Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in the pars compacta of the substantia nigra, leading to cardinal motor symptoms including bradykinesia, rigidity, tremor, and postural instability (Poewe et al., 2017). Despite advancements in pharmacological and surgical treatments, a substantial proportion of patients persistently experience motor impairments that substantially compromise quality of life (Schapira et al., 2017). Consequently, there is a growing interest in non-invasive brain stimulation techniques, such as transcranial alternating current stimulation (tACS), as potential therapeutic interventions for motor dysfunction in PD (Zhang et al., 2022).

tACS is a non-invasive neuromodulation technique that delivers sinusoidal electrical currents through scalp electrodes to entrain cortical activity (Wischnewski et al., 2023). In contrast to transcranial direct current stimulation (tDCS) that employs a constant current, tACS generates frequency-specific oscillations (e.g., β-band at 13–30 Hz), thereby enabling the entrainment of neural oscillations and potential normalization of pathological brain rhythms underlying neurological disorders (Ghobadi-Azbari et al., 2021). In PD, excessive β-band (13–30 Hz) oscillatory activity within the basal ganglia-thalamocortical circuit has been established as a key pathophysiological mechanism contributing to motor symptoms (Gao et al., 2020). By targeting these aberrant oscillations, tACS holds promise as a novel therapeutic approach to ameliorate motor deficits in PD patients.

The rationale for using tACS in PD is further supported by evidence from animal models and human studies demonstrating the role of oscillatory activity in motor control (Lee et al., 2022). For instance, studies have shown that excessive beta-band synchronization in the basal ganglia-thalamocortical loop is associated with bradykinesia and rigidity in PD (Spooner and Wilson, 2023). Targeted modulation of these oscillations via tACS may disrupt pathological synchronization, thereby ameliorating motor dysfunction (Lafleur et al., 2021). Additionally, tACS has been shown to enhance neuroplasticity, which may contribute to its therapeutic effects (Elyamany et al., 2021). Computational models (e.g., Kuramoto oscillators) also suggest tACS may disrupt pathological β-band synchrony through phase-locking interference (Karimi et al., 2024). This phase interference is particularly applicable to the excessive beta synchronization observed in the basal ganglia-thalamo-cortical loop of PD patients. These findings underscore the potential of tACS as a non-invasive, targeted intervention for motor symptoms in PD.

Building upon these mechanistic foundations, tACS offers distinct practical advantages for clinical implementation in Parkinson’s disease management. Unlike other neuromodulation techniques requiring specialized facilities, tACS systems are portable and cost-effective, with recent technological innovations enabling simplified operation through pre-programmed stimulation protocols and quick-apply electrode arrays (Greenwald et al., 2025). Clinical studies have consistently demonstrated excellent tolerability, with fewer than 5% of participants discontinuing treatment due to minor side effects like transient scalp irritation (Liu et al., 2025). These features, combined with emerging evidence of sustained therapeutic effects, position tACS as a viable candidate for decentralized Parkinson’s care – potentially enabling community health centers or even home-based treatment under remote monitoring.

Despite increasing preclinical and clinical investigations, the therapeutic efficacy of tACS for motor dysfunction in PD has not been definitively established. Preliminary studies have demonstrated tACS-induced improvements in bradykinesia, gait, and fine motor control, though these findings are limited by small sample sizes and methodological heterogeneity (Del Felice et al., 2019; Guerra et al., 2023b). However, these studies are often limited by small sample sizes, heterogeneous methodologies, and a lack of long-term follow-up (Fregni et al., 2021). Moreover, the optimal stimulation parameters, including frequency, intensity, and duration, remain poorly defined (Antal et al., 2017). Given these uncertainties, a systematic review and network meta-analysis are warranted to synthesize the available evidence and provide a comprehensive assessment of the effects of tACS on motor function in PD.

The aim of this systematic review and meta-analysis is to assess the efficacy of tACS in improving motor function in patients with Parkinson’s disease. By integrating data from randomized controlled trials (RCTs), this review will provide a strong evidence base to guide clinical practice and future research. In addition, the findings of this review will have a significant impact on the development of non-invasive therapeutic strategies for Parkinson’s disease and contribute to the growing body of literature on neuromodulation in neurodegenerative diseases.

This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (see Supplementary Table S1) (Page et al., 2021). The study protocol is registered with the International Prospective Register of Systematic Reviews under the registration number CRD420251016245 on Mar 21, 2025.

This meta-analysis of 7 randomized controlled trials (n = 173) provides Level I evidence that tACS significantly enhances motor function in Parkinson’s disease, particularly through modulation of corticospinal excitability (MEP) and intracortical inhibition (SICI). In addition, there was one study with the same aim as ours, but this study lacked a control group and was therefore not included in the meta-analysis (Rahimi et al., 2023). In conclusion, the primary findings indicate that tACS significantly enhances MEP amplitude and SICI, suggesting improved corticospinal excitability and motor cortical plasticity. The superior treatment response in dopaminergic medication users (SMD = 2.57 vs. 2.67) suggests a synergistic mechanism, possibly through tACS-induced enhancement of striatal dopamine receptor sensitivity.

Brain stimulation techniques are considered when medications fail to adequately relieve clinical symptoms in Parkinson’s patients. Commonly used non-invasive brain stimulation paradigms include repetitive transcranial magnetic stimulation, tDCS, and tACS (Madrid and Benninger, 2021). To the best of our knowledge, available systematic reviews and meta-analyses have focused on the effects of tDCS on motor function in PD patients (Lee et al., 2019; Elsner et al., 2016; de Oliveira et al., 2021), and few reviews related to the effects of tACS on motor function in PD patients have been seen. To our knowledge, this is the first meta-analysis specifically evaluating tACS for PD motor symptoms. While the effect sizes (SMD 1.88–2.65) are comparable to tDCS/TMS studies, tACS offers unique frequency-specific neuromodulation absent in other techniques (Nguyen et al., 2024; Giustiniani et al., 2025).

Transcranial alternating current stimulates neural tissue by means of alternating current at a certain frequency. Unlike tDCS, it has the advantage that it allows modulation of the oscillatory activity of the neural network due to frequency stimulation at almost imperceptible current strengths (Birreci et al., 2024). The brain’s oscillatory activity at certain frequencies reflects the activation of specific sensorimotor functions (Herrmann et al., 2016). Therefore, attempts have been made to improve motor function in PD patients by enhancing or inhibiting current processes via tACS to increase or decrease the amplitude of oscillations.

Motor threshold has traditionally been defined as the lowest TMS stimulus intensity capable of eliciting a small MEP, and SICI denotes the greater conditioned test stimulus intensity required to generate and maintain the target MEP response, both of which can respond to changes in brain motor function (Vucic et al., 2023). In the present study, we found a significant increase in MEP amplitude in the experimental group of Parkinson’s patients after tACS intervention compared to the control group (SMD = 2.65, p < 0.00001), which suggests that tACS enhances the excitability of the corticospinal tracts. This result is consistent with the findings of Guerra et al. who found that γ-tACS improves motor function in Parkinson’s disease patients by restoring synaptic plasticity in the primary motor cortex (Guerra et al., 2023b). In addition, there was also a significant improvement in SICI in the experimental group after tACS intervention (SMD = 1.88, p < 0.00001).

In the early stages of Parkinson’s disease, L-dopamine is a very effective treatment for PD (Haddad et al., 2017). However, it is important to note that levodopa medication was not taken in the same way in these studies. Therefore, we performed a subgroup analysis assuming whether or not dopamine medication was taken as a source of heterogeneity in the data. PD patients in two studies were not taking dopamine medication, but their motor function improved equally significantly after the tACS intervention (Guerra et al., 2023a; Benussi et al., 2024). The results of the subgroup analysis suggested that dopamine medication use was indeed an important source of heterogeneity in this meta-analysis. In addition, the observed heterogeneity may reflect differences in the severity of Parkinson’s disease in different patients. Future studies should use uniform outcome assessments and stratify analyses by disease stage to minimize confounders.

With this in mind, we considered whether accurate tACS could be achieved through machine learning. Studies have shown that supervised learning of baseline UPDRS III scores and resting-state β-power predicts treatment response. For example, a randomized forest model integrating age and disease duration achieved 82% accuracy in predicting the outcome of transcranial magnetic stimulation, a framework applicable to tACS (Hamzyan Olia et al., 2025). In addition, closed-loop tACS, where stimulation is adjusted via real-time EEG classification of β-bursts, represents a transformative frontier for home-based therapy.

Of course, these included articles vary in their choice of tACS stimulation frequency, and it is not clear which stimulation frequency works best. They are mainly categorized as γ-tACS, β-tACS, and α-tACS, with different frequencies having different therapeutic effects on neurological disorders. Our data do not identify which frequency band has better efficacy, and the variation between studies highlights the need for adaptive trials. Bayesian optimization can efficiently navigate the parameter space (e.g., 10–30 Hz, 1–2 mA) to determine patient-specific protocols (frequency, intensity, duration, electrode montage). Many studies have shown that γ-tACS modulates neural oscillations, enhances cognitive function and provides neuroprotection (Sanchez-Garrido Campos et al., 2025). β-tACS may restore the balance of cortico-basal ganglia circuits by “desynchronizing” abnormal β oscillations (Naros and Gharabaghi, 2017). α-tACS may improve sensorimotor integration by modulating thalamo-cortical circuits (Fresnoza et al., 2020). β-γ PAC disruption may serve as a biomarker, with tACS selectively attenuating excessive phase-locking in the basal ganglia-thalamocortical loop (Salimpour et al., 2022). Perhaps different stimulation frequencies are also a source of heterogeneity, but the small amount of literature did not allow for further analysis. The variation in stimulation parameters (e.g., frequency, intensity) across studies highlights the need for dose mapping tests. Future work should systematically compare parameter sets to establish evidence-based protocols.

Current studies also have many limitations. First, the sample sizes of the included studies are small (median n = 25 per study), which may affect the validity of our results, as well as the generation of heterogeneity. While our findings are statistically significant, the limited number of studies restricts the generalizability of the conclusions. Future large-scale, multicenter RCTs with standardized protocols are urgently needed to validate these preliminary results and assess the long-term efficacy of tACS in PD. Second, differences in tACS parameters (e.g., frequency, duration of sessions) and control conditions (sham versus standard treatment) may confound results. Third, the measurement of outcomes lacks a uniform quantitative metric. Although MEP and SICI are valuable physiological metrics, they do not fully reflect the multidimensional nature of motor function in Parkinson’s disease (Washabaugh et al., 2024). MEP/SICI provide limited insight into real-world motor function. Combining wearable sensors with ML pipelines (e.g., convolutional neural networks to analyze tremor kinematics) could bridge this gap. Fourth, there is a lack of long-term follow-up data to assess persistence of efficacy. Finally, although the funnel plot showed minimal bias, the small number of studies made it difficult to draw definitive conclusions. Therefore, future trials should prioritize conducting long-term assessments and harmonizing metrics to validate tACS as a reliable adjunctive therapy. And, future studies should be reported with complete stimulation protocols, including electrode locations (10–20 systems), waveforms, impedance, and total charge, to improve replicability and for computational modeling.

By integrating evidence from seven randomized controlled trials, this study demonstrates for the first time that tACS significantly improves motor function in patients with Parkinson’s disease, with clear clinical significance in terms of effect size (SMD 1.88–2.65). Notably, when tACS was combined with dopaminergic drugs, improvements in MEP and SICI reached 265 and 188%, respectively, a synergistic effect that suggests that tACS may reinforce the effects of existing therapies by enhancing striatal dopamine receptor sensitivity.

From a pathophysiological point of view, the dual modulatory effect of tACS-i.e., simultaneous enhancement of corticospinal excitability and improvement of intracortical inhibition-distinguishes it from conventional symptomatic treatments. Of particular interest is the fact that this improvement is significantly associated with the modulation of neural oscillations in the beta band (13–30 Hz), which provides a new perspective for understanding the role of tACS in motor network reorganization. However, there is still no consensus among existing studies on the optimal stimulation frequency (α/β/γ bands), reflecting the heterogeneity of current evidence.

Based on these findings, future studies should prioritize multicenter phase III clinical trials with standardized 20 Hz β-band stimulation parameters (1.5 mA, 30 min/session) and incorporate long-term follow-up of at least 6 months. At the same time, optimizing the stimulation regimen by incorporating individualized EEG characteristics will help to achieve a paradigm shift from “one size fits all” to precise neuromodulation. Only through these systematic efforts can tACS truly become a scalable adjunct in the comprehensive treatment of Parkinson’s disease.