Timeline, experimental procedures, and kinematic results. (A, B) Rats (n = 10) underwent electromyographic (EMG) recording electrode implantation, implantation of spinal cord epidural stimulating electrodes (L2 and S1), and a complete spinal cord transection (ST at ∼T8). Rats were trained to step bipedally using a bipolar epidural stimulation regimen (40 Hz). (C) Cartoon of the spinal cord depicts nine combinations (trials) of epidural stimulation parameters administered randomly (1-2, bipolar stimulation; 3-4, monopolar stimulation; 5-9, spatiotemporally-independent monopolar stimulation to electrically-enabled motor control (SIM-eEmc) with L2 stimulation at 40 Hz and S1 stimulation at five different frequencies) during EMG and kinematics data collection. (D) A given SIM-eEmc trial progressed from initial stimulation at L2 at 40 Hz, switching “on” of S1 stimulation at frequencies depending upon the trial (SIM-eEmc), switching “off” L2 stimulation, switching “on” L2 (SIM-eEmc), and switching “off” S1 stimulation. Trials 8-9 generally resulted in a higher number of plantar toe contacts, reflective of good stepping (E). (F) The mean joint probability distributions of the y coordinates of the left and right metatarsophalangeal (MTP) joint markers during bipedal stepping before (pre-spinal cord injury) and post-ST for all rats are shown for all stimulation combinations. The dotted lines separate the data points that lie outside the 20% of data points for left and right y coordinates. Percentage indicates the percent of all data points outside the 20% margins for the L-shaped pattern. (G-I) By keeping the L2 epidural stimulation constant at 40 Hz, higher frequencies of stimulation at S1 (either S1-40 Hz alone or S1-20 Hz) generally result in greater consistency of hip (G) and ankle (H) angles and greater step heights (I), compared with the other stimulation conditions. The red dotted line in E, G, H and I indicates the mean values for bipolar L2-S1 stimulation (trial 1). Values are mean ± standard deviation for 8-12 steps/rat for all 10 rats. *, †: Significantly different from trials 1 and 2, and trials 3 and 4, respectively. *Significantly different from trial 1. †Significantly different from trial 4. †Significantly different from trial 3. ‡Significantly different from trials 5-8. ‡Significantly different from trials 5 and 6. The numbers and color code for each stimulation combination shown in (C) is maintained throughout the figures. Color image is available online at www.liebertpub.com/neu