Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia

Abstract

Background: Oscillatory electroencephalogram (EEG) abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR) generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions. Sixteen healthy control subjects (HC) and 18 chronic schizophrenia patients (SZ) listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data.

Results: Phase locking factor (PLF) and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources.

Conclusion: These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by an increased propensity for high-frequency synchronization in modality-specific cortical areas.

Figure 1

Analyses of scalp EEG data. (A) Time-frequency and topographic maps of phase locking factor (PLF) for healthy controls (HC) and schizophrenia patients (SZ). The time-frequency maps show responses at electrode Fz. Topographic maps are oriented so that the top of the map is anterior and the bottom is posterior. (B) Time-frequency and topographic maps of evoked power for HC and SZ, as in A. (C) Dipole model of the ASSR based on the HC grand average. Labels are for left hemisphere tangential (LH tan), left hemisphere radial (LH rad), right hemisphere tangential (RH tan), right hemisphere radial (RH rad), and Residual (Res) dipoles. (D) Global field power (blue) of the scalp ASSR and percent residual variance (%RV) of the dipole model (red). The period during which the dipole model was fit (30–550 ms) is shaded.

Figure 2

PLF time-frequency maps of source activity for HC and SZ.

Figure 3

Evoked power time-frequency maps of source activity for HC and SZ.

Figure 4

Auditory hallucination correlations and cross-frequency interaction data. (A and B) Scatterplots of LH radial dipole PLF vs. Auditory Hallucination symptom ratings. The HC values are displayed for comparison with the range of SZ values. (A) LH radial dipole PLF over all trials (ρ = 0.541, p < 0.05). (B) LH radial dipole PLF in the 120–180° phase bin for 2 Hz modulation (ρ = 0.617, p < 0.01). (C and D) ASSR PLF plotted as a function of 2 Hz phase for the LH radial (C) and RH tangential (D) dipoles. HC = filled squares, SZ = open circles. In (C), the asterisk indicates the significant reduction of LH radial dipole PLF in SZ for the 120–180° phase bin.