Epidural Stim And Standing: Four For Four

Posted by Sam Maddox in Research News on July 24, 2015 # The Big Idea

A research study was published today in the journal PLOS One by the Susan Harkema lab at the University of Louisville, looking again at the benefits of epidural spinal cord stimulation, this time with regard to standing.

PLOS is an open access journal; you can read the paper, Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans, in its entirety.

Image courtesy of PLOS One: EMG recorded during standing at lower and higher stimulation frequency.

This paper features data from experiments with the "four guys" we all got to know from a widely discussed 2014 research study reported in Brain. In that earlier study, the unprecedented take home message was that voluntary movement was possible in subjects with complete motor and sensory paralysis.

In the new paper, the Louisville research team shows that four out of four did it again: they all "achieved full weight-bearing standing with minimal self-balance assistance when their specific stimulation parameters were used to stimulate the lumbosacral spinal cord."

Let's see how media gatekeepers spin this standing story. It may not stoke the public imagination about spinal cord injury recovery the way last year's news did. Research literature is not scored on drama; today's paper builds the theoretical base for spinal cord stimulation and the ability of the spinal cord to reboot motor function without input from the brain. It also asks more questions about fine tuning the process that can only be learned by further study.

From the paper:

We hypothesized that: 1) clinically detectable supraspinal [connected to the brain] sensory sparing was not required to achieve full weight-bearing standing with epidural stimulation; 2) weight-bearing related sensory input projected to the spinal circuitry enabled the generation of EMG patterns sufficient for standing when epidural stimulation was provided; and 3) stimulation parameters similar to the ones that facilitated standing in the first AIS B participant [Rob Summers, from a 2011 study] could promote standing with the least amount of assistance also in the other three SCI individuals. The results of the present study have important implications with respect to: 1) how lumbosacral neural networks can be selectively modulated by varying the epidural stimulation parameters, and 2) identifying the most efficacious strategies for improved motor function for standing after sensory and motor complete paralysis.

What the Harkema group found was that while the guys were sitting down, with stimulation switched on, there was no detectable motor activity in their legs. But once standing, sensory cues fed into the spinal cord circuitry, which responded with motor function. From the paper:

During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing.

The research recognizes the importance of tailoring stimulation settings to each individual, with electrode placement as an added critical variable.

In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs' muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants.

...the intrinsic complexity of the spinal circuitry reorganized after a clinically complete spinal cord injury requires individualized stimulation parameters in order to finely modulate the sensory-motor pathways impacted by epidural stimulation and generate motor output effective for standing.

Regarding electrodes and the stimulation itself, this research again makes a case for customization.

...standing with the least amount of assistance was achieved with different electrode configurations across individuals, although active electrodes (cathodes) were consistently placed in the caudal portion [higher up the lumbar cord area] of the array.

Electrode placement and programing are still being worked out with this line of research. Here, the research team speculates on why parameters of stimulation vary between individuals.

The observation that stimulation parameters optimized for one individual did not promote sufficient EMG patterns to support full weight-bearing standing in the other participants was an unexpected challenge. Spinal cord anatomy and the position of the electrode array with respect to the spinal cord may have played a role in such individual-specific motor responses. ...It is likely that individual characteristics of the lesion and following plasticity of the spinal neural circuitry, among many, are factors that may have contributed to the different motor responses across research participants induced by stimulation parameters optimized for one individual. Further investigations on this topic are important for the development of epidural stimulation as a tool to improve the recovery of motor function after SCI.

Harkema acknowledges that available stimulator technology is a limiting factor. She cites literature from the Reggie Edgerton lab at UCLA regarding a high-density array in development. Such a tool would help with both electrode location and anode–cathode orientation.

Clinical relevance? Yes.

...the goal was to achieve full body weight-bearing standing with the least amount of assistance while enabling the lumbosacral neural networks to modulate motor pool activity by integrating the postural and weight-bearing related sensory information being projected in real time to the spinal circuitry. These initial results indicate the potential for those even with the diagnosis of clinically sensory and motor complete to regain the ability to stand in their daily life if provided with activity-based rehabilitation combined with individualized epidural stimulation. This capacity not only improves their function but may also combat many of the secondary consequences on health resulting from inactivity.