Theta tACS Over the Medial Frontal Cortex Modulates Executive Function in Parkinson's Disease: A Randomized, Sham-Controlled Study
In brief
6-Hz HD-tACS speeds trail-making and boosts semantic fluency in Parkinson's disease
In a sham-controlled trial of 28 Parkinson's patients, ten daily sessions of 6-Hz high-definition tACS over the medial frontal cortex led to faster performance on both parts of the Trail Making Test and better semantic verbal fluency, while also reducing the Simon interference effect. No benefits were seen on digit-span or stop-signal reaction times, suggesting a selective cognitive enhancement that warrants larger confirmation studies.
- Journal
- CNS neuroscience & therapeutics (Q1)
- Published
- 1 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Ke Dong, Yan Zhao, Xiaoxia Zhu, Jiating Li, Bo Peng, Yushu Zhang, et al.
- PMID
- 42499269
- DOI
- 10.1002/cns.71055
Why clinicians should know about it
- Picked for Geriatrics and Gerontology (paper of the day, 26 July 2026).
- Picked for Neurology (clinical) (paper of the day, 26 July 2026).
- Picked for Psychiatry and Mental Health (paper of the day, 26 July 2026).
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (paper of the day, 26 July 2026): High-quality evidence in a top journal
Abstract
BACKGROUND: Executive dysfunction is a common non-motor symptom of Parkinson's disease (PD) and has been linked to dysfunction of the medial frontal cortex (MFC). This randomized, sham-controlled study investigated whether high-definition transcranial alternating current stimulation (HD-tACS) over the MFC could improve executive function in PD. METHODS: Twenty-eight PD patients were randomized to receive either active 6-Hz HD-tACS or sham stimulation over the MFC for 10 daily sessions. Executive function was assessed using the Digit Span Test (DST), Trail Making Test (TMT), Verbal Fluency Test (VFT), the Simon task, and the stop-signal task (SST). Functional near-infrared spectroscopy (fNIRS) was employed to assess prefrontal hemodynamic responses during a separate VFT task. RESULTS: Relative to sham stimulation, active 6-Hz HD-tACS induced significant improvements in TMT-A, TMT-B, and semantic VFT performance, along with reduced VFT-evoked oxyhemoglobin responses in the right dorsolateral prefrontal cortex. Baseline-adjusted post-intervention analyses revealed a smaller Simon effect and a higher inhibition rate in the active HD-tACS group. No significant stimulation-specific effects were observed for forward or backward DST, phonemic VFT, or SST reaction time. CONCLUSION: These findings provide neurobehavioral evidence that 6-Hz HD-tACS over the MFC may selectively improve executive function in PD, highlighting the potential of oscillatory neuromodulation for cognitive rehabilitation. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (No. NCT07240272) on November 20, 2025.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.