Neurophysiological, Behavioral, and Cognitive Networks in Movement Disorders

The purpose of this study is to investigate the brain activity associated with motor and non-motor symptoms of movement disorders, including Parkinson's disease (PD) and essential tremor. These movement disorders commonly have significant non-motor features, such as depression, cognitive and memory impairment, decreased attention, speech and language disturbances, and slower processing speeds. The investigators are interested in the brain activity associated with these motor and non-motor symptoms, and propose to investigate changes in brain activity while the investigators perform recordings of the surface and deep structures of the brain, in addition to the typical recordings the investigators perform, during routine deep brain stimulation (DBS) surgery.

Movement disorders are a prominent cause of disability worldwide. In the United States, it is estimated that more than 4 million people suffer from Parkinson's disease (PD), essential tremor (ET), and dystonia, making them some of the most prevalent of neurologic disorders. Of these, PD is the most common, and is primarily characterized by tremor, rigidity, and bradykinesia. However, though primarily characterized by motor symptoms, many patients also have prominent non-motor features, including depression and cognitive impairment, with deficiencies in processing speed, memory, attention, and learning. Some of the most debilitating cognitive deficiencies include deficits in goal-directed response selection and response inhibition, language, and/or speech difficulties, all of which substantially contribute to reduced quality of life. Unfortunately, these features of movement disorders are less well-studied and lack effective treatment options, necessitating that new treatments be investigated. Deep brain stimulation (DBS), while a highly effective treatment for the cardinal features of PD, is essentially ineffective for, and can even worsen other cognitive domains, and there are few studies currently investigating how different parameters of DBS may improve these symptoms. In addition, speech abnormalities are common with Parkinson's disease and DBS can sometimes worsen speech problems. These impairments consists primarily of hypophonia, but cognitive deficits can result in actual language disturbance. It is often difficult to know whether the speech problems are related to language processing or articulation (related to the movement disorder). In an effort to begin addressing these questions, we propose to study motor and non-motor symptoms in patients with movement disorders, and to correlate movement and cognition with underlying neural electrophysiology.

After creation of the burr hole and prior to DBS electrode placement, 1-2 subdural strip electrodes will be placed anteriorly or posteriorly from the cranial opening. These electrodes are routinely placed using this technique for seizure mapping, with arrays of electrodes (up to 6) being placed around the perimeter of the opening.14 Subdural strips vary in length and contact size (e.g., the 6-contact Ad-Tech strip), and are currently placed predominantly for studies of sensorimotor function,13 including at our institution (IRB-140327003). Placement over prefrontal areas is performed at other institutions.11-13 The DBS surgery will then proceed according to routine practice, and following lead placement in the optimal desired location, the research task paradigm will begin.

In the Simon task, participants are instructed to respond with a right or left button press (Right = Red, Left = Blue) according to how a word is printed on a screen ("RED" or "BLUE"), regardless of the color in which the word is printed. This is a measurement of accuracy (% correct, ranging from 0-100, with higher scores indicating better performance)

In the Simon task, participants are instructed to respond with a right or left button press (Right = Red, Left = Blue) according to how a word is printed on a screen ("RED" or "BLUE"), regardless of the color in which the word is printed. This is a measurement of accuracy (% correct, ranging from 0-100, with higher scores indicating better performance)

In the Simon task, participants are instructed to respond with a right or left button press according to the word "RIGHT" or "LEFT" that appears on a screen, regardless of where on the screen it actually appears. This is a measurement response times (continuous measure, from 0-4000 milliseconds) between correct and incorrect responses.

In the Simon task, participants are instructed to respond with a right or left button press according to the word "RIGHT" or "LEFT" that appears on a screen, regardless of where on the screen it actually appears. This is a measurement response times (continuous measure, from 0-4000 milliseconds) between correct and incorrect responses.

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in response times between congruent and incongruent trials

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in response times between congruent and incongruent trials

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in accuracy between congruent and incongruent trials

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in accuracy between congruent and incongruent trials

Participants will undergo motor evaluation using the validated United Parkinson's disease Rating Scale (UPDRS) part 3

Participants will undergo motor evaluation using the validated United Parkinson's disease Rating Scale (UPDRS) part 3

Participants will undergo neuropsychological testing as part of routine care, including the Dementia Rating Scale

Participants will undergo intracranial monitoring during DBS surgery in which a prefrontal strip electrode will be placed, enabling measurement of brain activity.

Participants will undergo intracranial monitoring during DBS surgery in which a DBS electrode will be placed, enabling measurement of brain activity at subcortical targets.

Participants will undergo intracranial monitoring during DBS surgery in which a DBS electrode will be placed, enabling measurement of brain activity at subcortical targets.

Participants will undergo intracranial monitoring during DBS surgery in which a prefrontal strip electrode will be placed, enabling measurement of brain activity.

Participants will undergo intracranial monitoring during DBS surgery in which a prefrontal strip electrode and DBS electrode will be placed, enabling measurements of connectivity between these structures.

Participants will undergo intracranial monitoring during DBS surgery in which a prefrontal strip electrode and DBS electrode will be placed, enabling measurements of connectivity between these structures.

In the Simon task, participants are instructed to respond with a right or left button press (Right = Red, Left = Blue) according to how a word is printed on a screen ("RED" or "BLUE"), regardless of the color in which the word is printed. This is a measurement of accuracy (% correct, ranging from 0-100, with higher scores indicating better performance)

In the Simon task, participants are instructed to respond with a right or left button press according to the word "RIGHT" or "LEFT" that appears on a screen, regardless of where on the screen it actually appears. This is a measurement response times (continuous measure, from 0-4000 milliseconds) between correct and incorrect responses.

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in response times between congruent and incongruent trials

Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in accuracy between congruent and incongruent trials

Participants will undergo motor evaluation using the validated United Parkinson's disease Rating Scale (UPDRS) part 3

Comparison of hemispheric differences in power spectral density (p-value, parametric two-tailed t-test)

Correlation of prefrontal power spectra between outpatient EEG and intraoperative ECOG (correlation coefficient)

Participants will perform the Simon task during pre- and post-operative study visits. Power spectra will be compared to intraoperative power spectra.

Inclusion Criteria: Eligible for DBS surgery based on multi-disciplinary consensus review Have a diagnosis of Parkinson's disease or Essential Tremor A minimum of 18 years of age Willingness to participate in the paradigms described in the protocol Exclusion Criteria: Inability to provide full and informed consent Are not surgical candidates due to co-morbid conditions or pregnancy Have not undergone an adequate trial of conservative medical management Have a clinical presentation for which DBS surgery is not indicated Are not able to participate in study-related activities