American Parkinson Disease Association

The American Parkinson Disease Association is using its 2020 distribution to fund:

  • Investigating prefrontal biomarkers of action control and effects of theta-burst deep brain stimulation in Parkinson’s Disease

    PROJECT TITLE:  Investigating prefrontal biomarkers of action control and effects of theta-burst deep brain stimulation in Parkinson’s Disease

    Investigator/Author:  J. Nicole Bentley, MD

    Objective:  To determine the signals arising from brain networks in the prefrontal cortex and basal ganglia that form the basis of cognitive control in Parkinson’s Disease (PD), and to investigate whether alternative patterns of deep brain stimulation (DBS) can improve cognitive task performance in PD. 

    Background:  Cognitive impairment is very common in PD and is a significant source of disability even after motor symptoms are well-controlled with medications or DBS. Cognitive impairment manifests in many different ways, including dysfunction in memory, attention, and processing speed. Of particular importance in PD is reduced inhibitory control, a cognitive process that allows for inhibition of an impulsive response to a stimulus. Impairments of inhibitory control can lead to an inability to adapt to changing environmental conditions and is associated with falls and freezing of gait.

    Neuronal oscillations, or brainwaves, underlie many cognitive processes, including inhibitory control. PD patients have reduced activity of various types of neuronal oscillations, which correlates with slower response times in cognitive tasks. DBS, while highly effective for motor symptoms, is ineffective for improving cognitive function under current high-frequency programming paradigms. There is data however, that low-frequency programming paradigms may have promise in improving cognitive performance.

    We will recruit 10 patients with PD who are undergoing DBS surgery for treatment of their PD motor symptoms. We will investigate neuronal oscillations in the prefrontal cortex and subcortical brain areas as the patients perform an inhibitory control cognitive task during DBS surgery. We will also measure changes in these patterns when we deliver low-frequency stimulation.   

    Our hypothesis is that patients with pre-existing mild cognitive impairment will have greater improvements in measures of inhibitory control during low frequency stimulation as compared to standard stimulation parameters.

    Relevance to Diagnosis/Treatment of Parkinson’s Disease: The findings from this study will help to inform future research protocols investigating the ability of DBS to improve cognitive performance in PD with cognitive impairment.

    October 2021 Project Update:

    We have enrolled 5 of the 10 planned participants, with 1 participant withdrawing from the task portion of the study due to intraoperative fatigue.

    We have found that overall performance during the inhibitory control cognitive task (Go/No-go task) trends toward improvement (decreased reaction times) during intermittent low frequency (intermittent theta-burst stimulation, iTBS) when compared to the off-stimulation condition.

    Continued experiments and analyses will consist of additional subject performance of the Go/No-go task at baseline and during iTBS and continuous theta-stimulation. We will also correlate behavioral and electrophysiologic metrics with baseline cognitive status and determine whether stimulation differentially affects subjects based on the presence of mild cognitive impairment.