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Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia

  • Juliann M. Mellin (a1), Sankaraleengam Alagapan (a1), Caroline Lustenberger (a1), Courtney E. Lugo (a1), Morgan L. Alexander (a1), John H. Gilmore (a1), L. Fredrik Jarskog (a1) and Flavio Fröhlich (a1) (a2) (a3) (a4) (a5) (a6)...

Abstract

Background:

Approximately 30% of patients with schizophrenia experience auditory hallucinations that are refractory to antipsychotic medications. Here, we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) that we hypothesized would improve auditory hallucination symptoms by enhancing synchronization between the frontal and temporo-parietal areas of the left hemisphere.

Method:

22 participants were randomized to one of three arms and received twice daily, 20 min sessions of sham, 10 Hz 2 mA peak-to-peak tACS, or 2 mA tDCS over the course of 5 consecutive days. Symptom improvement was assessed using the Auditory Hallucination Rating Scale (AHRS) as the primary outcome measure. The Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS) were secondary outcomes.

Results:

Primary and secondary behavioral outcomes were not significantly different between the three arms. However, effect size analyses show that tACS had the greatest effect based on the auditory hallucinations scale for the week of stimulation (1.31 for tACS; 1.06 and 0.17, for sham and tDCS, respectively). Effect size analysis for the secondary outcomes revealed heterogeneous results across measures and stimulation conditions.

Conclusions:

To our knowledge, this is the first clinical trial of tACS for the treatment of symptoms of a psychiatric condition. Further studies with larger sample sizes are needed to better understand the effect of tACS on auditory hallucinations.

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Copyright

Corresponding author

*115 Mason Farm Rd., NRB 4109F, Chapel Hill, NC 27599, United States. E-mail address: flavio_frohlich@med.unc.edu

Footnotes

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1.

Authors contributed equally.

Footnotes

References

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Juliann M. Mellin is a study coordinator in the Carolina Center for Neurostimulation and Department of Psychiatry at the University of North Carolina Chapel Hill. She received her undergraduate degree in Psychology from the University of North Carolina Greensboro. Her research interests include brain stimulation as a possible treatment for Schizophrenia and Major Depressive Disorder.

Dr. Sankaraleengam Alagapan is a postdoctoral research associate in the Carolina Center for Neurostimulation and Department of Psychiatry at the University of North Carolina Chapel Hill. He received his PhD in Biomedical Engineering from University of Florida. His research interests include brain stimulation, cognition and biological signal processing.

Dr. Caroline Lustenberger is currently a postdoctoral associate at the ETH Zurich in the Mobile Health Systems Lab led by Prof. Walter Karlen. Since 2013, she holds a PhD in Neuroscience with a focus on sleep and memory from the ETH Zurich (group of Prof. Reto Huber, Children’s Hospital Zurich). From 2014 to 2017 she performed a postdoctoral stay at the University of North Caroline at Chapel Hill with Prof. Flavio Frohlich where she gained expertise in advanced brain stimulation approaches. Her research investigates the role of cortical activity during sleep in brain and body health using advanced feedback-controlled brain stimulation techniques.

Courtney E. Lugo is a study coordinator in the Carolina Center for Neurostimulation and Department of Psychiatry at the University of North Carolina at Chapel Hill. She received her Masters in Public Health and her Bachelors of Science in Biology from East Carolina University. Her research areas include Major Depressive Disorder and Schizophrenia.

Morgan L. Alexander is a study coordinator in the Carolina Center for Neurostimulation and Department of Psychiatry at the University of North Carolina at Chapel Hill. She received her undergraduate degrees in psychology and mathematics from the University of North Carolina at Chapel Hill. She is interested in how novel treatments, such as brain stimulation, can treat patients with severe mental illnesses.

Dr. John H. Gilmore is the Thad and Alice Eure Distinguished Professor and Vice Chair for Research and Scientific Affairs in the Department of Psychiatry at the University of North Carolina at Chapel Hill and directs the UNC Center for Excellence in Community Mental Health. Dr. Gilmore received his BA in Political and Social Thought from the University of Virginia and his MD from the University of North Carolina at Chapel Hill. Dr. Gilmore’s has an active research program focused on brain development and risk for schizophrenia. He pioneered the use of magnetic resonance imaging to study early childhood brain development.

Dr. L. Fredrik Jarskog is Professor of Psychiatry and Research Director of the North Carolina Psychiatric Research Center at the University of North Carolina at Chapel Hill. Dr. Jarskog’s research is focused on the pathophysiology and treatment of schizophrenia. He currently receives research funding from the National Institute of Health, several academic/industry collaborations and The Foundation of Hope for Research and Treatment of Mental Illness, Raleigh, NC. Current studies include novel treatments for cognitive deficits in people with schizophrenia, treatment-resistant psychosis, tardive dyskinesia and antipsychotic-associated weight gain.

Dr. Flavio Frohlich received a degree in electrical engineering at ETH Zurich, an International Diploma at the Imperial College in London, and his PhD in neurobiology at UC San Diego. After a postdoctoral fellowship at Yale University, he joined UNC – Chapel Hill as faculty, where he currently is an associate professor. He directs the Frohlich Lab, which studies brain oscillations in animal models and computer simulations, and the Carolina Center for Neurostimulation, which focuses on research and clinical use of brain stimulation. Dr. Frohlich authored the textbook Network Neuroscience and is the founder and chief scientific officer of Pulvinar Neuro LLC.

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Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia

  • Juliann M. Mellin (a1), Sankaraleengam Alagapan (a1), Caroline Lustenberger (a1), Courtney E. Lugo (a1), Morgan L. Alexander (a1), John H. Gilmore (a1), L. Fredrik Jarskog (a1) and Flavio Fröhlich (a1) (a2) (a3) (a4) (a5) (a6)...

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Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia

  • Juliann M. Mellin (a1), Sankaraleengam Alagapan (a1), Caroline Lustenberger (a1), Courtney E. Lugo (a1), Morgan L. Alexander (a1), John H. Gilmore (a1), L. Fredrik Jarskog (a1) and Flavio Fröhlich (a1) (a2) (a3) (a4) (a5) (a6)...
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