Magnetic-Resonance Guided Focused Ultrasound Pallidothalamic Tractotomy for Parkinson's Disease

This study is evaluating MR-guided Focused Ultrasound (MRgFUS) treatment for people with Parkinson's disease (PD) who have disabling tremor, bradykinesia, and rigidity despite optimal medical therapy. The study uses the Exablate Neuro System, which delivers ultrasound energy on a specific brain target and generates a small lesion (ablation) without making a surgical incision. This study evaluates three treatment approaches targeting different brain structures involved in Parkinson's motor symptoms: * Pallidothalamic Tractotomy (PTT): targeting pathways connecting the globus pallidus to the thalamus and subthalamic region structures. * Thalamotomy (VIM): targeting the ventral intermediate nucleus of the thalamus, a structure involved in pathogenesis of tremor. * Combined PTT+VIM: targeting both structures during a single treatment procedure. Participants will be randomly assigned to one of four groups: PTT, VIM, PTT+VIM, or "delayed treatment". Participants in the delayed-treatment group will continue best medical therapy for 6 months before receiving MRgFUS treatment. The study aims to determine whether PTT provides greater improvement in motor symptoms than optimized medical therapy alone, whether adding VIM treatment to PTT improves tremor control, and whether adding PTT to VIM treatment provides additional improvement in bradykinesia and rigidity. The main outcome measures are changes in the MDS-UPDRS Part III motor scores: 1. Overall motor symptoms: change in the contralateral body-side MDS-UPDRS Part III motor score at 6 months after randomization, comparing PTT with delayed treatment. 2. Tremor: change in the contralateral tremor score at 6, 12 months after treatment, comparing PTT+VIM with PTT alone. 3. Bradykinesia and rigidity: change in the contralateral bradykinesia and rigidity score at 6, 12 months after treatment, comparing PTT+VIM with VIM alone. MDS-UPDRS Part III is a standard clinical scale used to assess Parkinson's motor symptoms. Assessments are performed in the OFF-medication state, meaning Parkinson's medications are temporarily withheld to better evaluate the treatment effect. In addition, changes in motor complications, tremor severity, quality of life, and medication requirements will be assessed using MDS-UPDRS Parts II-IV, the Clinical Rating Scale for Tremor (CRST), the Parkinson's Disease Questionnaire (PDQ-39), and levodopa equivalent daily dose (LEDD). Treatment-related adverse events, cognitive function, and ablation spot characteristics will also be evaluated throughout follow-up.

Inclusion Criteria: 1. Men or women, age 18 years and older 2. Subject is able and willing to give informed consent and able to attend all study visits 3. Subject with a diagnosis of idiopathic PD established according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease; Hoehn and Yahr stage 2-3 in the practically defined medication-OFF state 4. Mixed motor phenotype of Parkinson's disease defined by the simultaneous presence of clinically significant limb rest tremor, bradykinesia, and rigidity on the more affected side in the medication-OFF state 5. Disease duration ≥3 years from the onset of motor symptoms. 6. Subject is Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state. 7. Subject has MDS-UPDRS Part III OFF ULE score of ≥ 15 on most affected side in the meds OFF condition. 8. Subject is on a stable dose of all PD medications for 30 days prior to screening visit PD assessments as determined by medical records 9. Subject is able to communicate sensations during the Exablate procedure. 10. Subject's pallidothalamic region can be targeted by the Exablate device. 11. Presence of contraindications to, or limitations precluding, deep brain stimulation (DBS), or patient refusal of DBS after being adequately informed about this treatment option. Exclusion Criteria: 1. Subject has other central neurodegenerative disease suspected on neurological examination. 2. Severe postural instability (Hoehn and Yahr stage 4-5 in the medication-OFF state), severe dysarthria, or severe dysphagia. 3. Significant cognitive impairment, defined as a Montreal Cognitive Assessment (MoCA) score \