Online left-hemispheric in-phase frontoparietal theta tacs for the treatment of negative symptoms of schizophrenia

Chuan Chia Chang, Cathy Chia Yu Huang, Yong An Chung, Jooyeon Jamie Im, Yen Yue Lin, Chin Chao Ma, Nian Sheng Tzeng, Hsin An Chang

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12 Scopus citations


Negative symptoms represent an unmet need for schizophrenia treatment. The effect of theta frequency transcranial alternating current stimulation (theta-tACS) applied during working memory (WM) tasks on negative symptoms has not been demonstrated as of yet. We conducted a randomized, double-blind, sham-controlled trial of 36 stabilized schizophrenia patients, randomized to receive either twice daily, 6 Hz 2 mA, 20 min sessions of in-phase frontoparietal tACS or sham for five consecutive weekdays. Participants were concurrently engaged in WM tasks during stimulation. The primary outcome measure was the change over time in the Positive and Negative Syndrome Scale (PANSS) negative subscale score measured from baseline through to the 1-month follow-up. Secondary outcome measures were other symptom clusters, neurocognitive performance, and relevant outcomes. The intention-to-treat analysis demonstrated greater reductions in PANSS negative subscale scores at the end of stimulation in the active (−13.84%) than the sham (−3.78%) condition, with a large effect size (Cohen’s d = 0.96, p = 0.006). The positive effect endured for at least one month. Theta-tACS also showed efficacies for cognitive symptoms, WM capacity, and psychosocial functions. Online theta-tACS offers a novel approach to modulate frontoparietal networks to treat negative symptoms of schizophrenia. The promising results require large-scale replication studies in patients with predominantly negative symptoms.

Original languageEnglish
Article number1114
JournalJournal of Personalized Medicine
Issue number11
StatePublished - Nov 2021


  • Frontoparietal theta coupling
  • Negative symptoms
  • Online stimulation
  • Schizophrenia
  • Transcranial alternating current stimulation
  • Working memory


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