Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

Abstract

Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi-and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based timefrequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contra-lateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.

MEG—measured auditory steady-state oscillations show high test–retest reliability: A sensor and source-space analysis

“…To this end, source-estimated signals would also be helpful for assessing laterality effects in ASSRs, e.g. as have been reported in ScZ (Edgar et al, 2014;Hamm et al, 2011;Hirano et al, 2015;Spencer et al, 2009;Teale et al, 2008). Since addressing differences in lateralization was outside the scope of the present study, we focused our assessment of ASSRs bilaterally such that there was a correspondence between results obtained for sensor-level and source space.…”

“…MEG source estimation employing beamforming may improve signal-to-noise (SNR) and confers an advantage over dipole-fitting (e.g. Lu et al, 2007;McFadden et al, 2014;Teale et al, 2008) through the use of head models based on individual anatomical MRI-data. In addition, it facilitates the definition of regions of interests (ROIs), such as the auditory areas, which are important for the generation of ASSRs (Hamm et al, 2011;McFadden et al, 2014;Pantev et al, 1996;Ross et al, 2000).…”

NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia

“…This method has been previously established in clinical studies of schizophrenia and autism and to examine power changes in those disorders. To evaluate the state of SNR in this model, baseline, evoked and total power were examined in high and low frequency ranges to determine if these two well established pharmacological models cause perturbations in the noise or stimulus-related signal similar to those found in schizophrenia (Behrendt, 2003; Behrendt and Young, 2004; Brenner et al, 2009; Canive et al, 1998; Dierks et al, 1995; Doheny et al, 2000; Ford et al, 2008; Fujisawa et al, 2004; Gaspar et al, 2009; Hall et al; Hall et al, 2009; Hong et al, 2004; Jensen and Lisman, 1996; Kessler and Kling, 1991; Kirino and Inoue, 1999; Kissler et al, 2000; Koukkou et al, 2000; Krause et al, 2003; Krishnan et al, 2009; Kwon et al, 1999; Leicht et al; Lifshitz et al, 1987; Light et al, 2006; Reinhart et al; Schellenberg and Schwarz, 1993; Spencer et al, 2004; Teale et al, 2008; Yamamoto, 1997). Additionally, inter-trial coherence, a measure for determining the trial to trial response consistency, was examined was analyzed in low and high frequency regions to determine whether or not a loss of response consistency is associated with changes in power.…”

Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia

“…Most of these studies have employed low-level perceptual processing tasks, finding impaired evoked gamma power during a visual backward-masking task (Wynn et al, 2005), decreased evoked gamma power (Haig et al, 2000;Symond et al, 2005) and synchrony (Slewa-Younan et al, 2004;Symond et al, 2005) in auditory oddball paradigms, decreased evoked gamma power and synchrony in auditory steady-state potential paradigms using click-train stimuli (Kwon et al, 1999;Light et al, 2006) or sustained tones (Brenner et al, 2003), and decreased gamma phase-locking, observed in visual (Spencer et al, 2008a) and auditory oddball tasks , with auditory tones (Teale et al, 2008;Krishnan et al, 2009), and immediately before spontaneous movement (Staykova et al, 2008). Impaired evoked gamma activity has also been found in response to transcranial magnetic stimulation (Ferrarelli et al, 2008), in association with sensory gating deficits in schizophrenia (Hong et al, 2004a), and in the unaffected relatives of schizophrenia patients (Hong et al, 2004b).…”