Brain Stimulation for Working Memory
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Psychotropics, Dopamine drugs, Nicotine, others
Disqualifiers: Neurological disorder, Seizures, Pregnancy, others
Trial Summary
What is the purpose of this trial?
This study will use novel transcranial alternating current stimulation (tACS) protocols and electroencephalography (EEG) to modulate and measure brain oscillations that underlie working memory. tACS is a noninvasive method used to modulate the timing and patterns of brain rhythms via weak electric currents passed through electrodes on the scalp.
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 data supports the effectiveness of the treatment Transcranial Alternating Current Stimulation (tACS) for improving working memory?
Research suggests that tACS can have small-to-medium positive effects on working memory, especially when using specific frequencies like theta and gamma. These effects have been observed in both healthy adults and those with cognitive deficits, indicating potential for tACS as a non-drug method to enhance cognitive performance.12345
Is transcranial alternating current stimulation (tACS) safe for humans?
How does the treatment Active tACS differ from other treatments for working memory issues?
Active tACS (Transcranial Alternating Current Stimulation) is unique because it uses specific frequencies to modulate brain waves, potentially enhancing working memory by aligning with natural brain oscillations. Unlike other treatments, it is non-invasive, cost-effective, and has a promising safety profile, making it an attractive option for cognitive enhancement, especially in older adults and those with cognitive deficits.12359
Eligibility Criteria
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.
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Trial Timeline
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
Treatment Details
Interventions
- Active tACS (Device)
- Placebo tACS (Device)
Trial OverviewThe 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.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Theta-nested gamma tACS applied during passive task epochsExperimental Treatment1 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 delaysExperimental Treatment1 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 delaysExperimental Treatment1 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 performancePlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Martinos Center for Biomedical ImagingCharlestown, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
References
Individually tuned theta HD-tACS improves spatial performance. [2023]Using transcranial alternating current stimulation (tACS) to improve visuospatial working memory (vsWM) has received considerable attention over the past few years. However, fundamental issues remain, such as the optimal frequency, the generality of behavioral effects, and the anatomical specificity of stimulation.
The effects of transcranial alternating current stimulation on memory performance in healthy adults: A systematic review. [2022]The recent introduction of Transcranial Alternating Current stimulation (tACS) in research on memory modulation has yielded some exciting findings. Whilst evidence suggests small but significant modulatory effects of tACS on perception and cognition, it is unclear how effective tACS is at modulating memory, and the neural oscillations underlying memory. The aim of this systematic review was to determine the efficacy with which tACS, compared to sham stimulation, can modify working memory (WM) and long-term memory (LTM) performance in healthy adults. We examined how these effects may be moderated by specific tACS parameters and study/participant characteristics. Our secondary goal was to investigate the neural correlates of tACS' effects on memory performance in healthy adults. A systematic search of eight databases yielded 11,413 records, resulting in 34 papers that included 104 eligible studies. The results were synthesised by memory type (WM/LTM) and according to the specific parameters of frequency band, stimulation montage, individual variability, cognitive demand, and phase. A second synthesis examined the correspondence between tACS' effects on memory performance and the oscillatory features of electroencephalography (EEG) and magnetencephalography (MEG) recordings in a subset of 26 studies. The results showed a small-to-medium effect of tACS on WM and LTM performance overall. There was strong evidence to suggest that posterior theta-tACS modulates WM performance, whilst the modulation of LTM is achieved by anterior gamma-tACS. Moreover, there was a correspondence between tACS effects on memory performance and oscillatory outcomes at the stimulation frequency. We discuss limitations in the field and suggest ways to improve our understanding of tACS efficacy to ensure a transition of tACS from an investigative method to a therapeutic tool.
Working Memory and Transcranial-Alternating Current Stimulation-State of the Art: Findings, Missing, and Challenges. [2023]Working memory (WM) is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer's disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The theta/gamma neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation (tACS) and repetitive transcranial magnetic stimulation (rTMS) are frequency-tuned non-invasive brain stimulation (NIBS) techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. 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, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits.
Prefrontal oscillatory stimulation modulates access to cognitive control references in retrospective metacognitive commentary. [2018]We intended to examine how theta-rhythm transcranial alternating current stimulation (tACS) (versus sham non-active stimulation) modulated associations between working memory accuracy and later retrospective self-evaluation scores.
The effect of γ-tACS on working memory performance in healthy controls. [2018]Transcranial Direct Current Stimulation (tDCS) has been widely investigated for its potential to enhance cognition, and in particular working memory, however to date standard approaches to stimulation have shown only modest effects. Alternative, more specialised, forms of current delivery may be better suited to cognitive enhancement. One such method is transcranial Alternating Current Stimulation (tACS) which delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscillations which underlie cognitive functioning. To date there has been no comparison of the effects of tACS to those of tDCS on cognitive enhancement. In a randomised repeated-measures study design we assessed the effect of gamma (γ)-tACS, tDCS and sham tDCS on working memory in 18 healthy participants who attended three sessions held at least 72h apart. Pre- and post-stimulation working memory performance was assessed using the 2 and 3-back. Our findings indicated the presence of a selective improvement in performance on the 3-back task following γ-tACS compared with tDCS and sham stimulation. The current findings provide support for further and more detailed investigation of the role of γ-tACS as a more specialised approach to neuromodulation.
A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. [2023]Transcranial alternating current stimulation (tACS) has attracted interest as a technique for causal investigations into how rhythmic fluctuations in brain neural activity influence cognition and for promoting cognitive rehabilitation. We conducted a systematic review and meta-analysis of the effects of tACS on cognitive function across 102 published studies, which included 2893 individuals in healthy, aging, and neuropsychiatric populations. A total of 304 effects were extracted from these 102 studies. We found modest to moderate improvements in cognitive function with tACS treatment that were evident in several cognitive domains, including working memory, long-term memory, attention, executive control, and fluid intelligence. Improvements in cognitive function were generally stronger after completion of tACS ("offline" effects) than during tACS treatment ("online" effects). Improvements in cognitive function were greater in studies that used current flow models to optimize or confirm neuromodulation targets by stimulating electric fields generated in the brain by tACS protocols. In studies targeting multiple brain regions concurrently, cognitive function changed bidirectionally (improved or decreased) according to the relative phase, or alignment, of the alternating current in the two brain regions (in phase versus antiphase). We also noted improvements in cognitive function separately in older adults and in individuals with neuropsychiatric illnesses. Overall, our findings contribute to the debate surrounding the effectiveness of tACS for cognitive rehabilitation, quantitatively demonstrate its potential, and indicate further directions for optimal tACS clinical study design.
A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. [2023]Transcranial alternating current stimulation (tACS) is a form of noninvasive brain stimulation that has experienced rapid growth within the aging population over the past decade due to its potential for modulating cognitive functioning across the "intact" to dementia spectrum. For this reason, we performed a systematic review of the literature to evaluate the efficacy of tACS on cognitive functioning in older adults, including those with cognitive impairment. Our review was completed in June 2023 using Psych INFO, Embase, PubMed, and Cochrane databases. Out of 479 screened articles, 21 met inclusion criteria and were organized according to clinical diagnoses. Seven out of nine studies targeted cognitively intact older adults and showed some type of cognitive improvement after stimulation, whereas nine out of twelve studies targeted clinical diagnoses and showed improved cognitive performance to varying degrees. Studies showed considerable heterogeneity in methodology, stimulation parameters, participant characteristics, choice of cognitive task, and analytic strategy, all of which reinforce the need for standardized reporting of tACS methods. Through this heterogeneity, multiple patterns are described, such as disease progression influencing tACS effects and the need for individualized tailoring. For clinical translation, it is imperative that the field (a) better understand the physiological effects of tACS in these populations, especially in respect to biomarkers, (b) document a causal relationship between tACS delivery and neurophysiological/cognitive effects, and (c) systematically establish dosing parameters (e.g., amplitude, stimulation frequency, number and duration of sessions, need for booster/maintenance sessions).
The Modulation of Cognitive Performance with Transcranial Alternating Current Stimulation: A Systematic Review of Frequency-Specific Effects. [2020]Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows the manipulation of intrinsic brain oscillations. Numerous studies have applied tACS in the laboratory to enhance cognitive performance. With this systematic review, we aim to provide an overview of frequency-specific tACS effects on a range of cognitive functions in healthy adults. This may help to transfer stimulation protocols to real-world applications. We conducted a systematic literature search on PubMed and Cochrane databases and considered tACS studies in healthy adults (age > 18 years) that focused on cognitive performance. The search yielded n = 109 studies, of which n = 57 met the inclusion criteria. The results indicate that theta-tACS was beneficial for several cognitive functions, including working memory, executive functions, and declarative memory. Gamma-tACS enhanced performance in both auditory and visual perception but it did not change performance in tasks of executive functions. For attention, the results were less consistent but point to an improvement in performance with alpha- or gamma-tACS. We discuss these findings and point to important considerations that would precede a transfer to real-world applications.
Neurodynamic correlates for the cross-frequency coupled transcranial alternating current stimulation during working memory performance. [2022]Transcranial current stimulation is a neuromodulation technique used to modulate brain oscillations and, in turn, to enhance human cognitive function in a non-invasive manner. This study investigated whether cross-frequency coupled transcranial alternating current stimulation (CFC-tACS) improved working memory performance. Participants in both the tACS-treated and sham groups were instructed to perform a modified Sternberg task, where a combination of letters and digits was presented. Theta-phase/high-gamma-amplitude CFC-tACS was administered over electrode F3 and its four surrounding return electrodes (Fp1, Fz, F7, and C3) for 20 min. To identify neurophysiological correlates for the tACS-mediated enhancement of working memory performance, we analyzed EEG alpha and theta power, cross-frequency coupling, functional connectivity, and nodal efficiency during the retention period of the working memory task. We observed significantly reduced reaction times in the tACS-treated group, with suppressed treatment-mediated differences in frontal alpha power and unidirectional Fz-delta-phase to Oz-high-gamma-amplitude modulation during the second half of the retention period when network analyses revealed tACS-mediated fronto-occipital dissociative neurodynamics between alpha suppression and delta/theta enhancement. These findings indicate that tACS modulated top-down control and functional connectivity across the fronto-occipital regions, resulting in improved working memory performance. Our observations are indicative of the feasibility of enhancing cognitive performance by the CFC-formed tACS.