A reduction in the early auditory evoked gamma-band response (aeGBR), a type of brain wave, is seen in both schizophrenia patients and healthy people given ketamine, which mimics the brain's excitation/inhibition imbalance thought to underlie the disorder. This change in brain activity is linked to negative symptoms. In a study of 24 healthy men, ketamine alone reduced the aeGBR amplitude and increased negative symptoms as measured by the PANSS scale. Pretreatment with the amino acid glycine lessened both the brain-wave alteration and the symptom increase in those who responded to glycine. The aeGBR may serve as a biomarker to identify schizophrenia patients with negative symptoms who could benefit from glutamatergic treatments.
Deficits in automatic auditory processing, measured by mismatch negativity (MMN), are linked to poor outcomes in schizophrenia and involve glutamate dysfunction. In a placebo-controlled crossover EEG study with 25 participants, ketamine—which induces schizophrenia-like symptoms—reduced MMN amplitudes, theta power, and P3a. Pretreatment with glycine, an NMDAR coagonist, did not prevent ketamine's effects on MMN or P3a amplitude but did block ketamine's reduction of theta power and phase consistency associated with duration deviant MMN. Elevated theta activity due to glycine predicted improvement in negative symptoms. The findings confirm the glutamate system's role in pre-attentive auditory processing deficits and suggest MMN's theta signature may help identify patients responsive to glutamatergic treatments.