A group of 17 schizophrenia patients and 16 normal-control subjects participated in the study. After a detailed description of the experimental protocol, all subjects gave written informed consent, and we obtained University Mental Health Research Institute Ethics Committee approval. The inclusion criteria were the following: 1) age between 18 and 45 years; 2) right-handed; 3) no alcohol and drug abuse in the last 5 years; 4) no neurological illness or head trauma that would result in an abnormal EEG; 5) no antiepileptic drugs; and 6) no alcohol use in the last 24 hours. Normal-controls had no Axis I psychiatric disorder. Two patients' data were excluded from the analysis because of artifacts related to limited cooperation during the experimental procedure. All patients were recruited from Eginition University Hospital and fulfilled the criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition–Text Revision (DSM-IV–TR; 2000). The Positive and Negative Symptoms Scale (PANSS) was used for assessment of symptoms. The detailed characteristics of the hallucinations were assessed with the Psychotic Symptom Rating Scales–Auditory Hallucinations Rating Scale (PSYRATS–AHRS).10 All clinical data were collected 1 day before the EEG recording.
Two groups of patients participated in the study; first: the SCZ-AVHs group consisted of 8 patients with drug-resistant spontaneous AVHs (4 men, 4 women; mean age: 36 (SD: 7) years; duration of illness: 15.5 (SD: 6) years; mean PANSS score: 70 (SD: 6); 6 of these patients were medicated with risperidone (mean dose: 7 mg/day) and 2 with amisulpride (mean dose: 800 mg/day); and second: the SCZ group, consisting of 7 patients who, at the time of enrollment, did not exhibit AVHs, as a result of effective antipsychotic drug treatment, (3 men, 4 women, mean age: 30 (SD: 9); duration of illness: 13 (SD: 8) years; mean PANSS score: 68 (SD: 8). Four of these patients were medicated with risperidone (mean dose: 7 mg/day), two with amisulpride (mean dose: 600 mg/day), and one with aripiprazole (dose: 25 mg/day). All participants were selected from a larger sample of subjects suffering from schizophrenia, but who had the ability to cooperate in the experimental procedure. The Control (NOR) group consisted of 16 subjects (8 men, 8 women); mean age: 31 (SD: 6) years.
Subjects were seated in a light- and sound-attenuated, double-skin Faraday cage. Electrodes (Fp1, Fp2, F7, F3, Fz, F4, F8, FT7, FC3, FCz, FC4, FT8, T7, C3, Cz, C4, T8, TP7, CP3, CPz, CP4, TP8, P7, P3, Pz, P4, P8, O1, Oz, O2) were placed on the scalp, using a standard cap. Recordings of the horizontal-plane eye-movement potentials were made by two electrodes fixed 1 cm bilateral to the outer canthus of each eye. The skin resistance of each electrode was kept at ≤5 kΩ for the entire session. The participants were instructed to report any experience of auditory hallucination. This was achieved by pressing a miniature optical switch with the middle finger of their dominant hand to indicate the onset and the duration of any experienced AVH. In order to validate our findings, the data obtained from the SCZ-AVHs group were compared with those obtained by the NOR and SCZ, where the participants were instructed to press the button in a voluntary basis, without any previous prompt. The above procedure was applied both during eyes-open (E-OP) and eyes-closed (E-CL) conditions. The EEG signals were acquired by a Synamps (Neuroscan Labs) amplifier module sampled at 500 Hz. The phase stability of selected sites was computed by the following equation:
expresses the temporal coupling of two preselected brain sites, α and b
as a function of frequency f
and time t
is the duration of the time window, varied from 50 to 200 msec; and ϕ is the phase of the convolved signal with the wavelet. In practice, the above formula was computed in a number of overlapped phase segments corresponded to a period of 1.5 sec preceding the end of the mark that denotes the end of the hallucination constituting, in this way, the parameter FSS. In order to evaluate the statistical significance of our findings against the background phase-difference fluctuations, FSS values obtained from original EEG signals were compared with those obtained from surrogate data-sets. The results gave the amount of coupling as a function of time, with value of 1 indicating the higher and 0 the lower coupling. This analytical technique is sensitive in the detection of frequency-related changes of the phase-synchrony and is accurate enough to study phasic-synchronous activity in single trials.11
Also, in order to investigate the spatial characteristics of α-band synchrony in association with auditory-hallucination states, a coupling index12
was computed across the reference and the remaining electrodes. The spatial-temporal average of this index constitutes the band-specific synchrony illustrated in Figure 1