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Changes in neural network function induced by tDCS treatment for auditory verbal hallucinations in schizophrenia
Auditory verbal hallucinations (AVH) involve the perception of voices in the absence of auditory stimuli, and occur in more than 70% of patients diagnosed with schizophrenia (SZ). A recent meta-analysis of six sham-controlled trials of tDCS treatment for AVH in SZ using the treatment protocol developed by Brunelin et al (2012) reported a 30% reduction in overall SZ AVH clinical severity (Lee et al., 2017; Cohen’s d=1.2). However, none of the clinical trials investigated potential neural mechanisms by which tDCS neuromodulation had its effect. A second issue is that while there a large reduction in mean AVH severity scores, there was considerable unexplained variability in treatment response. To address these issues, finite element modeling (FEM) was used to compute tDCS current dose delivery in inferior prefrontal cortex (iPFC) and temporoparietal junction (TPJ) in a group of participants with schizophrenia and frequent, treatment-resistant AVH (N=6). AVH severity was assessed with the Psychotic Symptom Rating scales (PSYRATS), and both fMRI and magnetoencephalography (MEG) were used to measure resting iPFC and TPJ resting activation pre- and post-treatment with the five-day, Brunelin et al (2012) tDCS protocol. Consistent with the findings of Lee et al (2017), tDCS treatment resulted in a 26% reduction in AVH severity (sd=7.6). FEM modeling indicated significant current delivery occurring to left hemisphere iPFC and TPJ for five of the six participants. Within-subjects MEG and fMRI analyses revealed a significant treatment-related reduction in resting activation in left TPJ. Across participants, the degree to which FEM-assessed current delivery successfully targeted TPJ (but not iPFC) predicted the extent of change in AVH severity scores. These results support a hyperexcitation model of schizophrenia AVH and the primacy of temporoparietal language regions in the genesis of AVH. They further suggest that neuromodulatory reduction of left hemisphere TPJ hyperexcitation is critical for reducing the severity of AVH in schizophrenia. Lastly, results suggest that it may be possible to improve the effectiveness of the Brunelin tDCS treatment protocol for AVH using individualized FEMs to target TPJ hyperexcitation.