Neurofeedback to Improve Working Memory in Mild Cognitive Impairment

Study Overview
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Brief Summary
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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.

Detailed Description
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This is a randomized, double-blind, clinical trial to test the efficacy of gamma-neurofeedback (G-NFB) compared to a placebo (P-NFB) in individuals with MCI. 112 consented participants will be randomized to receive G-NFB (n=56) or placebo-NFB (n=56) during 30-45 minute sessions twice per week for 12 weeks (24 total sessions). Memory and other cognitive domains will be measured using paper and pencil and computerized tests every 4 weeks during the study and at 4 weeks post completion of study.

Official Title
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Enhancing Gamma Band Response in Mild Cognitive Impairment to Improve Working Memory

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Neurofeedback
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet criteria for mild cognitive impairment (MCI). Living independently. Literate in English. Competent to participate in the informed consent process and provide voluntary informed consent. Exclusion Criteria: Frontal temporal dementia Active alcohol or substance use disorder within the past year. Brain cancer Stroke within the last 2 years Anti-epileptic medication Prior head injury involving loss of consciousness Seizure disorder Use of medications likely to affect cognitive function (cf. donepezil, memantine). We will not exclude for other medications but will examine their effects and include medications as covariates as appropriate (e.g., presence v. absence; anticholinergic load). The potential benefits of the study do not outweigh the potential risks of the study, as determined by the PI.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: MCI subjects will be assigned to active intervention or placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>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. | Behavioral: Neurofeedback<br>* Neurofeedback is a technique where brain functions are made accessible to the subject in the form of a metaphor. For instance, frontal brain activity may be shown as an airplane flying. Once the activity is made accessible, the subject can modulate it in a pre-specified direction. The parameters used to achieve successful feedback are made difficult over time and hence the brain is taught or conditioned to improve performance.<br>|
| Sham Comparator: Placebo<br>Video and music progression will be random and will not depend on brain activity. Any progression will be by random chance alone. | Other: Placebo<br>* Subjects in this arm will undergo all of the same testing as active treatment. Music and video progression will not depend on brain activity. Instead feedback will be random.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Working Memory accuracy | Change in the computerized test, N-back will be used to measure working memory. | From baseline to 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of Change in Working Memory accuracy | Change in the computerized test, N-back will be used to measure working memory. | From baseline to 4weeks post end of study | 
| Change in Gamma Band Response | Change in Gamma oscillations will be measured while the subject performs the n-back task. | From baseline to 12 weeks of treatment | 
| Durability of Gamma Band Response | Change in Gamma oscillations will be measured while the subject performs the n-back task. | From baseline to 4weeks post end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurofeedback