Long-range synchrony of γ oscillations and auditory hallucination symptoms in schizophrenia

Abstract

Phase locking in the gamma-band range has been shown to be diminished in patients with schizophrenia. Moreover, there have been reports of positive correlations between phase locking in the gamma-band range and positive symptoms, especially hallucinations. The aim of the present study was to use a new methodological approach in order to investigate gamma-band phase synchronization between the left and right auditory cortex in patients with schizophrenia and its relationship to auditory hallucinations. Subjects were 18 patients with chronic schizophrenia (SZ) and 16 healthy control (HC) subjects. Auditory hallucination symptom scores were obtained using the Scale for the Assessment of Positive Symptoms. Stimuli were 40-Hz binaural click trains. The generators of the 40Hz-ASSR were localized using eLORETA and based on the computed intracranial signals lagged interhemispheric phase locking between primary and secondary auditory cortices was analyzed. Current source density of the 40 ASSR response was significantly diminished in SZ in comparison to HC in the right superior and middle temporal gyrus (p<0.05). Interhemispheric phase locking was reduced in SZ in comparison to HC for the primary auditory cortices (p<0.05) but not in the secondary auditory cortices. A significant positive correlation was found between auditory hallucination symptom scores and phase synchronization between the primary auditory cortices (p<0.05, corrected for multiple testing) but not for the secondary auditory cortices. These results suggest that long-range synchrony of gamma oscillations is disturbed in schizophrenia and that this deficit is related to clinical symptoms such as auditory hallucinations.

Fig. 1

Diffusion Tensor Imaging (DTI) results comparing schizophrenic patients with auditory hallucinations and schizophrenic patients without hallucinations; a) the blue arrow shows an area in the posterior part of the corpus callosum (CC) with significantly increased Fractional Anisotropy (FA) in patients with auditory hallucinations; b) The Witelson Classification suggests increased FA values in the part of the CC where the auditory fibers cross (Witelson 1989). F: Frontal fibers, M: Motor fibers, Ss: Somatosensory fibers, A: Auditory fibers, T/P: Temporal and parietal fibers, V: Visual fibers. Reprinted and modified with permission from Hubl et al., Archives of General Psychiatry, 2004, 61(7):658–668, Copyright © (2004) American Medical Association. All rights reserved.

Fig. 2

Regions of interest for the lagged phase synchronization analyses. Yellow: Primary Auditory Cortex (BA 41, Heschl’s Gyrus). Green: Secondary Auditory Cortex (BA 42, Superior Temporal Gyrus).

Fig. 3

Scalp EEG data: Time-frequency and topographic maps of evoked power for healthy controls (HC) and schizophrenia patients (SZ) at electrode Fz. Modified from Spencer et al. 2009 (BMC Neurosci 10:85).

Fig. 4

Statistical map demonstrating differences between HC and SZ at p<0.05. There are only regions with increased activation in HC than in SZ (yellow-red): The right superior and middle temporal gyrus. No regions with increased activation in patients can be found. A: Anterior, S: Superior, P: Posterior.

Fig. 5

Phase synchronization during the ASSR in HC (blue) and SZ (green); a) BA 41, b) BA42. Auditory stimulation starts at 0ms and ends at 500ms.

Fig. 6

Spearman’s Correlations between SAPS (scale for the assessment of positive symptoms) auditory hallucination scores and phase synchrony between left and right primary auditory cortex.