This $227,205 Project Grant awarded by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research conducted by Dr. Frank Diaz at Cedars-Sinai Medical Center in West Hollywood, CA. The project aims to identify pathological markers and molecular signatures in the motor cortex of amyotrophic lateral sclerosis (ALS) patients using advanced MRI techniques, postmortem tissue analysis, and single-nucleus RNA sequencing. Key objectives include correlating in vivo MRI findings with neuropathological and transcriptomic data to better understand upper motor neuron dysfunction in ALS. The long-term goal is to develop non-invasive imaging biomarkers and identify novel therapeutic targets for this neurodegenerative disease. The 5-year project period runs from December 2024 through November 2029.