Combined STN and NBM Deep Brain Stimulation for Mild Cognitive Impairment in Parkinson's Disease

Neurostimulation of the Nucleus Basalis of Meynert for the Cognitive-Motor Syndrome in Parkinson's Disease

The goal of this clinical trial is to evaluate the safety and tolerability of a novel deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM) to treat cognitive and cognitive-motor symptoms in individuals with Parkinson's disease. The main question it aims to answer is: Is a combined deep brain stimulation approach targeting the STN and NBM with four DBS leads safe and tolerable for cognitive and cognitive-motor symptoms in individuals with Parkinson's disease with Mild Cognitive Impairment. Ten participants are anticipated to be enrolled. Participants will undergo a modification of the traditional STN DBS approach for motor symptoms of PD. In addition to the two leads placed within the STN, two additional leads will be placed with the NBM for treatment of cognitive and cognitive-motor symptoms. Novel stimulation patterns will be used within the NBM to target cognitive and cognitive-motor symptoms using an investigational software. Participants will be followed over two years while receiving this therapy with assessments at baseline and every six months. Assessments will include a combination of neuropsychological evaluations, cognitive assessments, motor tasks (including gait/walking), and questionnaires to evaluate the treatment. Two different surgical trajectories will be used, with half the cohort randomized to each group. This will allow comparison of the impact of surgical trajectory on the intervention.

All participants will receive the interventional treatment. Two different surgical trajectories will be used for placing the leads in the NBM. Half the cohort will be randomized to each trajectory.

Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a vertical trajectory targeting the nucleus itself.

Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a lateral trajectory targeting the lateral efferent bundle from the NBM

This intervention is a 4-lead deep brain stimulation approach targeting the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM)

Any untoward medical occurrence that occurs during this study whether or not considered related to the study device, study procedures, or study requirements that is identified or worsens during the duration of the study

Swing time variability will be measured using the dual force plates in the SIP task and IMUs for TBC. It is defined as the mean swing time coefficient of variation (CV) of both legs.

Duration of freezing episodes during SIP will be measured using IMUs and force plates using a validated offline algorithm.

Stride time coefficient of variation will be measured using the dual force plates in the SIP task and IMUs. Stride time coefficient of variation is defined as the mean stride time coefficient of variation (CV) of both legs. A greater stride time CV is indicative of less rhythmic gait/stepping.

Shank angular velocity will be measured from IMUs work on the participant's leg/ankle. Reductions in this value are indicative of FOG and gait impairment.

The interstrike-interval of alternating tapping will be measured using an engineered piano keyboard. A higher interstrike-interval indicates slower tapping

The variability of the interstrike-interval of alternating tapping, as quantified by the coefficient of variation, will be measured using an engineered piano keyboard. A higher coefficient of variation indicates worse rhythmicity

PD symptoms will be assessed clinically using the MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Section III. This is a motor examination to evaluate speech, facial expression, tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements, rapid alternating movement of hands, leg agility, arising from chair, posture, gait, freezing of gait, posture, body bradykinesia, and postural stability. Each item is scored on a scale from 0 (normal) to 4 (severe), with the total possible score ranging from 0 to 132.

Each trial of the SAT will be categorized as a Hit (H), Miss (M), or False Alarm (FA). The SAT score is defined as ((H - FA) / [2× (H + FA) - (H + FA)2]), which ranges from - 1.0 (100% incorrect performance; all misses and false alarms) to +1.0 (100% correct performance; all hits and correct rejections).

Cognitive scale composed of 9 tasks that assesses the full range of cognitive dysfunction in PD. It is a scale of 0 to 134, with 134 being the best score.

Total score to assess of this rapid screening test of different cognitive domains. It is a scale of 0 to 30, with 30 being the best score.

Total score on questionnaire regarding participant's mood the last 2 weeks. The scale ranges from 0 to 27 with a score of 27 indicating the most severe symptoms.

Total score on questionnaire regarding participant's anxiety the last two weeks.The scale ranges from 0 to 21 with a score of 21 indicating the most severe symptoms.

Total score evaluating the non-motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.

Total score evaluating the motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.

Total score of motor complications experienced by the participant. It is a scale from 0 to 24 with 24 being the most severe symptoms.

Total score for symptom severity and distress via questionnaire. It is a scale from 0 to 60 with 60 indicating worse symptoms.

Total score for Parkinson's disease-specific health related quality over the last month across 8 quality of life dimensions assessed via questionnaire. Score ranges from 0 to 100 with 100 indicating more symptoms and problems.

Total score on caregiver self-report to assess the stress-levels of family caregivers. It is a scale from 0 to 88 with higher scores indicating greater or worse burden.

Inclusion Criteria: Diagnosis of Parkinson's disease (PD) Approved (or planning on) for subthalamic nucleus (STN) deep brain stimulation (DBS) Willingness to withdraw from clinical medication regimen when necessary for research visits Ability to provide informed consent Exclusion Criteria: Dementia Unstable medical, psychiatric conditions including significant untreated depression, history of suicidal attempt, or current suicide ideation History of seizures Pregnant Requires MRI Unable to walk 100 feet without an assistive device