Modulatory Effects of Deep Brain Stimulation on Cerebral Cortical Activity
Condition: DBS; Parkinson Disease; Essential Tremor; Healthy
MeSH terms: Parkinson Disease; Essential Tremor
Study type: Interventional

Summary: 
      The purpose of this study is to learn about how deep brain stimulation (DBS) affects brain
      activity in those with Parkinson's disease (PD) and essential tremor (ET). The effect of
      therapeutic and non-therapeutic stimulation settings will be assessed. Additionally, DBS
      effects in the presence and absence of anti-PD medication will be studied. Also of interest
      are differences in stimulation effects while at rest versus while performing a task.
    

Detailed description: 
      Deep brain stimulation (DBS) is a standard-of-care, FDA approved therapy for Parkinson's
      disease (PD) and tremor and well over 1,000 patients have been implanted at the Cleveland
      Clinic in the past 20 years. The therapy involves stereotactic implantation of one or more
      leads into specific sensorimotor brain regions, with each lead consisting of an array of four
      to eight contacts. The proximal end of the lead is tunneled to an implantable pulse generator
      (IPG) placed under the skin of the chest. Post-operatively, a health care professional
      carefully programs the IPG: adjusting the delivery location (i.e., contact selection) and
      titrating the frequency, amplitude, and width of the stimulus pulses to maximize therapeutic
      benefit while minimizing any side effects. It is hypothesized that the chronic, electrical
      stimulation of the target region has both local and circuit-wide effects, the net effect of
      which is to disrupt the pathophysiological neural activity present across both cortical and
      subcortical brain regions that is thought to underlie disease manifestation.

      Study-related activities will begin in the morning, with participants reporting to the Center
      for Neurological Restoration outpatient clinic desk in the S-building. Those participants
      with a diagnosis of Parkinson's disease will be asked to arrive in the "practically defined
      OFF" state (i.e., will come for testing having taken PD medications as usual up to midnight
      of the preceding day, and none on the morning of testing). To help to minimize off-medication
      risks, patients with PD will be offered the option to stay overnight at an on-campus hotel at
      no cost. Patients will be provided with lunch and additional rest breaks, as needed,
      throughout the day.

      A technician will apply either Ag/AgCl clinical scalp electrodes or an elastic cap
      pre-populated with electrodes after which electroencephalographic (EEG) activity will be
      monitored and recorded throughout the remainder of the study. Participants will undergo an
      initial stimulation threshold evaluation to establish DBS-related sensorimotor side effect
      thresholds.

      Throughout testing, participants will be seated comfortably in a quiet room. Continuous EEG
      and EMG recordings will be made as the parameters of the patients IPG are systematically
      modified (i.e., changes in pulse frequency, amplitude, width and active contacts) with the
      patient at rest and, for specific settings, again while the patient performs a simple,
      continuous motor task using the upper extremity (e.g., computer-generated sine tracking).
      Visual and auditory evoked potentials will be elicited using stimuli delivered via goggles
      (or other light source) and headphones, respectively. Somatosensory evoked potentials will be
      elicited through electrical stimulation of the median or posterior tibialis nerve using
      standard clinical techniques at approximately 125% of motor threshold. Event related
      potentials tasks will include simple and choice reaction time, NoGo, as well as auditory
      oddball tasks repeated in one or more DBS conditions. Note that the precise order of test
      administration may be randomized in order to minimize order effects. Also note that patients
      diagnosed with PD will be instructed to take their usual dose of anti-PD medication
      approximately mid-way through the test session, after which a subset of the evoked potential
      testing will be repeated.

      In this study, the investigators will use multiple non-invasive physiological metrics,
      including scalp electroencephalography and surface electromyography, to characterize the
      spatiotemporal pattern of cortical and corticomuscular modulation associated with
      therapeutic, non-therapeutic, and side-effect-inducing parameters of DBS to address the
      specific aims.
    

Intervention name(s): EMG; EEG
Intervention type(s): Other; Other
Intervention description(s): recordings of muscle electrical activity during nerve stimulation using EMG; recordings of brain activity using EEG
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Study N = 180 participants 60 participants with diagnosis of essential tremor having DBS implanted 70 participants with diagnosis of Parkinson Disease having DBS implanted 50 healthy controls
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Deep Brain Stimulation