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N-methyl-D-aspartate receptor antagonism impairs sensory gating in the auditory cortex in response to speech stimuli.

Sara de la Salle, Joëlle Choueiry, Judy McIntosh, Hayley Bowers, Vadim Ilivitsky, Verner Knott

Psychopharmacology July 2022 DOI: 10.1007/s00213-022-06090-z (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental pharmacological study in healthy volunteers Peer reviewed
Sample size 22
Population Healthy human adults
Intervention Ketamine
Dose subanesthetic dose
Measures P50 event-related potential (ERP), eLORETA
Keywords Auditory sensory gating N-methyl-d-aspartate receptor nmdar Schizophrenia Symptomatology
Key findings Ketamine impaired P50 sensory gating indices at scalp-sensor and auditory-cortex source levels in healthy participants, and preliminary evidence suggested modest positive associations between impaired gating and ketamine-induced dissociative symptoms. The authors argue these findings tentatively support an NMDAR hypofunction model of disturbed auditory sensory gating in schizophrenia.

Abstract

Deficits in early auditory sensory processing in schizophrenia have been linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction, but the role of NMDARs in aberrant auditory sensory gating (SG) in this disorder is unclear. This study, conducted in 22 healthy humans, examined the acute effects of a subanesthetic dose of the NMDAR antagonist ketamine on SG as measured electrophysiologically by suppression of the P50 event-related potential (ERP) to the second (S2) relative to the first (S1) of two closely paired (500 ms) identical speech stimuli. Ketamine induced impairment in SG indices at sensor (scalp)-level and at source-level in the auditory cortex (as assessed with eLORETA). Together with preliminary evidence of modest positive associations between impaired gating and dissociative symptoms elicited by ketamine, tentatively support a model of NMDAR hypofunction underlying disturbances in auditory SG in schizophrenia.