Metabolic Correlates of Pedunculopontine Nucleus Deep Brain Stimulation in Parkinson’s Disease

Lay Summary

Imaging Neural Processes of a New Deep Brain Stimulation Treatment for Parkinson’s Disease

Investigators will study eight Parkinson’s disease patients who are undergoing treatment with deep brain stimulation of the peduculopontine nucleus and ask if PET (positron emission tomography) imaging can be used to predict which patients benefit from the treatment.

Parkinson’s disease (PD) is a progressive neurodegenerative disease whose symptoms include slowed movement, muscle stiffness, tremor, and problems with balance. The disease is caused by loss of brain nerve cells (neurons) that produce the neurotransmitter dopamine.  PD symptoms can be treated by medications that help restore brain dopamine levels, but these medications often have undesirable side effects.  In recent years, researchers have shown that both PD symptoms and medication side effects can be improved by a surgical treatment called deep-brain stimulation (DBS).  In DBS, electrodes are placed in the brain to stimulate structures that normally act in cooperation with dopamine-producing neurons to control movement.  Through processes that are still not fully understood, this DBS helps to rebalance neural circuit activity and alleviate symptoms.

Until now, most DBS therapy has targeted a structure called the subthalamic nucleus (STN).  However, stimulation of this area does not provide equally good results in all patients.  Recently, stimulation of a different structure, the peduculopontine nucleus (PPN), has proved beneficial for some patients who do not respond to STN stimulation. Thus, just as is true for antidepressant therapy, different forms of DBS therapy seem to work better for different individuals.  The challenge is to figure out in advance which patients will respond best to which therapy.

PET imaging can be used to assess brain function and changes that occur after therapy. When done with a form of sugar called glucose, PET imaging can measure increases and decreases in regional brain activity.  By performing PET scans on PD patients before and after the initiation of DBS of the PPN, the investigators will determine how brain circuit activity is modified by this treatment. They will then try to identify specific patterns of brain activity that distinguish patients who respond positively this intervention compared to those who do not.

Significance:  This work will provide insights into how DBS improves the symptoms of PD and will aid in the selection of DBS brain targets for patients with advanced PD.