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Mismatch negativity predicts psychotic experiences induced by NMDA receptor antagonist in healthy volunteers
Daniel Umbricht1, Rene Koller, Franz X Vollenweider
1Psychiatric University Hospital Zurich, Department of Psychiatric Research, Zurich, Switzerland.
Background:
Previous studies indicate that mismatch negativity (MMN)-a preattentive auditory event-related potential (ERP)-depends on NMDA receptor (NMDAR) functioning. To explore if the strength of MMN generation reflects the functional condition of the NMDAR system in healthy volunteers, we analyzed correlations between MMN recorded before drug administration and subsequent responses to the NMDAR antagonist ketamine or the 5-HT2a agonist psilocybin.
Methods:
In two separate studies, MMN was recorded to both frequency and duration deviants prior to administration of ketamine or psilocybin. Behavioral and subjective effects of ketamine and psilocybin were assessed with the Brief Psychiatric Rating Scale and the OAV Scale-a rating scale developed to measure altered states of consciousness. Correlations between ERP amplitudes (MMN, N1, and P2) and drug-induced effects were calculated in each study group and compared between them.
Results:
Smaller MMN to both pitch and duration deviants was significantly correlated to stronger effects during ketamine, but not psilocybin administration. No significant correlations were observed for N1 and P2.
Conclusions:
Smaller MMN indicates a NMDAR system that is more vulnerable to disruption by the NMDAR antagonist ketamine. MMN generation appears to index the functional state of NMDAR-mediated neurotransmission even in subjects who do not demonstrate any psychopathology.
Insights
Smaller mismatch negativity (MMN) suggests NMDA receptor (NMDAR) systems are more vulnerable to ketamine disruption. This finding indicates MMN reflects NMDAR neurotransmission function in healthy individuals.
Area of Science:
- Neuroscience
- Psychopharmacology
- Auditory Event-Related Potentials
Background:
- Mismatch negativity (MMN), a preattentive auditory event-related potential (ERP), is linked to N-methyl-D-aspartate receptor (NMDAR) function.
- Previous research suggests a connection between MMN and NMDAR activity.
Purpose of the Study:
- To investigate if MMN amplitude reflects the functional state of the NMDAR system in healthy volunteers.
- To examine the relationship between pre-drug MMN and responses to ketamine and psilocybin.
Main Methods:
- MMN was recorded in response to frequency and duration deviants before administering ketamine or psilocybin.
- Behavioral and subjective effects were assessed using the Brief Psychiatric Rating Scale and OAV Scale.
- Correlations between MMN, N1, P2 amplitudes and drug effects were analyzed.
Main Results:
- Reduced MMN amplitude correlated with stronger ketamine effects.
- No significant correlations were found between MMN and psilocybin effects.
- N1 and P2 amplitudes did not show significant correlations with drug effects.
Conclusions:
- Lower MMN amplitude indicates greater NMDAR system vulnerability to ketamine.
- MMN generation serves as an indicator of NMDAR-mediated neurotransmission function, even in individuals without psychopathology.
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