PM370. Mismatch negativity and theta band oscillation in schizophrenia and rodent NMDAR models
Year: 2016
Type: conference-abstract
Abstract: Objective: Mismatch negativity (MMN) is a reliable biomarker of N-methyl-D-aspartate receptor (NMDAR) dysfunction in schizophrenia. The present study investigates effects of the NMDAR antagonist PCP in rodents on MMN-related event-related spectral perturbation (ERSP) patterns, vs. deficit patterns observed in schizophrenia. Method: Rats (n=21) were implanted with skull electrodes over frontal, parietal and bilateral auditory cortex. MMN was obtained to both frequency and duration (10% each) against a background of more frequency standards. PCP (15 mg/kg/d) was administered by osmotic minipump with or without simultaneous oral glycine treatment. EEG was collected from control (n=7), PCP (n=8) and PCP+glycine (n=6) groups, at baseline, 2-week, and 4-week time points. In parallel clinical MMN was collected from schizophrenia (n=69) and control (n=38) subjects using a similar paradigm. Results: Rodent MMN varied significantly across groups (F(1,18)=12.5 p<.001), with significant reduction by PCP (p<.001 vs. control) and restoration by glycine (p<.001 vs. PCP alone). In ITC analysis, MMN was associated with increased activity in theta and gamma frequencies that were reduced by PCP treatment. Simultaneous, glycine treatment increased activity within gamma frequency bands vs. PCP alone(F(1,12)=4.6 p<.05). In humans, MMN deficits were associated with both reduced ITC and ERSP of theta frequency response to deviant stimuli (F(1,105)=62.2 p<.001; F(1,105)=15.2 p<.001) and reduced alpha frequency response to standards (t=3.8 p<.00; t=3.2 p<.00), similar to the pattern of deficit observed in the rodent PCP model and reversed by glycine treatment(F(1,12)=6.1 p<.05). Conclusion: These findings demonstrate first that deficits in MMN generation correspond primarily to reductions in theta frequency activity in humans consistent with prior reports [1], and second that rodent chronic PCP treatment may serve as an appropriate animal model for schizophrenia treatment development. Glycine treatment partially reversed ERSP induced by PCP treatment, suggesting sensitivity to NMDAR agonist intervention. Reference 1. Javitt DC, Shelley A, Ritter W. Associated deficits in mismatch negativity generation and tone matching in schizophrenia. Clin Neurophysiol 2000;111:1733–1737.
Authors: Migyung Lee, Andrea Balla, Daniel C Javitt
Institution: Columbia University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,693
OpenAlex ID: W3184593880