Journal articles: 'Intraspinal Microstimulations'

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Pikov, V. "Clinical Applications of Intraspinal Microstimulation." Proceedings of the IEEE 96, no. 7 (July 2008): 1120–28. http://dx.doi.org/10.1109/jproc.2008.922583.

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Snow, S., K. W. Horch, and V. K. Mushahwar. "Intraspinal Microstimulation using Cylindrical Multielectrodes." IEEE Transactions on Biomedical Engineering 53, no. 2 (February 2006): 311–19. http://dx.doi.org/10.1109/tbme.2005.857638.

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Sunshine, Michael D., Comron N. Ganji, Paul J. Reier, David D. Fuller, and Chet T. Moritz. "Intraspinal microstimulation for respiratory muscle activation." Experimental Neurology 302 (April 2018): 93–103. http://dx.doi.org/10.1016/j.expneurol.2017.12.014.

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Khaled, Imad, Salma Elmallah, Cheng Cheng, Walied A. Moussa, Vivian K. Mushahwar, and Anastasia L. Elias. "A Flexible Base Electrode Array for Intraspinal Microstimulation." IEEE Transactions on Biomedical Engineering 60, no. 10 (October 2013): 2904–13. http://dx.doi.org/10.1109/tbme.2013.2265877.

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Zimmermann, Jonas B., Kazuhiko Seki, and Andrew Jackson. "Reanimating the arm and hand with intraspinal microstimulation." Journal of Neural Engineering 8, no. 5 (August 10, 2011): 054001. http://dx.doi.org/10.1088/1741-2560/8/5/054001.

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Toossi, Amirali, Dirk G. Everaert, Austin Azar, Christopher R. Dennison, and Vivian K. Mushahwar. "Mechanically Stable Intraspinal Microstimulation Implants for Human Translation." Annals of Biomedical Engineering 45, no. 3 (August 25, 2016): 681–94. http://dx.doi.org/10.1007/s10439-016-1709-0.

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Holinski, B. J., K. A. Mazurek, D. G. Everaert, A. Toossi, A. M. Lucas-Osma, P. Troyk, R. Etienne-Cummings, R. B. Stein, and V. K. Mushahwar. "Intraspinal microstimulation produces over-ground walking in anesthetized cats." Journal of Neural Engineering 13, no. 5 (September 13, 2016): 056016. http://dx.doi.org/10.1088/1741-2560/13/5/056016.

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Rouhani, Ehsan, and Abbas Erfanian. "Block-based robust control of stepping using intraspinal microstimulation." Journal of Neural Engineering 15, no. 4 (June 13, 2018): 046026. http://dx.doi.org/10.1088/1741-2552/aac4b8.

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Saigal, R., C. Renzi, and V. K. Mushahwar. "Intraspinal Microstimulation Generates Functional Movements After Spinal-Cord Injury." IEEE Transactions on Neural Systems and Rehabilitation Engineering 12, no. 4 (December 2004): 430–40. http://dx.doi.org/10.1109/tnsre.2004.837754.

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Grahn, Peter J., Stephan J. Goerss, J. Luis Lujan, Grant W. Mallory, Bruce A. Kall, Aldo A. Mendez, James K. Trevathan, Joel P. Felmlee, Kevin E. Bennet, and Kendall H. Lee. "MRI-Guided Stereotactic System for Delivery of Intraspinal Microstimulation." SPINE 41, no. 13 (July 2016): E806—E813. http://dx.doi.org/10.1097/brs.0000000000001397.

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Gaunt, R. A., A. Prochazka, V. K. Mushahwar, L. Guevremont, and P. H. Ellaway. "Intraspinal Microstimulation Excites Multisegmental Sensory Afferents at Lower Stimulus Levels Than Local α-Motoneuron Responses." Journal of Neurophysiology 96, no. 6 (December 2006): 2995–3005. http://dx.doi.org/10.1152/jn.00061.2006.

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Microstimulation within the motor regions of the spinal cord is often assumed to activate motoneurons and propriospinal neurons close to the electrode tip. However, previous work has shown that intraspinal microstimulation (ISMS) in the gray matter activates sensory afferent axons as well as α-motoneurons (MNs). Here we report on the recruitment of sensory afferent axons and MNs as ISMS amplitudes increased. Intraspinal microstimulation was applied through microwires implanted in the dorsal horn, intermediate region and ventral horn of the L5–L7 segments of the spinal cord in four acutely decerebrated cats, two of which had been chronically spinalized. Activation of sensory axons was detected with electroneurographic recordings from dorsal roots. Activation of MNs was detected with electromyographic (EMG) recordings from hindlimb muscles. Sensory axons were nearly always activated at lower stimulus levels than MNs irrespective of the stimulating electrode location. EMG response latencies decreased as ISMS stimulus intensities increased, suggesting that MNs were first activated transsynaptically and then directly as intensity increased. ISMS elicited antidromic activity in dorsal root filaments with entry zones up to 17 mm rostral and caudal to the stimulation sites. We posit that action potentials elicited in localized terminal branches of afferents spread antidromically to all terminal branches of the afferents and transsynaptically excite MNs and interneurons far removed from the stimulation site. This may help explain how focal ISMS can activate many MNs of a muscle even though they are distributed in long thin columns.

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Dalrymple, Ashley N., David A. Roszko, Richard S. Sutton, and Vivian K. Mushahwar. "Pavlovian control of intraspinal microstimulation to produce over-ground walking." Journal of Neural Engineering 17, no. 3 (June 2, 2020): 036002. http://dx.doi.org/10.1088/1741-2552/ab8e8e.

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Kasten, M. R., M. D. Sunshine, E. S. Secrist, P. J. Horner, and C. T. Moritz. "Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury." Journal of Neural Engineering 10, no. 4 (May 28, 2013): 044001. http://dx.doi.org/10.1088/1741-2560/10/4/044001.

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Lemay, Michel A., and Warren M. Grill. "Modularity of Motor Output Evoked By Intraspinal Microstimulation in Cats." Journal of Neurophysiology 91, no. 1 (January 2004): 502–14. http://dx.doi.org/10.1152/jn.00235.2003.

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We studied the forces produced at the cat's hindpaw by microstimulation of the ipsi- and contralateral lumbar spinal cord in spinal intact α-chloralose anesthetized ( n = 3) or decerebrate ( n = 3) animals. Isometric force and EMG responses were measured at 9-12 limb configurations, with the paw attached to a force transducer and with the hip and femur fixed. The active forces elicited at different limb configurations were summarized as force fields representing the sagittal plane component of the forces produced at the paw throughout the workspace. The forces varied in amplitude over time but the orientations were stable, and the pattern of an active force field was invariant through time. The active force fields divided into four distinct types, and a few of the fields showed convergence to an equilibrium point. The fields were generally produced by coactivation of the hindlimb muscles. In addition, some of the fields were consistent with known spinal reflexes and the stimulation sites producing them were in laminae where the interneurons associated with those reflexes are known to be located. Muscle activation produced by intraspinal stimulation, as assessed by intramuscular EMG activity, was modified with limb configuration, suggesting that the responses were not fixed, but were modified by position-dependent sensory feedback. The force responses may represent basic outputs of the spinal circuitry and may be related to similar spinal primitives found in the frog and rat.

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Mercier, L. M., E. J. Gonzalez-Rothi, K. A. Streeter, S. S. Posgai, A. S. Poirier, D. D. Fuller, P. J. Reier, and D. M. Baekey. "Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury." Journal of Neurophysiology 117, no. 2 (February 1, 2017): 767–76. http://dx.doi.org/10.1152/jn.00721.2016.

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Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5–21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100–200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable “closed-loop-like” ISMS approaches to sustain ventilation after severe SCI. NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals.

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Mushahwar, V. K., Y. Aoyagi, R. B. Stein, and A. Prochazka. "Movements generated by intraspinal microstimulation in the intermediate gray matter of the anesthetized, decerebrate, and spinal cat." Canadian Journal of Physiology and Pharmacology 82, no. 8-9 (July 1, 2004): 702–14. http://dx.doi.org/10.1139/y04-079.

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The intermediate laminae of the lumbosacral spinal cord are suggested to contain a small number of specialized neuronal circuits that form the basic elements of movement construction ("movement primitives"). Our aim was to study the properties and state dependence of these hypothesized circuits in comparison with movements elicited by direct nerve or muscle stimulation. Microwires for intraspinal microstimulation (ISMS) were implanted in intermediate laminae throughout the lumbosacral enlargement. Movement vectors evoked by ISMS were compared with those evoked by stimulation through muscle and nerve electrodes in cats that were anesthetized, then decerebrated, and finally spinalized. Similar movements could be evoked under anesthesia by ISMS and nerve and muscle stimulation, and these covered the full work space of the limb. ISMS-evoked movements were associated with the actions of nearby motoneuron pools. However, after decerebration and spinalization, ISMS-evoked movements were dominated by flexion, with few extensor movements. This indicates that the outputs of neuronal networks in the intermediate laminae depend significantly on descending input and on the state of the spinal cord. Frequently, the outputs also depended on stimulus intensity. These experiments suggest that interneuronal circuits in the intermediate and ventral regions of the spinal cord overlap and their function may be to process reflex and descending activity in a flexible manner for the activation of nearby motoneuron pools.Key words: intraspinal microstimulation, spinal cord, gray matter, movement primitives.

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Grahn, Peter J., Kendall H. Lee, Aimen Kasasbeh, Grant W. Mallory, Jan T. Hachmann, John R. Dube, Christopher J. Kimble, et al. "Wireless control of intraspinal microstimulation in a rodent model of paralysis." Journal of Neurosurgery 123, no. 1 (July 2015): 232–42. http://dx.doi.org/10.3171/2014.10.jns132370.

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OBJECT Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury. METHODS The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 μm in diameter, with a 30- to 60-μm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue. RESULTS The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences between movements evoked by either of the 2 targeting techniques were revealed. However, frame-based targeting required fewer electrode penetrations to evoke target movements. CONCLUSIONS Clinical restoration of functional movement via ISMS remains a distant goal. However, the technology presented herein represents the first step toward restoring functional independence for individuals with chronic spinal cord injury.

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Sunshine, Michael D., Frances S. Cho, Danielle R. Lockwood, Amber S. Fechko, Michael R. Kasten, and Chet T. Moritz. "Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury." Journal of Neural Engineering 10, no. 3 (April 3, 2013): 036001. http://dx.doi.org/10.1088/1741-2560/10/3/036001.

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Bamford, J. A., C. T. Putman, and V. K. Mushahwar. "Muscle Plasticity in Rat Following Spinal Transection and Chronic Intraspinal Microstimulation." IEEE Transactions on Neural Systems and Rehabilitation Engineering 19, no. 1 (February 2011): 79–83. http://dx.doi.org/10.1109/tnsre.2010.2052832.

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Tomatsu, Saeka, Geehee Kim, Joachim Confais, and Kazuhiko Seki. "Muscle afferent excitability testing in spinal root-intact rats: dissociating peripheral afferent and efferent volleys generated by intraspinal microstimulation." Journal of Neurophysiology 117, no. 2 (February 1, 2017): 796–807. http://dx.doi.org/10.1152/jn.00874.2016.

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Presynaptic inhibition of the sensory input from the periphery to the spinal cord can be evaluated directly by intra-axonal recording of primary afferent depolarization (PAD) or indirectly by intraspinal microstimulation (excitability testing). Excitability testing is superior for use in normal behaving animals, because this methodology bypasses the technically challenging intra-axonal recording. However, use of excitability testing on the muscle or joint afferent in intact animals presents its own technical challenges. Because these afferents, in many cases, are mixed with motor axons in the peripheral nervous system, it is crucial to dissociate antidromic volleys in the primary afferents from orthodromic volleys in the motor axon, both of which are evoked by intraspinal microstimulation. We have demonstrated in rats that application of a paired stimulation protocol with a short interstimulus interval (ISI) successfully dissociated the antidromic volley in the nerve innervating the medial gastrocnemius muscle. By using a 2-ms ISI, the amplitude of the volleys evoked by the second stimulation was decreased in dorsal root-sectioned rats, but the amplitude did not change or was slightly increased in ventral root-sectioned rats. Excitability testing in rats with intact spinal roots indicated that the putative antidromic volleys exhibited dominant primary afferent depolarization, which was reasonably induced from the more dorsal side of the spinal cord. We concluded that excitability testing with a paired-pulse protocol can be used for studying presynaptic inhibition of somatosensory afferents in animals with intact spinal roots. NEW & NOTEWORTHY Excitability testing of primary afferents has been used to evaluate presynaptic modulation of synaptic transmission in experiments conducted in vivo. However, to apply this method to muscle afferents of animals with intact spinal roots, it is crucial to dissociate antidromic and orthodromic volleys induced by spinal microstimulation. We propose a new method to make this dissociation possible without cutting spinal roots and demonstrate that it facilitates excitability testing of muscle afferents.

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Boyce, Vanessa S., and Michel A. Lemay. "Modularity of Endpoint Force Patterns Evoked Using Intraspinal Microstimulation in Treadmill Trained and/or Neurotrophin-Treated Chronic Spinal Cats." Journal of Neurophysiology 101, no. 3 (March 2009): 1309–20. http://dx.doi.org/10.1152/jn.00034.2008.

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Chronic spinal cats with neurotrophin-secreting fibroblasts (NTF) transplants recover locomotor function. To ascertain possible mechanisms, intraspinal microstimulation was used to examine the lumbar spinal cord motor output of four groups of chronic spinal cats: untrained cats with unmodified-fibroblasts graft (Op-control) or NTF graft and locomotor-trained cats with unmodified-fibroblasts graft (Trained) or NTF graft (Combination). Forces generated via intraspinal microstimulation at different hindlimb positions were recorded and interpolated, generating representations of force patterns at the paw. Electromyographs (EMGs) of hindlimb muscles, medial gastrocnemius, tibialis anterior, vastus lateralis, and biceps femoris posterior, were also collected to examine relationships between activated muscles and force pattern types. The same four force pattern types obtained in spinal-intact cats were found in chronic spinal cats. Proportions of force patterns in spinal cats differed significantly from those in intact cats, but no significant differences in proportions were observed among individual spinal groups (Op-control, NTF, Trained, and Combination). However, the proportions of force patterns differed significantly between trained (Trained and Combination) and untrained groups (Op-control and NTF). Thus the frequency of expression of some response types was modified by injury and to a lesser extent by training. Force pattern laminar distribution differed in spinal cats compared with intact, with more responses obtained dorsally (0–1,000 μm) and fewer ventrally (3,200–5,200 μm). EMG analysis demonstrated that muscle activity highly predicted some force pattern types and was independent of hindlimb position. We conclude that spinal motor output modularity is preserved after injury.

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Lau, B., L. Guevremont, and V. K. Mushahwar. "Strategies for Generating Prolonged Functional Standing Using Intramuscular Stimulation or Intraspinal Microstimulation." IEEE Transactions on Neural Systems and Rehabilitation Engineering 15, no. 2 (June 2007): 273–85. http://dx.doi.org/10.1109/tnsre.2007.897030.

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Lemay, M. A., D. Grasse, and W. M. Grill. "Hindlimb Endpoint Forces Predict Movement Direction Evoked by Intraspinal Microstimulation in Cats." IEEE Transactions on Neural Systems and Rehabilitation Engineering 17, no. 4 (August 2009): 379–89. http://dx.doi.org/10.1109/tnsre.2009.2023295.

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Roshani, Amir, and Abbas Erfanian. "The Effects of Stimulation Strategy on Joint Movement Elicited by Intraspinal Microstimulation." IEEE Transactions on Neural Systems and Rehabilitation Engineering 24, no. 7 (July 2016): 794–805. http://dx.doi.org/10.1109/tnsre.2015.2508099.

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Bamford, Jeremy A., Kathryn G. Todd, and Vivian K. Mushahwar. "The effects of intraspinal microstimulation on spinal cord tissue in the rat." Biomaterials 31, no. 21 (July 2010): 5552–63. http://dx.doi.org/10.1016/j.biomaterials.2010.03.051.

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Moritz, Chet T., Timothy H. Lucas, Steve I. Perlmutter, and Eberhard E. Fetz. "Forelimb Movements and Muscle Responses Evoked by Microstimulation of Cervical Spinal Cord in Sedated Monkeys." Journal of Neurophysiology 97, no. 1 (January 2007): 110–20. http://dx.doi.org/10.1152/jn.00414.2006.

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Documenting the forelimb responses evoked by stimulating sites in primate cervical spinal cord is significant for understanding spinal circuitry and for potential neuroprosthetic applications involving hand and arm. We examined the forelimb movements and electromyographic (EMG) muscle responses evoked by intraspinal microstimulation in three M. nemestrina monkeys sedated with ketamine. Trains of three stimulus pulses (10–80 μA) at 300 Hz were delivered at sites in regularly spaced tracks from C6 to T1. Hand and/or arm movements were evoked at 76% of the 745 sites stimulated. Specifically, movements were evoked in digits (76% of effective sites), wrist (15% of sites), elbow (26%), and shoulder (17%). To document the muscle activity evoked by a stimulus current just capable of eliciting consistent joint rotation, stimulus-triggered averages of rectified EMG were calculated at each site where a movement was observed. Typically, many muscles were coactivated at threshold currents needed to evoke movements. Out of the 13–15 muscles recorded per animal, only one muscle was active at 14% of the effective sites and two to six muscles were coactivated at 47% of sites. Thus intraspinal stimulation at threshold currents adequate for evoking movement typically coactivated multiple muscles, including antagonists. Histologic reconstruction of stimulation sites indicated that responses were elicited from the dorsal and ventral horn and from fiber tracts in the white matter, with little somatotopic organization for movement or muscle activation. The absence of a clear somatotopic map of output sites is probably a result of the stimulation of complex mixtures of fibers and cells.

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Asadi, A., and A. Erfanian. "Adaptive Neuro-Fuzzy Sliding Mode Control of Multi-Joint Movement Using Intraspinal Microstimulation." IEEE Transactions on Neural Systems and Rehabilitation Engineering 20, no. 4 (July 2012): 499–509. http://dx.doi.org/10.1109/tnsre.2012.2197828.

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Mazurek, Kevin A., Bradley J. Holinski, Dirk G. Everaert, Vivian K. Mushahwar, and Ralph Etienne-Cummings. "A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion." IEEE Transactions on Biomedical Circuits and Systems 10, no. 4 (August 2016): 902–11. http://dx.doi.org/10.1109/tbcas.2015.2501419.

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Bamford, J. A., C. T. Putman, and V. K. Mushahwar. "Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat." Journal of Physiology 569, no. 3 (December 2005): 873–84. http://dx.doi.org/10.1113/jphysiol.2005.094516.

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Roshani, Amir, and Abbas Erfanian. "A modular robust control framework for control of movement elicited by multi-electrode intraspinal microstimulation." Journal of Neural Engineering 13, no. 4 (July 19, 2016): 046024. http://dx.doi.org/10.1088/1741-2560/13/4/046024.

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Dalrymple, Ashley N., and Vivian K. Mushahwar. "Intelligent Control of a Spinal Prosthesis to Restore Walking After Neural Injury: Recent Work and Future Possibilities." Journal of Medical Robotics Research 05, no. 01n02 (March 2020): 2041003. http://dx.doi.org/10.1142/s2424905x20410032.

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This review focuses on the development of intelligent, intuitive control strategies for restoring walking using an innovative spinal neural prosthesis called intraspinal microstimulation (ISMS). These control strategies are inspired by the control of walking by the nervous system and are aimed at mimicking the natural functionality of locomotor-related sensorimotor systems. The work to date demonstrates how biologically inspired control strategies, some including machine learning methods, can be used to augment remaining function in models of complete and partial paralysis developed in anesthetized cats. This review highlights the advantages of learning predictions to produce automatically adaptive control of over-ground walking. This review also speculates on the possible future applications of similar machine learning algorithms for challenging walking tasks including navigating obstacles and traversing difficult terrain. Finally, this review explores the potential for plasticity and motor recovery with long-term use of such intelligent control systems and neural interfaces.

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Guevremont, L., C. G. Renzi, J. A. Norton, J. Kowalczewski, R. Saigal, and V. K. Mushahwar. "Locomotor-Related Networks in the Lumbosacral Enlargement of the Adult Spinal Cat: Activation Through Intraspinal Microstimulation." IEEE Transactions on Neural Systems and Rehabilitation Engineering 14, no. 3 (September 2006): 266–72. http://dx.doi.org/10.1109/tnsre.2006.881592.

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Shahdoost, Shahab, Shawn B. Frost, David J. Guggenmos, Jordan A. Borrell, Caleb Dunham, Scott Barbay, Randolph J. Nudo, and Pedram Mohseni. "A brain-spinal interface (BSI) system-on-chip (SoC) for closed-loop cortically-controlled intraspinal microstimulation." Analog Integrated Circuits and Signal Processing 95, no. 1 (January 17, 2018): 1–16. http://dx.doi.org/10.1007/s10470-017-1093-1.

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Barthélemy, D., H. Leblond, and S. Rossignol. "Characteristics and Mechanisms of Locomotion Induced by Intraspinal Microstimulation and Dorsal Root Stimulation in Spinal Cats." Journal of Neurophysiology 97, no. 3 (March 2007): 1986–2000. http://dx.doi.org/10.1152/jn.00818.2006.

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Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T13 1 wk before (untrained) or after 3–5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L3–S1 at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L3 and L4 segments or a complete second spinal lesion at L3–L4 abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L3 or L4 and restricted ventral lesions at L4 further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L3–L4 segments are critical for the induction of locomotion by ISMS at L5 to S1 or by DRS at these caudal segments.

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ElBasiouny, Sherif M., and Vivian K. Mushahwar. "Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study." Journal of Applied Physiology 103, no. 1 (July 2007): 276–86. http://dx.doi.org/10.1152/japplphysiol.01222.2006.

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We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to ∼25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system.

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Dalrymple, Ashley N., Dirk G. Everaert, David S. Hu, and Vivian K. Mushahwar. "A speed-adaptive intraspinal microstimulation controller to restore weight-bearing stepping in a spinal cord hemisection model." Journal of Neural Engineering 15, no. 5 (August 23, 2018): 056023. http://dx.doi.org/10.1088/1741-2552/aad872.

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Yakovenko, Sergiy, Jan Kowalczewski, and Arthur Prochazka. "Intraspinal Stimulation Caudal to Spinal Cord Transections in Rats. Testing the Propriospinal Hypothesis." Journal of Neurophysiology 97, no. 3 (March 2007): 2570–74. http://dx.doi.org/10.1152/jn.00814.2006.

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Many laboratories have reported the successful regeneration of neurons across damaged portions of the spinal cord. Associated improvements in hindlimb locomotor movements have been attributed to the formation of functional neuronal connections with the locomotor central pattern generator (CPG). However, regenerating axons generally extend no more than 10 mm caudal to the lesion sites, terminating about 20 mm short of the lumbar segments thought to contain the CPG. It has therefore tacitly been assumed that the locomotor improvements arose from activation of propriospinal neurons relaying excitation to the CPG. Here we report a test of this assumption, which we call the propriospinal hypothesis. Intraspinal microstimulation (ISMS) was used to activate the putative propriospinal relay neurons. Approximately 2–3 wk after complete spinal cord transection at T8–T9 in rats, an array of six Pt–Ir microwires was chronically implanted in the intermediate and ventral gray matter of T10–T12 segments. ISMS pulse trains with amplitudes of 0.8–0.9 times threshold for activating axial muscles were delivered during open-field locomotor tests (BBB). ISMS significantly increased BBB scores over control tests, but did not produce limb coordination and weight bearing sufficient for locomotion. These results support the main assumption of the propriospinal hypothesis: that neuronal activity elicited in thoracic spinal segments caudal to a complete spinal cord transection may propagate caudally and activate the locomotor CPG.

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McPherson, Jacob G., Robert R. Miller, and Steve I. Perlmutter. "Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury." Proceedings of the National Academy of Sciences 112, no. 39 (September 14, 2015): 12193–98. http://dx.doi.org/10.1073/pnas.1505383112.

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Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury.

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Toossi, Amirali, Dirk G. Everaert, Peter Seres, Jacob L. Jaremko, Kevin Robinson, C. Chris Kao, Peter E. Konrad, and Vivian K. Mushahwar. "Ultrasound-guided spinal stereotactic system for intraspinal implants." Journal of Neurosurgery: Spine 29, no. 3 (September 2018): 292–305. http://dx.doi.org/10.3171/2018.1.spine17903.

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OBJECTIVEThe overall goal of this study was to develop an image-guided spinal stereotactic setup for intraoperative intraspinal microstimulation (ISMS). System requirements were as follows: 1) ability to place implants in various segments of the spinal cord, targeting the gray matter with a < 0.5-mm error; 2) modularity; and 3) compatibility with standard surgical tools.METHODSA spine-mounted stereotactic system was developed, optimized, and tested in pigs. The system consists of a platform supporting a micromanipulator with 6 degrees of freedom. It is modular and flexible in design and can be applied to various regions of the spine. An intraoperative ultrasound imaging technique was also developed and assessed for guidance of electrode alignment prior to and after electrode insertion into the spinal cord. Performance of the ultrasound-guided stereotactic system was assessed both in pigs (1 live and 6 fresh cadaveric pigs) and on the bench using four gelatin-based surrogate spinal cords. Pig experiments were conducted to evaluate the performance of ultrasound imaging in aligning the electrode trajectory using three techniques and under two conditions. Benchtop experiments were performed to assess the performance of ultrasound-guided targeting more directly. These experiments were used to quantify the accuracy of electrode alignment as well as assess the accuracy of the implantation depth and the error in spatial targeting within the gray matter of the spinal cord. As proof of concept, an intraoperative ISMS experiment was also conducted in an additional live pig using the stereotactic system, and the resulting movements and electromyographic responses were recorded.RESULTSThe stereotactic system was quick to set up (< 10 minutes) and provided sufficient stability and range of motion to reach the ISMS targets reliably in the pigs. Transverse ultrasound images with the probe angled at 25°–45° provided acceptable contrast between the gray and white matter of the spinal cord. In pigs, the largest electrode alignment error using ultrasound guidance, relative to the minor axis of the spinal cord, was ≤ 3.57° (upper bound of the 95% confidence interval). The targeting error with ultrasound guidance in bench testing for targets 4 mm deep into the surrogate spinal cords was 0.2 ± 0.02 mm (mean ± standard deviation).CONCLUSIONSThe authors developed and evaluated an ultrasound-guided spinal stereotactic system for precise insertion of intraspinal implants. The system is compatible with existing spinal instrumentation. Intraoperative ultrasound imaging of the spinal cord aids in alignment of the implants before insertion and provides feedback during and after implantation. The ability of ultrasound imaging to distinguish between spinal cord gray and white matter also improves confidence in the localization of targets within the gray matter. This system would be suitable for accurate guidance of intraspinal electrodes and drug or cell injections.

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Barthélemy, Dorothy, Hugues Leblond, Janyne Provencher, and Serge Rossignol. "Nonlocomotor and Locomotor Hindlimb Responses Evoked by Electrical Microstimulation of the Lumbar Cord in Spinalized Cats." Journal of Neurophysiology 96, no. 6 (December 2006): 3273–92. http://dx.doi.org/10.1152/jn.00203.2006.

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As a preliminary step to using intraspinal microstimulation (ISMS) for rehabilitation purposes, the distribution of various types of hindlimb responses evoked by ISMS in spinal cats (T13) is described. The responses to ISMS applied through a single electrode was assessed, before and after an intravenous injection of clonidine (noradrenergic agonist), using kinematics and electromyographic recordings in subacute (5–7 days, untrained) or chronic (3–5 wk trained on a treadmill) spinal cats. ISMS was applied in the dorsal, intermediate and ventral areas of segments L3–L7, from midline to 3 mm laterally. Uni- and bilateral non-locomotor responses as well as rhythmical locomotor responses were evoked. In the subacute cats, ipsilateral flexion was elicited in the dorsal region of L3–L7, whereas ipsilateral extension was evoked more ventrally and mainly in the caudal segments. Dorsal stimuli could induce ipsilateral flexion followed by ipsilateral extension. Sites inducing bilateral flexion and bilateral extension were similarly distributed to those evoking ipsilateral flexion and extension in the rostrocaudal axis but were evoked from more medial sites. Ipsilateral flexion with crossed extension was evoked from intermediate and ventral zones of all segments and lateralities. Unilateral ipsilateral locomotion was rarely observed. Contralateral locomotion was more frequent and mainly evoked medially, whereas bilateral locomotion was evoked exclusively from dorsal regions. With some exceptions, those distribution gradients were similar in the four conditions (subacute, chronic, pre- and postclonidine), but the proportion of each response could vary. The distribution of ISMS-evoked responses is discussed as a function of known localization of interneurons and motoneurons.

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Mondello, S. E., M. D. Sunshine, A. E. Fischedick, S. J. Dreyer, G. D. Horwitz, P. Anikeeva, P. J. Horner, and C. T. Moritz. "Optogenetic surface stimulation of the rat cervical spinal cord." Journal of Neurophysiology 120, no. 2 (August 1, 2018): 795–811. http://dx.doi.org/10.1152/jn.00461.2017.

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Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. Here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats, adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.

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Saltiel, Philippe, Kuno Wyler-Duda, Andrea D'Avella, Matthew C. Tresch, and Emilio Bizzi. "Muscle Synergies Encoded Within the Spinal Cord: Evidence From Focal Intraspinal NMDA Iontophoresis in the Frog." Journal of Neurophysiology 85, no. 2 (February 1, 2001): 605–19. http://dx.doi.org/10.1152/jn.2001.85.2.605.

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This paper relates to the problem of the existence of muscle synergies, that is whether the CNS command to muscles is simplified by controlling their activity in subgroups or synergies, rather than individually. We approach this problem with two methods that have been recently introduced: intraspinal N-methyl-d-aspartate (NMDA) microstimulation and a synergy-extracting algorithm. To search for a common set of synergies encoded for by the spinal cord whose combinations would account for a large range of electromyographic (EMG) patterns, we chose, rather than examining a large range of natural behaviors, to chemically microstimulate a large number of spinal cord interneuronal sites in different frogs. A possible advantage of this complementary method is that it is task-independent. Visual inspection suggested that the NMDA-elicited EMG patterns recorded from 12 leg muscles might indeed be constructed from smaller subgroups of muscles whose activity co-varied, suggestive of synergies. We used a modification of our extracting computational algorithm whereby a nonnegative least-squares method was employed to iteratively update both the synergies and their coefficients of activation in reconstructing the EMG patterns. Using this algorithm, a limited set of seven synergies was found whose linear combinations accounted for more than 91% of the variance in the pooled EMG data from 10 frogs, and more than 96% in individual frogs. The extracted synergies were similar among frogs. Further, preferred combinations of these synergies were clearly identified. This was found by extracting smaller sets of four, five, or six synergies and fitting each synergy from those sets as a combination from the set of seven synergies extracted from the same frog; the synergy combinations from each frog were then pooled together to examine their frequency of occurrence. Concordance with this method of identifying synergy combinations was found by examining how the synergies from the set of seven correlated pair-wise as they reconstructed the EMG data. These results support the existence of muscle synergies encoded within the spinal cord, which through preferred combinations, account for a large repertoire of spinal cord motor output. These findings are contrasted with previous approaches to the problem of synergies.

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Riddle, C. Nicholas, and Stuart N. Baker. "Convergence of Pyramidal and Medial Brain Stem Descending Pathways Onto Macaque Cervical Spinal Interneurons." Journal of Neurophysiology 103, no. 5 (May 2010): 2821–32. http://dx.doi.org/10.1152/jn.00491.2009.

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We investigated the control of spinal interneurons by corticospinal and medial brain stem descending tracts in two macaque monkeys. Stimulating electrodes were implanted in the left pyramidal tract (PT), and the right medial longitudinal fasciculus (MLF), which contains reticulospinal, vestibulospinal, and some tectospinal fibers. Single unit discharge was recorded from 163 interneurons in the intermediate zone of the right spinal cord (segmental levels C6–C8) in the awake state; inputs from descending pathways were assessed from the responses to stimulation through the PT and MLF electrodes. Convergent input from both pathways was the most common finding (71/163 cells); responses to PT and MLF stimulation were of similar amplitude. Interneuron discharge was also recorded while the animal performed a reach and grasp task with the right hand; the output connections of the recorded cells were determined by delivering intraspinal microstimulation (ISMS) at the recording sites. Convergent input from MLF/PT stimulation was also common when analysis was restricted to cells that increased their rate during grasp (14/23 cells) or to cells recorded at sites where ISMS elicited finger or wrist movements (23/57 cells). We conclude that medial brain stem and corticospinal descending pathways have largely overlapping effects on spinal interneurons, including those involved in the control of the hand. This may imply a more important role for the brain stem in coordinating hand movements in primates than commonly assumed; brain stem pathways could contribute to the restoration of function seen after lesions to the corticospinal tract.

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Chang, Jiaqi, Dongkai Shen, Yixuan Wang, Na Wang, and Ya Liang. "A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of Respiratory Function after Cervical Spinal Cord Injury." Applied Bionics and Biomechanics 2020 (September 17, 2020): 1–12. http://dx.doi.org/10.1155/2020/8882430.

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Background. Spinal cord injury (SCI) is a common severe trauma in clinic, hundreds of thousands of people suffer from which every year in the world. In terms of injury location, cervical spinal cord injury (CSCI) has the greatest impact. After cervical spinal cord injury, the lack of innervated muscles is not enough to provide ventilation and other activities to complete the respiratory function. In addition to the decline of respiratory capacity, respiratory complications also have a serious impact on the life of patients. The most commonly used assisted breathing and cough equipment is the ventilator, but in recent years, the functional electrical stimulation method is being used gradually and widely. Methods. About hundred related academic papers are cited for data analysis. They all have the following characteristics: (1) basic conditions of patients were reported, (2) patients had received nerve or muscle stimulation and the basic parameters, and (3) the results were evaluated based on some indicators. Results. The papers mentioned above are classified as four kinds of stimulation methods: muscle electric/magnetic stimulation, spinal dural electric stimulation, intraspinal microstimulation, and infrared light stimulation. This paper describes the stimulation principle and application experiment. Finally, this paper will compare the indexes and effects of typical stimulation methods, as well as the two auxiliary methods: training and operation. Conclusions. Although there is limited evidence for the treatment of respiratory failure by nerve or muscle stimulation after cervical spinal cord injury, the two techniques seem to be safe and effective. At the same time, light stimulation is gradually applied to clinical medicine with its strong advantages and becomes the development trend of nerve stimulation in the future.

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Giszter, Simon F., William J. Kargo, Michelle Davies, and Motohide Shibayama. "Fetal Transplants Rescue Axial Muscle Representations in M1 Cortex of Neonatally Transected Rats That Develop Weight Support." Journal of Neurophysiology 80, no. 6 (December 1, 1998): 3021–30. http://dx.doi.org/10.1152/jn.1998.80.6.3021.

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Giszter, Simon, William Kargo, Michelle Davies, and Motohide Shibayama. Fetal transplants rescue axial muscle representations in M1 cortex of neonatally transected rats that develop weight support. J. Neurophysiol. 80: 3021–3030, 1998. Intraspinal transplants of fetal spinal tissue partly alleviate motor deficits caused by spinal cord injury. How transplants modify body representation and muscle recruitment by motor cortex is currently largely unknown. We compared electromyographic responses from motor cortex stimulation in normal adult rats, adult rats that received complete spinal cord transection at the T8–T10 segmental level as neonates (TX rats), and similarly transected rats receiving transplants of embryonic spinal cord (TP rats). Rats were also compared among treatments for level of weight support and motor performance. Sixty percent of TP rats showed unassisted weight-supported locomotion as adults, whereas ∼30% of TX rats with no intervention showed unassisted weight-supported locomotion. In the weight-supporting animals we found that the transplants enabled motor responses to be evoked by microstimulation of areas of motor cortex that normally represent the lumbar axial muscles in rats. These same regions were silent in all TX rats with transections but no transplants, even those exhibiting locomotion with weight support. In weight-supporting TX rats low axial muscles could be recruited from the rostral cortical axial representation, which normally represents the neck and upper trunk. No operated animal, even those with well-integrated transplants and good weight-supported locomotion, had a hindlimb motor representation in cortex. The data demonstrate that spinal transplants allow the development of some functional interactions between areas of motor cortex and spinal cord that are not available to the rat lacking the intervention. The data also suggest that operated rats that achieve weight support may primarily use the axial muscles to steer the pelvis and hindlimbs indirectly rather than use explicit hindlimb control during weight-supported locomotion.

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Shinoda, Y., T. Yamaguchi, and T. Futami. "Multiple axon collaterals of single corticospinal axons in the cat spinal cord." Journal of Neurophysiology 55, no. 3 (March 1, 1986): 425–48. http://dx.doi.org/10.1152/jn.1986.55.3.425.

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To investigate intraspinal branching patterns of single corticospinal neurons (CSNs), we recorded extracellular spike activities from cell bodies of 408 CSNs in the motor cortex in anesthetized cats and mapped the distribution of effective stimulating sites for antidromic activation of their terminal branches in the spinal gray matter. To search for all spinal axon branches belonging to single CSNs in the "forelimb area" of the motor cortex, we microstimulated the gray matter from the dorsal to the ventral border at 100-micron intervals at an intensity of 150-250 microA and systematically mapped effective stimulating penetrations at 1-mm intervals rostrocaudally from C3 to the most caudal level of their axons. From the depth-threshold curves, the comparison of the antidromic latencies of spikes evoked from the gray matter and the lateral funiculus, and the calculated conduction times of the collaterals, we could ascertain that axon collaterals were stimulated in the gray matter rather than stem axons in the corticospinal tract due to current spread. Virtually all CSNs examined in the forelimb area of the motor cortex had three to seven branches at widely separated segments of the cervical and the higher thoracic cord. In addition to terminating at the brachial segments, they had one to three collaterals to the upper cervical cord (C3-C4), where the propriospinal neurons projecting to forelimb motoneurons are located. About three quarters of these CSNs had two to four collaterals in C6-T1. This finding held true for both fast and slow CSNs. About one third of the CSNs in the forelimb area of the motor cortex projected to the thoracic cord below T3. These CSNs also sent axon collaterals to the cervical spinal cord. CSNs in the "hindlimb area" of the motor cortex had three to five axon branches in the lumbosacral cord. These branches were mainly observed at L4 and the lower lumbosacral cord. None of these CSNs had axon collaterals in the cervical cord. CSNs terminating at different segments of the cervical and the thoracic cord were distributed in a wide area of the motor cortex and were intermingled. To determine the detailed trajectory of single axon branches, microstimulation was made at a matrix of points of 100 or 200 micron at the maximum intensity of 30 microA, and their axonal trajectory was reconstructed on the basis of the location of low-threshold foci and the latency of antidromic spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

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Sunshine, Michael Daniel, Comron Nassar Ganji, Paul J. Reier, Chet Thomas Moritz, and David D. Fuller. "Intraspinal microstimulation induced respiratory phase resetting." FASEB Journal 31, S1 (April 2017). http://dx.doi.org/10.1096/fasebj.31.1_supplement.1055.9.

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Lee, Andy, Mason Schindle, Neil Tyreman, and Vivian Mushahwar. "Neuroregenerative Effects of Intraspinal Microstimulation (ISMS) Following Spinal Cord Injury (SCI)." Eureka 6, no. 1 (August 9, 2021). http://dx.doi.org/10.29173/eureka28758.

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Background Intraspinal microstimulation (ISMS) is a novel electrical stimulation technique that has demonstrated mobility restoration in animals with spinal cord injury (SCI). This project investigated: 1) the capacity of ISMS to restore functional walking in rats with SCI through 4 weeks of stimulation, and 2) the degree of walking deficit caused by ISMS surgery. Methods Thirteen Sprague Dawley rats were divided into three groups: 1) rats with hemi-section SCI (hSCI) and no implants (control group), 2) rats with hSCI and passive ISMS implants (ISMS sham group), and 3) rats with hSCI and implants with active electrical stimulation (ISMS group). All groups were trained to walk on a horizontal ladder and their performance was quantified pre- and post-surgery. Results We hypothesized that the rats with active ISMS implants would demonstrate the greatest improvement in functional walking compared to both control groups, and that the ISMS sham group would underperform the most. The preoperative functional walking scores of control, sham and ISMS rats were 5.7±0.2, 5.5±0.3 and 5.7±0.1, respectively (7-point scale; mean ± standard error). The post-surgery scores were 3.2±0.9, 2.6±0.6 and 3.3±0.8 for control, sham, and ISMS rats, respectively. Conclusions As the difference between the post-surgery functional walking scores of ISMS and control rats was not statistically significant, this may indicate that four weeks of ISMS stimulation is not enough to cause rehabilitative effects. Additionally, the ISMS sham group demonstrated impaired functional walking compared to the hSCI control group as predicted. Future studies will employ a larger sample size to fully elucidate this trend and utilize thinner microwires to mitigate cellular damage.

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Yousefpour, Abolhasan, and Abbas Erfanian. "A general framework for automatic closed-loop control of bladder voiding induced by intraspinal microstimulation in rats." Scientific Reports 11, no. 1 (February 9, 2021). http://dx.doi.org/10.1038/s41598-021-82933-7.

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AbstractIndividuals with spinal cord injury or neurological disorders have problems in voiding function due to the dyssynergic contraction of the urethral sphincter. Here, we introduce a closed-loop control of intraspinal microstimulation (ISMS) for efficient bladder voiding. The strategy is based on asynchronous two-electrode ISMS with combined pulse-amplitude and pulse-frequency modulation without requiring rhizotomy, neurotomy, or high-frequency blocking. Intermittent stimulation is alternately applied to the two electrodes that are implanted in the S2 lateral ventral horn and S1 dorsal gray commissure, to excite the bladder motoneurons and to inhibit the urethral sphincter motoneurons. Asynchronous stimulation would lead to reduce the net electric field and to maximize the selective stimulation. The proposed closed-loop system attains a highly voiding efficiency of 77.2–100%, with an average of 91.28 ± 8.4%. This work represents a promising approach to the development of a natural and robust motor neuroprosthesis device for restoring bladder functions.

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Kim, Hojeong, and Youngchang Ju. "Effective Stimulation Type and Waveform for Force Control of the Motor Unit System: Implications for Intraspinal Microstimulation." Frontiers in Neuroscience 15 (June 28, 2021). http://dx.doi.org/10.3389/fnins.2021.645984.

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The input–output properties of spinal motoneurons and muscle fibers comprising motor units are highly non-linear. The goal of this study was to investigate the stimulation type (continuous versus discrete) and waveform (linear versus non-linear) controlling force production at the motor unit level under intraspinal microstimulation. We constructed a physiological model of the motor unit with computer software enabling virtual experiments on single motor units under a wide range of input conditions, including intracellular and synaptic stimulation of the motoneuron and variation in the muscle length under neuromodulatory inputs originating from the brainstem. Continuous current intensity and impulse current frequency waveforms were inversely estimated such that the motor unit could linearly develop and relax the muscle force within a broad range of contraction speeds and levels during isometric contraction at various muscle lengths. Under both continuous and discrete stimulation, the stimulation waveform non-linearity increased with increasing speed and level of force production and with decreasing muscle length. Only discrete stimulation could control force relaxation at all muscle lengths. In contrast, continuous stimulation could not control force relaxation at high contraction levels in shorter-than-optimal muscles due to persistent inward current saturation on the motoneuron dendrites. These results indicate that non-linear adjustment of the stimulation waveform is more effective in regard to varying the force profile and muscle length and that the discrete stimulation protocol is a more robust approach for designing stimulation patterns aimed at neural interfaces for precise movement control under pathological conditions.

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Journal articles on the topic 'Intraspinal Microstimulations'

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