Brain Stimulation for Working Memory Issues

Overseen By Brian Kavanaugh, PsyD ABPP

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Bradley Hospital

Must not be taking: Seizure threshold reducers

Disqualifiers: Epilepsy, Seizures, Substance abuse, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called intermittent Theta Burst Stimulation (iTBS) to determine its effectiveness in improving working memory issues in teenagers with ADHD. The study examines how this brain stimulation affects areas involved in memory processes and aims to identify the best treatment targets. It includes both active and sham (inactive) treatment sessions for comparison. Teens aged 12-18 years with working memory problems and an ADHD diagnosis may be suitable candidates for this trial. Participants will receive compensation, and joining the trial does not require changes to existing medical care. As an unphased trial, this study offers participants a unique opportunity to contribute to groundbreaking research and potentially benefit from innovative treatment.

Will I have to stop taking my current medications?

The trial does not require changes to your current medications unless you are taking medications that lower the seizure threshold, which may exclude you from participating. Psychostimulant medications are allowed if deemed safe by the medical review process.

What prior data suggests that this brain stimulation technique is safe for adolescents?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe. Studies have found that iTBS can enhance thinking skills, such as memory and attention, in individuals with mild memory problems and other conditions. This suggests that iTBS could be safe for teenagers with memory challenges.

One study found that iTBS helped individuals with mild memory issues and early Alzheimer's disease think more clearly. Another study showed that iTBS might improve focus and task management in people with depression.

No major reports of serious side effects have emerged with iTBS, indicating its safety. Individuals considering participation in an iTBS trial can feel confident about its safety based on these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about intermittent Theta Burst Stimulation (iTBS) for working memory issues because it offers a novel and non-invasive approach to brain stimulation. Unlike standard treatments, which might include medications or cognitive therapies, iTBS directly targets and stimulates specific brain areas, such as the dorsolateral prefrontal cortex or inferior parietal lobule. This treatment aims to enhance brain activity associated with working memory by using rhythmic bursts of magnetic pulses, potentially improving cognitive function more quickly and effectively than traditional methods. Additionally, its precision in targeting brain regions based on individual brain imaging sets it apart from more generalized approaches.

What evidence suggests that this trial's treatments could be effective for working memory issues?

Research has shown that intermittent theta burst stimulation (iTBS) might improve working memory issues. Some studies found that iTBS can enhance cognitive skills, particularly in individuals with mild memory problems or those recovering from a stroke. In this trial, participants will receive either active iTBS or sham iTBS through random assignment. iTBS sends quick bursts of magnetic energy to the brain, promoting change and adaptation. This treatment has also shown promise in other conditions, such as depression and ADHD, by targeting specific brain areas involved in memory and attention. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adolescents aged 13-17 with an IQ over 80 and diagnosed ADHD, who struggle with working memory. They must be fluent in English, able to consent (with parental permission), and have a parent-reported BRIEF-2 Working Memory score above the norm. Exclusions include certain neurological conditions, metal implants affecting the brain or spinal cord, active psychosis or mania, current pregnancy, substance abuse within six months, and other specific medical criteria.

Inclusion Criteria

I have been diagnosed with ADHD.

English fluency of the participant and the legal guardian/parent

Parent rating on BRIEF-2 Working Memory: Greater than 1.0 SD above normative mean

Exclusion Criteria

I have a history of seizures or epilepsy, or a close family member does.

I am experiencing symptoms of high pressure inside my skull.

I have had fainting spells that might be seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent theta burst stimulation (iTBS) at the left dorsolateral prefrontal cortex (DLPFC) or inferior parietal lobule (IPL) with both active and sham sessions

1 session

2 visits (in-person)

Follow-up

Participants are monitored for changes in theta-gamma coupling and working memory performance after iTBS sessions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active Intermittent Theta Burst Stimulation
• Intermittent Theta Burst Stimulation
• Sham Intermittent Theta Burst Stimulation

Trial Overview

The study tests whether non-invasive brain stimulation called Intermittent Theta Burst Stimulation can improve working memory in teens by targeting prefrontal and parietal brain regions. Participants will receive either the active treatment or a sham (placebo) version to compare effects on neural mechanisms underlying memory deficits.

How Is the Trial Designed?

Group I: Sham intermittent Theta Burst Stimulation Experimental Treatment 1 Intervention

In a 2x2 factorial double-blind design, researchers will randomize a sample of adolescents with WM deficits to intermittent theta burst stimulation (iTBS) at the left dorsolateral prefrontal cortex (DLPFC) or inferior parietal lobule (IPL), based on each participant's structural brain MRI. Participants in both arms will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography (EEG) during a Sternberg spatial WM task (SWMT) immediately before and after iTBS.

Group II: Active intermittent Theta Burst Stimulation Experimental Treatment 1 Intervention

In a 2x2 factorial double-blind design, researchers will randomize a sample of adolescents with WM deficits to intermittent theta burst stimulation (iTBS) at the left dorsolateral prefrontal cortex (DLPFC) or inferior parietal lobule (IPL), based on each participant's structural brain MRI. Participants in both arms will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography (EEG) during a Sternberg spatial WM task (SWMT) immediately before and after iTBS.

Intermittent Theta Burst Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression

Approved in European Union as iTBS for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Bradley Hospital

Lead Sponsor

Trials

22

Recruited

1,900+

Published Research Related to This Trial

Theta burst stimulation (iTBS and rTMS) significantly improved working memory performance in rats, as evidenced by faster completion times in a T-maze task compared to a control group.

Both iTBS and rTMS enhanced theta and gamma brain wave activity in the medial prefrontal cortex, suggesting that these stimulation techniques improve working memory by modulating neural activity and connectivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of theta burst stimulation on the coherence of local field potential during working memory task in rats. Wang, T., Guo, M., Wang, N., et al.[2023]

Continuous theta-burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) significantly impairs working memory performance for about 15 minutes, particularly affecting tasks with a 2-back load.

The impact of cTBS on working memory performance is load-dependent, as higher memory loads (3-back) and non-memory tasks (0-back) were not significantly affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous theta burst stimulation over the left dorsolateral prefrontal cortex decreases medium load working memory performance in healthy humans. Schicktanz, N., Fastenrath, M., Milnik, A., et al.[2018]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

A 63-year-old male with mild receptive aphasia showed significant improvements in working memory and language skills after receiving 10 sessions of intermittent theta-burst stimulation (iTBS) combined with computerized working memory training.

The combined treatment not only enhanced specific language tasks like naming and reading but also positively impacted the participant's overall quality of life, suggesting that this approach could be beneficial in aphasia rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation and Working Memory Training to Address Language Impairments in Aphasia: A Case Study. Kranou-Economidou, D., Kambanaros, M.[2023]

Intermittent theta-burst stimulation (iTBS) improved working memory performance in healthy subjects, while continuous theta-burst stimulation (cTBS) did not show this effect, indicating that iTBS may be more effective for enhancing cognitive function.

The study involved 51 participants and assessed working memory using various tasks, finding no significant differences in effects based on which hemisphere was stimulated, suggesting that the benefits of TBS on working memory are not lateralized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous theta-burst stimulation over the dorsolateral prefrontal cortex inhibits improvement on a working memory task. Vékony, T., Németh, VL., Holczer, A., et al.[2019]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

In a study involving 19 healthy participants, intermittent theta burst stimulation (iTBS) to the left dorsolateral prefrontal cortex significantly improved working memory performance for up to 40 minutes compared to sham stimulation.

The cognitive improvements were linked to increased synchronization of theta waves and enhanced gamma band power in the brain, suggesting that specialized stimulation techniques may offer more effective neuromodulation for cognitive enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls. Hoy, KE., Bailey, N., Michael, M., et al.[2018]

In a study involving 24 healthy participants, intermittent theta-burst stimulation (iTBS) significantly improved working memory response times compared to placebo, while transcranial direct current stimulation (tDCS) did not show similar effects.

No serious adverse effects were reported for any of the stimulation protocols, indicating that these non-invasive brain stimulation techniques are safe for use in enhancing cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance. Razza, LB., Luethi, MS., Zanão, T., et al.[2022]

A study involving 31 healthy adults tested the effects of intermittent theta burst stimulation (iTBS) on working memory by targeting the left and right dorsolateral prefrontal cortex, but found no significant memory enhancement beyond practice effects.

While participants showed improvements in accuracy and reaction times on working memory tasks after stimulation, these improvements were not attributed to the iTBS itself, indicating that a single session of iTBS may not effectively enhance memory performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does intermittent theta burst stimulation improve working memory capacity? A randomized controlled cross-over experiment. Feng, Y., Zhang, JJ., Zhu, J., et al.[2022]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7387875/

Intermittent theta burst stimulation (iTBS) combined with ...

This study will provide scientific evidence for improving cognitive deficits, especially working memory deficits, and elucidate the neuroplasticity mechanism of ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S3050529125000996

Intermittent theta burst stimulation as a potential ...

Several studies show that rTMS can enhance overall cognitive functioning of patients with mild cognitive impairment and post-stroke (Chen et al.

3.

trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04563-0

Intermittent theta burst stimulation (iTBS) combined with ...

This study will provide scientific evidence for improving cognitive deficits, especially working memory deficits, and elucidate the ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03745768

NCT03745768 | iTBS Study for Depression (Randomized)

iTBS delivers high frequency (50Hz) magnetic pulses in "bursts" of 3 stimuli. It is posited that this intervention induces plasticity in the human cortex.

5.

medrxiv.org

medrxiv.org/content/10.1101/2025.09.03.25335033v1.full-text

Intermittent theta burst stimulation for attention deficit ...

A recent meta-analysis found a medium effect size for rTMS to the dorsolateral prefrontal cortex (DLPFC) efficacy on overall ADHD symptoms(6).

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12465570/

Effects of intermittent theta-burst stimulation on cognition ...

These findings suggest that iTBS can produce delayed cognitive enhancement in individuals with amnestic MCI and very mild AD, while the impact ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S3050529125000042

Neurocognitive effects of theta burst stimulation for ...

Results suggested that TBS for TRD may produce neurocognitive enhancement across specific neurocognitive domains including executive functioning, attention, ...

8.

pilotfeasibilitystudies.biomedcentral.com

pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-025-01625-5

A pilot randomized controlled double-blind trial of intermittent ...

This innovative study aims to test the feasibility of iTBS as a cognitive enhancement strategy in MCI.

9.

nature.com

nature.com/articles/s41591-023-02764-z

Connectivity-guided intermittent theta burst versus ...

MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks.

10.

frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1124819/full

Dose and time-dependence of acute intermittent theta ...

The results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD.