Tracking Phantoms of our Reality

Those in neuroscience have most likely heard of the neuroscientist V.S. Ramachandran and his work in studying abnormalities observed between the mind body relationship. He has inspired many, including me to have a deep curiosity about the world through the lens of neuroscience. In his book “Phantoms in the Brain”, he describes the phenomenon of phantom limp pain (PLP) and phantom limb sensation (PLS) in amputees. These experienced symptoms are associated with how the somatosensory cortex represents the entire body. This cortical mapping and the brains’ ability for neuroplasticity or cortical reorganization is one mechanism that explains why amputees still have the experience of the limb that is no longer present. To continue Ramachandran’s work 1998, I would like to briefly show where we are at with understanding PLP/PLS and what is being done to alleviate its symptoms. In spirit of Ramachandran, I would like to keep in mind the deeper implications of how we relate to our bodies, what is us and other, and what does it mean to be embodied beings.

PLP has a tremendous impact on quality of life in amputees. The number of amputees each year is increasing and not just due to traumatic car accidents but also due to the increase in diabetes and tumors. Many techniques used to alleviate PLP/PLS have evolved since the classical mirror therapy developed my Ramachandran. Since then, Transcranial Magnetic Stimulation (TMS) has been used over the cortical maps to activate the areas representing the absent limb. Acupuncture, drug treatments, and spinal cord stimulation are other therapies but none of them alone have had consistent success in dealing with PLP/PLS.

During a neuroscience seminar, I had the honor to listen to Dr. Dumanian’s talk on the incredible work he is doing with using Target Muscle Reinnervation (TMR) to alleviate PLP. His work seems very promising compared to the other therapies offered. What previous procedures had done was just innervated the amputated sense nerves into the nearby muscle flesh. Dr. Dumanian’s approach was to innervate the sense nerve with a nearby motor nerve that wouldn’t critically impact other motor functions. The reasoning behind is ingenious. Instead of having an open loop motor-sensory system with the nerve just embedded in the muscle, innervating the sense and motor nerve together creates the closed loop system. As Dr. Dumanian states, giving the sense nerve “something to do” could reduce the effects of cortical reorganization. Over the course of the year, patients reported PLP had reduced compared to the standard procedure.

TMR research focuses on what new treatments might look like in the future, but we are only looking at the peripheral nerve system. What have we learned in the CNS with cortical reorganization? What Ramachandran hypothesized was that neurons in the brain are always in competition with each other. If part of the somatosensory cortex is inactive due to an amputated limb, these areas don’t atrophy but get taken over by surrounding areas. A study that caught my attention was looking beyond the somatosensory cortex in how other areas are becoming reorganized. Particularly the right parietal cortex. The work done by Bao et al. 2021 in their study “Parietal Lobe Reorganization and Widespread Functional Connectivity Integration in Upper-Limb Amputees: A rs-fMRI Study”, looked at how areas in the right parietal cortex might become reorganized.

Amputees that have had upper-limb amputations have also been shown to have body image disorders. DSM-V describes this condition as having an intense anxiety due to the sense that their image of their body does not match reality. The right parietal cortex is a region of interest (ROI) since patients with lesions to this area have various body disorders. Using resting state fMRI (rs-fMRI), a technique used to measure brain activity but not needing to perform a task, the researchers have identified two indicators in the right parietal cortex that were significantly different from a healthy control group. They showed that there was a positive correlation with these indicators and self-reports of PLS. What these indicators show is that this is a decrease connectivity between various brain regions. The limitation to this study is that it is only post operative and that there needs to be a longitudinal study to see how these areas continually reorganize.

This study is a started point in understanding the brain and the body as a whole. Future research is needed not only for understanding the mechanisms behind reorganization, but for better therapies for amputees. The questions that still arises for me is how does the body (particularly the nervous system) maintain itself as a dynamical self-organizing system? In Dr. Dumanian’s work, he demonstrates that closed-loop systems are critical. In Bao’s et al. work, they showed that areas of the parietal cortex might serve as hubs to how we maintain our sense of embodiment. It is exciting to see where research has gone since Ramachandran and how more areas of research are converging on better understanding the complexities of life.

 

References:

Bao, Wei, H., Luo, P., Zhu, H., Hu, W., Sun, Y., Shen, J., Zhu, T., Lin, J., Huang, T., Li, J., Wang, Z., Li, Y., & Zheng, X. (2021). Parietal Lobe Reorganization and Widespread Functional Connectivity Integration in Upper-Limb Amputees: A rs-fMRI Study. Frontiers in Neuroscience, 15, 704079–704079. https://doi.org/10.3389/fnins.2021.704079

Dumanian, Potter, B. K., Mioton, L. M., Ko, J. H., Cheesborough, J. E., Souza, J. M., Ertl, W. J., Tintle, S. M., Nanos, G. P., Valerio, I. L., Kuiken, T. A., Apkarian, A. V., Porter, K., & Jordan, S. W. (2019). Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Annals of Surgery, 270(2), 238–246. https://doi.org/10.1097/SLA.0000000000003088

Improvements in Amputation and the Fitting of Prothesis

    There are many reasons someone would potentially lose a limb; be it from disease, an accident, or from partaking in armed conflict. This loss is never easy, and takes a complete retraining of behaviors. One thing that cannot be trained however is how your body reacts to the loss of the limb. Many people who have lost a limb experience phantom limb pain that stems from neuromas. These neuromas are cut nerve endings that are encased in scar tissue. In, “Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees,” Dumanian et al. looked into a possible treatment for these issues that plague amputees. There had been a few treatments that had been created, but there had not been one that was proven to be consistently effective at treatment. Dumanian took a different approach from what had been previously done, instead he removed the terminal neuroma and then took the new end and implanted it into a nearby motor nerve. This was called “targeted muscle reinnervation,” and it was observed to lessen patients' phantom pain. With some more fine-tuning, patients could have even less pain.

    In, “Targeted Muscle Reinnervation for Prosthesis Optimization and Neuroma Management in the Setting of Transradial Amputation,” written by Pierrie et al., take the procedure by Dumanian and improve upon it. They make sure that their patients have enough soft tissue at the end of the amputated limb. They make sure that the donor and target nerves are similar enough, and reinforce the site of connection if they are not similar enough. Adipose flaps and synthetic grafts are used to help isolate the muscle signals of the newly connected nerves. Patients are then given a stump shrinker, and then given a simple prosthesis and simple terminal end device. The addition of quickly fitting patients with a simple prosthesis have helped improve limb edema and prosthetic utilization rates.

    It is impressive to see how this medical procedure has progressed as time has gone on. They were already able to lessen the phantom pain found in patients, and now they have been able to lessen the edema that patients might experience after an amputation. While they have helped improve the prosthetic utilization rates, I’m sure there are still more ways to improve upon it. Starting off with a simple prosthesis might be good, but giving a more complex prosthesis to patients as soon as possible might have improved results. Patients most likely had decent control over their limbs before amputation, so it would be safe to assume that they would be able to control a more complex prosthesis if they were given some time. Even if that were not the case, I’m sure there is some way that we could make the adjustment to a prosthesis easier than it is now.

Works Cited

Dumanian, G. A., Potter, B. K., Mioton, L. M., Ko, J. H., Cheesborough, J. E., Souza, J. M., Ertl, W. J., Tintle, S. M., Nanos, G. P., Valerio, I. L., Kuiken, T. A., Apkarian, A. V., Porter, K., & Jordan, S. W. (2019). Targeted muscle reinnervation treats neuroma and Phantom Pain in major limb amputees. Annals of Surgery, 270(2), 238–246. https://doi.org/10.1097/sla.0000000000003088

Pierrie, S. N., Gaston, R. G., & Loeffler, B. J. (2019). Targeted muscle reinnervation for prosthesis optimization and neuroma management in the setting of Transradial amputation. The Journal of Hand Surgery, 44(6). https://doi.org/10.1016/j.jhsa.2018.11.019