Poster #: 30
Topic: Computational models
Friday, Sep 11, 2015
Effects of NMDAR antagonism on mismatch negativity and repetition suppression
1Institute of Neurology, University College London, London, United Kingdom
2Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom
3Centre for Developmental Cognitive Neuroscience, University College London, London, United Kingdom
Deficiencies in generating an auditory mismatch negativity (MMN) were one of the earliest electroencephalographic (EEG) markers of brain dysfunction in patients with schizophrenia. These EEG features can be replicated pharmacologically with the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. More recent studies have furthermore shown a ketamine-induced impairment of context dependent modulation of the MMN at the prefrontal electrodes, consistent with a predictive coding account of mismatch negativity generation.
Here, we report the effects of ketamine administration at two different doses on the auditory MMN in a double blind, crossover, placebo-controlled study in 16 healthy nvolunteers. Pure tones were presented in a roving paradigm, where each frequency is both a deviant stimulus (following a frequency change), before becoming a new standard after a few repetitions. This study design has two advantages: (i) deviants and standards do not differ in their physical properties, but only in their preceding auditory context, and (ii) it discloses the ‘relearning’ of new standards after frequency changes (i.e. repetition suppression).
There is a significant effect of ketamine on the response to standard stimuli, consistent with a defective sensory learning of new standards. Using dynamic causal modelling for EEG, we estimated the underlying changes in directed, effective connectivity between the sources of the relevant frontotemporal network. This study replicates some of the findings from a previous, independent study, but further focusses on the ketamine-induced difference in repetition suppression when ‘relearning’ a novel standard. These results give a mechanistic account of pharmacologically induced neurophysiological changes in synaptic plasticity.