TMS‐EEG as a measure of cortical hyperexcitability in motor and parietal cortex in Alzheimer’s disease: A pilot study

Abstract

AbstractBackgroundPatients with Alzheimer’s disease (AD) have abnormally high cortical excitability, with an increased risk of seizures and epileptiform discharges. Transcranial magnetic stimulation with electroencephalography (TMS‐EEG) can noninvasively measure cortical excitability in local brain regions, and has shown increased excitability in motor cortex in AD. However, practical applications of TMS‐EEG measures are currently limited by a dearth of data from brain regions involved early‐on in AD, such as the parietal cortex. This pilot study investigated the feasibility of using TMS‐EEG to compare "Excitability Gain" across multiple brain regions in AD.MethodThree biomarker‐confirmed AD participants (mean age 71, 1 female) and 4 healthy control participants (HC, mean age 68, 2 female) enrolled in this pilot study. Single‐pulse TMS stimulation was applied to left primary motor cortex (M1) and inferior parietal cortex (IPL), with 120 pulses given at both 120% and 135% resting motor threshold (RMT). We assessed tolerability of this protocol. TMS‐evoked potentials (TEPs) were measured as the average EEG response after a TMS pulse. The percent change in TEP between the two stimulation intensities was calculated (TEP Excitability Gain, %change). A power calculation for two sample means was performed to determine the number of subjects needed to demonstrate a between‐group difference in IPL excitability.ResultThe procedure was well‐tolerated; one HC participant complained of a mild positional neck discomfort. In HCs, TEP Excitability Gain was 12 (±19 SD) percent in M1, and ‐5 (±12 SD) percent in IPL. In AD participants, TEP Excitability Gain was 39 (±50 SD) percent in M1, and 31 (±31 SD) percent in IPL (Figure 1). Assuming a SD of 31 for IPL stimulation, a sample size of 13 in each group would have a >80% power to detect a between‐group difference of 36% in TEP Excitability Gain with an alpha of 0.05.ConclusionTMS‐EEG measures of "Excitability Gain" are feasible in AD participants. A sample size of 13 in each group will be required to test for a between‐group difference of cortical excitability in the parietal lobe. TMS‐EEG may be a useful tool to measure cortical excitability across multiple brain regions in AD.