Investigating Inhibitory Control Networks in Parkinson's Disease
Investigating Inhibitory Control Networks in Parkinson's Disease
The purpose of this study is to investigate the brain activity associated with non-motor
 symptoms of movement disorders, including Parkinson's disease and essential tremor. These
 movement disorders commonly have significant non-motor features also, including depression,
 cognitive impairment, decreased attention, and slower processing speeds. The investigators
 are interested in the brain activity associated with these symptoms, and perform recordings
 of the surface 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, 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, many patients also have prominent non-motor features, including depression and
 cognitive impairment, with deficiencies in processing speed, memory, attention, and learning.
 One of the most debilitating cognitive deficiencies is in response inhibition (RI), or the
 inability to suppress a habitual action. PD patients have significant difficulty with RI, and
 report its substantial contribution in limiting their quality of life. While some studies
 show that dopamine can improve this aspect of cognitive function, many patients remain
 considerably impaired.

 RI manifests clinically in many different and important ways, with reduced mental
 flexibility, task-switching, and concentration. RI may also contribute to motor impairment,
 with gait dysfunction, falls, and freezing of gait. Unfortunately, these features of PD and
 RI 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 motor manifestations, is essentially ineffective for, and can even worsen cognition, with
 few studies currently investigating how different parameters may improve NMS. In an effort to
 begin addressing these debilitating features of PD, the investigators propose to study RI in
 patients with movement disorders, and to correlate movement and cognition with underlying
 neural electrophysiology before and during tasks of motion and response inhibition.

 During routine DBS surgery, the stimulating electrode is implanted with the aid of
 intraoperative recordings in the awake state. These routine recordings enable neurologists
 and neurosurgeons to directly observe neuronal firing in the brain, identifying
 characteristic patterns to delineate anatomic structures. Once in place, the DBS electrode is
 tested using stimulation parameters known to be clinically efficacious for motor impairment.
 This allows acute, intraoperative testing for therapeutic benefit and side effects, and give
 information for how a patient will respond to the therapy once the cranial electrode is
 connected to the battery and turned on.

 In addition to this routine recording and stimulation, this setting also provides a unique
 opportunity to study neural electrophysiology, with minimal increased risk. By measuring
 brain activity in the outer layers (cortex) as well as from the DBS electrode itself, while
 patients perform various tasks, it is possible to correlate behavioral function and neural
 activity. Our center, and several others, already have research paradigms in place to achieve
 these goals, by placing a subdural strip electrode over cortex prior to placing the DBS lead.
 These strip electrodes lie along the surface of the brain, and have historically been used
 for several decades to perform seizure mapping, typically as an array of electrodes placed
 via a burr hole. Their use has only more recently been implemented for investigation of
 neural circuits during DBS surgery, however, their safety in this specific setting is now
 well-established, and their temporary placement is currently being performed in similar
 studies at this institution. However, though previous studies have placed these strips over
 prefrontal areas, the vast majority of research in this area is focused on motor circuits,
 with placement over sensorimotor cortex. In order to study NMS, strips will be placed over
 prefrontal cortex, with recordings made during various motor and cognitive tasks and during
 different stimulation patterns.
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