Closing the loop between researchers and patients

9 min readJul 16, 2020

The growing role of closed-loop neuroprosthetics in rehabilitation

by Isaiah Levy, MD

*Source: Rehab Neural Engineering Labs at the University of Pittsburgh*

Beep…beep…. John pauses, pondering exactly how to put into words the sensations he is feeling, and traces on the tablet the distribution of the sensation. He is a fit middle-aged man, a former marathoner, strapped into a standing frame to remain upright. He has electrode pads taped to his legs and wired to nearby computers to capture real time EMG data from his intact leg and his residual leg. He has a transtibial amputation which occurred after complications from osteomyelitis in the setting of his intensive running and injuries. A few days prior, he had two spinal cord stimulators inserted along portions of his thoracic and lumbar spine. Now, those stimulators were releasing electric discharges of varying frequencies and amplitude in order to elicit sensation. “It’s like a tingling in my knee…” beep…beep… “a buzz in the back of my thigh” beep…beep… John’s eyes widen just so slightly. “I feel it in my big toe!” “Which side?” the researchers ask excitedly. “My left side,” he says, referring to his amputated side. The stimulator had successfully replicated natural sensation in his missing limb. For a brief moment, a sensory link previously lost was restored.

During my intern year, I had the opportunity to participate in a research elective at the Rehab Neural Engineering Labs at the University of Pittsburgh assessing the use of spinal cord stimulators in a patient with a transtibial amputation to restore sensation in the missing limb. The study aims to use the stimulators to replicate natural sensation, those of pressure and movement, that would provide feedback to patients to help improve balance control, reduce falling risk, and potentially decrease phantom limb pain. Imagine: a lower extremity prosthetic, that as pressure is applied with walking, applies electrical stimulation to the spinal cord corresponding to the force to give improved information of the ground below the patient. This study demonstrates another advance in the growing field of neuroprosthetics. Neuroprosthetics, devices using electrodes that interface directly with either the central or peripheral nervous system, have been increasingly utilized as a modality for rehabilitation in patients with amputations. A goal of utilizing neuroprosthetics over traditional prosthetic devices is to facilitate the creation of “closed-loop” devices, those that can reforge the link between sensory input and motor output to enhance control of the device. By reestablishing sensory input either peripherally or centrally, motor output can be reestablished, either as fine-tuned volitional control or via reflex arcs, to allow improved movement for patients.

Source: Rehab Neural Engineering Labs at the University of Pittsburgh

Over the last few decades, there have been remarkable advances in the field of neuroprosthetics in the pursuit of closed-looped devices. These advances have been helped by the wide range of electrode types and targets. Examples include peripheral nervous system (PNS) electrodes which can be divided into three categories: surface electrodes (cuff electrodes) which wrap around the peripheral nerve, penetrating electrodes which penetrate the epineurium and are placed inside fascicles, and regenerative electrodes which facilitate regrowth of a severed nerve around the electrode (Rijnbeek, Eleveld, & Olthuis, 2018). Central nervous system electrodes — brain-computer interfaces — range from those that monitor signals from large areas of the brain, such as scalp EEG which processes electrical activity in regions of interest, to more invasive intracortical and depth electrocorticography (ECoG) electrodes that can offer bidirectional recording and direct sensory stimulation (Adewole et al., 2016). Other novel approaches are also being developed, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) which apply non-invasive magnetic and electrical currents, respectively, to also modulate sensory feedback to patients. Additional approaches, as described above in the case of Robert, include spinal cord stimulators placed in varying positions (e.g. dorsal root ganglia) in order to provide sensory input and potentially reform spinal reflex arcs.

These neuroprosthetic applications have been utilized to improve functionality in patients with stroke (Grimm & Gharabaghi, 2016), spinal cord injury (López-Larraz et al., 2016), and amputation. In upper extremity amputees, prior studies have found that PNS-targeted neuroprosthetics evoke sensation and have shown the ability to restore stable chronic tactile perceptions in the phantom limb with subsequent improvement with tasks requiring fine motor control in the prosthetic limb (Francesco M. Petrini et al., 2019; Raspopovic et al., 2014; Tan, Schiefer, Keith, Anderson, & Tyler, 2015; Tan et al., 2014; Valle et al., 2018). In lower extremity amputees, PNS-targeted neuroprosthetics demonstrated faster walking speeds, decreased metabolic costs (as measured by O2 consumption), and decreased phantom pain (Francesco Maria Petrini et al., 2019). An important caveat for all of these studies is that sample sizes are small, and generalizability is still to be determined. However, many of these pilot studies demonstrate the potential for how neuroprosthetics may be able to improve patients’ lives.

While many of these devices and interventions are still very much in an early phase of development, it is important for clinicians to be aware and knowledgeable of such studies. However, there is often a lack of knowledge of the emerging neuroprosthetic technologies that might be beneficial to patients. For example, a recent Canadian survey among neurologists and physiatrists showed most had relatively poor knowledge of numerous aspects of brain-computer interfaces, while still acknowledging high potential to improve their patients’ quality of life (Letourneau et al., 2020). Patients living with disability are often more aware of many of the emerging technologies in the neuroprosthetic space that could have the potential to improve their quality of life and function. As physiatrists, it is up to us to be cognizant of the potential for such technologies and screen for potentially viable candidates for research, without relying on the patients’ awareness of the emerging technology. However, it is also important to educate ourselves and patients on the risks of such technologies and to monitor our patients’ and our own expectations. As physiatrists, we can help provide an important link between patients and researchers to enable the creation of devices that are patient centric. We can close the loop between the incredible work done by researchers and our patients.

Isaiah is a PGY-2 in PM&R at the University of Pittsburgh Medical Center.

References

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Grimm, F., & Gharabaghi, A. (2016). Closed-Loop Neuroprosthesis for Reach-to-Grasp Assistance: Combining Adaptive Multi-channel Neuromuscular Stimulation with a Multi-joint Arm Exoskeleton. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2016.00284

Letourneau, S., Zewdie, E. T., Jadavji, Z., Andersen, J., Burkholder, L. M., & Kirton, A. (2020). Clinician awareness of brain computer interfaces: A Canadian national survey. Journal of NeuroEngineering and Rehabilitation. https://doi.org/10.1186/s12984-019-0624-7

López-Larraz, E., Trincado-Alonso, F., Rajasekaran, V., Pérez-Nombela, S., del-Ama, A. J., Aranda, J., … Montesano, L. (2016). Control of an ambulatory exoskeleton with a brain-machine interface for spinal cord injury gait rehabilitation. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2016.00359

Petrini, Francesco M., Valle, G., Strauss, I., Granata, G., Di Iorio, R., D’Anna, E., … Micera, S. (2019). Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback. Annals of Neurology. https://doi.org/10.1002/ana.25384

Petrini, Francesco Maria, Bumbasirevic, M., Valle, G., Ilic, V., Mijović, P., Čvančara, P., … Raspopovic, S. (2019). Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain. Nature Medicine. https://doi.org/10.1038/s41591-019-0567-3

Raspopovic, S., Capogrosso, M., Petrini, F. M., Bonizzato, M., Rigosa, J., Pino, G. Di, … Micera, S. (2014). Bioengineering: Restoring natural sensory feedback in real-time bidirectional hand prostheses. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.3006820

Rijnbeek, E. H., Eleveld, N., & Olthuis, W. (2018). Update on peripheral nerve electrodes for closed-loop neuroprosthetics. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2018.00350

Tan, D. W., Schiefer, M. A., Keith, M. W., Anderson, J. R., & Tyler, D. J. (2015). Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees. Journal of Neural Engineering. https://doi.org/10.1088/1741-2560/12/2/026002

Tan, D. W., Schiefer, M. A., Keith, M. W., Anderson, J. R., Tyler, J., & Tyler, D. J. (2014). A neural interface provides long-term stable natural touch perception. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.3008669

Valle, G., Mazzoni, A., Iberite, F., D’Anna, E., Strauss, I., Granata, G., … Micera, S. (2018). Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis. Neuron. https://doi.org/10.1016/j.neuron.2018.08.033

Rijnbeek, E. H., Eleveld, N., & Olthuis, W. (2018). Update on peripheral nerve electrodes for closed-loop neuroprosthetics. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2018.00350

Closing the loop between researchers and patients

Written by Resident Fellow Council, AAP

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