Abstract
Schizophrenia is a complex disorder about which much is still unknown. Potential treatments, such as transcranial magnetic stimulation (TMS), have not been exploited, in part because of the variability in behavioral response. This can be overcome with the use of response biomarkers. It has been however shown that repetitive transcranial magnetic stimulation (rTMS) can the relieve positive and negative symptoms of schizophrenia, particularly auditory verbal hallucinations (AVH). This exploratory work aims to establish a quantitative methodological tool, based on high-density electroencephalogram (HD-EEG) data analysis, to assess the effect of rTMS on patients with schizophrenia and AVH. Ten schizophrenia patients with drug-resistant AVH were divided into two groups: the treatment group (TG) received 1 Hz rTMS treatment during 10 daily sessions (900 pulses/session) over the left T3-P3 International 10-20 location. The control group (CG) received rTMS treatment over the Cz (vertex) EEG location. We used the P300 oddball auditory paradigm, known for its reduced amplitude in schizophrenia with AVH, and recorded high-density electroencephalography (HD-EEG, 256 channels), twice for each patient: pre-rTMS and 1 week post-rTMS treatment. The use of HD-EEG enabled the analysis of the data in the time domain, but also in the frequency and source-space connectivity domains. The HD-EEG data were linked with the clinical outcome derived from the auditory hallucinations subscale (AHS) of the Psychotic Symptom Rating Scale (PSYRATS), the Quality of Life Scale (QoLS), and the Depression, Anxiety and Stress Scale (DASS). The general results show a variability between subjects, independent of the group they belong to. The time domain showed a higher N1-P3 amplitude post-rTMS, the frequency domain a higher power spectral density (PSD) in the alpha and beta bands, and the connectivity analysis revealed a higher brain network integration (quantified using the participation coefficient) in the beta band. Despite the small number of subjects and the high variability of the results, this work shows a robust data analysis and an interplay between morphology, spectral, and connectivity data. The identification of a trend post-rTMS for each domain in our results is a first step toward the definition of quantitative neurophysiological parameters to assess rTMS treatment.
Highlights
Hallucinations are sensory perceptions occurring in the absence of an external stimulus
Two subjects (T2, in treatment group (TG) and C3, in control group (CG)) presented an improvement in the psychometric score post-Transcranial magnetic stimulation (TMS), and the two others presented a stagnation in the psychometric (C2, in CG) or a decrement (T5, in TG)
There were no significant changes on Auditory verbal hallucinations (AVH) severity measured with Psychotic Symptom Rating Scales (PSYRATS) auditory hallucinations subscale (AHS), in QoL and Depression Anxiety Stress Scales (DASS) global scores after repetitive TMS (rTMS) between TG and CG
Summary
Hallucinations are sensory perceptions occurring in the absence of an external stimulus. An increased interaction among the auditory-language and striatal brain regions occurs while patients hallucinate (Curcic Blake et al, 2017). Wassermann et al (1996) and Chen et al (1997) reported that 1 Hz repetitive TMS (rTMS) reduces the excitability of cortical neurons in healthy individuals. Based on these effects, Hoffman et al (1999) hypothesized that 1 Hz rTMS delivered to the left temporoparietal cortex reduced activity in receptive language areas associated with AVH in patients with schizophrenia. Neuroimaging studies of AVH showed an increased activation in the absence of an external stimulus in the left primary auditory cortex of subjects with this symptom (Kompus et al, 2011)
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