Horacek J, Novak T, Brunovsky M, Klirova M, Zaytseva Y, Spaniel F, Koprivova J, Bravermanova A, Höschl C. From functional neuroanatomy to the stereo-selective treatment: rTMS in schizophrenia. Abstracts of the 5th Biennial Cambridge & Bedford International Conference on Mental Health. Clare College, Cambridge University 11-14 Sept 2015

11. 9. 2015 - 14. 9. 2015

Prague Psychiatric Center, Prague 8, Czech Republic
National Institute of Mental Health, Czech Republic
Third Medical Faculty of Charles University, Prague, Czech Republic

E mail; horacek@pcp.lf3.cuni.cz

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of the left temporo-parietal cortex (LTPC) has been proposed as a useful therapeutic method for auditory hallucinations (AHs).

Study 1: Stereotactic neuronavigation enables the magnetic coil to be targeted according to the individual parameters obtained from neuroimaging. Individualized rTMSneuronavigated according to 18-fluorodeoxyglucose positron emission tomography ((18)FDG PET) allows us to focus the coil explicitly on a given area with detected maxima of specific abnormalities, thus presuming a higher therapeutic effect of the method. The objective of this study is to test clinical efficacy of neuronavigated LF-rTMS administered according to the local maxima of (18)FDG PET uptake of LTPC and to compare it with treatment effects of standard and sham rTMS. In a double-blind, sham-controlled design, patients with AHs underwent a 10-day series of LF-rTMS using (1) (18)FDG PET-guided "neuronavigation," (2) "standard" anatomically guided positioning, and (3) sham coil. The effect of different rTMS conditions was assessed by the Auditory Hallucinations Rating Scale (AHRS) and the Positive and Negative Syndrome Scale (PANSS). Fifteen patients were randomized to a treatment sequence and ten of them completed all three treatment conditions. The intention-to-treat analysis of AHRS score change revealed superiority of the (18)FDG PET-guided rTMS over both the standard and the sham rTMS. The analyses of the PANSS scores failed to detect significant difference among the treatments.

Study 2: The aims were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n=10) or sham (n=9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40% vs. 12%; p=0.01).sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group.

Conclusions:The active LF-rTMS attenuated AHs and induced a decrease of higher EEG frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.Our neuronavigatedrTMSdata showedthe acute efficacy of (18)FDG PET-guided rTMS in the treatment of AHs. NeuronavigatedrTMS was found to be more effective than standard, anatomically guided rTMS.

Acknowledgments: Supported by Ministry of Health of the Czech RepublicAZV 15-29370A and IGA NT/13843 and by the Charles University research program PRVOUK P34.