tRAS Brain Stimulation for Executive Dysfunction

(TRAS Trial)

Overseen By Lauren Jackson, BS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must not be taking: Benzodiazepines, Antipsychotics, Antiepileptics, Stimulants

Disqualifiers: ADHD, Neurological disorder, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking medications like benzodiazepines, antipsychotics, antiepileptics, or central nervous system stimulants, you will need to stop taking them to participate in the trial.

What data supports the effectiveness of the tRAS Brain Stimulation treatment for Executive Dysfunction?

Research shows that non-invasive brain stimulation, like transcranial direct current stimulation (tDCS), can improve executive functions such as working memory and problem-solving in people with brain injuries or disorders. This suggests that similar treatments, like tRAS, might also help with executive dysfunction. ^{1 2 3 4 5}

Is tRAS brain stimulation safe for humans?

Transcranial electrical stimulation (TES), which includes methods like tRAS, has been shown to be generally safe in humans. Over 18,000 sessions have been conducted without serious adverse events, though mild effects like headaches or skin sensations can occur. Safety is consistent across different groups, including children and the elderly. ^{6 7 8 9 10}

How does tRAS Brain Stimulation differ from other treatments for executive dysfunction?

tRAS Brain Stimulation is unique because it involves transcranial electrical stimulation (tES), which is a non-invasive method that uses electrical currents to stimulate specific brain areas, potentially improving executive functions. Unlike traditional drug treatments, this approach directly targets brain activity and may offer benefits without the side effects associated with medications. ^{2 5 11 12 13}

What is the purpose of this trial?

Working memory (WM) is the ability to hold relevant information in mind in the absence of sensory input. The capacity for WM is a foundation for cognitive control and higher cognitive function more broadly. Previous research demonstrated that during the delay period of WM tasks, oscillatory electrical activity in the prefrontal cortex in the theta-frequency band (4-8 Hz) increased in amplitude. However, other groups found that the slope of the aperiodic signal in the brain was positively correlated with individual differences in WM capacity. Since low-frequency power and a steeper slope of the aperiodic signal are confounded in many analyses, it is not clear whether the slope of the aperiodic signal or the amplitude of low-frequency oscillations underlie WM capacity. With many studies investigating the causal role of theta oscillations in WM, the purpose of this project is to investigate the role of the aperiodic signal in WM performance.

Research Team

Justin Riddle, PhD

Principal Investigator

Florida State University

Eligibility Criteria

This trial is for individuals aged 18-35 with normal or corrected-to-normal vision, who can understand English without a translator and are not color-blind. Participants must be able to consent to the study and commit to its duration.

Inclusion Criteria

My vision is normal or corrected to normal.

Willing to comply with all study procedures and be available for the duration of the study

Ability to speak, read and understand English without a translator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Session

Participants undergo a baseline session with EEG recording during working memory task performance

2 hours

1 visit (in-person)

Stimulation Session

Participants receive transcranial random aperiodic stimulation (tRAS) in different waveforms while performing the working memory task

3 hours

1 visit (in-person)

Follow-up

Participants are monitored for aftereffects of tRAS on brain activity using resting-state EEG recording

1-2 weeks

Treatment Details

Interventions

• Flat-tRAS
• Sham-tRAS
• Steep-tRAS

Trial Overview The study examines how different types of transcranial alternating current stimulation (tRAS) affect working memory. It compares Sham-tRAS (a placebo), Flat-tRAS, and Steep-tRAS on their ability to influence cognitive function.

Participant Groups

Group I: Steep-tRAS, Experimental Treatment 1 Intervention

Transcranial random aperiodic stimulation (tRAS) delivers 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA at the return electrode. The condition of interest, steep-tRAS, mimics a steep slope of the aperiodic signal characterized by greater low relative to high frequency power. Participants receive all three types of stimulation in an intermixed, balanced, and randomized order. There are twelve total blocks of approximately five minutes of stimulation with four blocks of each type of stimulation.

Group II: Flat-tRAS Active Control 1 Intervention

Transcranial random aperiodic stimulation (tRAS) delivers 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA at the return electrode. The active control, flat-tRAS, mimics a flat slope aperiodic signal characterized by greater high relative to low frequency power. Participants receive all three types of stimulation in an intermixed, balanced, and randomized order. There are twelve total blocks of approximately five minutes of stimulation with four blocks of each type of stimulation.

Group III: Sham-tRAS Placebo Group 1 Intervention

Transcranial random aperiodic stimulation (tRAS) delivers 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA at the return electrode. For active sham stimulation, steep-tRAS or flat-tRAS is delivered for only 15 seconds at the beginning and end of the block. This mimics the skin sensations (e.g., itching, burning, tingling) to assist with blinding the participant. Participants receive all three types of stimulation in an intermixed, balanced, and randomized order. There are twelve total blocks of approximately five minutes of stimulation with four blocks of each type of stimulation.

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Findings from Research

A patient with cognitive deficits after severe traumatic brain injury showed significant improvements in verbal fluency, naming, and executive function after 10 sessions of High Definition-transcranial Direct Current Stimulation (HD-tDCS) targeting the pre-Supplementary Motor Area (pre-SMA).

The benefits of HD-tDCS persisted for up to 14 weeks post-treatment, indicating that this non-invasive brain stimulation technique may promote long-lasting neuroplasticity and serve as an effective therapy for cognitive deficits in chronic TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Improving Verbal Retrieval Deficits With High Definition Transcranial Direct Current Stimulation Targeting the Pre-Supplementary Motor Area in a Patient With Chronic Traumatic Brain Injury. Chiang, HS., Shakal, S., Vanneste, S., et al.[2023]

Transcranial electrical stimulation (tES), including both tACS and tDCS, significantly improved aspects of executive function, particularly inhibition and cognitive flexibility, in a study involving 229 healthy adults.

tDCS showed greater neural efficiency by decreasing functional connectivity in relevant brain areas compared to tACS, suggesting it may offer better neural benefits during stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new perspective for evaluating the efficacy of tACS and tDCS in improving executive functions: A combined tES and fNIRS study. Lu, H., Zhang, Y., Qiu, H., et al.[2023]

A systematic review and meta-analysis of 63 studies involving 1537 participants found that excitatory non-invasive brain stimulation positively influenced performance on tasks like the Stop Signal Task and Go/No-Go Task, indicating its potential to enhance certain aspects of executive functioning.

In contrast, inhibitory brain stimulation showed a small negative effect on Flanker Task performance, while no significant effects were observed on working memory and flexibility tasks, suggesting that the impact of non-invasive brain stimulation varies across different executive functioning domains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of non-invasive brain stimulation on executive functioning in healthy controls: A systematic review and meta-analysis. de Boer, NS., Schluter, RS., Daams, JG., et al.[2021]

Transcranial direct current stimulation (tDCS) applied to the right dorsolateral prefrontal cortex significantly improved executive functions and functional communication in 20 chronic patients with severe aphasia after just ten days of treatment.

The improvements in cognitive abilities, such as selective attention and planning, not only enhanced language skills but also persisted for at least one month after the intervention, highlighting the potential of tDCS as a valuable rehabilitation tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Executive Function Training Impact on Communication? A Randomized Controlled tDCS Study on Post-Stroke Aphasia. Pisano, F., Manfredini, A., Castellano, A., et al.[2022]

The study proposes a home-based rehabilitation protocol combining working memory training with non-invasive transcranial direct current stimulation (tDCS) to improve cognitive functions in patients with acquired brain injury, focusing on enhancing working memory and executive functioning.

Patients will be divided into two groups receiving either active tDCS or sham stimulation during a 2-week training period, with outcomes assessed to determine the effectiveness of tDCS in enhancing training gains and its potential impact on everyday activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAINSTORMING: A study protocol for a randomised double-blind clinical trial to assess the impact of concurrent brain stimulation (tDCS) and working memory training on cognitive performance in Acquired Brain Injury (ABI). Assecondi, S., Hu, R., Eskes, G., et al.[2021]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

In a study involving 1,019 participants across 4 sites, adverse events (AEs) following multiple sessions of transcranial electrical stimulation (tES) were found to be influenced more by factors like testing site and session number rather than the stimulation itself, suggesting a good safety profile for repeated use.

The effectiveness of blinding procedures was found to be less reliable for tDCS and tACS compared to tRNS, indicating a need for improved blinding methods, especially when using higher stimulation intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. Sheffield, JG., Ramerpresad, S., Brem, AK., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

In a study involving 7 participants with disordered consciousness after severe traumatic brain injury, repetitive transcranial magnetic stimulation (rTMS) was found to have a relatively safe profile, with only 75 mild nonserious adverse events and 1 serious adverse event (a seizure).

Despite the potential for seizure induction, the study suggests that rTMS can be safely administered to this vulnerable population, indicating that future research could include a broader range of patients who were previously excluded due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury. Kletzel, SL., Aaronson, AL., Guernon, A., et al.[2022]

Transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal lobe significantly improved executive function in 24 stroke patients with post-stroke executive impairment, as evidenced by better scores on neuropsychological tests after 7 days of treatment.

The increase in executive function was associated with a rise in theta band power in the EEG, indicating that tDCS may enhance cognitive processes through changes in brain activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct-current stimulation on executive function and resting EEG after stroke: A pilot randomized controlled study. Wang, Z., Li, J., Wang, X., et al.[2022]

A meta-analysis of 27 studies found that single-session transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) did not significantly improve overall executive function in healthy individuals, although some specific effects were noted.

Anodal unilateral tDCS showed a significant positive effect on updating tasks, particularly when using smaller anodes and extracranial cathodes, suggesting that the configuration of the stimulation can influence its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis. Imburgio, MJ., Orr, JM.[2019]

A study involving 18 Parkinson's disease patients demonstrated that transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) led to significant long-term improvements in executive function, as measured by the Trail Making Test B, compared to a sham treatment.

The results suggest that tDCS may serve as a beneficial non-pharmacological therapy for addressing cognitive symptoms in Parkinson's disease without negatively impacting motor function, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tDCS on executive function in Parkinson's disease. Doruk, D., Gray, Z., Bravo, GL., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Improving Verbal Retrieval Deficits With High Definition Transcranial Direct Current Stimulation Targeting the Pre-Supplementary Motor Area in a Patient With Chronic Traumatic Brain Injury. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A new perspective for evaluating the efficacy of tACS and tDCS in improving executive functions: A combined tES and fNIRS study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The effect of non-invasive brain stimulation on executive functioning in healthy controls: A systematic review and meta-analysis. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Does Executive Function Training Impact on Communication? A Randomized Controlled tDCS Study on Post-Stroke Aphasia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

BRAINSTORMING: A study protocol for a randomised double-blind clinical trial to assess the impact of concurrent brain stimulation (tDCS) and working memory training on cognitive performance in Acquired Brain Injury (ABI). [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

8. Italy pubmed.ncbi.nlm.nih.gov

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury. [2022]

11. Scotland pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct-current stimulation on executive function and resting EEG after stroke: A pilot randomized controlled study. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis. [2019]

13. Ireland pubmed.ncbi.nlm.nih.gov

Effects of tDCS on executive function in Parkinson's disease. [2022]