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The combination of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) is an increasingly recognized neuromodulation strategy in the treatment of Parkinsonian syndromes, showing particular potential in improving both motor and non-motor symptoms. Typical motor symptoms such as bradykinesia, rigidity, and tremor, along with various non-motor symptoms including pain, depression, and fatigue, collectively contribute to the major burden of the disease. tDCS modulates cortical excitability via weak electrical currents, while TMS induces neuronal depolarization using time-varying magnetic fields. Their combined application allows synergistic multi-target intervention on the motor cortex and related neural networks. However, high-quality randomized controlled trials focusing on the combined tDCS-TMS approach in Parkinsonian syndromes remain relatively limited, and its long-term efficacy and underlying mechanisms have not yet been systematically established.Beyond systematically evaluating the efficacy and safety of combined tDCS-TMS on motor and non-motor functions in patients with Parkinsonian syndromes, this study also aims to integrate multimodal neuroimaging and neurophysiological techniques to investigate the key mechanisms by which the combined modulation acts on basal ganglia-cortical circuits and the default mode network. Furthermore, we will analyze the specificity and synergism of its effects across different symptomatic domains.
Full description
Parkinson's disease is a neurodegenerative disorder caused by the degeneration of dopaminergic neurons, with pathological mechanisms involving abnormal activity in neural networks. tDCS modulates the excitability of cortical neurons via weak electrical currents, while TMS stimulates specific brain regions using magnetic fields. Both techniques are capable of regulating brain network activity. Their combined application may enable more comprehensive modulation of pathological neural networks and theoretically produce synergistic improvements across multiple symptoms of Parkinson's disease.Parkinsonian syndromes are characterized not only by motor symptoms but also by non-motor manifestations such as cognitive impairment, depression, and sleep disturbances. The combination of tDCS and TMS may not only enhance the effects of each technique applied alone but also allow simultaneous multi-target interventions, leading to more holistic symptom management.Although research on combined tDCS-TMS in Parkinsonian syndromes remains limited, evidence from related fields supports the feasibility and potential benefits of such neuromodulatory strategies. This study employs a randomized, double-blind design to evaluate the efficacy and safety of combined tDCS-TMS treatment in patients with Parkinsonian syndromes. By using single-pulse resting-state EEG and functional magnetic resonance imaging (fMRI), we aim to directly capture changes in cortical activity mechanisms within the M1 region before and after the intervention.
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Inclusion criteria
① The diagnosis of primary Parkinson's disease conforms to the clinical diagnostic criteria for PD established by the Movement Disorders Society (MDS) in 2015.
The diagnosis of Parkinson's plus syndromes conforms to the following: The diagnosis of multiple system atrophy conforms to the clinical diagnostic criteria for MSA established by the MDS in 2022; the diagnosis of progressive supranuclear palsy conforms to the clinical diagnostic criteria for PSP established by the MDS in 2017.
Having one or more of the following conditions: Complicating with one or more sleep disorders; Complicating with cognitive impairment, with a Mini-Mental State Examination (MMSE) score < 27 points and/or a Montreal Cognitive Assessment (MoCA) score < 26 points; Complicating with freezing of gait; Accompanied by one or more types of PD pain, with a Numerical Rating Scale (NRS) score ≥ 3 points and lasting for 3 months or more.
The medications for treating PD have been stably used for more than 2 weeks, and the original medication treatment regimen is maintained during the transcranial magnetic stimulation (TMS) treatment period.
Analgesic medications such as non-steroidal anti-inflammatory drugs have been stably used for more than 16 weeks, and the original treatment dosage is maintained unchanged during the trial period.
⑥ There is no obvious atrophy and no other characteristic changes in the head CT/MRI examination.
⑦ The patient and their family members have been informed of the examination items to be carried out, have given their informed consent, and have signed the informed consent form.
Exclusion criteria
① Patients with other diseases that may affect the sensation of peripheral nerves, including diabetes mellitus, herpes infection, long-term use of specific medications or excessive alcohol consumption, stroke, spinal cord lesions, etc.;
Patients complicated with severe depression or mental disorders;
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40 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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