rTMS to Enhance Cognitive Performance and Promote Resilience

Safety and Efficacy of an Accelerated Protocol of Intermittent Theta Burst Transcranial Magnetic Stimulation (TMS) to Enhance Performance and Promote Resilience in Astronauts: Study 1

The purpose of this study is to determine the most effective dose of brief, non-invasive brain stimulation (repetitive transcranial magnetic stimulation, rTMS) for improving cognitive functions such as attention and memory as well as to improve the ability to recover from stressful situations (stress resilience).

Study Overview

• Status: Completed
• Conditions: Cognition; Stress Reaction
• Intervention / Treatment: Device: rTMS

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) works by rapidly turning a focused magnetic field on-and-off repeatedly over your head, which passes directly through your hair, scalp, and skull and onto your brain, and can temporarily increase brain activity under the magnetic field. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for depression, and is used commonly to treat people for their depression. The rTMS treatment regime used in this study is different from the FDA approved treatment because you will receive up to ten treatments per day over five days instead of the FDA approved rTMS treatment regime of 25 treatments over 25 days. This sort of accelerated or high dose protocol has been shown to be safe and effective in the treatment of depression. We are hoping to find out if this treatment can be used as a treatment for improving cognitive function and stress resilience.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. No history of mental or physical illness
2. No implanted metal in the body
3. College graduates (Associates degree or higher)
4. Negative urine pregnancy test, if female subject of childbearing potential
5. Able to read and understand questionnaires and informed consent

Exclusion Criteria:

1. Any current psychiatric diagnosis or current Clinical Global Impression ratings of psychiatric illness > 1
2. Current physical illness
3. History of CNS disease, concussion, overnight hospitalization, tumors, seizures, meningitis, encephalitis, abnormal CT/MRI of the brain
4. Moderate to severe traumatic brain injury (TBI)
5. History of a continuing significant laboratory finding
6. Frequent or severe headaches
7. Any history of psychotropic medication prior to study enrollment
8. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
9. active participation or plan for enrollment in another evidence-based clinical trial affecting psychosocial function
10. repeated abuse or dependence upon drugs (excluding nicotine and caffeine)
11. implanted devices/ferrous metal of any kind

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 2; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 2 is 10 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 3; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 3 is 15 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 4; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 4 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 1; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is 5 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 5; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 5 is 25 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 6; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 6 is 30 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 7; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 7 is 35 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 8; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 8 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 9; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 9 is 45 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Experimental: Dose 10; All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 50 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.	Device: rTMS; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Score of Neurocognitive Performance (Fluid Cognition)	Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. This composite includes all the tests noted above that are fluid ability measures: Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting and Pattern Comparison. This composite score is derived by averaging the standard scores of each of the measures, and then deriving standard scores based on this new distribution. Higher values (positive changes from baseline) indicate better performance. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.	Baseline (Day 1)
Change From Baseline in Neurocognitive Performance at 1 Week Post Treatment (Fluid Cognition)	Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. This composite includes all the tests noted above that are fluid ability measures: Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting and Pattern Comparison. This composite score is derived by averaging the standard scores of each of the measures, and then deriving standard scores based on this new distribution. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.	Post-treatment (within 1 week of completing rTMS)
Change From Baseline in Neurocognitive Performance at 1 Month Post Treatment (Fluid Cognition)	Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. This composite includes all the tests noted above that are fluid ability measures: Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting and Pattern Comparison. This composite score is derived by averaging the standard scores of each of the measures, and then deriving standard scores based on this new distribution. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.	Post-treatment (within 1 month of completing rTMS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Score of Stress Resilience as Assessed by Connor Davidson Resilience Scale	Participants would complete a series of questionnaires Connor Davidson Resilience Scale is a self-reported scale consisting of 10-items measuring resilience. Respondents rate items on a 5-point Likert scale, ranging from 0 (not true at all) to 4 (true nearly all the time). Each item has a minimum score of 0 and a maximum score of 4. The minimum value is a 0 and the maximum value is a 100. A higher score indicates higher resilience, which indicates a better outcome. -Questions are rated on a scale from 0-4, where a higher score reflects greater resilience.	Baseline (Day 1)
Mean Score of Stress Resilience as Assessed by Perceived Stress Scale-10	The investigators will use the Perceived Stress Scale 10 (PSS-10) to assess perceived stress using a 5-point Likert scale. Scoring Instructions: Total score is determined by adding together the scores of each of the four items. Questions 2 and 3 are reverse coded. Questions 1 and 4: 0 = Never; 1 = Almost never; 2 = Sometimes; 3 = Fairly often; 4 = Very often Questions 2 and 3: 4 = Never; 3 = Almost never; 2 = Sometimes; 1 = Fairly often; 0 = Very often. Scores range from 0 to 40 with higher scores indicating more stress.	Baseline (Day 1)
Mean Score of Stress Resilience as Assessed by Inventory of Depression and Anxiety Symptoms-II	The Inventory of Depression and Anxiety Symptoms-II (IDAS-II) is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). In this study, a composite score was calculated by summing responses across multiple relevant subscales (e.g., Dysphoria, Panic, Insomnia, Well-Being) to assess overall emotional distress and stress resilience. Minimum possible score: 99 (if all items scored 1) Maximum possible score: 495 (if all items scored 5) Higher scores indicate greater symptom severity and worse outcomes. Lower scores reflect better emotional functioning and greater resilience.	Baseline (Day 1)
Mean Score of Stress Resilience as Assessed by Connor Davidson Resilience Scale	The Connor Davidson Resilience Scale (CD-RISC 10) is a unidimensional self-reported scale consisting of 10-items measuring resilience. Respondents rate items on a 5-point Likert scale, ranging from 0 (not true at all) to 4 (true nearly all the time). Each item has a minimum score of 0 and a maximum score of 4. The minimum value is a 0 and the maximum value is a 100. A higher score indicates higher resilience, which indicates a better outcome.	Post-treatment (within 1 week of completing rTMS)
Mean Score of Stress Resilience as Assessed by Perceived Stress Scale-10	The investigators will use the Perceived Stress Scale 10 (PSS-10) to assess perceived stress using a 5-point Likert scale. Scoring Instructions: Total score is determined by adding together the scores of each of the four items. Questions 2 and 3 are reverse coded. Questions 1 and 4: 0 = Never; 1 = Almost never; 2 = Sometimes; 3 = Fairly often; 4 = Very often Questions 2 and 3: 4 = Never; 3 = Almost never; 2 = Sometimes; 1 = Fairly often; 0 = Very often. Scores range from 0 to 40 with higher scores indicating more stress.	Post-treatment (within 1 week of completing rTMS)
Mean Score of Stress Resilience as Assessed by Inventory of Depression and Anxiety Symptoms-II	The Inventory of Depression and Anxiety Symptoms-II (IDAS-II) is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). In this study, a composite score was calculated by summing responses across multiple relevant subscales (e.g., Dysphoria, Panic, Insomnia, Well-Being) to assess overall emotional distress and stress resilience. Minimum possible score: 99 Maximum possible score: 495 Higher scores indicate greater symptom severity and worse outcomes. Lower scores reflect better emotional functioning and greater resilience.	Post-treatment (within 1 week of completing rTMS)
Mean Score of Stress Resilience as Assessed by Connor Davidson Resilience Scale	The Connor Davidson Resilience Scale (CD-RISC 10) is a unidimensional self-reported scale consisting of 10-items measuring resilience. Respondents rate items on a 5-point Likert scale, ranging from 0 (not true at all) to 4 (true nearly all the time). Each item has a minimum score of 0 and a maximum score of 4. The minimum value is a 0 and the maximum value is a 100. A higher score indicates higher resilience, which indicates a better outcome.	Post-treatment (within 1 month of completing rTMS)
Mean Score of Stress Resilience as Assessed by Perceived Stress Scale-10	The investigators will use the Perceived Stress Scale 10 (PSS-10) to assess perceived stress using a 5-point Likert scale. Scoring Instructions: Total score is determined by adding together the scores of each of the four items. Questions 2 and 3 are reverse coded. Questions 1 and 4: 0 = Never; 1 = Almost never; 2 = Sometimes; 3 = Fairly often; 4 = Very often Questions 2 and 3: 4 = Never; 3 = Almost never; 2 = Sometimes; 1 = Fairly often; 0 = Very often. Scores range from 0 to 40 with higher scores indicating more stress.	Post-treatment (within 1 month of completing rTMS)
Mean Score of Stress Resilience as Assessed by Inventory of Depression and Anxiety Symptoms-II	The Inventory of Depression and Anxiety Symptoms-II (IDAS-II) is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). In this study, a composite score was calculated by summing responses across multiple relevant subscales (e.g., Dysphoria, Panic, Insomnia, Well-Being) to assess overall emotional distress and stress resilience. Minimum possible score: 99 Maximum possible score: 495 Higher scores indicate greater symptom severity and worse outcomes. Lower scores reflect better emotional functioning and greater resilience.	Post-treatment (within 1 month of completing rTMS)
Mean Score of Neurocognitive Performance (WINSCAT Composite)	The WINSCAT battery includes 5 subtests: Code Substitution (CDS), Code Substitution Delayed Recognition (CDD), Delayed Matching to Sample (MSP), Mathematical Processing (MTH), and Running Memory Continuous Performance (CPT). Each subtest produces a standardized score (range: 0-100). Composite score is the sum of all subtests (range: 0-500). Higher scores indicate better cognitive performance. Baseline scores reflect initial neurocognitive status. WINSCAT assesses attention, memory, visual processing, and executive function.	Baseline (Day 1)
Mean Score of Neurocognitive Performance (WINSCAT Composite)	The WINSCAT battery includes 5 subtests: Code Substitution (CDS), Code Substitution Delayed Recognition (CDD), Delayed Matching to Sample (MSP), Mathematical Processing (MTH), and Running Memory Continuous Performance (CPT). Each subtest produces a standardized score (range: 0-100). Composite score is the sum of all subtests (range: 0-500). Higher scores indicate better cognitive performance. This measure reflects post-treatment neurocognitive status following rTMS. Scores are compared to baseline to assess improvement. WINSCAT evaluates attention, memory, visual processing, and executive function.	Post-treatment (within 1 week of completing rTMS)
Mean Score of Neurocognitive Performance (WINSCAT Composite)	The WINSCAT battery includes 5 subtests: Code Substitution (CDS), Code Substitution Delayed Recognition (CDD), Delayed Matching to Sample (MSP), Mathematical Processing (MTH), and Running Memory Continuous Performance (CPT). Each subtest produces a standardized score (range: 0-100). Composite score is the sum of all subtests (range: 0-500). Higher scores indicate better cognitive performance. This measure reflects neurocognitive status 1 month after rTMS treatment. Scores are compared to baseline and 1-week post-treatment to assess sustained or enhanced cognitive improvement. WINSCAT evaluates attention, memory, visual processing, and executive function.	Post-treatment (within 1 month of completing rTMS)
Mean Score of Neurocognitive Performance (Stress Total Score)	is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. For this outcome, a subset of items was used to assess stress resilience, likely drawn from the Well-Being or related subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). Scores were summed across selected items. Minimum possible score: 0 Maximum possible score: 15 Lower scores indicate greater resilience and better emotional functioning. Higher scores indicate greater symptom severity and worse outcomes.	Baseline (Day 1)
Mean Score of Neurocognitive Performance (Stress Total Score)	is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. For this outcome, a subset of items was used to assess stress resilience, likely drawn from the Well-Being or related subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). Scores were summed across selected items. Minimum possible score: 0 Maximum possible score: 15 Lower scores indicate greater resilience and better emotional functioning. Higher scores indicate greater symptom severity and worse outcomes.	Post-treatment (within 1 week of completing rTMS)
Mean Score of Neurocognitive Performance (Stress Total Score)	is a 99-item self-report questionnaire assessing emotional and psychological symptoms across 18 subscales. For this outcome, a subset of items was used to assess stress resilience, likely drawn from the Well-Being or related subscales. Each item is rated on a 5-point Likert scale from 1 ("Not at all") to 5 ("Extremely"). Scores were summed across selected items. Minimum possible score: 0 Maximum possible score: 15 Lower scores indicate greater resilience and better emotional functioning. Higher scores indicate greater symptom severity and worse outcomes.	Post-treatment (within 1 month of completing rTMS)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Structural MRI - FLAIR	FLAIR sequences	Baseline (Day 1)
Baseline Structural MRI - Diffusion	Diffusion sequences	Baseline (Day 1)
Baseline Structural MRI - T2	T2 sequences	Baseline (Day 1)
Baseline Structural MRI - Volumetric	Volumetric sequences	Baseline (Day 1)
Change from baseline in structural MRI at 1 week post treatment - FLAIR	FLAIR sequences	Post-treatment (within 1 week of completing rTMS)
Change from baseline in structural MRI at 1 week post treatment - Diffusion	Diffusion sequences	Post-treatment (within 1 week of completing rTMS)
Change from baseline in structural MRI at 1 week post treatment - T2	T2 sequences	Post-treatment (within 1 week of completing rTMS)
Change from baseline in structural MRI at 1 week post treatment - Volumetric	Volumetric sequences	Post-treatment (within 1 week of completing rTMS)

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Aeronautics and Space Administration (NASA); The Translational Research Institute for Space Health (TRISH)
• Investigators: Principal Investigator: Donna Roberts, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2019
• Primary Completion (Actual): September 27, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: memory; adult; cognition; Transcranial Magnetic Stimulation; Stress, Psychological; attention; prefrontal cortex
• Additional Relevant MeSH Terms: Wounds and Injuries; Behavioral Symptoms; Fractures, Bone; Behavior; Stress, Psychological; Fractures, Stress
• Other Study ID Numbers: 00084982

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.: No