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Funded Studies

Effect of Deep Brain Stimulation on Cortical Cross Frequency Coupling in Parkinson's Disease: An Electrocorticography Study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common treatment for Parkinson’s disease (PD). Much research has focused on the effects of DBS on the STN and other structures of the basal ganglia, but its effects on the cortex are not known. Our goal is to understand the effects of DBS on cortical function, by recording electrical activity (local field potentials) from the cortex during therapeutic stimulation of the basal ganglia in patients with PD. Our hypothesis is that DBS changes the interaction between low and high frequency cortical oscillations (cross frequency coupling).

Project Description:
Cortical local field potentials from primary motor cortex will be recorded during DBS implantation surgery, using a temporary subdural electrode strip passed through the standard skull opening. Recording will be done both during rest, and during a movement task. Patients will face a touch screen on which visual cues will be displayed indicating where and when to start to move the arm. Movement timing and speed will be measured. Data collection will occur at four time points: prior to insertion of the DBS lead, immediately after insertion of the DBS lead but prior to stimulation, during therapeutic STN stimulation and after stimulation. Changes in the clinical symptoms will be determined by assessment of contralateral limb rigidity using the UPDRS scale. For each task condition, cortical oscillations will be analyzed, using a variety of statistical measures of cross-frequency interactions.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The mechanism of action of STN DBS is still unclear, hindering the development of rationale programming strategies and the discovery of new brain targets. This study will lead to a better understanding of the mechanism of action of DBS at the cortical level. This knowledge could result in the development of cortically based therapies that are safer and simpler than current techniques as well as the development of closed loop stimulation paradigms using a cortical signal to inform stimulation parameters.

Anticipated Outcome:
Interactions between low and high frequency rhythms are a normal part of cortical function, but are altered in PD. We anticipate that therapeutic STN stimulation will reduce pathological patterns of cortical cross frequency coupling, and that this effect will be most marked during movement planning.

Final Outcome

We tested the hypothesis that the mechanism of therapeutic deep brain stimulation (DBS) involves desynchronization of neuronal activity in the motor cortex. We studied population neuronal activity in primary motor cortex in Parkinson’s disease (PD) patients undergoing DBS implantation, before, during and after therapeutic subthalamic stimulation, using subdural electrocorticography. Patients performed a computer controlled arm movement task that included 3 distinct steps; hold, movement preparation, and movement execution. We showed a reversible effect of acute therapeutic DBS in reducing the excessive neuronal synchronization, and more specifically the pathological pattern of interaction between low and high frequency oscillations observed PD patients. The effect of DBS was not restricted to a particular phase of the arm reaching task but rather affected all phases, from holding to planning and execution of the movement. The finding suggests that an overall reduction of this excessive synchrony is required in order to release patients’ symptoms. This study showed that altered cortical synchrony is a biomarker of the parkinsonian state that could be used to improve the DBS treatment by developing close-loop DBS devices able to record cortical activity, evaluate the level of synchrony and determine computationally how to stimulate subcortical structures in a manner that best minimizes abnormal network activity.    


  • Coralie de Hemptinne, PhD

    San Francisco, CA United States

  • Philip Starr, MD, PhD

    San Francisco, CA United States

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