This innovative study aims to explore the impact of Ketamine on cortical neurophysiological functions in patients with Treatment Resistant Depression (TRD). Utilizing sophisticated, non-invasive techniques such as Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG), the research delves into how Ketamine influences cortical excitability and oscillatory activity. The study is motivated by three key preclinical findings: Ketamine's role in enhancing glutamate neurotransmission, initiating synaptic plasticity, and rapidly improving depression symptoms. In this open-label study, TRD patients will receive a low dose of Ketamine (0.5 mg/kg) over 40 minutes. TMS will be used to assess motor cortical excitability, particularly in the primary motor cortex and the Left Dorsolateral Prefrontal Cortex (Left DLPFC) or Left Brodmann Area 6. EEG recordings will complement these procedures, capturing brain activity during specific tasks designed to evoke auditory steady-state responses. This approach is expected to provide deeper insights into the neurophysiological changes associated with Ketamine treatment in TRD patients, potentially paving the way for new therapeutic strategies.