Targeted Sensory and Muscle Reinnervation
Targeted Sensory and Muscle Reinnervation: A Technological and Surgical Advancement in Upper-Limb Prosthetics and Cortical Map Integration
Abstract
Upper-limb amputations are a devastating injury which changes how a person lives. Current prosthetics do not enrich an individual’s experience and are associated with physical and psychological injuries. Targeted sensory and muscle innervation (TSMR) is a surgical endeavour that redirects remaining nerves to intact muscles and skin areas. These redirections interact with a TSMR prosthetic that can be moved by signals from the primary motor cortex and can relay information back to the primary somatosensory cortex. Projections in these corticesinteract with the brain’s representation of the missing limb. Even though upper-limb amputations have been shown to induce cortical reorganisation, TSMR usage can reinstate upper-limb representations and bring back most of the original cortical functions. Due to the novelty of this innovation, questions related to wide-spread use, extent of research for bilateral amputations and the long-term effects of TSMR are discussed. Potential solutions as future experimental directives are also provided.
Introduction
Upper-limb amputations are a lifechanging disability that interferes with everyday life. For these individuals, rehabilitation challenges focus on readjusting behaviour around a prosthetic limb’s capacity for movement. Though current designs physically resemble the dimensions of the missing limb, intuitive control is difficult to regain and can contribute to psychological disturbances. Furthermore, even if an individual has access to a myoelectric prosthetic, there is a bias to rely on intact limbs which in turn can contribute to overuse injuries (Chadwell et al., 2018). Cumulatively, these issues restrict individuals with an upperlimb amputation from returning to normalcy. Recent innovations have addressed these concerns by increasing the cognitive input to prostheses. Targeted sensory and muscle innervation (TSMR) surgically couples residual nerves to muscle targets and skin regions. By rerouting motor projections to intact muscles near the amputation, neural signals that would originally be used to move the limb can be decoded to move a prosthetic. Similarly, a sense of touch can be established by affixing remaining sensory nerves to distinct skin regions. These skin regions become stimulated when a prosthetic is engaged with an object and relay “feeling” back to the brain (Image 1). In order to be effective, TSMR surgery combines knowledge of how the body is cortically mapped and what changes occur post-amputation. TSMR prosthetics are then able to interact with these maps and behave as if they were an ordinary limb. By frequently revisiting and updating current understanding of brain maps, future TSMR prosthetics can continue to provide upper-limb amputees the best possible outcome.
Upper-Limb Brain Maps
Experience of the external world arises via integration of brain maps. In this context, a map is a representation of a sensory system in an identifiable anatomical region. Each map encodes and decodes highly specific information about the target it oversees. For TSMR prosthetics, the primary motor (M1) and primary somatosensory (S1) cortices are of particular interest. Respectively, these cortices and their modalities contribute to how the body executes movements and registers sensations. To a certain extent, these regions are highly plastic and can modulate cortical real estate depending on an individual’s need for specificity (Hirano et al., 2019). In both M1 and S1, upper-limb representations are extensive due to the need to perform intricate manoeuvres and detect slight impressions. Consequently, in states of upper-limb amputations, cortical reorganisation is induced where neighbouring limb representations expand into previously devoted regions (Weiss et al., 2000).
TSMR Reinstates Upper-Limb Representation
Extensive neurophysiological studies in human amputees are rare but overall observations suggest that TSMR reinstates upper-limb representations in M1 and S1. In TSMR patients, the M1 region displays cortical normalisation which is comparable in extent, strength and topography of a typically organised cortex (Serino et al., 2017). This finding is reiterated in other TSMR studies that have shown upper-limb motor maps gradually relocating to their original position (Chen et al., 2013). However, it should be noted that due to the novelty of this innovation, the sample size and latency period in both these studies was not expansive. At most, three TSMR patients were used - all of whom had varying degrees of amputations. Nevertheless, in mice models, significant cortical reorganisation has been shown to occur rapidly after injury (Kossut & Juliano, 1999). This suggests that all experimental patients would have had enough cortical reorganisation for each study to indicate TSMR’s ability to reinstate original representations. Additionally, since the findings were comparable across the non-homogenous populations, it can be inferred that TSMR use is beneficial regardless of the type of upper-limb amputation. Analogous findings transpired in S1 representations. Prior to TSMR surgery, the contralateral S1 cortex does not display clear temporal or spatial patterns when stimulated (Yao et al., 2015). Conversely, there is increased ipsilateral plasticity indicating a redistribution of connections in order to increase sensitivity in the remaining limb (Figure 1). Once TSMR prosthetics are utilised the findings are comparable to M1 normalisation, and the extent and topography of the S1 cortex is restored (Serino et al., 2017). However, unlike M1, activation strength remains weaker than healthy controls. Currently, there is no empirical explanation for this observation but reduced interhemispheric connectivity between S1 and its secondary regions may be the cause (Bramati et al., 2019). If there are fewer dynamic connections between S1 and its supplementary regions, then a greater level of stimulation may be required to achieve the same degree of somatosensory awareness. This suggests that while TSMR can restore upper-limb representation in M1 and S1, there are other downstream effects of limb amputation that might modulate the extent of rehabilitation.
TSMR Considerations and Future Experiments
TSMR is a highly sophisticated development that combines neurophysiological research and bioengineering. The current surgery and prosthetic design show great promise in becoming standardised protocol for upper-limb amputees. In saying that, there are a few considerations that must be acknowledged. Firstly, TSMR prosthetics require intact nerves that derive from M1 and S1. This requirement is not always guaranteed as issues such as axonal degeneration and the formation of neuromas are strongly associated with amputations (Watson et al., 2010). The pathophysiology of these problems is not well-understood, however potential solutions involve the implantation of internal TSMR electrodes. If the intact nerve is deeper within the body, and a low signal-to-noise ratio is being detected externally, then an internal device could access the neural information needed for prosthetic movement and sensation. Future research into this solution should consider the long-term viability of such electrodes and balance the burden of invasive technology with the proposed benefits for the patient.
Secondly, current TSMR research predominantly focuses on unilateral amputations. This is a significant research lapse as brain map differences between unilateral and bilateral amputees may impact TSMR effectiveness. Foundational research into these differences are sparse, however as presented in hand allograft studies, variations in stimulation intensity and representation of motor maps have been observed (Vargas et al., 2009). Furthermore, TSMR prosthetics are clinically relevant to bilateral amputees as quality of life issues are more pronounced in these cases. The present innovation has an opportunity to address these concerns. Future brain map experiments should address this research gap and determine how contralateral and ipsilateral changes may vary depending on the number of amputations. Findings from this can motivate forthcoming TSMR experimentation to determine how multiple prostheses can healthily engage with a user.
Finally, as previously mentioned, upper-limb sensations not only rely on integration within S1 but also through a heavily distributed network of multisensory cortices. Regions such as the posterior parietal cortex contribute to the holistic interpretation of somatosensory input. These regions are integral in bodily-conscious behaviour and perceptions of limb ownership. Therapeutically, these connections can be exploited to provide relief in cases of phantom limb (Finn et al., 2017). Post-amputation the connections between S1 and its supplementary areas become highly variable across individuals and are less connected with the overall sensorimotor network (Serino et al., 2017). These findings are not related to the length of TSMR prosthetic use but are indicative of an underlying neurological change that occurs post-operatively. This information does not change the short-term benefits of TSMR prosthetics but does raise questions surrounding the long-term use of the device. In the short run, an individual is able to return to some degree of normalcy, but whether deeper issues arise because of this oversight is difficult to predict. The same way phantom limb was not predicted as a potential outcome from amputations, deeper neurological disorders that occurs from this hypoconnectivity are difficult to determine. Future experiments can observe behavioural changes in animal models and calculate an odds ratio for apparent risks. Alternatively, the relative risk ratio can be calculated but only with an increase sample size and over a long period of time.
In conclusion, TSMR is a novel innovation that combines current understanding of brain maps and technology. By using this knowledge to design more dynamic and interactive artificial limbs, upper-limb amputees will be able to return to a degree of normalcy. Due to the infancy of this field, there are still several considerations that need to be addressed. However, with future experimentation and the continual expansion of scientific understanding, this intersection shows great promise as the next frontier in upper-limb prosthetic design.
References
Bramati, I.E., Rodrigues, E.C., Simões, E.L., Melo, B., Höfle, S., Moll, J., Lent, R. and Tovar-Moll, F. (2019). Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity. Scientific Reports, 9(1).
Chadwell, A., Kenney, L., Granat, M.H., Thies, S., Head, J., Galpin, A., Baker, R. and Kulkarni, J. (2018). Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance. Scientific Reports, 8(1).
Chen, A., Yao, J., Kuiken, T. and Dewald, J.P.A. (2013). Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation. NeuroImage: Clinical, 3, pp.498–506.
Hirano, M., Kimoto, Y. and Furuya, S. (2019). Specialized Somatosensory–Motor Integration Functions in Musicians. Cerebral Cortex.
Kossut, M. and Juliano, S.L. (1999). Anatomical correlates of representational map reorganization induced by partial vibrissectomy in the barrel cortex of adult mice. Neuroscience, 92(3), pp.807–817.
Motherboard (2016). The Mind-Controlled Bionic Arm With a Sense of Touch. YouTube. Available at: https://www.youtube.com/watch?v=F_brnKz_2tI.
Serino, A., Akselrod, M., Salomon, R., Martuzzi, R., Blefari, M.L., Canzoneri, E., Rognini, G., van der Zwaag, W., Iakova, M., Luthi, F., Amoresano, A., Kuiken, T. and Blanke, O. (2017). Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation. Brain, 140(11), pp.2993–3011.
Vargas, C.D., Aballéa, A., Rodrigues, É.C., Reilly, K.T., Mercier, C., Petruzzo, P., Dubernard, J.M. and Sirigu, A. (2009). Re-emergence of hand-muscle representations in human motor cortex after hand allograft. Proceedings of the National Academy of Sciences, [online] 106(17), pp.7197–7202. Available at: https://www.pnas.org/content/106/17/7197.short [Accessed 7 May 2020].
Watson, J., Gonzalez, M., Romero, A. and Kerns, J. (2010). Neuromas of the Hand and Upper Extremity. The Journal of Hand Surgery, 35(3), pp.499–510.
Weiss, T., Miltner, W.H.R., Huonker, R., Friedel, R., Schmidt, I. and Taub, E. (2000). Rapid functional plasticity of the somatosensory cortex after finger amputation. Experimental Brain Research, 134(2), pp.199–203.
Yao, J., Chen, A., Kuiken, T., Carmona, C. and Dewald, J. (2015). Sensory cortical re-mapping following upper-limb amputation and subsequent targeted reinnervation: A case report. NeuroImage: Clinical, 8, pp.329–336.
Upper-limb amputations are a devastating injury which changes how a person lives. Current prosthetics do not enrich an individual’s experience and are associated with physical and psychological injuries. Targeted sensory and muscle innervation (TSMR) is a surgical endeavour that redirects remaining nerves to intact muscles and skin areas. These redirections interact with a TSMR prosthetic that can be moved by signals from the primary motor cortex and can relay information back to the primary somatosensory cortex. Projections in these corticesinteract with the brain’s representation of the missing limb. Even though upper-limb amputations have been shown to induce cortical reorganisation, TSMR usage can reinstate upper-limb representations and bring back most of the original cortical functions. Due to the novelty of this innovation, questions related to wide-spread use, extent of research for bilateral amputations and the long-term effects of TSMR are discussed. Potential solutions as future experimental directives are also provided.
Introduction
Upper-limb amputations are a lifechanging disability that interferes with everyday life. For these individuals, rehabilitation challenges focus on readjusting behaviour around a prosthetic limb’s capacity for movement. Though current designs physically resemble the dimensions of the missing limb, intuitive control is difficult to regain and can contribute to psychological disturbances. Furthermore, even if an individual has access to a myoelectric prosthetic, there is a bias to rely on intact limbs which in turn can contribute to overuse injuries (Chadwell et al., 2018). Cumulatively, these issues restrict individuals with an upperlimb amputation from returning to normalcy. Recent innovations have addressed these concerns by increasing the cognitive input to prostheses. Targeted sensory and muscle innervation (TSMR) surgically couples residual nerves to muscle targets and skin regions. By rerouting motor projections to intact muscles near the amputation, neural signals that would originally be used to move the limb can be decoded to move a prosthetic. Similarly, a sense of touch can be established by affixing remaining sensory nerves to distinct skin regions. These skin regions become stimulated when a prosthetic is engaged with an object and relay “feeling” back to the brain (Image 1). In order to be effective, TSMR surgery combines knowledge of how the body is cortically mapped and what changes occur post-amputation. TSMR prosthetics are then able to interact with these maps and behave as if they were an ordinary limb. By frequently revisiting and updating current understanding of brain maps, future TSMR prosthetics can continue to provide upper-limb amputees the best possible outcome.
Upper-Limb Brain Maps
Experience of the external world arises via integration of brain maps. In this context, a map is a representation of a sensory system in an identifiable anatomical region. Each map encodes and decodes highly specific information about the target it oversees. For TSMR prosthetics, the primary motor (M1) and primary somatosensory (S1) cortices are of particular interest. Respectively, these cortices and their modalities contribute to how the body executes movements and registers sensations. To a certain extent, these regions are highly plastic and can modulate cortical real estate depending on an individual’s need for specificity (Hirano et al., 2019). In both M1 and S1, upper-limb representations are extensive due to the need to perform intricate manoeuvres and detect slight impressions. Consequently, in states of upper-limb amputations, cortical reorganisation is induced where neighbouring limb representations expand into previously devoted regions (Weiss et al., 2000).
TSMR Reinstates Upper-Limb Representation
Extensive neurophysiological studies in human amputees are rare but overall observations suggest that TSMR reinstates upper-limb representations in M1 and S1. In TSMR patients, the M1 region displays cortical normalisation which is comparable in extent, strength and topography of a typically organised cortex (Serino et al., 2017). This finding is reiterated in other TSMR studies that have shown upper-limb motor maps gradually relocating to their original position (Chen et al., 2013). However, it should be noted that due to the novelty of this innovation, the sample size and latency period in both these studies was not expansive. At most, three TSMR patients were used - all of whom had varying degrees of amputations. Nevertheless, in mice models, significant cortical reorganisation has been shown to occur rapidly after injury (Kossut & Juliano, 1999). This suggests that all experimental patients would have had enough cortical reorganisation for each study to indicate TSMR’s ability to reinstate original representations. Additionally, since the findings were comparable across the non-homogenous populations, it can be inferred that TSMR use is beneficial regardless of the type of upper-limb amputation. Analogous findings transpired in S1 representations. Prior to TSMR surgery, the contralateral S1 cortex does not display clear temporal or spatial patterns when stimulated (Yao et al., 2015). Conversely, there is increased ipsilateral plasticity indicating a redistribution of connections in order to increase sensitivity in the remaining limb (Figure 1). Once TSMR prosthetics are utilised the findings are comparable to M1 normalisation, and the extent and topography of the S1 cortex is restored (Serino et al., 2017). However, unlike M1, activation strength remains weaker than healthy controls. Currently, there is no empirical explanation for this observation but reduced interhemispheric connectivity between S1 and its secondary regions may be the cause (Bramati et al., 2019). If there are fewer dynamic connections between S1 and its supplementary regions, then a greater level of stimulation may be required to achieve the same degree of somatosensory awareness. This suggests that while TSMR can restore upper-limb representation in M1 and S1, there are other downstream effects of limb amputation that might modulate the extent of rehabilitation.
TSMR Considerations and Future Experiments
TSMR is a highly sophisticated development that combines neurophysiological research and bioengineering. The current surgery and prosthetic design show great promise in becoming standardised protocol for upper-limb amputees. In saying that, there are a few considerations that must be acknowledged. Firstly, TSMR prosthetics require intact nerves that derive from M1 and S1. This requirement is not always guaranteed as issues such as axonal degeneration and the formation of neuromas are strongly associated with amputations (Watson et al., 2010). The pathophysiology of these problems is not well-understood, however potential solutions involve the implantation of internal TSMR electrodes. If the intact nerve is deeper within the body, and a low signal-to-noise ratio is being detected externally, then an internal device could access the neural information needed for prosthetic movement and sensation. Future research into this solution should consider the long-term viability of such electrodes and balance the burden of invasive technology with the proposed benefits for the patient.
Secondly, current TSMR research predominantly focuses on unilateral amputations. This is a significant research lapse as brain map differences between unilateral and bilateral amputees may impact TSMR effectiveness. Foundational research into these differences are sparse, however as presented in hand allograft studies, variations in stimulation intensity and representation of motor maps have been observed (Vargas et al., 2009). Furthermore, TSMR prosthetics are clinically relevant to bilateral amputees as quality of life issues are more pronounced in these cases. The present innovation has an opportunity to address these concerns. Future brain map experiments should address this research gap and determine how contralateral and ipsilateral changes may vary depending on the number of amputations. Findings from this can motivate forthcoming TSMR experimentation to determine how multiple prostheses can healthily engage with a user.
Finally, as previously mentioned, upper-limb sensations not only rely on integration within S1 but also through a heavily distributed network of multisensory cortices. Regions such as the posterior parietal cortex contribute to the holistic interpretation of somatosensory input. These regions are integral in bodily-conscious behaviour and perceptions of limb ownership. Therapeutically, these connections can be exploited to provide relief in cases of phantom limb (Finn et al., 2017). Post-amputation the connections between S1 and its supplementary areas become highly variable across individuals and are less connected with the overall sensorimotor network (Serino et al., 2017). These findings are not related to the length of TSMR prosthetic use but are indicative of an underlying neurological change that occurs post-operatively. This information does not change the short-term benefits of TSMR prosthetics but does raise questions surrounding the long-term use of the device. In the short run, an individual is able to return to some degree of normalcy, but whether deeper issues arise because of this oversight is difficult to predict. The same way phantom limb was not predicted as a potential outcome from amputations, deeper neurological disorders that occurs from this hypoconnectivity are difficult to determine. Future experiments can observe behavioural changes in animal models and calculate an odds ratio for apparent risks. Alternatively, the relative risk ratio can be calculated but only with an increase sample size and over a long period of time.
In conclusion, TSMR is a novel innovation that combines current understanding of brain maps and technology. By using this knowledge to design more dynamic and interactive artificial limbs, upper-limb amputees will be able to return to a degree of normalcy. Due to the infancy of this field, there are still several considerations that need to be addressed. However, with future experimentation and the continual expansion of scientific understanding, this intersection shows great promise as the next frontier in upper-limb prosthetic design.
References
Bramati, I.E., Rodrigues, E.C., Simões, E.L., Melo, B., Höfle, S., Moll, J., Lent, R. and Tovar-Moll, F. (2019). Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity. Scientific Reports, 9(1).
Chadwell, A., Kenney, L., Granat, M.H., Thies, S., Head, J., Galpin, A., Baker, R. and Kulkarni, J. (2018). Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance. Scientific Reports, 8(1).
Chen, A., Yao, J., Kuiken, T. and Dewald, J.P.A. (2013). Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation. NeuroImage: Clinical, 3, pp.498–506.
Hirano, M., Kimoto, Y. and Furuya, S. (2019). Specialized Somatosensory–Motor Integration Functions in Musicians. Cerebral Cortex.
Kossut, M. and Juliano, S.L. (1999). Anatomical correlates of representational map reorganization induced by partial vibrissectomy in the barrel cortex of adult mice. Neuroscience, 92(3), pp.807–817.
Motherboard (2016). The Mind-Controlled Bionic Arm With a Sense of Touch. YouTube. Available at: https://www.youtube.com/watch?v=F_brnKz_2tI.
Serino, A., Akselrod, M., Salomon, R., Martuzzi, R., Blefari, M.L., Canzoneri, E., Rognini, G., van der Zwaag, W., Iakova, M., Luthi, F., Amoresano, A., Kuiken, T. and Blanke, O. (2017). Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation. Brain, 140(11), pp.2993–3011.
Vargas, C.D., Aballéa, A., Rodrigues, É.C., Reilly, K.T., Mercier, C., Petruzzo, P., Dubernard, J.M. and Sirigu, A. (2009). Re-emergence of hand-muscle representations in human motor cortex after hand allograft. Proceedings of the National Academy of Sciences, [online] 106(17), pp.7197–7202. Available at: https://www.pnas.org/content/106/17/7197.short [Accessed 7 May 2020].
Watson, J., Gonzalez, M., Romero, A. and Kerns, J. (2010). Neuromas of the Hand and Upper Extremity. The Journal of Hand Surgery, 35(3), pp.499–510.
Weiss, T., Miltner, W.H.R., Huonker, R., Friedel, R., Schmidt, I. and Taub, E. (2000). Rapid functional plasticity of the somatosensory cortex after finger amputation. Experimental Brain Research, 134(2), pp.199–203.
Yao, J., Chen, A., Kuiken, T., Carmona, C. and Dewald, J. (2015). Sensory cortical re-mapping following upper-limb amputation and subsequent targeted reinnervation: A case report. NeuroImage: Clinical, 8, pp.329–336.
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