Auditory Cortex Volume and Gamma Oscillation Abnormalities in Schizophrenia.

We investigated whether the gray matter volume of primary auditory cortex (Heschl's gyrus [HG]) was associated with abnormal patterns of auditory γ activity in schizophrenia, namely impaired γ synchronization in the 40-Hz auditory steady-state response (ASSR) and increased spontaneous broadband γ power. (The γ data were previously reported in Hirano et al, JAMA Psychiatry, 2015;72:813-821). Participants were 24 healthy controls (HC) and 23 individuals with chronic schizophrenia (SZ). The ASSR was obtained from the electroencephalogram to click train stimulation at 20, 30, and 40 Hz rates. Dipole source localization of the ASSR was used to provide a spatial filter of auditory cortex activity, from which ASSR evoked power and phase locking factor (PLF), and induced γ power were computed. HG gray matter volume was derived from structural magnetic resonance imaging at 3 T with manually traced regions of interest. As expected, HG gray matter volume was reduced in SZ compared with HC. In SZ, left hemisphere ASSR PLF and induced γ power during the 40-Hz stimulation condition were positively and negatively correlated with left HG gray matter volume, respectively. These results provide evidence that cortical gray matter structure, possibly resulting from reduced synaptic connectivity at the microcircuit level, is related to impaired γ synchronization and increased spontaneous γ activity in schizophrenia.

Phase-Amplitude Coupling of the Electroencephalogram in the Auditory Cortex in Schizophrenia.

BACKGROUND: Cross-frequency interactions may coordinate neural circuits operating at different frequencies. While neural oscillations associated with particular circuits in schizophrenia (SZ) are impaired, few studies have examined cross-frequency interactions. Here we examined phase-amplitude coupling (PAC) in the electroencephalograms of individuals with SZ and healthy control subjects (HCs). We computed PAC during the baseline period of 40-Hz auditory steady-state stimulation and rest. We hypothesized that subjects with SZ would show abnormal theta/gamma coupling during stimulation, especially in the left auditory cortex, and coupling with high frequencies would be higher during stimulation than during rest. METHODS: We reanalyzed data from 18 subjects with SZ and 18 HCs. Auditory cortex electroencephalogram activity was estimated using dipole source localization. PAC was computed using the debiased PAC measure, calculated with the generalized Morse wavelet transform. PAC clusters were identified using cluster-corrected permutation testing and interrogated in analyses of variance with correction for multiple tests. RESULTS: Overall, coupling of high beta and gamma amplitude was higher during the auditory steady-state response, while alpha/beta PAC was higher during rest. Theta/alpha PAC was higher in subjects with SZ than in HCs. Theta/gamma PAC was lateralized to the left hemisphere in HCs but was not lateralized in subjects with SZ. CONCLUSIONS: PAC involving high frequencies was state dependent and not abnormal in SZ. Increased theta/alpha PAC in subjects with SZ was consistent with other evidence of increased low-frequency activity. Hemispheric lateralization of theta/gamma PAC was reduced in subjects with SZ, consistent with evidence for left hemisphere auditory cortex abnormalities in subjects with SZ. PAC may reveal new insights into neural circuitry abnormalities in SZ and other neuropsychiatric disorders.