Loudness- and time-dependence of auditory evoked potentials is blunted by the NMDA channel blocker MK-801.

Amplitudes of auditory evoked potentials (AEP) increase with the intensity/loudness of sounds (loudness-dependence of AEP, LDAEP), and the time between adjacent sounds (time-dependence of AEP, TDAEP). Both, blunted LDAEP and blunted TDAEP are markers of altered auditory function in schizophrenia (SZ). However, while blunted LDAEP has been attributed to altered serotonergic function, blunted TDAEP has been linked to altered NMDA receptor function. Despite phenomenological similarities of the two effects, no common pharmacological underpinnings have been identified. To test whether LDAEP and TDAEP are both affected by NMDA receptor blockade, two rhesus macaques passively listened to auditory clicks of 5 different intensities presented with stimulus-onset asynchronies ranging between 0.2 and 6.4s. 8 AEP components were analyzed, including the N85, the presumed human N1 homolog. LDAEP and TDAEP were estimated as the slopes of AEP amplitude with intensity and the logarithm of stimulus-onset asynchrony, respectively. On different days, AEPs were collected after systemic injection of MK-801 or vehicle. Both TDAEP and LDAEP of the N85 were blunted by the NMDA blocker MK-801 and recapitulate the SZ phenotype. In summary, LDAEP and TDAEP share important pharmacological commonalities that may help identify a common pharmacological intervention to normalize both electrophysiological phenotypes in SZ.
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