In the basal ganglia-thalamocortical motor circuit, network activity is precisely timed to facilitate execution of voluntary movement. In Parkinson's Disease (PD), this functional network is impaired by excessive neuronal synchronization that disrupts local oscillations necessary for integrated motor performance. The role of the cortex within this distributed hypersynchronous state is not well understood. Functional imaging studies in PD patients suggest decreased resting state metabolic activity in movement preparatory areas such as the premotor cortex (PreMC), while other studies suggest increased resting state metabolic activity in primary motor cortex (M1). In a previous study (Crowell et al., 2012), our la demonstrated an increase in M1 gamma frequency power spectral density over a very broad band (30-250 Hz) in PD patients versus controls, indicative of increased resting state activity. However, it was not clear if this alteration is also associated with voluntary movement. This is a critical question because one potential explanation for diminished motor performance in PD is that pathological overactivity in M1 at rest reduces the dynamic range over which it can respond to other frontal areas involved in executive motor control. An alternative explanation is that, prir to motor tasks, premotor cortical areas are not appropriately recruited to prepare movement sequences, resulting in attenuated motor execution. A third explanation is that abnormal oscillatory activity in the basal ganglia prevents appropriate selection of motor plans required fo goal-directed movement. Here, we propose a novel approach to testing these hypotheses in patients with basal ganglia dysfunction: electrocorticographic (ECoG) recordings of PreMC and M1 in PD patients performing motor tasks during awake DBS surgery along with detailed structural mapping of cortico-basal ganglia pathways in these same patients using diffusion tensor imaging (DTI). The advantage of this approach is high spatial and temporal resolution of cortical activity matched with precise cortical gyral anatomy of activated and deactivated subcortical pathways. The novelty of this approach is further enhanced in that one motor task will consist of a Go-No Go exercise in which the patient must activate or suppress cued reaching movements to a touch-screen device. This will allow the critical evaluation of the basal ganglia's role in response inhibition at the level of the premotor and motor cortices. We hypothesize that increases in broadband gamma activity (BGA) will be suppressed in PreMC and M1 in PD patients before and during Go trials versus patients without a movement disorder. We also predict that the pattern of PreMC and M1 BGA will be unchanged between successful and unsuccessful No Go trials in patients with PD.

Public Health Relevance

Parkinson's Disease affects between 500,000 and 1 million people in the United States and is the second most common neurodegenerative disorder. Surgical treatment of Parkinson's Disease provides an opportunity to record directly from the motor-related brain areas of affected patients, thus allowing us to study fundamental mechanisms of movement disorders. We propose to investigate dynamic changes in local field potentials in the cerebral cortex of Parkinson's patients during deep brain stimulation surgery in order to determine how impaired cortical function may contribute to symptoms in this disorder.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-F01-F (20))
Program Officer
Sieber, Beth-Anne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code