Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats - PubMed (original) (raw)
Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats
Parag Gad et al. J Neuroeng Rehabil. 2013.
Erratum in
- Erratum: development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.
Gad P, Choe J, Nandra MS, Zhong H, Roy RR, Tai YC, Edgerton VR. Gad P, et al. J Neuroeng Rehabil. 2015 Mar 29;12:33. doi: 10.1186/s12984-015-0019-3. J Neuroeng Rehabil. 2015. PMID: 25889487 Free PMC article. No abstract available.
Abstract
Background: Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array.
Methods: We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats.
Results: In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia.
Conclusions: Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.
Figures
Figure 1
Experimental design for the parylene-based multi-electrode array. Parylene based electrode array with multiplexer control and its position and layout with respect to the spinal cord when implanted in the rat. Inset shows the dimensions and design of the platinum electrodes.
Figure 2
Dorsal and ventral surface of the multi-electrode array implant and zoomed in view of the electrodes. A) Ventral view of the implant system: external omnetics connector that is secured to the skull (headplug connector), Teflon coated stainless steel wires from the connector to the circuit board (control wires), electrode array, EMG wires, and ground wires. B) Dorsal surface of the implant. C) Zoomed in view of the multi-electrode array: note the plantinum electrodes, platinum traces, and the holes used to thread the array during implantation. D) Zoomed in view of a single electrode along with the platinum traces. Note the grid-like pattern formed by the parylene on the electrode used to prevent delamination. E) Expanded view of the parylene-based array with platinum electrodes.
Figure 3
Block diagram of the experimental setup. Block diagram showing the experimental setup of the stimulation and recording system. The arrows indicate the direction of the flow of the signals.
Figure 4
Schematic of the multiplexer circuit board. Multiplexer circuit schematic. The 9 lines on the left along with the 3 power lines (12 V, 5 V, and Gnd, not shown) represent the 12 control lines used to interface the array and EMG wires with the external electronics. Black tags represent the spinal cord electrodes and EMG wire pairs.
Figure 5
Schematic of the stimulator circuit board. Stimulator circuit used describing the use of the Pulse Width Modulation (PWM) to generate the required voltage between Stim+ and Stim-. Mode controls current mode vs. voltage mode, and the CurrSense signals allow the stimulating host computer to measure the drawn current.
Figure 6
Location of the motor pools for selected ankle flexor and extensor muscles with respect to the spinal cord level and the sites of electrode implantation. Vertebral (yellow) and spinal cord (red) levels with respect to the 27 electrodes on the array (black circles) and the location of the motor pools of an ankle flexor (TA, tibialis anterior) and two ankle extensor (MG, medial gastrocnemius, and Soleus) muscles.
Figure 7
EMG response to stimulation at rostral electrodes on the array during standing. A) EMG from ankle flexor and extensor muscles bilaterally while the spinal rat transitions from a crouched to a standing position facilitated by epidural stimulation (40 Hz). B) EMG from the right (R) and/or left (L) MG, Sol, and TA muscles during standing under the influence of epidural stimulation (expansion of highlighted region in A). C) Average responses of the 20 evoked potentials during full weight-bearing standing under the influence of epidural stimulation shown in B. MR represents the middle response and the LR represents the long latency late response. Note the different amplitude scales for each muscle.
Figure 8
EMG responses to electrode array stimulation during stepping. Average (10 consecutive steps) rectified EMG (linear envelope) for an ankle flexor (TA) and two ankle extensor (Sol and MG) muscles during stimulation (at 40 Hz, pulse width 0.2 ms, and 3–4 V) using different electrode combinations. A and B: coordinated bilateral stepping with good body weight support. C and D: bilateral stepping with lower body weight support compared to A and B. A, B, C, and D: cases demonstrating good rhythmic bilateral stepping ability with varying degrees of body weight support depending on the position of the cathode and anode on the spinal cord. E: Uncoordinated and non-rhythmic stepping during stimulation with the cathode positioned more caudal than the anode demonstrating the importance of having the cathode at a more rostral segment compared to the anode. Note that the time scale for E is the longest due to extended periods of dragging. F: rhythmic stepping movements with very low (near zero) body weight support, demonstrating the need to position the cathode and anode at different columns to facilitate stepping with good body weight support. Note the EMG amplitude scale in A and B are an order of magnitude higher than in C-F.
Figure 9
Effects of low frequency monopolar stimulation on the ER. Early responses (1–3 ms latency) recorded in the MG (top row) and TA (bottom row) bilaterally during low frequency (1 Hz) monopolar stimulation (3–6 V) at each electrode on the array. The height of each bar indicates the amplitude and the color indicates the latency of the response. The black box indicates a case where no response was recorded for that particular window.
Figure 10
Effects of low frequency monopolar stimulation on the MR. Middle responses (4–6 ms latency) recorded in the MG (top row) and TA (bottom row) bilaterally during low frequency (1 Hz) monopolar stimulation (3–6 V) at each electrode on the array. The height of each bar indicates the amplitude and the color indicates the latency of the response. The black box indicates a case where no response was recorded for that particular window.
Figure 11
Effects of low frequency monopolar stimulation on the LR. Late responses (7–10 ms latency) recorded in the MG (top row) and TA (bottom row) bilaterally during low frequency (1 Hz) monopolar stimulation (3–6 V) at each electrode on the array. The height of each bar indicates the amplitude and the color indicates the latency of the response. The black box indicates a case where no response was recorded for that particular window.
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