One of the hallmarks of ALS is the death of upper motor neurons in the cerebral cortex. However, it is not known whether more subtle changes in cortical circuits precede upper motor neuron degeneration. Dr. Brown will study the excitatory and inhibitory neurons of the motor cortex, and their patterns of connectivity, to determine whether functional changes in these circuits represent early events in the development of the disease. The goal of this work is to identify primary events in the disease process that can suggest new preventative strategies and therapeutic targets in ALS.