Targeted Sensory Reinnervation
Targeted Sensory Reinnervation
The brain integrates sensory information with motor
control information to refine movement (Click image
Amputation results in not only the loss of the limb, but also loss of the receptors and pathways of the somatosensory system, which transmits sensory and positional information back to the brain.
Amputees must therefore rely exclusively on visual feedback to monitor their prostheses. This creates an overwhelming cognitive load for individuals with amputations: they must constantly watch their prosthesis to monitor where it is and what it is doing.
Tactile feedback is important for successful manipulation of objects  and plays a role in learning of new tasks and refining active movement . Loss of sensory feedback also impairs the ability to perform fine motor tasks [3, 4] or to control limb posture , and affects the sense of ‘ownership’ of a limb.
TMR surgery was developed to allow access to motor control information intended for the missing limb, but an unexpected discovery after the first TMR procedure indicates that TMR may also provide a pathway to allow sensory feedback from a prosthesis.
A patient reacts to receiving tactile feedback for the
Sensory nerve fibers from transferred nerves can grow through the muscle and into the overlying skin, reestablishing functional connections with sensory end organs. This phenomenon, termed transfer sensation, allows patients to “feel” as if their missing hand or arm is being touched. The video shows the reaction of an individual wearing a tactor when she ‘feels’ her missing arm after being touched on her reinnervated skin.
Transfer sensation differs from phantom limb sensation, which likely results from changes in functional connectivity and reorganization within the central nervous system (and thus is difficult to localize) . Transfer sensation arises from the reactivation of amputated and transferred sensory afferents, and is thus felt as being precisely located to discrete areas on the missing limb.
A recent case study in which sensory nerve fascicles were directly transferred to surgically bisected cutaneous sensory nerves (during conventional TMR surgery) demonstrated discrete, separate sensory percepts of individual digits, which enabled precise sensory feedback while controlling a myoelectric arm .
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Zhang W, Johnston JA, Ross MA, et al. Effects of carpal tunnel syndrome on adaptation of multi-digit forces to object weight for whole-hand manipulation. PloS One 2011; 6(11):e27715.
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- Flor H, Muhlnickel W, Karl A, et al. A neural substrate for nonpainful phantom limb phenomena. Neuroreport, 2000; 11(7):1407-1411.
- Novel Targeted Sensory Reinnervation Technique to Restore Functional Hand Sensation After Transhumeral Amputation. Hebert, JS, Olson JL, Morhart MJ, Dawson MR, Marasco PD, Kuiken TA, and Chang KM. IEEE Trans Neural Syst Rehabil Eng, 2014; 22(4) 765-773
Characterization of Transfer Sensation in TMR patients
Mapping of Transfer Sensation – A grid of points was drawn on amputees’ reinnervated skin. After each point was pressed with a set force, amputees reported the location of the resulting sensation on a map of their hand and arm. As a result, a map of the sensory percepts of the reinnervated skin could be created .
Creating a sensory map of reinnervated skin. Sensations
referred to the missing limb resulting from force applied
(300 g) to the reinnervated chest skin shoulder
disarticulation TMR patient. [From Kuiken et al, PNAS
USA 104(50): 20061-20066, 2007.] (Click image to
- Sensitivity of reinnervated skin – Touch threshold sensitivity tests suggest that relative pressure sensitivity is maintained in reinnervated skin. In addition, the reinnervated target skin also appears to have thermosensation thresholds reflective of normally innervated hand skin .
- Mechanoreceptor Complement – Sensitivity to vibration stimuli was examined using a set of specific frequencies (5, 30, 250, and 400 Hz) to determine which skin mechanoreceptors were present. Results suggest: (1) A normal number of mechanoreceptors–Merkel cells, Meissner’s corpuscles, and Pacinian corpuscles–were reinnervated; (2) The location of perceived limb sensation changed depending on the frequency of vibration; (3) The reinnervated skin environment influences the sensitivity of the receptor terminal more than the reinnervating afferents .
- Tactile Acuity – Based on results from psychophysical experiments, reinnervated chest skin has a similar tactile acuity to the skin on the palm of the hand. This suggests that reconnecting afferents from the highly behaviorally relevant hand area of the brain to a new, less behaviorally important skin site increases the tactile acuity of the reinnervated skin .
- Cortical mapping studies – A rat TMR model indicated that the area of sensory cortex corresponding to the amputated limb was reactivated following TMR. This brain region was silenced following amputation. This suggested that the reinnervated afferents were able to form new connections within the sensory cortex. Further studies indicated that these connections consisted of both direct connections between reinnervated skin and sensory cortex, and some occurred through indirect, lateral pathways .
G10 tactor, which can provide sensation of contact,
pressure, vibration, shear force, and temperature.
(Picture provided courtesy of Kinea Design, LLC.)
(Click image to enlarge)
In human TMR subjects, cortical activity corresponding to stimulation of skin on the residual limb exhibited a diffuse pattern distributed over both hemispheres of the brain. This pattern is characteristic of individuals with an amputation, and may represent central changes and alterations in connected pathways. After TMR, a similar pattern was observed at the 6 and 12 month intervals; however, 24 months after surgery, the activity became localized in the contralateral hemisphere, a more normal distribution of activity that suggests a return to pre-amputation cortical mapping following reinnervation of residual skin.
- Kuiken TA, Marasco PD, Lock BA, Harden RN, Dewald JP. Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation. Proceedings of the National Academy of Sciences USA, 2007; 104(50):20061-20066.
Schultz AE, Marasco PD, Kuiken TA. Vibrotactile detection thresholds for chest skin of amputees following targeted reinnervation surgery. Brain Research, 2009; 1251:121-129.
- Marasco PD, Kim K, Colgate JE, Peshkin MA, Kuiken TA. Robotic touch shifts perception of embodiment to a prosthesis in targeted reinnervation amputees. Brain, 2011; 134(Pt 3):747-758.
Marasco PD, Kuiken TA. Amputation with median nerve redirection (targeted reinnervation) reactivates forepaw barrel subfield in rats. Journal of Neuroscience, 2010; 30(47):16008-16014.
Application of Transfer Sensation for Sensory Feedback
Haptic devices, or tactors—robotic devices that provide mechanical stimulation in proportion to touch input measured by sensors on the prosthetic hand—may be used to create an artificial sense of touch [1, 2].
Successfully integrating graded pressure sensation, vibration detection, and a sense of cognitive investment into prosthetic limbs could greatly benefit amputees, allowing them to experience useful touch input. Additionally, this type of interface could provide information on surface texture (vibration detection) and temperature (thermosensation).
As increasingly sophisticated prosthetic limb components become available, future approaches to sensory feedback could include sensors that detect touch input from multiple digits and the palm of the hand. Any future device will likely use the rich array of touch feedback made available with targeted sensory reinnervation.
In addition to providing direct sensory feedback from a prosthesis, transfer sensation provides a physiologically relevant way to tap into cognitive mechanisms of limb embodiment.
The brain is intrinsically flexible or ‘plastic.’ Long-term use of sensory feedback could capitalize on these plasticity mechanisms to make the most effective use of the restored sensory input.
Motor control is most effective in combination with input from the sensory system. Adding sensory feedback to a brain-machine interface enhances motor control , thus implementing bidirectional interfaces will further improve the function of prosthetic devices for people with limb loss.
- Kim PS, Ko JH, O'Shaughnessy KK, Kuiken TA, Pohlmeyer EA, Dumanian GA. The effects of targeted muscle reinnervation on neuromas in a rabbit rectus abdominis flap model. Journal of Hand Surgery, 2012; 37(8):1609-1616.
Raspopovic S, Capogrosso M, Petrini FM, et al. Restoring natural sensory feedback in real-time bidirectional hand prostheses. Science Translational Medicine, 2014; 6(222):222ra219.
- Suminski AJ, Tkach DC, Fagg AH, Hatsopoulos NG. Incorporating feedback from multiple sensory modalities enhances brain-machine interface control. Journal of Neuroscience, 2010; 30(50):16777-16787.
Paul Marasco, PhD, received a BA in Biology from the University of Colorado, Colorado Springs, CO, and a PhD in Neuroscience from Vanderbilt University. In addition, he studied targeted sensory reinnervation as a post-doctoral fellow at the Center for Bionic Medicine. Dr. Marasco is an Associate Staff Scientist in the Department of Biomedical Engineering in the Lerner Research Institute at the Cleveland Clinic. He is also a Principal Investigator in the Advanced Platform Technology Center of Excellence and the Director of Amputee Research in the Department of Physical Medicine and Rehabilitation at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center. His research focuses on sensory integration with prosthetic devices within the context of systems level mechanisms of brain organization, neural plasticity, and cognition.