Adaptive Deep Brain Stimulation to Improve Motor and Gait Functions in Parkinson's Disease
Adaptive Deep Brain Stimulation to Improve Motor and Gait Functions in Parkinson's Disease
This is a single-center phase I clinical study aiming to improve gait functions in patients
 with Parkinson's disease (PD) by using adaptive neurostimulation to the pallidum. The
 investigators will use a bidirectional deep brain stimulation device with sensing and
 stimulation capabilities to 1) decode the physiological signatures of gait and gait
 adaptation by recording neural activities from the motor cortical areas and the globus
 pallidus during natural walking and a gait adaptation task, and 2) develop an adaptive deep
 brain stimulation (DBS) paradigm to selectively stimulate the pallidum during different
 phases of the gait cycle and measure improvements in gait parameters. This is the first
 exploration of network dynamics of gait in PD using chronically implanted cortical and
 subcortical electrodes. In addition to providing insights into a fundamental process, the
 proposed therapy will deliver personalized neurostimulation based on individual physiological
 biomarkers to enhance locomotor skills in patients with PD. Ten patients with idiopathic
 Parkinson's disease undergoing evaluation for DBS implantation will be enrolled in this
 single treatment arm study.
This study will allow the investigators to evaluate the efficacy of an adaptive stimulation
 paradigm in deep brain stimulation (DBS) to treat motor-related behaviours and motor skill
 learning in Parkinson's disease (PD). Parkinson's disease patients will be implanted
 unilaterally or bilaterally with a totally internalized bidirectional neural interface,
 Medtronic Summit RC+S.

 While current DBS therapy improves motor symptoms of PD, it does not address problems with
 acquiring additional motor skills (i.e. adapting gait patterns to avoid falls)) in PD,
 therefore, limiting benefits of physical rehabilitation programs aimed at improving mobility.
 Motor skill learning is critical in acquiring any new behaviors related to motor function.
 The overall objective is to identify personalized electrophysiological signatures of motor
 skill learning in PD patients and use adaptive control algorithms to enhance these
 signatures. The study will discover new ways to rehabilitate the disease brain circuits using
 adaptive neuromodulation.

 In a small, double-blinded trial, ten patients with idiopathic PD and motor fluctuations will
 be implanted with unilateral or bilateral RC+S devices, each connected to a standard
 quadripolar DBS lead implanted in the basal ganglia, along with a 4-contact paddle type
 electrode placed subdurally over the motor cortex. The investigators will compare the overall
 efficacy of closed-loop and open-loop paradigms in terms of behavioral performance
 improvements in validated motor skill learning tasks and measurements from wearable devices.
 During this chronic adaptive DBS phase, adaptive DBS and open-loop stimulation settings will
 be randomized for 30-day periods and motor skill and gait related measurements will be
 obtained from a combination of computerized motor tasks and wearable devices that track
 movement kinematics. Patients will participate in daily, if possible, motor learning and gait
 tasks at home with triggered stimulation settings and recordings.

 The investigators expect to successfully develop a prototype adaptive DBS algorithm based on
 cortical and / or basal ganglia LFPs (local field potentials). The investigators hypothesize
 that an adaptive paradigm will provide improvements in motor skilled learning compared to the
 conventional, open-loop paradigm, in which stimulation parameters remain constant until
 changed by the patient or clinician using an external programmer.
Inclusion Criteria:

 -  Ability to give informed consent for the study

 -  Movement disorder symptoms that are sufficiently severe, in spite of best medical
 therapy, to warrant surgical implantation of deep brain stimulators according to
 standard clinical criteria

 -  Patient has requested surgical intervention with deep brain stimulation for their
 disorder

 -  No movement -elated abnormalities that suggest an alternative diagnosis or
 contraindicate surgery

 -  Absence of significant cognitive impairment (score of 21 or greater on the Montreal
 Cognitive Assessment (MoCA),

 -  Signed informed consent

 -  Ability to comply with study follow-up visits for brain recording, testing of adaptive
 stimulation, and clinical assessment.

 -  Age 21-75

 -  Diagnosis of idiopathic PD with duration of motor symptoms for 3 years or greater

 -  Patient has undergone appropriate therapy with oral medications with inadequate relief
 as determined by a movement disorders neurologist.

 -  UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in
 the baseline UPDRS-III on medication score, compared to the baseline off-medication
 score, and motor fluctuations with at least 2 hours per day of on time without
 dyskinesia or with non-bothersome dyskinesia. OR Patients with tremor-dominant PD (a
 tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant,
 with significant functional disability despite maximal medical management

 -  Patients with gait impairments: slowed gait, shuffling steps, postural instability, or
 freezing of gait off medication.

 -  Ability of patient and/or caregivers to recharge the system evaluated by all
 clinicians and study personnel.

 -  Geographical proximity and/or ability to travel to study sites for patient to receive
 re-programming via investigational devices (e.g. Summit Research Laboratory
 Programmer).

 Exclusion Criteria:

 -  Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of
 seizures, heart disease, or other medical conditions considered to place the patient
 at elevated risk for surgical complications

 -  Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion
 or "while unobserved", symptoms that are inconsistent over time or incongruent with
 clinical condition, plus other manifestation such as "false" signs, multiple
 somatizations, or obvious psychiatric disturbance.

 -  Pregnancy: all women of child bearing potential will have a negative urine pregnancy
 test prior to undergoing their surgical procedure.

 -  Significant untreated depression (BDI-II score >20). History of suicidal attempt or
 active suicidal ideation (Yes to #2-5 on C-SSRS)

 -  Any personality or mood symptoms that study personnel believe will interfere with
 study requirements.

 -  Subjects who require electroconvulsive therapy (ECT), repetitive transcranial magnetic
 stimulation (rTMS) or diathermy

 -  Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator, or
 neurostimulator

 -  Previous cranial surgery

 -  Drug or alcohol abuse

 -  Meets criteria for Parkinson's disease with mild cognitive impairment (PD-MCI). These
 criteria are: performance of more than two standard deviations below appropriate
 norms, for tests from two or more of these five cognitive domains: attention,
 executive function, language, memory, and visuospatial tests.

 -  Known allergies to the implantable device components including titanium, polyurethane,
 silicone, and nylon.