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Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity

Ranlund, S; Adams, RA; Díez, Á; Constante, M; Dutt, A; Hall, MH; Maestro Carbayo, A; ... Bramon, E; + view all (2015) Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity. Human Brain Mapping , 37 (1) pp. 351-365. 10.1002/hbm.23035. Green open access

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Abstract

The mismatch negativity (MMN) evoked potential, a preattentive brain response to a discriminable change in auditory stimulation, is significantly reduced in psychosis. Glutamatergic theories of psychosis propose that hypofunction of NMDA receptors (on pyramidal cells and inhibitory interneurons) causes a loss of synaptic gain control. We measured changes in neuronal effective connectivity underlying the MMN using dynamic causal modeling (DCM), where the gain (excitability) of superficial pyramidal cells is explicitly parameterised. EEG data were obtained during a MMN task-for 24 patients with psychosis, 25 of their first-degree unaffected relatives, and 35 controls-and DCM was used to estimate the excitability (modeled as self-inhibition) of (source-specific) superficial pyramidal populations. The MMN sources, based on previous research, included primary and secondary auditory cortices, and the right inferior frontal gyrus. Both patients with psychosis and unaffected relatives (to a lesser degree) showed increased excitability in right inferior frontal gyrus across task conditions, compared to controls. Furthermore, in the same region, both patients and their relatives showed a reversal of the normal response to deviant stimuli; that is, a decrease in excitability in comparison to standard conditions. Our results suggest that psychosis and genetic risk for the illness are associated with both context-dependent (condition-specific) and context-independent abnormalities of the excitability of superficial pyramidal cell populations in the MMN paradigm. These abnormalities could relate to NMDA receptor hypofunction on both pyramidal cells and inhibitory interneurons, and appear to be linked to the genetic aetiology of the illness, thereby constituting potential endophenotypes for psychosis. Hum Brain Mapp, 2015. © 2015 The Authors Human BrainMapping Published byWiley Periodicals, Inc.

Type: Article
Title: Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hbm.23035
Publisher version: http://dx.doi.org/10.1002/hbm.23035
Language: English
Additional information: Copyright © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: DCM, NMDA receptor, cortical excitability, cortical gain, dynamic causal modeling, effective connectivity, genetic risk, psychosis, schizophrenia, unaffected relatives
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/1474004
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