1. A method for optimizing therapeutic stimulation parameters for a patient suffering from pain or depression using therapy electrodes that have been positioned at a target therapy site within the central nervous system, the method comprising: applying an electrical stimulus at a sub-threshold current intensity level relative to a threshold level for neurons at the target therapy site; sensing a response to the electrical stimulus at a sensing device that has been positioned at a sense location of the patient; selecting an alternate stimulus parameter while maintaining a constant electrode configuration, wherein the alternate stimulus parameter comprises decreasing the sub-threshold current intensity to a lower level; applying the alternate stimulus parameter; correlating a change in a sensed response to determine a stimulus/response relationship that is expected to improve efficacy according to the stimulus/response relationship; repeating the applying, sensing, selecting and correlating procedures using the alternate stimulus parameter; choosing the electrical stimulus corresponding to the sensed response that is within a desired range and/or provides a better result compared to other sensed responses; and repeating (a) the decreasing the sub-threshold current intensity to a lower level, (b) re-applying decreased sub-threshold stimulus the lower current intensity to the neurons, and (c) further determining whether application of the decreased sub-threshold current intensity further decreased a membrane activation threshold for the population of neurons until the membrane activation threshold by or to a selected level.