Understanding tDCS effects in schizophrenia: a systematic 5 review of clinical data and an integrated computation modeling analysis

10 Andre Russowsky Brunoni*, Pedro Shiozawa, Dennis Truong, Daniel C Javitt, Hélio Elkis, Felipe Fregni and Marom Bikson Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil Service of Interdisciplinary Neuromodulation (SIN) and Interdisciplinary Center for Applied Neuromodulation (CINA), University of São Paulo, São Paulo, Brazil Laboratory of Clinical Neuromodulation, Santa Casa Medical School, São Paulo, Brazil Department of Biomedical Engineering, The City College of New York (CCNY), The City University of New York (CUNY), NY, USA Division of Experimental Therapeutics, Department of Psychiatry, Columbia College of Physicians and Surgeons, NY, USA Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA *Author for correspondence: Tel.: +55 113 091 9241 Fax: +55 113 091 9241 [email protected] Although recent clinical studies using transcranial direct current stimulation (tDCS) for schizophrenia showed encouraging results, several tDCS montages were employed and their current flow pattern has not been investigated. We performed a systematic review to identify clinical tDCS studies in schizophrenia. We then applied computer head modeling analysis for 15 prediction of current flow. Out of 41 references, we identified 12 relevant studies. The most employed montage was anode and cathode over the left dorsolateral prefrontal and temporoparietal cortex, respectively. Computational model analysis predicted activation and under-activation under the anode and the cathode, respectively, occurring in areas respectively associated with negative and positive symptoms. We also identified tDCS-induced electrical 20 currents in cortical areas between the electrodes (frontoparietal network) and, to a lesser extent, in deeper structures involved in schizophrenia pathophysiology. Mechanisms of tDCS effects in schizophrenia and the usefulness of computer modeling techniques for planning tDCS trials in schizophrenia are discussed.