Theta tACS Over the Medial Frontal Cortex Modulates Executive Function in Parkinson's Disease: A Randomized, Sham-Controlled Study.

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BackgroundExecutive 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.MethodsTwenty-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.ResultsRelative 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.ConclusionThese 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 registrationThis trial was registered at ClinicalTrials.gov (No. NCT07240272) on November 20, 2025.

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