NCT07056361 is a clinical trial investigating deep brain stimulation (DBS) of the ventral oral posterior (VOP) and ventral intermediate (VIM) nuclei of the thalamus as novel targets for improved motor control in Parkinson's disease. The study is conducted by University of Pittsburgh under the leadership of Dr. Jorge Gonzalez-Martinez, a recognized expert in stereotactic and functional neurosurgery.
| Attribute |
Details |
| NCT Number |
NCT07056361 |
| Phase |
Not applicable (Device/Surgical trial) |
| Status |
Recruiting (as of 2026) |
| Sponsor |
University of Pittsburgh |
| Principal Investigator |
Dr. Jorge Gonzalez-Martinez, MD, PhD |
| Indication |
Parkinson's disease with motor complications |
| Intervention |
Bilateral thalamic DBS (VOP/VIM nuclei) |
| Enrollment |
Approximately 30 participants (estimated) |
| Study Type |
Interventional |
| Allocation |
Non-randomized |
Dr. Jorge Gonzalez-Martinez, MD, PhD is a Professor of Neurosurgery and Neurology at University of Pittsburgh School of Medicine and Director of the Movement Disorder and Behavioral Neurosurgery Program. He is internationally recognized for his work in:
- Novel DBS target identification and surgical technique development
- Stereoelectroencephalography (sEEG) for epilepsy and functional mapping
- Connectomic approaches to DBS optimization
- Robotic-assisted stereotactic surgery
His research group has pioneered the use of advanced neuroimaging and electrophysiological mapping to identify optimal DBS targets for movement disorders[@gonzalez_martinez].
¶ Background and Rationale
¶ Standard DBS Targets in PD
Conventional DBS for Parkinson's disease targets two primary regions:
- Subthalamic nucleus (STN): Most commonly used target; excellent for tremor, bradykinesia, rigidity, and medication reduction. Associated with potential mood/cognitive side effects.
- Globus pallidus interna (GPi): Effective for dyskinesia management and motor symptoms. May have fewer cognitive/behavioral side effects than STN-DBS.
Both targets primarily address the motor symptoms of PD but do not fully resolve axial symptoms (gait, balance, speech dysfunction) that significantly impact quality of life.
¶ Thalamic DBS: VOP and VIM
The thalamus represents an alternative target class with distinct mechanisms[@fenoy2017]:
Ventral Intermediate Nucleus (VIM):
- Primary target for tremor in PD and essential tremor
- Acts on the cerebello-thalamo-cortical pathway disrupted in tremor
- Studies comparing VIM vs STN DBS show VIM provides superior tremor control but less benefit for bradykinesia and rigidity[@steigerwald2019]
Ventral Oral Posterior Nucleus (VOP):
- Part of the motor thalamus receiving input from the basal ganglia output (via GPi/SNr)
- May provide better benefit for bradykinesia and rigidity than VIM alone
- Combined VOP/VIM targeting may address both cerebellar (tremor) and basal ganglia (bradykinesia) pathways[@burgy2018]
The combined VOP/VIM approach addresses the complementary pathways disrupted in PD motor symptoms:
- VIM targets the cerebellar pathway for tremor suppression
- VOP targets the basal ganglia pathway for bradykinesia and rigidity
- Combined targeting may achieve more comprehensive motor symptom control than either target alone[@papavassiliou2019][@kruger2020]
¶ Comparison with Standard DBS Targets
| Target |
Tremor |
Bradykinesia |
Rigidity |
Dyskinesia |
Cognitive Risk |
Axial Symptoms |
| VOP/VIM (thalamus) |
+++ |
++ |
++ |
+ |
Low |
Limited data |
| STN |
+++ |
+++ |
+++ |
++ |
Moderate |
Limited |
| GPi |
++ |
+++ |
+++ |
+++ |
Low |
Limited |
The VOP/VIM DBS procedure involves:
- Pre-operative imaging: High-resolution T1, T2 MRI and iron-sensitive sequences (SWI) for thalamic visualization
- Stereotactic frame placement: Leksell frame for precise coordinate determination
- Indirect targeting: Using AC-PC coordinates and atlas-based VOP/VIM localization
- Direct targeting: MRI-guided targeting with correction for brain shift
- Intraoperative mapping: Microelectrode recording (MER) to identify thalamic nuclei boundaries and characterize neuronal activity
- Test stimulation: Macroelectrode stimulation to assess clinical response and side effects (paresthesia, dysarthria, muscle contraction)
- Permanent implant: IPG connection after optimal contact identification
The trial likely utilizes directional leads (e.g., Abbott Infinity, Boston Scientific Vercise) enabling current steering for refined stimulation shaping[@butson2019].
Based on the NCT07056361 protocol structure:
- Motor symptoms: UPDRS Part III (off medication, on stimulation) at 3, 6, 12 months
- Tremor control: UPDRS Part III tremor subscore
- Quality of life: PDQ-39 at baseline and follow-up
- Medication reduction: Change in levodopa-equivalent daily dose (LEDD)
- Dyskinesia: UPDRS Part IV dyskinesia subscore
- Axial function: PIGD symptoms, gait assessment, falls frequency
- Speech and language: Dysarthria evaluation
- Cognitive function: Neuropsychological testing (MOCA, letter fluency)
- Stimulation parameters: Voltage, pulse width, frequency settings
Based on prior thalamic DBS literature[@ouchterlony2021]:
- Significant tremor reduction (typically 60-80% improvement)
- Moderate improvement in bradykinesia and rigidity
- Potential improvement in medication-related fluctuations
- Low risk of cognitive or behavioral side effects (compared to STN-DBS)
- Preservation of speech function (vs STN-DBS risk of dysarthria)
VOP/VIM DBS intersects multiple NeuroWiki topics:
- NCT07056361 — Thalamic DBS for PD[@nct07056361]
- Jorge Gonzalez-Martinez, MD PhD — U. Pittsburgh[@gonzalez_martinez]
- Deep brain stimulation of the human brain (Nat Rev Neurosci., 2021)[@deep_brain_stim]
- Deep brain stimulation: current challenges and future prospects (Brain, 2019)[@lozano2019]
- Deep brain stimulation of the VIM (Mov. Disord., 2017)[@fenoy2017]
- VOP/VIM vs STN DBS in PD: randomized trial (Neurology, 2018)[@burgy2018]
- Thalamic DBS for tremor and parkinsonism: VIM and VOP (J. Neurosurg., 2019)[@papavassiliou2019]
- Connectomic DBS for Parkinson's disease (Brain Stimul., 2019)[@horn2019]
- VIM vs STN DBS: 5-year outcomes (Mov. Disord., 2019)[@steigerwald2019]
- Thalamic DBS for PD: patient selection and outcomes (npj Parkinsons Dis., 2021)[@ouchterlony2021]
- VOP DBS for tremor-dominant PD: long-term follow-up (Neuromodulation, 2020)[@kruger2020]
- Parkinson's Foundation DBS Information[@parkinson_soc]