Neurology · Medical Literature
Theta tACS Over the Medial Frontal Cortex Modulates Executive Function in Parkinson's Disease: A Randomized, Sham-Controlled Study.
Abstract
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. 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. 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. 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. This trial was registered at ClinicalTrials.gov (No. NCT07240272) on November 20, 2025.
Clinical relevance
Executive dysfunction affects a substantial proportion of Parkinson's disease (PD) patients and remains an undertreated non-motor symptom with limited pharmacological options. This randomized, sham-controlled trial addresses a critical gap by evaluating high-definition transcranial alternating current stimulation (HD-tACS) — a non-invasive, oscillatory neuromodulation technique — as a targeted cognitive rehabilitation strategy for PD. Given the growing burden of cognitive impairment in PD populations and the lack of disease-modifying cognitive therapies, these findings are of immediate clinical and translational relevance to movement disorder specialists and neurologists.
Key findings
1. Active 6-Hz HD-tACS over the medial frontal cortex (MFC) delivered across 10 daily sessions produced significant improvements in Trail Making Test parts A (TMT-A) and B (TMT-B) relative to sham stimulation, reflecting gains in processing speed and cognitive flexibility, respectively. 2. Semantic Verbal Fluency Test (VFT) performance was significantly improved in the active HD-tACS group compared to sham; notably, phonemic VFT showed no significant stimulation-specific effect, suggesting domain-selective modulation of semantic retrieval networks. 3. Functional near-infrared spectroscopy (fNIRS) demonstrated reduced VFT-evoked oxyhemoglobin responses in the right dorsolateral prefrontal cortex (DLPFC) following active stimulation, consistent with enhanced neural efficiency rather than compensatory hyperactivation. 4. Baseline-adjusted post-intervention analyses revealed a significantly smaller Simon effect in the active HD-tACS group, indicating improved conflict monitoring and response selection — core executive sub-processes mediated by the MFC. 5. The active HD-tACS group demonstrated a higher inhibition rate on the stop-signal task (SST), suggesting enhanced response inhibition, though SST reaction time did not differ significantly between groups. 6. No significant stimulation-specific effects were observed for forward or backward Digit Span Test (DST) performance, indicating that the 6-Hz MFC protocol selectively targets frontal executive networks rather than producing global cognitive enhancement across working memory domains.
Practice implications
Movement disorder specialists may consider 6-Hz HD-tACS over the MFC as an adjunctive, non-pharmacological intervention for PD patients presenting with clinically significant executive dysfunction, particularly deficits in cognitive flexibility, semantic fluency, and conflict monitoring. Patient selection should prioritize those with documented frontal-executive impairment on standardized assessments (e.g., TMT-B, semantic VFT) while acknowledging that this protocol does not appear to benefit phonemic fluency, digit span, or stop-signal reaction time, underscoring the need for outcome-matched patient profiling. Replication in larger, multi-site trials with longer follow-up durations, dose-optimization studies, and direct comparison with standard cognitive rehabilitation will be necessary before this protocol can be integrated into routine clinical practice.