Hallucinations and cognitive impairments associated with psychosis may be underpinned by N-methyl D-
aspartate (NMDA) receptor hypofunction. Within the Research Domain Criteria (RDoC) developed by the
National Institute of Mental Health, features of psychosis illness, which can also be transiently produced in
healthy normal subjects given NMDA receptor antagonists, fall under the Cognitive System domain. Within
this domain, auditory perception and processing speed are most relevant to the proposed work. Research
focused on the abnormal functioning of this cognitive system in both psychosis and psychosis vulnerability
subject groups may increase understanding of these symptoms.
Electroencephalography (EEG) has great potential to elucidate the potential link between NMDA receptor
hypofunction and symptoms of illness. Gamma (30-80Hz) oscillations are known to be generated by fast-
spiking interneuron and pyramidal neuron microcircuits, and NMDA receptors play an important role in fast-
spiking interneuron activity. Using spectral decomposition to analyze EEG, frequency-specific oscillations,
including the gamma band, can be isolated and extracted on a millisecond basis. The auditory steady-state
response (ASSR) is often used to study impaired EEG gamma oscillations in schizophrenia. These tasks use
short-duration trains of repetitive auditory stimulation at a fixed frequency (e.g., every 25ms or 40-Hz) to evoke
an ASSR at that same frequency. In particular, the 40-Hz ASSR is typically reduced in evoked response
power and exhibits more oscillation phase variability, or reduced phase synchrony, across trials in
schizophrenia. These deficits have also been observed in first-degree relatives and individuals at clinical-high
risk (CHR) for psychosis. More recently, two additional measures derived from ASSR have demonstrated
sensitivity to psychosis pathophysiology. These measures are (1) spontaneous gamma band power in the pre-
stimulus baseline period, which is abnormally elevated in schizophrenia, and (2) the 40-Hz ASSR oscillation
phase angle, which is significantly delayed in schizophrenia.
In a series of previously conducted studies across 9 laboratories, we collected 40-Hz ASSRs from
chronically ill (i.e. > 5 years duration) psychosis patients, early illness (i.e. <= 5 years duration) psychosis
patients, CHR subjects, and a wide age range of healthy comparison controls. We propose to align these
existing EEG data from over one thousand males and females (12-61 years old), across diagnoses and the
wellness spectrum. This project will extend prior work by using ASSR phase delay and spontaneous
(baseline) gamma power to compare stages of psychosis illness. Any association between these
gamma measures and hallucination symptom ratings, neuropsychological speed of processing tests,
age, or sex will be determined. Longitudinal effects on 40-Hz ASSR will be assessed in CHR.
