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Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study

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Abstract

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

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Acknowledgements

The authors would like to recognize David Spradley and Joan Showalter, whose recruitment efforts were essential for this study. The authors would also like to thank Megan Gaunnac for her help with study start up and regulatory matters. The authors would like to thank Emmalee Metzler and Emily Good for helping to organize and run study visits, as well as Pamela Simmons and Becky McMahon for helping to maintain the treatment setting. The authors would also like to thank the Eskenazi Health Midtown Community Mental Health Center for its continued research support.

The authors would like to thank the Brain and Behavior Research Foundation for providing funding for this study and Neuronetics for providing material support.

Funding

Financial support was provided by a Brain & Behavior Research Foundation NARSAD Young Investigator Grant (#20911, PI: Michael Francis). Research materials, including the Neurostar XPLOR system, were provided by a Neuronetics Investigator Initiated Trial Program award. This award did not provide financial support. These sources had no further role in study design, data collection and analysis, the writing of the report, and in the decision to submit the paper for publication.

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Contributions

Drs. Francis and Hummer conceived and designed the study. Dr. Francis, Dr. Hummer, Nikki Mehdiyoun, Andrew Visco, Matthew Yung, and Teresa Kulig were responsible for data acquisition. Dr. Francis, Dr. Hummer, Ziyi Yang, Dr. Vohs, Matthew Yung, Mehrdad Motamed, Dr. Zhang, and Dr. Breier analyzed and interpreted the data. Dr. Francis, Dr. Hummer, and Nikki Mehdiyoun supervised the study. Dr. Francis, Dr. Hummer, Ziyi Yang, and Dr. Zhang were responsible for drafting the manuscript. All authors contributed to and have approved the final manuscript.

Corresponding author

Correspondence to Michael M. Francis.

Ethics declarations

All procedures performed in this study were in accordance with the ethical standards of the Indiana University School of Medicine Institutional Review Board, the Indiana University Department of Psychiatry Data Safety Monitoring Board, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Conflict of interest

Dr. Francis received a Neuronetics Investigator Initiated Program award which supplied research materials, but not financial support, for this study. Dr. Liffick was an employee at Indiana University at the time the research was completed. She is currently employed at Eli Lilly and Company. She is also a minor shareholder in the company. All other authors declare that they have no conflicts of interest.

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Francis, M.M., Hummer, T.A., Vohs, J.L. et al. Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study. Brain Imaging and Behavior 13, 852–861 (2019). https://doi.org/10.1007/s11682-018-9902-4

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