Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in Early Phase Psychosis

Abstract

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.

Keywords: Auditory steady state response; Event-related potentials; Magnetic resonance spectroscopy; Mismatch negativity; Psychosis; Schizophrenia.

Fig. 1.

Location of MRS voxel of interest (VOI) in medial frontal lobe and representative spectrum. VOI placement in sagittal and axial views, together with a representative MR spectrum (red: LCModel fit, dashed: raw data, solid black line: fitted baseline) from a EPP subject, showing the peaks of Cho, Cre, Glx and NAA.

Fig. 2.

Event-related potential grand average responses to deviant and standard tones in the EPP (dashed line) and Control group (solid line). Deviant - Standard grand average difference waveforms showing the MMN deflection (third column).

Fig. 3.

ASSR grand average responses to 500 Hz click trains in the EPP and Control groups (left column). Grand Average power spectra showing 40 Hz power in the two groups (right column).