Brain Stimulation for Working Memory

Overseen By Hamdi Eryilmaz, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Psychotropics, Dopamine drugs, Nicotine, others

Disqualifiers: Neurological disorder, Seizures, Pregnancy, others

Compensation: Varies

Number of Visits: 4

Duration: 4 sessions over 4 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how brain stimulation can improve working memory using a technique called tACS (Transcranial Alternating Current Stimulation). This method applies gentle electrical currents to the scalp to influence brain activity. Participants will receive either active tACS during certain memory tasks or a placebo. The trial is suitable for English speakers without neurological or psychiatric disorders who are not on specific medications. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on brain stimulation and memory enhancement.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, especially those that affect brain stimulation, like psychotropic drugs and others that alter brain chemicals. It's best to discuss your specific medications with the trial team.

What prior data suggests that transcranial alternating current stimulation (tACS) is safe for modulating brain oscillations?

Research has shown that transcranial alternating current stimulation (tACS) is generally safe. Studies have used both theta-nested gamma tACS and gamma tACS without causing serious side effects.

Theta-nested gamma tACS has improved working memory in young and older adults. This treatment applies weak electric currents to the brain, and most people tolerate it well. No major negative effects were reported in these studies.

Gamma tACS has been tested on healthy individuals and those with mild memory issues. Research suggests it can improve memory and thinking skills when combined with brain exercises. Again, no significant safety concerns were found.

Overall, current research considers both types of tACS used in this trial safe. They are non-invasive, meaning they don't require surgery or internal procedures, which generally lowers the risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these brain stimulation treatments for improving working memory because they offer a novel approach compared to traditional cognitive therapies or medications. Unlike standard treatments, these techniques use transcranial alternating current stimulation (tACS), which involves applying gentle electrical currents to the brain to potentially enhance memory performance. The treatments are unique in targeting specific brain rhythms, like theta and gamma, during different phases of memory tasks. This targeted stimulation could lead to more precise and effective improvements in working memory, providing new hope for individuals looking for alternatives to current therapies.

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

This trial will compare different brain stimulation techniques for working memory. Research has shown that theta-nested gamma tACS, a treatment participants in this trial may receive, can improve working memory. Studies have found it more effective in memory tasks than placebo treatments, with a noticeable impact. This method uses specific electrical patterns to influence brain activity related to memory.

Another treatment option in this trial is gamma tACS, which has shown mixed results. Some studies suggest it can enhance thinking skills, especially in people with mild memory problems. However, its effect on working memory is less reliable compared to theta-nested gamma tACS. Overall, both treatments have potential, but theta-nested gamma tACS is more closely linked to improvements in working memory. ^{6 7 8 9 10}

Who Is on the Research Team?

Hamdi Eryilmaz, Ph.D.

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for individuals who can give informed consent and are fluent in English. It's designed to explore how working memory functions by using a noninvasive brain stimulation technique.

Inclusion Criteria

Fluent in English.

Able to provide informed consent

Exclusion Criteria

Contraindications for tACS (e.g., history of seizures, metallic implants in the head or neck, implanted brain stimulators, vagus nerve stimulators, pacemakers, pregnancy)

History of a neurological/psychiatric disorder

I am currently taking medication for my mental health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo four tACS sessions with EEG recording before and after each session

4 sessions over 4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active tACS
• Placebo tACS

Trial Overview The study tests two types of transcranial alternating current stimulation (tACS): 'Active tACS' which actually modulates brain activity, and 'Placebo tACS', which does not have an active effect. The impact on working memory will be measured with EEG.

How Is the Trial Designed?

Group I: Theta-nested gamma tACS applied during passive task epochs Experimental Treatment 1 Intervention

Participants will receive single-session administration of tACS during performance of a working memory task. tACS will be applied during fixation periods between consecutive task trials. EEG will be acquired before and immediately after the intervention.

Group II: Theta-nested gamma tACS applied during memory delays Experimental Treatment 1 Intervention

Participants will receive single-session administration of tACS during performance of a working memory task. tACS will be applied during memory delays. EEG will be acquired before and immediately after the intervention.

Group III: Gamma tACS applied during memory delays Experimental Treatment 1 Intervention

Participants will receive single-session administration of tACS during performance of a working memory task. tACS will be applied during memory delays. The stimulation will be phase locked to the peaks of ongoing theta rhythms of the participant. EEG will be acquired before and immediately after the intervention.

Group IV: Placebo tACS applied during task performance Placebo Group 1 Intervention

Participants will receive single-session administration of placebo tACS during performance of a working memory task. EEG will be acquired before and immediately after the intervention.

Active tACS is already approved in United States, European Union for the following indications:

Approved in United States as Active tACS for:

• Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline

Approved in European Union as Active tACS for:

• Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Transcranial Alternating Current Stimulation (tACS) has shown a small-to-medium effect on improving both working memory (WM) and long-term memory (LTM) in healthy adults, based on a systematic review of 104 studies.

Specific tACS parameters, such as posterior theta-tACS for WM and anterior gamma-tACS for LTM, were found to effectively modulate memory performance, with results correlating with brain oscillatory activity measured by EEG and MEG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcranial alternating current stimulation on memory performance in healthy adults: A systematic review. Booth, SJ., Taylor, JR., Brown, LJE., et al.[2022]

Cross-frequency coupled transcranial alternating current stimulation (CFC-tACS) significantly improved working memory performance in participants, as evidenced by reduced reaction times during a modified Sternberg task.

The study revealed that CFC-tACS modulated brain activity, specifically enhancing functional connectivity and top-down control between fronto-occipital regions, which suggests a promising non-invasive method for cognitive enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurodynamic correlates for the cross-frequency coupled transcranial alternating current stimulation during working memory performance. Kim, SE., Kim, HS., Kwak, Y., et al.[2022]

Transcranial alternating-current stimulation (tACS) is a promising non-invasive brain stimulation technique that may enhance working memory (WM) performance, particularly in older adults and individuals with cognitive deficits, due to its superior safety and tolerability compared to repetitive transcranial magnetic stimulation (rTMS).

Research indicates that tACS can effectively manipulate brain oscillations associated with WM, suggesting its potential as a non-pharmacological tool for cognitive rehabilitation in aging populations and those with conditions like dementia and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Working Memory and Transcranial-Alternating Current Stimulation-State of the Art: Findings, Missing, and Challenges. Al Qasem, W., Abubaker, M., Kvašňák, E.[2023]

Theta-rhythm transcranial alternating current stimulation (tACS) significantly improved working memory accuracy in healthy participants compared to sham stimulation, indicating its potential efficacy in enhancing cognitive function.

The improvement in working memory was linked to better self-evaluation scores after the stimulation, suggesting that tACS may enhance the connection between cognitive performance and metacognitive awareness, which could be beneficial for treating cognitive impairments in conditions like schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal oscillatory stimulation modulates access to cognitive control references in retrospective metacognitive commentary. Meiron, O., Lavidor, M.[2018]

Transcranial alternating current stimulation (tACS) has been shown to lead to modest to moderate improvements in cognitive function across various domains, including working memory and attention, based on a systematic review of 102 studies involving 2893 participants.

The most significant cognitive improvements were observed after tACS treatment (offline effects) rather than during the stimulation (online effects), and studies that optimized stimulation based on current flow models yielded better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Grover, S., Fayzullina, R., Bullard, BM., et al.[2023]

Transcranial alternating current stimulation (tACS) has been shown to enhance cognitive functions in healthy adults, with theta-tACS improving working memory, executive functions, and declarative memory across 57 studies.

Gamma-tACS specifically improved auditory and visual perception but did not affect executive function tasks, indicating that different frequencies of tACS can target specific cognitive abilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Modulation of Cognitive Performance with Transcranial Alternating Current Stimulation: A Systematic Review of Frequency-Specific Effects. Klink, K., Paßmann, S., Kasten, FH., et al.[2020]

Transcranial alternating current stimulation (tACS) shows promise in improving cognitive functioning in older adults, with 7 out of 9 studies on cognitively intact individuals reporting cognitive improvements after stimulation.

However, there is significant variability in study methodologies and outcomes, highlighting the need for standardized protocols and a better understanding of how tACS affects different populations, particularly regarding dosing and physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. Kraft, JD., Hampstead, BM.[2023]

In a study involving 18 healthy participants, gamma (γ)-tACS showed a selective improvement in working memory performance on a 3-back task compared to tDCS and sham stimulation, suggesting its potential for cognitive enhancement.

The results indicate that γ-tACS may be a more effective method for neuromodulation than traditional tDCS, warranting further investigation into its applications for improving cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of γ-tACS on working memory performance in healthy controls. Hoy, KE., Bailey, N., Arnold, S., et al.[2018]

Transcranial alternating current stimulation (tACS) at a frequency tailored to individual brain activity (Tuned condition) significantly improved visuospatial working memory (vsWM) and mental rotation tasks in 20 adults, compared to a sham stimulation.

The improvement in performance was linked to increased synchrony in the fronto-parietal brain network, suggesting that targeted stimulation can enhance specific cognitive functions related to spatial abilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individually tuned theta HD-tACS improves spatial performance. Zhang, DW., Moraidis, A., Klingberg, T.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10257732/

Efficacy of tACS in the enhancement of working memory ... Results revealed a significant, heterogeneous positive effect of active tACS in improving WM performance over sham. A prior meta-analysis assessed tACS on ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ... The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These ...

3. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2017.00651/full

The Effects of Theta and Gamma tACS on Working Memory ... Gamma tACS did not significantly affect working memory performance compared to sham, and theta tACS led to inconsistent changes in performance on the n-back ...

4. nature.com nature.com/articles/s41539-022-00152-9

A meta-analysis showing improved cognitive performance ... Online-tACS with gamma frequency band on posterior parietal cortex was effective for improving cognitive performances, and the cognitive ...

5. mdpi.com mdpi.com/2076-328X/13/1/39

10 Minutes Frontal 40 Hz tACS—Effects on Working ... We hypothesized that a 10-min gamma tACS administered over the frontal cortex would significantly improve working memory outcomes. Young ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8882605/

Working Memory and Transcranial-Alternating Current ... This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1094715923000090

Efficacy of Transcranial Alternating Current Stimulation in ... Our findings indicate that active tACS enhances WM performance in healthy individuals compared with sham.

8. translationalneurodegeneration.biomedcentral.com translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-024-00423-y

Transcranial alternating current stimulation (tACS) at gamma ... We outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10862495/

The impact of gamma transcranial alternating current ... The results suggest that gamma tACS, in combination with rigorous brain exercises, could promote better working memory and cognitive function in clinical ...

10. frontiersin.org frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00214/full

Transcranial Alternating Current Stimulation (tACS) ... Alekseichuk et al. (2016) found that spatial working memory depends on theta-gamma, cross-frequency coupling. An experiment applying feedback-controlled 12 Hz ...