Parkinson Disease
Conditions
Keywords
Cognition, Hippocampus, Language, Memory, Neuromodulation, Randomized controlled trial
Brief summary
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.
Interventions
DEVICESTN DBS 10Hz
Stimulation of existing DBS device at 100Hz, with other parameters at baseline
DEVICESTN DBS 130Hz
Stimulation of existing DBS device at 130Hz, with other parameters at baseline
DEVICESTN DBS off
Existing DBS device turned off
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delis-Kaplan Executive Function System Verbal Fluency | 5-15 minutes following stimulation frequency setting change. | Number of words per category in one minute |
| Delis-Kaplan Executive Function System Color Word Interference Task | 5-15 minutes following stimulation frequency setting change. | Time to completion of a color-word interference task |
| Random Number Generation | 5-15 minutes following stimulation frequency setting change. | 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 |
Countries
United States
Participant flow
Pre-assignment details
12 participants, each tested at off, 10 Hz and 130 Hz
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All Study Participants | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 8.2 | — |
| Primary language Chinese | 1 Participants | — |
| Primary language English | 9 Participants | — |
| Primary language Spanish | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 12 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 12 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Delis-Kaplan Executive Function System Color Word Interference Task
Time to completion of a color-word interference task
Time frame: 5-15 minutes following stimulation frequency setting change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| STN DBS Off | Delis-Kaplan Executive Function System Color Word Interference Task | Word reading | 24.58 Seconds | Standard Error 1.96 |
| STN DBS Off | Delis-Kaplan Executive Function System Color Word Interference Task | Color reading | 33.83 Seconds | Standard Error 2.68 |
| STN DBS Off | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word interference | 67.92 Seconds | Standard Error 4.58 |
| STN DBS Off | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word switching | 72.42 Seconds | Standard Error 7.17 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word switching | 74.25 Seconds | Standard Error 7.74 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Word reading | 24.75 Seconds | Standard Error 1.74 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word interference | 70.00 Seconds | Standard Error 6.84 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color reading | 35.00 Seconds | Standard Error 2.51 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word interference | 67.92 Seconds | Standard Error 10.54 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Word reading | 24.17 Seconds | Standard Error 5.62 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color reading | 34.33 Seconds | Standard Error 6.61 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Color Word Interference Task | Color-word switching | 70.25 Seconds | Standard Error 18.98 |
Primary
Delis-Kaplan Executive Function System Verbal Fluency
Number of words per category in one minute
Time frame: 5-15 minutes following stimulation frequency setting change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| STN DBS Off | Delis-Kaplan Executive Function System Verbal Fluency | Letter | 12.75 Words per minute | Standard Error 1.7 |
| STN DBS Off | Delis-Kaplan Executive Function System Verbal Fluency | Nonepisodic | 13.83 Words per minute | Standard Error 1.36 |
| STN DBS Off | Delis-Kaplan Executive Function System Verbal Fluency | Episodic | 17.17 Words per minute | Standard Error 1.56 |
| STN DBS Off | Delis-Kaplan Executive Function System Verbal Fluency | Category Switching | 14 Words per minute | Standard Error 1.76 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Verbal Fluency | Category Switching | 25.00 Words per minute | Standard Error 5.23 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Verbal Fluency | Letter | 13.25 Words per minute | Standard Error 1.54 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Verbal Fluency | Episodic | 18.00 Words per minute | Standard Error 1.47 |
| STN DBS 10Hz | Delis-Kaplan Executive Function System Verbal Fluency | Nonepisodic | 11.33 Words per minute | Standard Error 2.93 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Verbal Fluency | Category Switching | 13.17 Words per minute | Standard Error 0.94 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Verbal Fluency | Nonepisodic | 11.83 Words per minute | Standard Error 1.11 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Verbal Fluency | Episodic | 15.46 Words per minute | Standard Error 1.47 |
| STN DBS 130Hz | Delis-Kaplan Executive Function System Verbal Fluency | Letter | 13.58 Words per minute | Standard Error 1.54 |
Primary
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
Time frame: 5-15 minutes following stimulation frequency setting change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| STN DBS Off | Random Number Generation | Count score 1 | -3.10 Index | Standard Error 0.41 |
| STN DBS Off | Random Number Generation | Evan's RNG | 0.35 Index | Standard Error 0.02 |
| STN DBS Off | Random Number Generation | Count score 2 | -3.27 Index | Standard Error 0.29 |
| STN DBS 10Hz | Random Number Generation | Count score 1 | -3.21 Index | Standard Error 0.38 |
| STN DBS 10Hz | Random Number Generation | Evan's RNG | 0.35 Index | Standard Error 0.02 |
| STN DBS 10Hz | Random Number Generation | Count score 2 | -2.65 Index | Standard Error 0.4 |
| STN DBS 130Hz | Random Number Generation | Evan's RNG | 0.37 Index | Standard Error 0.01 |
| STN DBS 130Hz | Random Number Generation | Count score 2 | -2.32 Index | Standard Error 0.25 |
| STN DBS 130Hz | Random Number Generation | Count score 1 | -2.90 Index | Standard Error 0.34 |