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2019 Alzheimer's Association Clinician Scientist Fellowship (AACSF)

Cortical Excitability as a Disease Marker in early Alzheimer’s Disease

Are overactive electrical signals in the brain an early indicator of Alzheimer’s?

Stephanie Buss, M.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States


Nerve cells in the brain use electrical signals to communicate with one another. This communication is essential for brain function, including learning and memory. In individuals with Alzheimer’s, however, these electrical signals in the brain can become overactive, a phenomenon known as “cortical hyperexcitability”. Scientists believe that this excessive brain cell activity may contribute to a higher risk of seizures in individuals with Alzheimer’s. Using the technique of electroencephalography or EEG (used to measure electrical signals in the brain) prior studies have shown that the presence of overactive electrical signals in the brain may be associated with faster cognitive decline in Alzheimer’s.
Another non-invasive technique called the Transcranial magnetic stimulation (TMS) uses magnetic fields to stimulate nerve cells in the brain. Past studies have used TMS to show abnormal excessive activity in certain brain regions. TMS combined with EEG, is a relatively new and non-invasive method to measure excessive brain cell activity.  Dr. Stephanie Buss and her colleagues will use this new technique to study whether excessive brain cell activity in two brain regions 1) motor cortex (region of the brain that initiates and controls body movement) and 2) inferior parietal lobe (IPL), an area of the brain— connected to the hippocampus— that many previous studies have shown is impacted early in Alzheimer’s could be an early indicator of Alzheimer’s.

Research Plan

Dr. Buss and her colleagues will use TMS with EEG to compare excitability in IPL and the motor cortex among two groups including 1) 30 individuals with early-stage Alzheimer’s and 2) 30 individuals who are cognitively unimpaired. The IPL is also connected to the hippocampus, a brain region important for learning and memory.
Dr. Buss believes that those with early-stage Alzheimer’s will show greater brain cell activity in the two brain regions than cognitively unimpaired individuals. Next, the researchers will determine if cortical hyperexcitability in the IPL region in the individuals with Alzheimer’s is related to their cognitive abilities overall. Dr. Buss believes that memory, but not cognition as a whole, may be related to increased excitability in the IPL region.
Finally, Dr. Buss and her colleagues will test whether the amount of excitability observed in IPL  in early Alzheimer’s is related to  brain changes observed in brain scans including Magnetic Resonance Imaging (MRI) and resting state functional connectivity (rs-fMRI). 


The study results may help determine whether overactive brain regions can be used as an early indicator of brain changes seen in Alzheimer’s disease. Families facing Alzheimer’s now and in the future will benefit greatly from early detection, allowing for important care and planning. Furthermore, when we have new therapies, we will be in a better position to know who needs treatment at the earliest time point. 

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