Enhancing gamma band response to improve working memory in individuals with mild cognitive impairment

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Abstract Alzheimer’s disease (AD) is the clinical manifestation of a neurodegenerative disorder characterized by pervasive and progressive cognitive decline with impairment in activities of daily living. According to the Centers for Disease Control the number of Americans with Alzheimer’s disease or dementia will grow to 13.9 million (2018 report) by 2060, making it an urgent public concern. Research in the last decade has focused on early identification of the disease and revealed a prodromal phase prior to the onset of functional impairments, known as mild cognitive impairment (MCI). Despite early identification, there are few treatment options to slow down progression from MCI to AD. Recent studies suggest that cognitive deficits may arise from abnormal synchronization of distributed neural networks. Synchronization or synchronous firing of neurons, binds cortical areas into functional networks in a task and state-dependent manner. Specifically, neural synchrony in the gamma band (30-45Hz) plays a central role in top-down attention, multisensory processing, perceptual binding and working memory (WM) in healthy individuals. Gamma band responses (GBR) are impaired in individuals with AD spectrum disorders, and animal studies in AD models targeting GBR have shown positive effects on cognition. Thus, developing similar treatments targeting GBR are expected to improve cognition in individuals with MCI. Our group has administered EEG-neurofeedback (EEG-NFB) targeting GBR in SCZ patients, with promising early results (research strategy). NFB is a low-cost, safe, easily administered closed-loop neuromodulation technique where subjects are shown their brain activity as a visual metaphor and asked to modulate it in a given direction. EEG- NFB has been employed in multiple disorders ranging from ADHD, depression, to anxiety and in multiple populations including children and older adults. Based on these encouraging results, we are proposing a study to 1) test the efficacy of EEG-NFB targeting GBR in individuals with amnestic MCI compared to a sham/placebo, 2) explore the mechanism underlying change in cognition and 3) explore pre-treatment characteristics that predict treatment response.