Efficacy of Deep-coil Based Repetitive Transcranial Magnetic Stimulation in the Treatment of Parkinson's Disease With Freezing of Gait and Its Neural Regulation Mechanism Study of Resting-state Cerebral Blood Flow

The protocol for repetitive transcranial magnetic stimulation (rTMS) in treating Parkinson's disease (PD) with freezing of gait (FOG) has not yet established an internationally unified standard, and the heterogeneity of treatment parameters is often the main factor leading to significant differences in efficacy. Based on descriptive analyses and existing data from studies with relatively small sample sizes, the current research primarily focuses on unilateral stimulation targets, without exploring the effectiveness of stimulating the bilateral primary motor centers for lower limbs (M1-LL). Moreover, most studies use figure-of-eight coils or circular coils, while deep-coil stimulation may be more effective for M1-LL. There is still a lack of research employing arterial spin labeling (ASL) imaging to explore the neural mechanisms of resting-state cerebral blood flow (CBF) regulation associated with rTMS treatment for FOG.

Therefore, this research project will focus on improving the above - mentioned issues. The high - frequency stimulation of bilateral M1 - LL using a deep - coil (double - cone coil) will be selected. The sample size will be further expanded to evaluate the efficacy of rTMS in treating freezing of gait (FOG). Combined with the three - dimensional arterial spin labeling (3D - ASL) imaging technique, the changes in resting - state cerebral blood flow (CBF) before and after treatment will be analyzed to explore the possible neural mechanisms of rTMS in treating FOG.

Magstim rapid 2 transcranial magnetic stimulation instrument was used with double-cone coils, and the stimulation target was bilateral M1-LL. The total stimulation time of each target was 10 minutes, once a day, 5 times a week (5 consecutive working days), and the treatment was continuous for 2 weeks, a total of 10 times.

Stimulus parameter setting:

* True stimulus group: 100% Rest Motor Threshold (RMT), 10Hz, each stimulus lasted 10 seconds, 55 seconds apart, a total of 10 strings. Once a day, each side of the lower extremity region of the primary motor cortex received a total of 1000 pulses.
* In the pseudo-stimulation group, the side of the double-cone coil was placed against the scalp, and the bull 's-eye of the coil was stimulated towards the air. Other treatment parameters were the same as those of true stimulation group.

Eligibility Criteria:
Inclusion Criteria:

* Meeting the clinical diagnostic criteria for Parkinson's disease established by the Movement Disorder Society (MDS) in 2015.
* Aged between 45 and 70 years old, regardless of gender.
* Regularly taking anti - Parkinson's disease medications for a long time (≥3 years), accompanied by freezing of gait, and with poor efficacy of medications;
* A score of ≥24 on the Mini - Mental State Examination (MMSE).
* Signing the informed consent form and being willing to actively cooperate with the treatment.

Exclusion Criteria:

* Freezing of gait caused by parkinsonism and parkinson plus syndromes.
* Having a history of central nervous system diseases such as cerebral infarction, cerebral hemorrhage, leukoencephalopathy, and migraine.
* Having been diagnosed with epilepsy or having had epileptic seizures.
* Having undergone craniocerebral surgery, having cerebral aneurysms or arteriovenous malformations, having metal implants in the skull, or having had a cardiac pacemaker implanted.
* Having a history of other mental illnesses or a family history of mental illnesses, such as schizophrenia, bipolar disorder, autism, mental retardation, depression, etc.
* Having received rTMS treatment.
* Severe PD (H\&Y grade ≥ 4).
* Severe organ dysfunction or severe physical diseases.