Objective/Rationale:
Deep brain stimulation (DBS) of basal ganglia structures is an effective treatment for Parkinson’s disease (PD). However, its mechanism of action is still unclear, hindering the development of rationale programming strategies. So far, most studies have utilized acute DBS and short recordings performed under the constraints of the human operating room. The next step to understanding the pathophysiology of PD and improve deep brain stimulation therapy requires long term intracranial recording.
Project Description:
The objectives of this pilot study are to assess the feasibility of chronic brain recording using a novel fully implantable device (Medtronic Activa PC&S) and to study chronic effects of therapeutic DBS on cortical (brain surface) physiology. Cortical signals will be recorded chronically, using electrodes permanently placed during the DBS implantation surgery. Patients enrolled in this pilot study will be tested at six time points over 12 months. Recordings will be done in different behavioral (resting, walking, performing a movement task), stimulation and medication conditions. Changes in the clinical symptoms will be determined by assessment of contralateral limb symptoms using standard rating scales. For each condition, cortical activity will be analyzed, using a variety of measures of neuronal synchronization.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Current DBS therapy consists of delivering continuous stimulation to deep structures of the brain, leading to habituation, side effects and low battery life. One way to improve DBS treatment is to develop a DBS device able to automatically adjust stimulation parameters when detecting pathophysiological changes. Such “smart” devices require a biomarker reflecting patient's clinical state and robust over time. Long term recordings will allow us to determine the ability to record cortical signal stable over time.
Anticipated Outcome:
PD is characterized by excessive synchronization between populations of cortical neurons that is reduced by acute therapeutic DBS. We anticipate that recordings of cortical signal will remain stable over time allowing us to measure the level of neuronal synchrony chronically and characterize the time course of DBS effect on cortical synchronization. Movements, medication and chronic DBS are expected to reduce altered synchrony.
Final Outcome
We have implanted five Parkinson’s disease (PD) patients with the Activa PC+S device. This device provides stimulation in deep parts of the brain (basal ganglia), like typical deep brain stimulation (DBS), but also allows recording brain signal data from the deep brain structure as well as the surface of the brain (motor cortex). These recordings have allowed us to access over time changes in brain activity associated with PD symptoms as well as side-effects associated with PD therapies. In particular, we have characterized a robust signature associated with dyskinesia which is very reliable over time. We are currently investigating whether this signal could be used as a signal to help customize DBS stimulation parameters or adjust medication doses.