Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury.

The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes. The effect of microelectrode stimulation was studied under light Propofol anesthesia at monthly intervals for up to 14 months. We found that electrical stimulation in the sacral parasympathetic nucleus at S(2) level or in adjacent ventrolateral white matter produced bladder contractions insufficient for inducing voiding, while stimulation at or immediately dorsal to the dorsal gray commissure at S(1) level produced strong (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg) external urethral sphincter relaxation, resulting in bladder voiding in 14 animals. In a subset of three animals, spinal cord transection was performed. For several months after the transection, intraspinal stimulation continued to be similarly or even more effective in inducing the bladder voiding as before the transection. We speculate that in the absence of the supraspinal connections, the plasticity in the local spinal circuitry played a role in the improved responsiveness to intraspinal stimulation.

Evaluation of the stability of intracortical microelectrode arrays.

In order to use recorded neural activities from the brain as control signals for neuroprosthesis devices, it is important to maintain a stable interface between chronically implanted microelectrodes and neural tissue. Our previous paper introduced a method to quantify the stability of the recording microelectrodes. In this paper, the method is refined 1) by incorporating stereotypical behavioral patterns into the spike sorting program and 2) by using a classifier based on Bayes theorem for assigning the recorded action potentials to the underlying neural generators. An improved method for calculating stability index is proposed. The results for the stability of microelectrode arrays that differ in structure are presented.

Arrays for chronic functional microstimulation of the lumbosacral spinal cord.

Our objective is to develop neural prostheses based on an array of microelectrodes implanted into the sacral spinal cord, that will allow persons with spinal cord injuries to regain control of their bladder and bowels. For our chronic cat model, we have developed two microelectrode arrays, one type containing nine discrete activated iridium microelectrodes and the second utilizing silicon substrate probes with multiple electrode sites on each probe. Both types can elicit an increase in the pressure within the urinary bladder of more than 40-mm Hg and/or relaxation of the urethral sphincter. A stimulus of 100 microA and 400 micros/ph at 20 Hz (charge-balanced pulses) was required to induce a large increase in bladder pressure or relaxation of the urethral sphincter. We found that 24 h of continuous stimulation with these parameters induced tissue injury (disrupted neuropil, infiltration of inflammatory cells, and loss of neurons close to the tip sites). However, a neural prosthesis that is intended to restore bladder control after spinal cord injury would not operate continuously. Thus, when this stimulus was applied for 24 h, at a 10% duty cycle (1 min of stimulation, then 9 min without stimulation) only minimal histologic changes were observed.

The effects of prolonged intracortical microstimulation on the excitability of pyramidal tract neurons in the cat.

This study was conducted to examine the excitability changes induced in cerebral cortical neurons during prolonged microstimulation with a spatially dense microelectrodes array. The arrays of 16 iridium microelectrodes were implanted chronically into the postcruciate gyrus of cats. Neuronal responses characteristic of single pyramidal tract axons (ULRs) were recorded in the medullary pyramid. 7 h of pulsing of individual electrodes at 50 Hz and at 4 nC/ph induced little or no change in the ULRs' electrical thresholds. The thresholds also were quite stable when 4 of the 16 microelectrodes were pulsed on each of 14 consecutive days. However, when all 16 microelectrodes were pulsed for 7 h at 4 nC/ph, the threshold of approximately half of the ULRs became elevated. Recovery of excitability required 2-18 days. Prolonged sequential (interleaved) pulsing of the 16 microelectrodes induced less depression of excitability than did simultaneous pulsing, but only when the stimulus amplitude was low (12 A, 1.8 nC/ph). Stimulation at a higher amplitude (15 nC/ph) induced much more depression of excitability. These findings imply that multiple processes mediate the stimulation-induced depression of neuronal excitability. The data also demonstrate that the depression can be reduced by employing a stimulus regimen in which the inherent spatial resolution of the array is maximized (sequential pulsing at an amplitude in which there is minimal overlap of the effective current fields).