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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of brain stimulation might aid executive dysfunction, which affects memory and thinking skills. Researchers use a technique called transcranial random aperiodic stimulation (tRAS) to examine its impact on working memory. Participants will experience three types of tRAS: Flat-tRAS, Steep-tRAS, and Sham-tRAS (placebo-like) to compare their effects. Suitable candidates have normal or corrected vision, can speak and read English, and are not currently receiving treatment for ADHD. As an unphased trial, this study allows participants to contribute to groundbreaking research in brain stimulation techniques.

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 prior data suggests that this brain stimulation technique is safe?

Research has shown that transcranial random aperiodic stimulation (tRAS) is being studied to improve working memory by targeting brain signals. These studies use a very low electrical current—just 1 milliampere—considered safe for people.

While specific information on flat-tRAS and steep-tRAS is limited, similar technologies have been used safely in other research. For instance, transcranial magnetic stimulation, a related method, has been used without serious side effects in many cases. It can sometimes cause minor skin sensations like itching or tingling, which are common and usually harmless.

The absence of serious side effects in related studies suggests that both flat-tRAS and steep-tRAS are likely safe. However, as with any medical study, unexpected side effects may occur. Participants should discuss any concerns with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the tRAS brain stimulation trial for executive dysfunction because it explores a novel approach using transcranial random aperiodic stimulation. Unlike typical treatments, which often involve medication or cognitive therapy, this method uses electrical stimulation to potentially enhance brain function. The trial includes three variations: Sham-tRAS, Flat-tRAS, and Steep-tRAS. Flat-tRAS is characterized by a flat slope signal with greater high-frequency power, while Steep-tRAS uses a steep slope signal with greater low-frequency power. This innovative approach could offer a non-invasive, quick-acting alternative to current therapies, potentially providing faster relief with fewer side effects.

What evidence suggests that this trial's treatments could be effective for executive dysfunction?

Research has shown that transcranial random aperiodic stimulation (tRAS) might enhance working memory by influencing brain waves. In this trial, participants will receive three types of stimulation: steep-tRAS, flat-tRAS, and sham-tRAS, in an intermixed, balanced, and randomized order. Some studies suggest that steep-tRAS, which uses electrical brain stimulation, can positively affect thinking skills, although these effects might be mild. Flat-tRAS aims to boost high-frequency brain activity, showing promise in enhancing working memory. Evidence from past studies on similar brain stimulation methods suggests potential benefits for mental skills, including working memory. These findings offer hope that tRAS could effectively improve cognitive performance. ^{1 2 3 6 7}

Who Is on the Research Team?

Justin Riddle, PhD

Principal Investigator

Florida State University

Are You a Good Fit for This Trial?

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

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

Not color-blind

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06126809

Causal Role of the Aperiodic Signal for Working Memory The active control, flat-tRAS, mimics a flat slope aperiodic signal characterized by greater high relative to low frequency power.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11220282/

Repetitive transcranial magnetic stimulation impacts the ... Repetitive transcranial magnetic stimulation impacts the executive function of patients with vascular cognitive impairment: a systematic review ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38962482/

a systematic review and meta-analysis Conclusion: rTMS is effective in the treatment of the executive function of VCI.

4. researchgate.net researchgate.net/publication/342858916_Transcranial_Random_Noise_Stimulation_is_More_Effective_than_Transcranial_Direct_Current_Stimulation_for_Enhancing_Working_Memory_in_Healthy_Individuals_Behavioural_and_Electrophysiological_Evidence

Transcranial Random Noise Stimulation is More Effective ... Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly ...

5. adhdevidence.org adhdevidence.org/blog/meta-analysis-finds-benefits-of-transcranial-direct-current-stimulation-for-adhd-symptoms-and-executive-function--but-evidence-remains-weak

Meta-analysis Finds Benefits of Transcranial Direct Current ... The authors concluded, "The findings of this systematic review suggest at least a partial improvement of symptoms and cognitive deficits in ADHD ...

6. researchgate.net researchgate.net/publication/10991454_Transcranial_magnetic_stimulation_Neurophysiological_applications_and_safety

Transcranial magnetic stimulation: Neurophysiological ... Single-pulse (<1Hz) TMS is safe in normal subjects. High frequency, high-intensity repetitive TMS (rTMS) can elicit seizures even in normal ...

7. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-05112-0

a randomized, double-blind, sham-controlled, clinical trial The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS.