United States. AD - Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. LA - eng GR - T32 MH018870/MH/NIMH NIH HHS/United States GR - R01 MH049334/MH/NIMH NIH HHS/United States GR - R01 MH107558/MH/NIMH NIH HHS/United States GR - R37 MH049334/MH/NIMH NIH HHS/United States GR - K23 MH108711/MH/NIMH NIH HHS/United States GR - R01 MH109289/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20210202 PL - Switzerland TA - Front Psychiatry JT - Frontiers in psychiatry JID - 101545006 PMC - PMC7884473 OTO - NOTNLM OT - auditory event related potential OT - auditory event-related potentials OT - clinical high-risk OT - fMRI OT - functional connectivity OT - location deviant OT - mismatch negativity OT - schizophrenia COIS- DJ reports Intellectual property for NMDAR agonists in schizophrenia, NMDAR antagonist in depression, fMRI for prediction of ECT response, and ERP biomarkers for diagnosis of mental disorders. Equity in Glytech, AASI, and NeuroRx. Scientific advisory board NeuroRx, Promentis, Consultant payments Autifony, SK Life Sciences, Biogen, Cadence, and Pfizer. RG has consulted for Noble Insights and receives royalties for books from Wipf and Stock and Routledge/Taylor and Francis. GP receives income and equity from Pfizer Inc. through family. AM reports intellectual property for ERP biomarkers for diagnosis of mental disorders. JK reports having received consulting payments within the last 24 months from Alphasights, Charles River Associates, Putnam Associates, Third Bridge, Piper Jaffray, MEDACorp, Parexel, GroupH, Simon Kucher, LifeSci Capital, ECRI Institute, ExpertConnect, Parexel, Schlesinger Group, CelloHealth, Acsel Health, Strafluence, Guidepoint, L.E.K. and System Analytic. He has serves on the MedinCell Psychiatry Advisory Board. He has conducted clinical research supported by the NIMH, Sunovion, Roche, Alkermes, the Stanley Foundation, Cerevance, Takeda, Taisho, Lundbeck, Boehringer Ingelheim, NeuroRX, Teva and Lilly within the last 24 months. JK was a co-investigator on a study that receives lumeteperone and reimbursement for safety testing for an investigator-initiated research from Intra-Cellular Therapies Inc. He owns a small number of shares of common stock from GSK. RG has consulted for Noble Insights and receives royalties for books from Wipf and Stock and Routledge/Taylor and Francis. GP receives income and equity from Pfizer Inc. through family. AM reports intellectual property for ERP biomarkers for diagnosis of mental disorders. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/02/20 06:00 MHDA- 2021/02/20 06:01 PMCR- 2021/02/02 CRDT- 2021/02/19 06:05 PHST- 2020/11/13 00:00 [received] PHST- 2020/12/28 00:00 [accepted] PHST- 2021/02/19 06:05 [entrez] PHST- 2021/02/20 06:00 [pubmed] PHST- 2021/02/20 06:01 [medline] PHST- 2021/02/02 00:00 [pmc-release] AID - 10.3389/fpsyt.2020.629144 [doi] PST - epublish SO - Front Psychiatry. 2021 Feb 2;11:629144. doi: 10.3389/fpsyt.2020.629144. eCollection 2020.