Visual cortical plasticity and the risk for psychosis: An interim analysis of the North American Prodrome Longitudinal Study

• Type of Material: Article
• Authors: Michael S Jacob, VA San Francisco Healthcare System; Brian J Roach, VA San Francisco Healthcare System; Holly K Hamilton, VA San Francisco Healthcare System; Ricardo E Carrion, North Shore Long Isl Jewish Hlth Syst; Aysenil Belger, University of North Carolina; Erica Duncan, Emory University; Jason Johannesen, Yale University; Matcheri Keshavan, Harvard Medical School; Sandra Loo, University of California Los Angeles; Margaret Niznikiewicz, Harvard Medical School; Jean Addington, University of Calgary; Carrie E Bearden, University of California Los Angeles; Kristin S Cadenhead, University of California San Diego; Tyrone D Cannon, Yale University; Barbara A Cornblatt, North Shore-Long Island Jewish Health System; Thomas H McGlashan, Yale University; Diana O Perkins, University of North Carolina; William Stone, Harvard Medical School; Ming Tsuang, University of California San Diego; Elaine Walker, Emory University; Scott W Woods, Yale University; Daniel H Mathalon, VA San Francisco Healthcare System
• Language: English
• Date: 2021-03-02
• Publisher: ELSEVIER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Published by Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.schres.2021.01.028
• Title of Journal or Parent Work: SCHIZOPHRENIA RESEARCH
• Volume: 230
• Start Page: 26
• End Page: 37
• Grant/Funding Information: This work was supported by grants from National Institute of Mental Health (U01MH081902 to TDC, P50 MH066286 to CEB, U01MH081988 to EFW, U01MH076989 to DHM, U01MH081944 to KSC, U01MH081984 to JA, U01MH082004 to DOP, U01MH081857 to BAC, U01MH081928 to LJS, U01MH082022 to SW).
• Keywords: BRAIN CONNECTIVITY; NMDA RECEPTOR ANTAGONISTS; Clinical high risk; Visual evoked potentials; STIMULATION; Psychosis; SCHIZOPHRENIA; SYNAPTIC PLASTICITY; Life Sciences & Biomedicine; Schizophrenia; EXPERIENCE-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; EXPRESSION; FRONTAL-CORTEX; EVOKED-POTENTIALS; Plasticity; Science & Technology; Psychiatry

Abstract

Background: Adolescence/early adulthood coincides with accelerated pruning of cortical synapses and the onset of schizophrenia. Cortical gray matter reduction and dysconnectivity in schizophrenia are hypothesized to result from impaired synaptic plasticity mechanisms, including long-term potentiation (LTP), since deficient LTP may result in too many weak synapses that are then subject to over-pruning. Deficient plasticity has already been observed in schizophrenia. Here, we assessed whether such deficits are present in the psychosis risk syndrome (PRS), particularly those who subsequently convert to full psychosis. Methods: An interim analysis was performed on a sub-sample from the NAPLS-3 study, including 46 healthy controls (HC) and 246 PRS participants. All participants performed an LTP-like visual cortical plasticity paradigm involving assessment of visual evoked potentials (VEPs) elicited by vertical and horizontal line gratings before and after high frequency (“tetanizing”) visual stimulation with one of the gratings to induce “input-specific” neuroplasticity (i.e., VEP changes specific to the tetanized stimulus). Non-parametric, cluster-based permutation testing was used to identify electrodes and timepoints that demonstrated input-specific plasticity effects. Results: Input-specific pre-post VEP changes (i.e., increased negative voltage) were found in a single spatio-temporal cluster covering multiple occipital electrodes in a 126–223 ms time window. This plasticity effect was deficient in PRS individuals who subsequently converted to psychosis, relative to PRS non-converters and HC. Conclusions: Input-specific LTP-like visual plasticity can be measured from VEPs in adolescents and young adults. Interim analyses suggest that deficient visual cortical plasticity is evident in those PRS individuals at greatest risk for transition to psychosis.