Systems and methods for applying electrical stimulation to different sub-populations of targeted neurological tissue for optimizing spinal cord stimulation are disclosed. According to an aspect, a method includes applying a first pattern of electrical stimulation to a first sub- population of targeted neurological tissue of a subject. The method also includes applying a second pattern of electrical stimulation to a second sub-population of targeted neurological tissue of the subject, the second pattern of electrical stimulation being applied at a different frequency than the first pattern of electrical stimulation.