A putative electrophysiological biomarker of auditory sensory memory encoding is sensitive to pharmacological alterations of excitatory/inhibitory balance in male macaque monkeys.

backgroundThe amplitude of the auditory evoked N1 component that can be derived from noninvasive electroencephalographic recordings increases as a function of time between subsequent tones. N1 amplitudes in individuals with schizophrenia saturate at a lower asymptote, thus giving rise to a reduced dynamic range. Reduced N1 dynamic range is a putative electrophysiological biomarker of altered sensory memory function in individuals with the disease. To date, it is not clear what determines N1 dynamic range and what causes reduced N1 dynamic range in individuals with schizophrenia. Here we test the hypothesis that reduced N1 dynamic range results from a shift in excitatory/inhibitory (E/I) balance toward an excitation-deficient or inhibition-dominant state.

methodsWe recorded auditory-evoked potentials (AEPs) while 4 macaque monkeys passively listened to sequences of sounds of random pitch and stimulus-onset asynchrony (SOA). Three independent experiments tested the effect of the

resultsKetamine, MK-801 and midazolam reduced peak N1 amplitudes for the longest SOAs. Other AEP components were also affected, but revealed distinct patterns of susceptibility for the glutamatergic and GABA-ergic drugs. Different patterns of susceptibility point toward differences in the circuitry maintaining E/I balance of individual components. LIMITATIONS: The study used systemic pharmacological interventions that may have acted on targets outside of the auditory cortex.

conclusionThe N1 dynamic range may be a marker of altered E/I balance. Reduced N1 dynamic range in individuals with schizophrenia may indicate that the auditory cortex is in an excitation-deficient or inhibition-dominant state. This may be the result of an incomplete compensation for a primary deficit in excitatory drive.