Summary/Abstract The pathophysiology of C9orf72- and GRN-related Frontotemporal Degeneration links TDP43 proteinopathy to neural network dysfunction, which ultimately manifests as symptoms of motor, cognitive, and/or behavioral impairment. Patients with ALS exhibit motor cortex hyper- excitability, which has been used as a physiologic biomarker to assist in diagnosis and outcomes monitoring in clinical trials. Most of this work has been done in patients with typical ALS, with questions remaining about whether this abnormal physiologic feature is present in patients with Frontotemporal Dementia and asymptomatic C9orf72 or GRN carriers. In this pilot project, we aim to investigate family members of individuals with C9orf72- or GRN- related FTD to determine whether this may be a universal feature of the illness and whether it is present prior to the onset of symptoms. We will also examine its relationship to resting-state functional MRI measures of large-scale brain network function. The ultimate goal of this research is to begin to determine whether these biomarkers of cortical physiology could be useful as an early, presymptomatic indicator of brain system dysfunction and whether it could be useful as an outcome measure for treatment trials.