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

Abstract

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 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 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.

Keywords::

• auditory hallucinations
• computer based modeling
• non-invasive brain stimulation
• schizophrenia
• transcranial direct current stimulation

Acknowledgements

The authors would like to thank the three anonymous reviewers for their comments and suggestions that significantly improved this manuscript.

Financial & competing interests disclosure

D Javitt is supported by NIMH grants R01MH049334 and P50MH086385. AR Brunoni was supported in part by the following grants: 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation (Grant Number 20493), 2013 FAPESP Young Researcher from the São Paulo State Foundation (Grant Number 20911-5) and National Council for Scientific and Technological Development (CNPq, Grant Number 470904). M Bikson has equity in Soteriz Medical Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention that changes cortical excitability according to the parameters of stimulation. It has been increasingly used in the treatment of mental disorders, such as major depression and schizophrenia.

• An important question is to determine optimal anode (excitability-increasing) and cathode (excitability-decreasing) positioning. tDCS trials determine electrode positioning according to neuroimaging findings regarding brain activity, although this approach might be difficult to apply in complex mental disorders such as schizophrenia.

• We performed a systematic review of all clinical studies using tDCS for the treatment of schizophrenia. Based on these studies, we identified the tDCS montages mostly used in these studies and thereafter performed computer head modeling simulation to predict electric flow between electrodes.

• Predicted current flow between these areas corroborated the rationale excitability decreasing over the cathode and increasing over the anode, but also revealed that current flows normal to these cortical regions (therefore inducing changes in cortical excitability) and also tangential to these regions, leading to synaptic strengthening. Current also reaches the deep brain structures involved in the pathophysiology of schizophrenia.

• tDCS, by simultaneously modulating two distinct brain areas as well as connectivity between temporoparietal and prefrontal regions, might be an interesting neuromodulatory treatment tool for schizophrenia, a disorder in which dysconnectivity between several brain areas is observed.

• In addition, the use of computer modeling techniques provides a framework to be applied in future studies exploring different tDCS montages in the treatment of positive and negative symptoms of schizophrenia and also in other mental disorders.

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