Neurofeedback for Mild Cognitive Impairment

Overseen By Joshua Phillips, B.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Anti-epileptics, Donepezil, Memantine

Disqualifiers: Frontal temporal dementia, Stroke, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 25

Duration: 12 weeks

112 Participants Needed

Trial Summary

What is the purpose of this trial?

Mild cognitive impairment (MCI) has been identified as an early phase of Alzheimer's disease (AD), a neurodegenerative disorder expected to affect 13.9 million Americans by 2060. AD causes a progressive cognitive decline, including problems related to learning and memory, that adversely affects life quality. Treatment intervention at the MCI stage of the disease could potentially slow down the rate at which people may convert from MCI to AD. Increasing evidence suggests that abnormal activity in frontal regions of the brain is associated with cognitive deficits observed in AD. Furthermore, previous research has shown that neurofeedback (NFB) training targeting these regions can improve memory, making it a potential treatment for AD. NFB is a technique where an individual learns to change his/her brain function in a particular direction, once that function has been made accessible through a visual or auditory metaphor. We are proposing a novel, computer-based brain-training program to enhance frontal gamma oscillatory activity in individuals with MCI. Results from this study will build the scientific foundation necessary for larger clinical trials dedicated to improving treatment options and outcomes for patients with MCI.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications likely to affect cognitive function, such as donepezil and memantine. Other medications are not excluded, but their effects will be examined during the study.

What data supports the effectiveness of the treatment Neurofeedback for Mild Cognitive Impairment?

Research shows that neurofeedback, a type of biofeedback that uses real-time brain activity to improve brain function, has been effective in enhancing cognitive functions like memory and attention in both healthy and older adults. Studies have demonstrated improvements in working memory and attention, suggesting potential benefits for those with mild cognitive impairment. ^{1 2 3 4 5}

Is neurofeedback safe for humans?

Neurofeedback, including methods like EEG and fMRI neurofeedback, has been studied in humans for various conditions, and no significant safety concerns have been reported in these studies. It is generally considered a non-invasive and safe method for modulating brain activity. ^{6 7 8 9 10}

How does the treatment Neurofeedback differ from other treatments for Mild Cognitive Impairment?

Neurofeedback is unique because it uses real-time brain activity monitoring to train the brain, aiming to improve memory and attention in people with Mild Cognitive Impairment. Unlike traditional treatments, it is non-invasive and involves training sessions that help enhance brain function by modulating brain waves, which has shown promising results in improving cognitive abilities. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for individuals living independently with mild cognitive impairment (MCI), who can read English and consent to participate. It's not suitable for those with frontal temporal dementia, brain cancer, or recent stroke; people taking certain cognitive-affecting drugs like donepezil; or those with a history of significant head injury, seizures, or active substance abuse within the last year.

Inclusion Criteria

I understand and agree to participate in this study voluntarily.

I live on my own without needing daily help.

Literate in English.

Exclusion Criteria

You have had problems with drugs or alcohol within the past year.

The potential benefits of the study do not outweigh the potential risks of the study, as determined by the PI.

I am taking medication for epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gamma-neurofeedback (G-NFB) or placebo-NFB during 30-45 minute sessions twice per week for 12 weeks

12 weeks

24 visits (in-person)

Follow-up

Participants are monitored for durability of gamma band response and working memory accuracy after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Neurofeedback

Trial Overview The study tests a computer-based neurofeedback program designed to improve working memory in MCI patients by enhancing brain activity. Participants will either receive this neurofeedback training or a placebo treatment to compare effectiveness in potentially slowing Alzheimer's progression.

Participant Groups

Group I: Active Treatment Experimental Treatment 1 Intervention

Subjects will be given a choice of videos consisting of still images set to music. Whether the video progresses and music continues to play will depend on the subject's ability to maintain frontal gamma oscillatory activity within a prespecified range. Over successive weeks, the parameters for positive feedback (music and video progression) will become incrementally more difficult.

Group II: Placebo Placebo Group 1 Intervention

Video and music progression will be random and will not depend on brain activity. Any progression will be by random chance alone.

Neurofeedback is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Neurofeedback for:

• Chronic low back pain
• Fibromyalgia
• Neuropathic pain

Approved in European Union as Neurofeedback for:

• Chronic pain
• Fibromyalgia
• Neuropathic pain

Approved in Canada as Neurofeedback for:

• Chronic pain
• Fibromyalgia

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Findings from Research

Neurofeedback, which provides real-time sensory rewards based on brain activity, shows promise in improving memory and cognition in both healthy young and older adults, although training typically requires multiple weeks with several sessions per week.

Despite the overall positive trend in memory improvement, individual responses to neurofeedback can vary significantly, with some individuals not benefiting from the training, highlighting the need for further research into psychological factors and personalized approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sharpening Working Memory With Real-Time Electrophysiological Brain Signals: Which Neurofeedback Paradigms Work? Jiang, Y., Jessee, W., Hoyng, S., et al.[2023]

Neurofeedback (NF) has been shown to enhance cognitive functions like attention and working memory, particularly in children with ADHD, and there is growing evidence that it can also benefit older adults by helping their brain function more like that of younger individuals.

Recent advancements in technology, such as wireless brain activity recording and machine learning, are paving the way for more effective NF training, offering hope for improving cognitive performance and combating age-related cognitive decline in older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tuning Up the Old Brain with New Tricks: Attention Training via Neurofeedback. Jiang, Y., Abiri, R., Zhao, X.[2020]

In a study involving 26 participants (16 healthy elderly and 10 with prodromal Alzheimer's disease), real-time fMRI neurofeedback training improved visuospatial memory performance, suggesting it may help counteract cognitive decline associated with aging and early Alzheimer's.

The training led to changes in cerebral connectivity, particularly involving the parahippocampus and precuneus, and increased grey matter volumes in the precuneus and frontal cortex, indicating potential structural brain changes linked to the neurofeedback intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Improvement and Brain Changes after Real-Time Functional MRI Neurofeedback Training in Healthy Elderly and Prodromal Alzheimer's Disease. Hohenfeld, C., Nellessen, N., Dogan, I., et al.[2022]

In a study with 25 participants, neurofeedback training targeting the sensorimotor rhythm (SMR) frequency band (12-15 Hz) improved attention by increasing perceptual sensitivity and reducing errors, indicating its effectiveness for enhancing attention.

Training on the beta1 frequency band (15-18 Hz) resulted in faster reaction times and greater brain response (P300 amplitudes) during attention tasks, suggesting it enhances arousal and alertness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EEG biofeedback of low beta band components: frequency-specific effects on variables of attention and event-related brain potentials. Egner, T., Gruzelier, JH.[2022]

Recent research on EEG-neurofeedback shows significant clinical benefits, particularly in enhancing cognitive and emotional functions in both healthy individuals and the elderly, with various protocols leading to improvements in attention, memory, and mood.

Out of 23 controlled studies reviewed, many demonstrated a correlation between neurofeedback learning and positive outcomes, suggesting that neurofeedback can effectively mediate cognitive gains and may have applications in both clinical and performance settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EEG-neurofeedback for optimising performance. I: a review of cognitive and affective outcome in healthy participants. Gruzelier, JH.[2022]

The study developed a new EEG-based neurofeedback method targeting the right inferior frontal gyrus (rIFG), which showed successful engagement of the intended brain region during training, as confirmed by fMRI results from a small group of 14 participants.

After two sessions of this EEG neurofeedback training with 41 participants, individuals demonstrated improved cognitive control by reducing their risk-taking behavior, indicating the method's potential efficacy for enhancing cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity. Or-Borichev, A., Gurevitch, G., Klovatch, I., et al.[2023]

In a pilot study involving 20 elderly patients with mild cognitive impairment (MCI), sensorimotor (SMR)/theta neurofeedback training over 10 weeks led to significant improvements in cognitive assessments, including the Montreal Cognitive Assessment and the Wechsler Adult Intelligence Scale.

The training also resulted in increased EEG theta and alpha power, indicating enhanced brain activity, with these improvements sustained at a 1-month follow-up, suggesting that neurofeedback could be a promising non-invasive method for cognitive rehabilitation in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SMR/Theta Neurofeedback Training Improves Cognitive Performance and EEG Activity in Elderly With Mild Cognitive Impairment: A Pilot Study. Marlats, F., Bao, G., Chevallier, S., et al.[2020]

In a study of 114 ADHD patients using QEEG-informed neurofeedback, response rates were high, with 85% showing at least a 25% reduction in symptoms and 55% achieving remission, replicating previous findings from a smaller sample.

The study suggests that individual EEG characteristics can help tailor neurofeedback protocols, potentially enhancing treatment effectiveness, while also identifying predictors of remission such as baseline hyperactivity levels and specific EEG markers in different genders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter effectiveness trial of QEEG-informed neurofeedback in ADHD: Replication and treatment prediction. Krepel, N., Egtberts, T., Sack, AT., et al.[2022]

Neurofeedback (NFB) enables individuals to consciously control their brain activity by using real-time feedback from their neural activity, which has been traditionally done with EEG and is now enhanced by fMRI for better spatial resolution.

fMRI-NFB is feasible and can serve as a supplementary therapy tool, potentially improving treatment outcomes by allowing for more precise targeting of brain regions involved in various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging (FMRI) neurofeedback: implementations and applications. Dewiputri, WI., Auer, T.[2022]

In a pilot study involving 11 participants with mild cognitive impairment (MCI), neurofeedback training led to significant improvements in memory performance after ten 30-minute sessions over 5 weeks.

The benefits of neurofeedback on memory were maintained for 30 days after training, suggesting that this intervention may be a promising approach for enhancing cognitive function in individuals with MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild Cognitive Impairment. Lavy, Y., Dwolatzky, T., Kaplan, Z., et al.[2022]

This study is testing a new way to improve attention in healthy adults using a P300-based brain-computer interface, with 45 participants involved in a single training session to see if personalized task difficulty enhances focus more than random difficulty adjustments.

The research aims to replicate previous findings that showed the P300 speller can effectively train attention, which could make this method a valuable tool for helping individuals with cognitive deficits, due to its noninvasive and user-friendly nature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive P300-Based Brain-Computer Interface for Attention Training: Protocol for a Randomized Controlled Trial. Noble, SC., Woods, E., Ward, T., et al.[2023]

This study will evaluate the effects of neurofeedback (NF) training on cognitive functions in 60 older adults with Mild Cognitive Impairment (MCI), aiming to improve memory and attention over 30 training sessions.

If successful, NF training could be a promising non-invasive and cost-effective intervention to slow cognitive decline in MCI patients, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effects between SMR/delta-ratio and beta1/theta-ratio neurofeedback training for older adults with Mild Cognitive Impairment: a protocol for a randomized controlled trial. Marlats, F., Djabelkhir-Jemmi, L., Azabou, E., et al.[2020]

References

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

Sharpening Working Memory With Real-Time Electrophysiological Brain Signals: Which Neurofeedback Paradigms Work? [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Tuning Up the Old Brain with New Tricks: Attention Training via Neurofeedback. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cognitive Improvement and Brain Changes after Real-Time Functional MRI Neurofeedback Training in Healthy Elderly and Prodromal Alzheimer's Disease. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

EEG biofeedback of low beta band components: frequency-specific effects on variables of attention and event-related brain potentials. [2022]

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

EEG-neurofeedback for optimising performance. I: a review of cognitive and affective outcome in healthy participants. [2022]

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

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

SMR/Theta Neurofeedback Training Improves Cognitive Performance and EEG Activity in Elderly With Mild Cognitive Impairment: A Pilot Study. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A multicenter effectiveness trial of QEEG-informed neurofeedback in ADHD: Replication and treatment prediction. [2022]

9. Malaysia pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging (FMRI) neurofeedback: implementations and applications. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild Cognitive Impairment. [2022]

11. Canada pubmed.ncbi.nlm.nih.gov

Adaptive P300-Based Brain-Computer Interface for Attention Training: Protocol for a Randomized Controlled Trial. [2023]

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

Comparison of effects between SMR/delta-ratio and beta1/theta-ratio neurofeedback training for older adults with Mild Cognitive Impairment: a protocol for a randomized controlled trial. [2020]