Disclosed are methods of treating depression, mania, post-traumatic stress disorder (PTSD), and various other neurologic conditions using synaptic pathway training. Methods of synaptic pathway training include, generally, achieving a favorable treatment result by activating a synaptic pathway using a pharmacologic agent, such as treating refractory symptoms of depression with ketamine, following by potentiation of the favorable result by repeatedly stimulating the activated pathway. Stimulation of a synaptic pathway may be achieved by intrinsic means, such as performance of cognitive exercised, or extrinsic means, such as by delivery of a sensory stimulus to the patient, placing a potential voltage difference across the brain or a brain region, or by placing the brain or a brain region in a magnetic field.