UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.

Baldeweg, T; Hirsch, SR; (2015) Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease. Int J Psychophysiol , 95 (2) 145 - 155. 10.1016/j.ijpsycho.2014.03.008. Green open access

[thumbnail of Article] PDF (Article)
1-s2.0-S0167876014000774-main.pdf

Download (1MB)
[thumbnail of Supplementary table] MS Word (Supplementary table)
mmc1.docx

Download (14kB)

Abstract

Cognitive impairment is an important predictor of functional outcome in patients with schizophrenia, yet its neurobiology is still incompletely understood. Neuropathological evidence of impaired synaptic connectivity and NMDA receptor-dependent transmission in superior temporal cortex motivated us to explore the correlation of in vivo mismatch negativity (MMN) with cognitive status in patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed a response proportional to the number of stimulus repetitions (memory trace effect). Preliminary evidence in patients with chronic schizophrenia suggests that attenuation of this MMN memory trace effect was correlated with the degree of neuropsychological memory dysfunction. Here we present data from a larger confirmatory study in patients with schizophrenia, bipolar disorder, probable Alzheimer's disease and healthy controls. We observed that the diminution of the MMN memory trace effect and its correlation with memory impairment was only found in the schizophrenia group. Recent pharmacological studies using the roving paradigm suggest that attenuation of the MMN trace effect can be understood as abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the convergence of the previously identified synaptic pathology in supragranular cortical layers with the intracortical locus of MMN generation accounts for the remarkable robustness of MMN impairments in schizophrenia. We further speculate that this layer-specific synaptic pathology identified in supragranular neurons plays a pivotal computational role, by weakening the encoding and propagation of prediction errors to higher cortical modules. According to predictive coding theory such breakdown will have grave implications not only for perception, but also for higher-order cognition and may thus account for the MMN-cognition correlations observed here. Finally, MMN is a sensitive and specific biomarker for detecting the early prodromal phase of schizophrenia and is well suited for the exploration of novel cognition-enhancing agents in humans.

Type: Article
Title: Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijpsycho.2014.03.008
Publisher version: http://dx.doi.org/10.1016/j.ijpsycho.2014.03.008
Language: English
Additional information: © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Keywords: Bipolar illness, Cognition, Mismatch negativity, Plasticity, Schizophrenia
UCL classification: UCL
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 Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1426258
Downloads since deposit
274Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item