UNIVERSITY PARK, Pa. — Losing feeling in your hands can make everyday activities like cooking, driving or texting a struggle. Procedures that use electricity to substitute for or help regain nerve function can help, but over time, these treatments lose effectiveness as the brain adjusts to artificial stimulation, a process known as habituation. A team of researchers, led by an engineer from Penn State, is using advanced imaging techniques to better understand the mechanics behind habituation, pinpointing optimized treatment settings that could eventually help address the problem in patients who have had strokes or amputations.
In a paper published in IEEE Transactions on Medical Imaging , the team monitored the brain activity of 10 healthy participants during transcutaneous nerve stimulation (TNS), a treatment that uses tiny electrodes placed on the body to stimulate nerves and, in turn, elicit a sensory response in the brain. Adjusting variables over several tests, the team identified optimal settings that allowed for sustained sensation over 45 minutes with no change in feeling or stability. Although participants reported no habituation, imaging showed that the engaged areas of the brain changed over the course of the experiment, offering new insight into this misunderstood brain phenomenon.
Sensory stimulation can be administered with electrodes placed on the skin, or even through electrodes implanted directly into a patient's brain. Regardless of the application method, Xiaogang Hu , Penn State Dorothy Foehr Huck and J. Lloyd Huck Chair in Neurorehabilitation, professor of mechanical engineering and corresponding author on the paper, said habituation is a consistent issue that makes effective, long-term stimulation difficult to achieve.
"Repetitive stimulation — regardless of whether you engage stimulation through the nerves, skin or directly targeting a part of the brain — will be perceived as declining or weakening over time," said Hu, who holds additional affiliations in the Departments of Kinesiology and of Physical Medicine and Rehabilitation. "With this work, we are trying to avoid or minimize that habituation, enabling a more stable sense of touch over a longer timeframe."
Over the last decade, Hu's lab has sought to restore feeling in people's bodies using systems that can translate the feeling of touch between a patient's brain and a prosthetic . Habituation has remained a constant challenge over that time, and despite its prevalence, Hu said scientists still don't entirely understand it on a mechanical level. Better understanding these changes, even in people without injury, could potentially help scientists understand the changes in people with brains that may have already rewired to help compensate for an amputation or stroke.
"Picture someone is holding a cup of water with their prosthetic — the sensation of touch is critical for them to maintain an appropriate grip force," Hu said. "We don't want them to crush the cup with too much force or for them to lose their sensation of touch over time and drop the cup, we need to ensure that the feeling is stable."
Beyond addressing habituation, the team wanted to learn how to best optimize TNS for long-term stability, and how those optimal conditions may change over time.
"It's a twofold study, really — we are looking for the best way to deliver stimulation that will minimize habituation, while also trying to understand what really happens to the brain during TNS," Hu said. "By answering those questions, we can more effectively identify the optimal stimulation parameters and strike that sort of engagement 'sweet spot' in their brain that triggers the touch response, evoking a stable and sustained sense of touch."
The team used a non-invasive imaging technique called functional near-infrared spectroscopy (fNIRS) to monitor which regions of the brain would activate during TNS, and in turn, how those regions might change over time. The approach uses a swimming-cap-like measurement tool placed on a participant's head, Hu said. Tiny electrodes dotted around the cap's surface project beams of infrared light into the brain, using tiny sensors to capture reflections of that light bouncing off the brain. These invisible signals can quantify the amount of oxygen in blood around the brain, which researchers use as a sort of proxy measurement for brain activity, according to Hu.
"This technique is very similar to an fMRI, which is a specialized type of MRI scan that tracks how blood oxygen fluctuates in the brain," Hu said. "However, using fNIRS, we can conduct similar imaging outside of a scanner, allowing us to better track brain activity during movement and with sensory stimulation."
With the cap placed and calibrated to target the somatosensory cortex, the region where touch is processed in the brain, researchers attached electrodes to specific areas on the participants' arms to stimulate nerves. Mild electrical pulses were administered, followed by a longer period of rest. Several conditions and intervals of electrical stimulation and rest were tested, culminating in a longer test of the most optimal conditions over the course of 45 minutes. The team reported that five seconds of stimulation, followed by a period of 40 seconds of rest, struck a balance where nerves were effectively stimulated, but the participants' perception of intensity did not diminish over time. Further testing showed that these conditions remained optimal, even when tested about 60 times over 45 minutes.
"Most people report that the TNS process feels like a tingling or gentle massage," said first author Susan Coltman, assistant professor at the University of Guelph, who was a postdoctoral researcher at the time of the work. "It may sound scary because it's the application of electricity to the body, but it's so mild that these machines are common in physical therapy and chiropractor offices."
Despite participants reporting no change in how TNS felt, imaging showed that brain activity varied, explained Coltman. fNIRS showed different regions of the brain lighting up like a holiday display over the course of the 45-minute testing window, suggesting that habituation was not exclusive to a specific region of the brain.
"Participants report that the sensation feels the same, but the active regions in their brain actually change over time, with changing intensity of activation and spatial distribution," Coltman said. "The signals start out in the somatosensory cortex, but over time, they move out beyond that origin area to different regions of the brain, reflecting progressive recruitment of distributed brain regions to process information during prolonged sensory stimulation."
Using this new understanding of habituation and optimized parameters as a guide, Hu said that future work will look to understand how optimal parameters might change between patients with different brain lesions. Although this initial study did not focus on participants with amputations or impaired brain function, Hu said he hopes it will lay the foundation to eventually apply this work as a rehabilitation technique in a larger clinical study.
Additional authors on the work include William B. Riggs, an undergraduate researcher at the time of the work who earned their degree in bioengineering and biomedical engineering from Penn State and is now bioengineering doctoral candidate at the University of Pittsburgh; and Androu Abdalmalak, an independent researcher, now a faculty at the University of Western Ontario.
This study was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research and the U.S. National Science Foundation's Division of Information and Intelligent Systems under grant numbers IIS-2330862 and IIS-2319139 . This content is the sole responsibility of the authors and does not necessarily reflect the views of the funders.
