Person:

Spencer, Kevin

Several studies have reported deficits in (\gamma) oscillatory activity elicited by sensory stimulation or cognitive processes in schizophrenia patients (SZ) compared to healthy control subjects (HC). However, the evidence for cortical hyperexcitability and reduced function of N-methyl-D-aspartate receptors (NMDARs) on parvalbumin-expressing inhibitory interneurons in schizophrenia leads to the prediction that (\gamma) activity should rather be increased in SZ, but data supporting this hypothesis have been lacking. One possibility is that baseline induced (\gamma) power is increased, an effect that might have gone unnoticed in studies of stimulus-locked oscillations. Here we addressed this question by re-analyzing the data from a previously published study on the 40 Hz auditory steady-state response (ASSR) in schizophrenia in which dipole source localization was used to examine (\gamma) responses in the left and right auditory cortices. Subjects were 16 HC and 18 chronic SZ, who listened to trains of clicks presented at 40 Hz during electroencephalogram recording. Independent component analysis was used to remove ocular artifacts. Power spectra were computed for the pre-stimulus baseline period. We found that baseline power was higher in SZ than HC at 40 Hz in the left auditory cortex. Baseline 40 Hz power in the left auditory cortex was also correlated with ASSR evoked power in SZ. Thus, (\gamma) oscillation abnormalities in schizophrenia may include abnormal increases in baseline power as well as deficits in evoked oscillations. These baseline increases could be the sign of NMDAR hypofunction on parvalbumin-expressing inhibitory interneurons, which would be consistent with acute NMDAR antagonism and genetic ablation models of schizophrenia.

Background: In chronic schizophrenia and chronic bipolar disorder, gamma band (30–100 Hz) auditory steady-state EEG responses (ASSRs) are reduced in power and phase locking, likely reflecting neural circuit dysfunction. Here we examined whether gamma ASSR deficits are also present at first hospitalization for psychosis. Methods: Subjects were 16 first episode schizophrenia patients (SZ), 16 first episode affective disorder patients (AFF) (13 with bipolar disorder), and 33 healthy controls (HC). Stimuli were 20, 30, and 40 Hz binaural click trains. ASSR phase locking and evoked power were analyzed using the Morlet wavelet transform. Results: At 40 Hz stimulation, SZ and AFF had significantly reduced phase locking compared to HC. This deficit was more pronounced over the left hemisphere in SZ. Evoked power at 40 Hz was also reduced in the patients compared to HC. At 30 Hz stimulation phase locking and evoked power were reduced in both patient groups. The 20 Hz ASSR did not differ between groups, but phase locking and evoked power of the 40 Hz harmonic of the 20 Hz ASSR were reduced in both SZ and AFF. Phase locking of this 40 Hz harmonic was correlated with total positive symptoms in SZ. Conclusions: The gamma ASSR deficit is present at first hospitalization for both schizophrenia and affective disorder, but shows a left hemisphere bias in first hospitalized SZ. Some of the neural circuitry abnormalities underlying the gamma ASSR deficit may be common to psychoses in general, while others may be specific to particular disorders.