Low Frequency Subthalamic Nucleus Deep Brain Stimulation to Improve Verbal Fluency

Evaluation of Neurocognitive Changes in Parkinson's Disease Patients Following Acute Low Frequency Deep Brain Stimulation

Rationale: Parkinson's disease patients with deep brain stimulation electrodes represent a unique opportunity to study the influence of basal ganglia on neurocognitive function.

Intervention: Patients' deep brain stimulators will be turned off or on and the frequency will be changed to either theta or gamma.

Objectives: To identify differences in higher cognitive functions with stimulation "on" and "off" and theta versus gamma frequency stimulation.

Study population: 12 patients who had previously undergone bilateral STN deep brain stimulation implantation.

Study methodology: Patients will undergo four sessions of neuropsychological testing (RNGT, verbal fluency, D-KEFS CWIT) at baseline, no stimulation, theta stimulation and gamma stimulation, in random order over one day.

Study outcomes: Test results of RNGT, verbal fluency, D-KEFS CWIT. Follow-up: none

Statistics: Test results will be analyzed using within-subjects statistical tests.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: STN DBS off; Device: STN DBS 10Hz; Device: STN DBS 130Hz

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of the University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients who had previously undergone bilateral STN deep brain stimulation implantation
2. Age >18 years old
3. Stable medication regimen for at least 3 months.
4. Patient informed and able to give written consent
5. Able to comply with all testing, follow-ups and study appointments and protocols

Exclusion Criteria:

1. History of epilepsy or seizure
2. History of major substance abuse
3. Patients with baseline settings at less than 1.5 V will be excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: STN DBS off	Device: STN DBS off; Existing DBS device turned off
Experimental: STN DBS 10Hz	Device: STN DBS 10Hz; Stimulation of existing DBS device at 100Hz, with other parameters at baseline
Active Comparator: STN DBS 130Hz	Device: STN DBS 130Hz; Stimulation of existing DBS device at 130Hz, with other parameters at baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delis-Kaplan Executive Function System Verbal Fluency	Number of words per category in one minute	5-15 minutes following stimulation frequency setting change.
Delis-Kaplan Executive Function System Color Word Interference Task	Time to completion of a color-word interference task	5-15 minutes following stimulation frequency setting change.
Random Number Generation	Listing of 100 numbers at 1 Hz in a random order. Evan's RNG: a measure of disproportion with which one number follows another in a sequence. Scores range from 0 (equal proportion of sequence pairs) to 1 (maximum disproportion of sequence pairs). A higher score indicates a lower randomness and poorer exective function. Count score 1: a measure of propensity to count in steps of 1. The length of each sequence with steps of 1 is squared. The total of these is summed. Scores range from 0 (no sequences with steps of 1) to 100000 (all sequences with steps of 1). A higher score indicates lower randomness and poorer exective function. Count score 2: a measure of propensity to count in steps of 2. The length of each sequence with steps of 2 is squared. The total of these is summed. Scores range from 0 (no sequences with steps of 2) to 100000 (all sequences with steps of 2). A higher score indicates lower randomness and poorer exective function. Evan's RNG, count score 1 and cou	5-15 minutes following stimulation frequency setting change.

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: Darrin J Lee, MD PhD, University of Southern California

Publications and helpful links

General Publications

• Evans FJ. Monitoring attention deployment by random number generation: An index to measure subjective randomness. Bull Psychon Soc 1978;12:35-8.
• Spatt J, Goldenberg G. Components of random generation by normal subjects and patients with dysexecutive syndrome. Brain Cogn. 1993 Nov;23(2):231-42. doi: 10.1006/brcg.1993.1057.
• Towse JN, Neil D. Analyzing human random generation behavior: A review of methods used and a computer program for describing performance. Behav Res Methods Instrum Comput 1998;30:583-91.

Helpful Links

• RGCalc

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Actual): March 3, 2020
• Study Completion (Actual): March 3, 2020

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Language; Neuromodulation; Randomized controlled trial; Memory; Hippocampus; Cognition
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: HS-19-00518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes