[ { "id": "authors:5mzfy-deh04", "collection": "authors", "collection_id": "5mzfy-deh04", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181105-083600090", "type": "article", "title": "Self-assisted standing enabled by non-invasive spinal stimulation after spinal cord injury", "author": [ { "family_name": "Sayenko", "given_name": "Dimitry", "clpid": "Sayenko-D" }, { "family_name": "Rath", "given_name": "Mrinal", "clpid": "Rath-M" }, { "family_name": "Ferguson", "given_name": "Adam R.", "clpid": "Ferguson-A-R" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Havton", "given_name": "Leif", "clpid": "Havton-L" }, { "family_name": "Edgerton", "given_name": "Victor Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y-P" } ], "abstract": "Neuromodulation of spinal networks can improve motor control after spinal cord injury (SCI). The objectives of this study were to (1) determine whether individuals with chronic paralysis can stand with the aid of non-invasive electrical spinal stimulation with their knees and hips extended without trainer assistance, and (2) investigate whether postural control can be further improved following repeated sessions of stand training. Using a double-blind, balanced, within-subject cross-over, and \"sham\"-controlled study design, 15 individuals with SCI of various severity received transcutaneous electrical spinal stimulation to regain self-assisted standing. The primary outcomes included qualitative comparison of need of external assistance for knee and hip extension provided by trainers during standing without and in the presence of stimulation in the same participants, as well as quantitative measures, such as the level of knee assistance and amount of time spent standing without trainer assistance. None of the participants could stand unassisted without stimulation or in the presence of \"sham\" stimulation. With stimulation all participants could maintain upright standing with minimum and some (n=7) without external assistance applied to the knees or hips, using their hands for upper body balance as needed. Quality of balance control was practice-dependent, and improved with subsequent training. During self-initiated body weight displacements in standing enabled by spinal stimulation, high level of leg muscle activity emerged, and depended on the amount of muscle loading. Our findings indicate that the lumbosacral spinal networks can be modulated transcutaneously using electrical spinal stimulation to facilitate self-assisted standing after chronic motor and sensory complete paralysis.", "doi": "10.1089/neu.2018.5956", "pmcid": "PMC6482915", "issn": "0897-7151", "publisher": "Mary Ann Liebert", "publication": "Journal of Neurotrauma", "publication_date": "2019-05", "series_number": "9", "volume": "36", "issue": "9", "pages": "1435-1450" }, { "id": "authors:fhd61-qrg34", "collection": "authors", "collection_id": "fhd61-qrg34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180529-075351546", "type": "article", "title": "Trunk Stability Enabled by Noninvasive Spinal Electrical Stimulation after Spinal Cord Injury", "author": [ { "family_name": "Rath", "given_name": "Mrinal", "clpid": "Rath-M" }, { "family_name": "Vette", "given_name": "Albert H.", "clpid": "Vette-A-H" }, { "family_name": "Ramasubramaniam", "given_name": "Shyamsundar", "clpid": "Ramasubramaniam-S" }, { "family_name": "Li", "given_name": "Kun", "clpid": "Li-Kun-CME" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Edgerton", "given_name": "Victor Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y-P" }, { "family_name": "Sayenko", "given_name": "Dimitry", "clpid": "Sayenko-D" } ], "abstract": "Electrical neuromodulation of spinal networks improves the control of movement of the paralyzed limbs after spinal cord injury (SCI). However, the potential of noninvasive spinal stimulation to facilitate postural trunk control during sitting in humans with SCI has not been investigated. We hypothesized that transcutaneous electrical stimulation of the lumbosacral enlargement can improve trunk posture. Eight participants with non-progressive SCI at C3-T9, American Spinal Injury Association Impairment Scale (AIS) A or C, performed different motor tasks during sitting. Electromyography of the trunk muscles, three-dimensional kinematics, and force plate data were acquired. Spinal stimulation improved trunk control during sitting in all tested individuals. Stimulation resulted in elevated activity of the erector spinae, rectus abdominis, and external obliques, contributing to improved trunk control, more natural anterior pelvic tilt and lordotic curve, and greater multi-directional seated stability. During spinal stimulation, the center of pressure (COP) displacements decreased to 1.36\u2009\u00b1\u20090.98\u2009mm compared with 4.74\u2009\u00b1\u20095.41\u2009mm without stimulation (p\u2009=\u20090.0156) in quiet sitting, and the limits of stable displacement increased by 46.92\u2009\u00b1\u200935.66% (p\u2009=\u20090.0156), 36.92\u2009\u00b1\u200930.48% (p\u2009=\u20090.0156), 54.67\u2009\u00b1\u200977.99% (p\u2009=\u20090.0234), and 22.70\u2009\u00b1\u200926.09% (p\u2009=\u20090.0391) in the forward, backward, right, and left directions, respectively. During self-initiated perturbations, the correlation between anteroposterior arm velocity and the COP displacement decreased from r\u2009=\u20090.5821 (p\u2009=\u20090.0007) without to r\u2009=\u20090.5115 (p\u2009=\u20090.0039) with stimulation, indicating improved trunk stability. These data demonstrate that the spinal networks can be modulated transcutaneously with tonic electrical spinal stimulation to physiological states sufficient to generate a more stable, erect sitting posture after chronic paralysis.", "doi": "10.1089/neu.2017.5584", "issn": "0897-7151", "publisher": "Mary Ann Liebert", "publication": "Journal of Neurotrauma", "publication_date": "2018-11", "series_number": "21", "volume": "35", "issue": "21", "pages": "2540-2553" }, { "id": "authors:01g95-6gc84", "collection": "authors", "collection_id": "01g95-6gc84", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151012-153837318", "type": "article", "title": "Integrating multiple sensory systems to modulate neural networks controlling posture", "author": [ { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Gerasimenko", "given_name": "Yury P.", "clpid": "Gerasimenko-Y-P" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Zhong", "given_name": "Hui", "clpid": "Zhong-Hui" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "In this study we investigated the ability of sensory input to produce tonic responses in hindlimb muscles to facilitate standing in adult spinal rats and tested two hypotheses: 1) whether the spinal neural networks below a complete spinal cord transection can produce tonic reactions by activating different sensory inputs and 2) whether facilitation of tonic and rhythmic responses via activation of afferents and with spinal cord stimulation could engage similar neuronal mechanisms. We used a dynamically controlled platform to generate vibration while weight bearing, epidural stimulation (at spinal cord level S1), and/or tail pinching to determine the postural control responses that can be generated by the lumbosacral spinal cord. We observed that a combination of platform displacement, epidural stimulation, and pinching the tail produces a cumulative effect that progressively enhances tonic responses in the hindlimbs. Tonic responses produced by epidural stimulation alone during standing were represented mainly by monosynaptic responses, whereas the combination of epidural stimulation and tail pinching during standing or epidural stimulation during stepping on a treadmill facilitated bilaterally both monosynaptic and polysynaptic responses. The results demonstrate that tonic muscle activity after complete spinal cord injury can be facilitated by activation of specific combinations of afferent inputs associated with load-bearing proprioception and cutaneous input in the presence of epidural stimulation and indicate whether activation of tonic or rhythmic responses are generated depends on the specific combinations of sources and types of afferents activated in the hindlimb muscles.", "doi": "10.1152/jn.00583.2015", "issn": "0022-3077", "publisher": "American Physiological Society", "publication": "Journal of Neurophysiology", "publication_date": "2015-12-01", "series_number": "6", "volume": "114", "issue": "6", "pages": "3306-3314" }, { "id": "authors:t7grk-1z628", "collection": "authors", "collection_id": "t7grk-1z628", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110706-083953684", "type": "article", "title": "Effect of epidural stimulation of the lumbosacral spinal cord\n on voluntary movement, standing, and assisted stepping\n after motor complete paraplegia: a case study", "author": [ { "family_name": "Harkema", "given_name": "Susan", "clpid": "Harkema-S-J" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y" }, { "family_name": "Hodes", "given_name": "Jonathan", "clpid": "Hodes-J" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Angeli", "given_name": "Claudia", "clpid": "Angeli-C" }, { "family_name": "Chen", "given_name": "Yangsheng", "clpid": "Chen-Yangsheng" }, { "family_name": "Ferreira", "given_name": "Christie", "clpid": "Ferreira-C" }, { "family_name": "Willhite", "given_name": "Andrea", "clpid": "Willhite-A" }, { "family_name": "Rejc", "given_name": "Enrico", "clpid": "Rejc-E" }, { "family_name": "Grossman", "given_name": "Robert G.", "clpid": "Grossman-R-G" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "Background:\nRepeated periods of stimulation of the spinal cord and training increased the ability to control movement in animal models of spinal cord injury. We hypothesised that tonic epidural spinal cord stimulation can modulate spinal circuitry in human beings into a physiological state that enables sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks.\n\nMethods:\nA 23-year-old man who had paraplegia from a C7\u2013T1 subluxation as a result of a motor vehicle accident in July 2006, presented with complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. After 170 locomotor training sessions over 26 months, a 16-electrode array was surgically placed on the dura (L1\u2013S1 cord segments) in December 2009, to allow for chronic electrical stimulation. Spinal cord stimulation was done during sessions that lasted up to 250 min. We did 29 experiments and tested several stimulation combinations and parameters with the aim of the patient achieving standing and stepping.\n\nFindings:\nEpidural stimulation enabled the man to achieve full weight-bearing standing with assistance provided only for balance for 4\u00b725 min. The patient achieved this standing during stimulation using parameters identified as specific for standing while providing bilateral load-bearing proprioceptive input. We also noted locomotor-like patterns when stimulation parameters were optimised for stepping. Additionally, 7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation.\n\nInterpretation:\nTask-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity. These interventions could be a viable clinical approach for functional recovery after severe paralysis.", "doi": "10.1016/S0140-6736(11)60547-3", "issn": "0140-6736", "publisher": "Elsevier", "publication": "Lancet", "publication_date": "2011-06-04", "series_number": "9781", "volume": "377", "issue": "9781", "pages": "1938-1947" }, { "id": "authors:9xjz2-ntn48", "collection": "authors", "collection_id": "9xjz2-ntn48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100823-154128926", "type": "book_section", "title": "Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face", "book_title": "Progress in Brain Research", "author": [ { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Ichiyama", "given_name": "Ronaldo M.", "clpid": "Ichiyama-R-M" }, { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Courtine", "given_name": "Gr\u00e9goire", "clpid": "Courtine-G" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y" }, { "family_name": "Tai", "given_name": "Y. C.", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "contributor": [ { "family_name": "Verhaagen", "given_name": "J.", "clpid": "Verhaagen-J" }, { "family_name": "Hol", "given_name": "Elly", "clpid": "Hol-E" }, { "family_name": "Huitinga", "given_name": "Inge", "clpid": "Huitinga-I" }, { "family_name": "Wijnholds", "given_name": "Jan", "clpid": "Wijnholds-J" }, { "family_name": "Bergen", "given_name": "Arthur", "clpid": "Bergen-A" }, { "family_name": "Boer", "given_name": "Gerard", "clpid": "Boer-G" }, { "family_name": "Swaab", "given_name": "Dick", "clpid": "Swaab-D" } ], "abstract": "Over the past 20 years, tremendous advances have been made in the field of spinal cord injury research. Yet, consumed with individual pieces of the puzzle, we have failed as a community to grasp the magnitude of the sum of our findings. Our current knowledge should allow us to improve the lives of patients suffering from spinal cord injury. Advances in multiple areas have provided tools for pursuing effective combination of strategies for recovering stepping and standing after a severe spinal cord injury. Muscle physiology research has provided insight into how to maintain functional muscle properties after a spinal cord injury.\nUnderstanding the role of the spinal networks in processing sensory information that is important for the generation of motor functions has focused research on developing treatments that sharpen the sensitivity of the locomotor circuitry and that carefully manage the presentation of proprioceptive and cutaneous stimuli to favor recovery. Pharmacological facilitation or inhibition of neurotransmitter systems, spinal cord stimulation, and rehabilitative motor training, which all function by modulating the physiological state of the spinal circuitry, have emerged as promising approaches. Early technological developments, such as robotic training systems and high-density electrode arrays for stimulating the spinal cord, can significantly enhance the precision and minimize the invasiveness of treatment after an injury.\n\nStrategies that seek out the complementary effects of combination treatments and that efficiently integrate relevant technical advances in bioengineering represent an untapped potential and are likely to have an immediate impact. Herein, we review key findings in each of these areas of research and present a unified vision for moving forward. Much work remains, but we already have the capability, and more importantly, the responsibility, to help spinal cord injury patients now.", "doi": "10.1016/S0079-6123(09)17526-X", "isbn": "978-0-12-374511-8", "publisher": "Elsevier", "publication_date": "2009", "pages": "393-418" }, { "id": "authors:xxv6b-d8v48", "collection": "authors", "collection_id": "xxv6b-d8v48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:LAVjns08b", "type": "article", "title": "Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input", "author": [ { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Courtine", "given_name": "Gr\u00e9goire", "clpid": "Courtine-G" }, { "family_name": "Dy", "given_name": "Christine J.", "clpid": "Dy-Christine-J" }, { "family_name": "van den Brand", "given_name": "Rubia", "clpid": "van-den-Brand-R" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y" }, { "family_name": "Zhong", "given_name": "Hui", "clpid": "Zhong-Hui" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-Roland-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "We investigated the role of afferent information during recovery of coordinated rhythmic activity of the hindlimbs in rats with a complete spinal cord section (approximately T8) and unilateral deafferentation (T12\u2013S2) to answer the following questions: (1) Can bilateral stepping be generated with only afferent projections intact on one side? (2) Can the sensory input from the non-deafferented side compensate for the loss of the afferent input from the deafferented side through the crossed connections within the lumbosacral spinal cord? (3) Which afferent projections to the spinal cord from the non-deafferented side predominantly mediate the effect of epidural stimulation to facilitate stepping? Recovery of stepping ability was tested under the facilitating influence of epidural stimulation at the S1 spinal segment, or epidural stimulation plus quipazine, a 5-HT agonist. All chronic spinal rats were able to generate stepping-like patterns on a moving treadmill on the non-deafferented, but not deafferented, side from 3 to 7 weeks after surgery when facilitated by epidural stimulation. Adaptation to the loss of unilateral afferent input was evident at 7 weeks after surgery, when some movements occurred on the deafferented side. Spinal-cord-evoked potentials were observed on both sides, although middle (monosynaptic) and late (long latency) responses were more prominent on the non-deafferented side. The afferent information arising from the non-deafferented side, however, eventually could mediate limited restoration of hindlimb movements on the deafferented side. These data suggest that facilitation of stepping with epidural stimulation is mediated primarily through ipsilateral afferents that project to the locomotor networks.", "doi": "10.1523/JNEUROSCI.1069-08.2008", "pmcid": "PMC2897701", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2008-07-30", "series_number": "31", "volume": "28", "issue": "31", "pages": "7774-7780" }, { "id": "authors:m7t2h-e7w19", "collection": "authors", "collection_id": "m7t2h-e7w19", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100726-104029245", "type": "article", "title": "Flexible parylene-based multielectrode array technology\n for high-density neural stimulation and recording", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Ameri", "given_name": "Hossein", "clpid": "Ameri-H" }, { "family_name": "Ahuja", "given_name": "Ashish K.", "clpid": "Ahuja-A-K" }, { "family_name": "Gutierrez", "given_name": "Christian", "clpid": "Gutierrez-C" }, { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Zhong", "given_name": "Hui", "clpid": "Zhong-Hui" }, { "family_name": "Menon", "given_name": "Parvathy R.", "clpid": "Menon-P-R" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord prosthetics. These arrays are microfabricated according to a single-metal-layer process and a revolutionary dual-metal-layer process that promises to meet the needs of extremely high-density stimulation applications. While in many cases thin-film platinum electrodes in parylene C would be sufficient, high surface-area platinum electroplating has been shown to extend the lifetime of stimulated electrodes to more than 430 million pulses without failing. Iridium electrode arrays with higher charge delivery capacity have also been fabricated using a new high-temperature stabilized parylene variant, parylene HT. In addition, a new heat molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and a chronic implantation study of the mechanical effects of parylene-based electrode arrays on the retina over a 6-month follow-up period has provided excellent results. Retinal stimulation from these parylene-based electrode arrays in an isolated tiger salamander preparation was shown to be comparable to light stimulation in terms of generation of action potentials in the inner retina. Finally, electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays.", "doi": "10.1016/j.snb.2007.10.069", "issn": "0925-4005", "publisher": "Elsevier", "publication": "Sensors and Actuators B: Chemical", "publication_date": "2008-06-16", "series_number": "2", "volume": "132", "issue": "2", "pages": "449-460" }, { "id": "authors:n39c5-ngj72", "collection": "authors", "collection_id": "n39c5-ngj72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:LAVjns08a", "type": "article", "title": "Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats", "author": [ { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Dy", "given_name": "Christine J.", "clpid": "Dy-Christine-J" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Gerasimenko", "given_name": "Yury", "clpid": "Gerasimenko-Y" }, { "family_name": "Courtine", "given_name": "Gr\u00e9goire", "clpid": "Courtine-G" }, { "family_name": "Zhong", "given_name": "Hui", "clpid": "Zhong-Hui" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-Roland-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "The importance of the in vivo dynamic nature of the circuitries within the spinal cord that generate locomotion is becoming increasingly evident. We examined the characteristics of hindlimb EMG activity evoked in response to epidural stimulation at the S1 spinal cord segment in complete midthoracic spinal cord-transected rats at different stages of postlesion recovery. A progressive and phase-dependent modulation of monosynaptic (middle) and long-latency (late) stimulation-evoked EMG responses was observed throughout the step cycle. During the first 3 weeks after injury, the amplitude of the middle response was potentiated during the EMG bursts, whereas after 4 weeks, both the middle and late responses were phase-dependently modulated. The middle- and late-response magnitudes were closely linked to the amplitude and duration of the EMG bursts during locomotion facilitated by epidural stimulation. The optimum stimulation frequency that maintained consistent activity of the long-latency responses ranged from 40 to 60 Hz, whereas the short-latency responses were consistent from 5 to 130 Hz. These data demonstrate that both middle and late evoked potentials within a motor pool are strictly gated during in vivo bipedal stepping as a function of the general excitability of the motor pool and, thus, as a function of the phase of the step cycle. These data demonstrate that spinal cord epidural stimulation can facilitate locomotion in a time-dependent manner after lesion. The long-latency responses to epidural stimulation are correlated with the recovery of weight-bearing bipedal locomotion and may reflect activation of interneuronal central pattern-generating circuits.", "doi": "10.1523/JNEUROSCI.0080-08.2008", "pmcid": "PMC2904311", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2008-06-04", "series_number": "23", "volume": "28", "issue": "23", "pages": "6022-6029" }, { "id": "authors:79vpj-n4367", "collection": "authors", "collection_id": "79vpj-n4367", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100505-150446478", "type": "article", "title": "Training locomotor networks", "author": [ { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Courtine", "given_name": "Gr\u00e9goire", "clpid": "Courtine-G" }, { "family_name": "Gerasimenko", "given_name": "Yury P.", "clpid": "Gerasimenko-Y-P" }, { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Ichiyama", "given_name": "Ronaldo M.", "clpid": "Ichiyama-R-M" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Cai", "given_name": "Lance L.", "clpid": "Cai-Lance-L" }, { "family_name": "Otoshi", "given_name": "Chad K.", "clpid": "Otoshi-C-K" }, { "family_name": "Tillakaratne", "given_name": "Niranjala J. K.", "clpid": "Tillakaratne-N-J-K" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" } ], "abstract": "For a complete adult spinal rat to regain some weight-bearing stepping capability, it appears that a sequence of specific proprioceptive inputs that are similar, but not identical, from step to step must be generated over repetitive step cycles. Furthermore, these cycles must include the activation of specific neural circuits that are intrinsic to the lumbosacral spinal cord segments. For these sensorimotor pathways to be effective in generating stepping, the spinal circuitry must be modulated to an appropriate excitability level. This level of modulation is sustained from supraspinal input in intact, but not spinal, rats. In a series of experiments with complete spinal rats, we have shown that an appropriate level of excitability of the spinal circuitry can be achieved using widely different means. For example, this modulation level can be acquired pharmacologically, via epidural electrical stimulation over specific lumbosacral spinal cord segments, and/or by use-dependent mechanisms such as step or stand training. Evidence as to how each of these treatments can \"tune\" the spinal circuitry to a \"physiological state\" that enables it to respond appropriately to proprioceptive input will be presented. We have found that each of these interventions can enable the proprioceptive input to actually control extensive details that define the dynamics of stepping over a range of speeds, loads, and directions. A series of experiments will be described that illustrate sensory control of stepping and standing after a spinal cord injury and the necessity for the \"physiological state\" of the spinal circuitry to be modulated within a critical window of excitability for this control to be manifested. The present findings have important consequences not only for our understanding of how the motor pattern for stepping is formed, but also for the design of rehabilitation intervention to restore lumbosacral circuit function in humans following a spinal cord injury.", "doi": "10.1016/j.brainresrev.2007.09.002", "pmcid": "PMC2288528", "issn": "0165-0173", "publisher": "Elsevier", "publication": "Brain Research Reviews", "publication_date": "2008-01", "series_number": "1", "volume": "57", "issue": "1", "pages": "241-254" }, { "id": "authors:39jpc-njm05", "collection": "authors", "collection_id": "39jpc-njm05", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170419-172819922", "type": "book_section", "title": "High-Density Flexible Parylene-Based Multielectrode Arrays for Retinal and Spinal Cord Stimulation", "book_title": "TRANSDUCERS 2007 - 2007 International Solid-State Sensors, Actuators and Microsystems Conference", "author": [ { "family_name": "Rodger", "given_name": "D. C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Fong", "given_name": "A. J.", "clpid": "Fong-Andy-J" }, { "family_name": "Li", "given_name": "W.", "orcid": "0000-0003-2543-2558", "clpid": "Li-Wei" }, { "family_name": "Ameri", "given_name": "H.", "clpid": "Ameri-H" }, { "family_name": "Lavrov", "given_name": "I.", "clpid": "Lavrov-I" }, { "family_name": "Zhong", "given_name": "H.", "clpid": "Zhong-Hui" }, { "family_name": "Saati", "given_name": "S.", "clpid": "Saati-S" }, { "family_name": "Menon", "given_name": "P.", "clpid": "Menon-P-R" }, { "family_name": "Meng", "given_name": "E.", "clpid": "Meng-E-M" }, { "family_name": "Burdick", "given_name": "J. W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "R. R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. R.", "clpid": "Edgerton-V-R" }, { "family_name": "Weiland", "given_name": "J. D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "M. S.", "clpid": "Humayan-M-S" }, { "family_name": "Tai", "given_name": "Y. C.", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord applications. These electrode arrays are microfabricated according to single-metal-layer and, most recently, dual-metal-layer processes. A new heat-molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and chronic implantation studies have been undertaken to study the mechanical effects of parylene-based prostheses on the retina, with excellent results to date. Electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays.", "doi": "10.1109/SENSOR.2007.4300401", "isbn": "1-4244-0841-5", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2007-06", "pages": "1385-1388" }, { "id": "authors:qp4tz-rtp55", "collection": "authors", "collection_id": "qp4tz-rtp55", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190620-093003693", "type": "article", "title": "Plasticity of functional connectivity in the adult spinal cord", "author": [ { "family_name": "Cai", "given_name": "L. L.", "clpid": "Cai-Lance-L" }, { "family_name": "Courtine", "given_name": "G.", "clpid": "Courtine-G" }, { "family_name": "Fong", "given_name": "A. J.", "clpid": "Fong-Andy-J" }, { "family_name": "Burdick", "given_name": "J. W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "R. R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. R.", "clpid": "Edgerton-V-R" } ], "abstract": "This paper emphasizes several characteristics of the neural control of locomotion that provide opportunities for developing strategies to maximize the recovery of postural and locomotor functions after a spinal cord injury (SCI). The major points of this paper are: (i) the circuitry that controls standing and stepping is extremely malleable and reflects a continuously varying combination of neurons that are activated when executing stereotypical movements; (ii) the connectivity between neurons is more accurately perceived as a functional rather than as an anatomical phenomenon; (iii) the functional connectivity that controls standing and stepping reflects the physiological state of a given assembly of synapses, where the probability of these synaptic events is not deterministic; (iv) rather, this probability can be modulated by other factors such as pharmacological agents, epidural stimulation and/or motor training; (v) the variability observed in the kinematics of consecutive steps reflects a fundamental feature of the neural control system and (vi) machine-learning theories elucidate the need to accommodate variability in developing strategies designed to enhance motor performance by motor training using robotic devices after an SCI.", "doi": "10.1098/rstb.2006.1884", "pmcid": "PMC1664672", "issn": "0962-8436", "publisher": "Royal Society of London", "publication": "Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences", "publication_date": "2006-09-29", "series_number": "1473", "volume": "361", "issue": "1473", "pages": "1635-1646" }, { "id": "authors:xhce1-0yr77", "collection": "authors", "collection_id": "xhce1-0yr77", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110720-113158743", "type": "book_section", "title": "Flexible Microfabricated Parylene Multielectrode Arrays for\n Retinal Stimulation and Spinal Cord Field Modulation", "book_title": "2006 International Conference on Microtechnologies in Medicine and Biology", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Ameri", "given_name": "Hossein", "clpid": "Ameri-H" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "The first flexible parylene-based multielectrode arrays (MEAs) designed for functional electrical stimulation (FES) in retinal prostheses, and the extension of this technology toward enabling reflex-arc neuromodulation in cases of spinal cord damage or transection, are presented. A single metal layer 16 \u00d7 16 retinal electrode array of 125 \u03bcm-diameter thin-film Ti/Pt electrodes and lines\nof 12 \u03bcm-pitch has been fabricated as a demonstration of this technology. To allow for even higher density arrays, a novel dual-layer process has also been implemented that enables leads to pass under overlying electrodes without making electrical contact to them. A biomimetic parylene-based electrode array consisting of 1024 electrodes of highly variable spacing, 60 of which have been connected in this manner, has been fabricated according to this paradigm. A parylene-parylene annealing process has also been developed to increase device longevity under accelerated-lifetime saline soak conditions. Surgical tests of novel anatomically-conformal\ngeometries that enable such parylene-based electrode systems to interact with their neuronal targets of interest while causing minimal mechanical damage to tissues or to the implants are also presented. The use of these flexible electrode arrays in spinal cord stimulation experiments in animal models has proven their efficacy in stimulating neurons.", "doi": "10.1109/MMB.2006.251482", "isbn": "978-1-4244-0337-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-05", "pages": "31-34" }, { "id": "authors:f8p41-wmg07", "collection": "authors", "collection_id": "f8p41-wmg07", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110209-103455742", "type": "book_section", "title": "Assist-as-needed training paradigms for robotic rehabilitation of spinal cord injuries", "book_title": "Proceedings 2006 IEEE International Conference on Robotics and Automation", "author": [ { "family_name": "Cai", "given_name": "Lance L.", "clpid": "Cai-Lance-L" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Liang", "given_name": "Yongqiang", "clpid": "Liang-Yongqiang" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "This paper introduces a new \"assist-as-needed\" (AAN)\ntraining paradigm for rehabilitation of spinal cord injuries via\nrobotic training devices. In the pilot study reported in this paper,\nnine female adult Swiss-Webster mice were divided into three\ngroups, each experiencing a different robotic training control\nstrategy: a fixed training trajectory (Fixed Group, A), an AAN\ntraining method without interlimb coordination (Band Group, B),\nand an AAN training method with bilateral hindlimb coordination\n(Window Group, C). Fourteen days after complete transection at\nthe mid-thoracic level, the mice were robotically trained to step in\nthe presence of an acutely administered serotonin agonist, quipazine,\nfor a period of six weeks. The mice that received AAN training\n(Groups B and C) show higher levels of recovery than Group\nA mice, as measured by the number, consistency, and periodicity\nof steps realized during testing sessions. Group C displays a\nhigher incidence of alternating stepping than Group B. These\nresults indicate that this training approach may be more effective\nthan fixed trajectory paradigms in promoting robust post-injury\nstepping behavior. Furthermore, the constraint of interlimb coordination\nappears to be an important contribution to successful\ntraining.", "doi": "10.1109/ROBOT.2006.1642237", "isbn": "0-7803-9505-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-05", "pages": "3504-3511" }, { "id": "authors:gk0c0-5bp89", "collection": "authors", "collection_id": "gk0c0-5bp89", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110216-142339556", "type": "book_section", "title": "A Robotic Training System for Studies of Post-SCI Stand Rehabilitation", "book_title": "Proceedings of the First IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics BioRob 2006", "author": [ { "family_name": "Liang", "given_name": "Yongqiang", "clpid": "Liang-Yongqiang" }, { "family_name": "Cai", "given_name": "Lance L.", "clpid": "Cai-Lance-L" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "This paper describes a robotic training system designed to rehabilitate the standing ability of mice after spinal cord injury(SCI). The system is composed of a 6 Degree-of-Freedom (DOF) parallel mechanism, an active weight support system, and other measuring equipments which can monitor the response of the mouse. Preliminary experiments showed that the mouse could generate a certain degree of weight-support stand response during the training.", "doi": "10.1109/BIOROB.2006.1639059", "isbn": "1-4244-0040-6", "publisher": "IEEE", "place_of_publication": "Piscataway, N.J.", "publication_date": "2006-02", "pages": "51-56" }, { "id": "authors:wedcf-26281", "collection": "authors", "collection_id": "wedcf-26281", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110223-105021175", "type": "book_section", "title": "Effects of Assist-as-needed Robotic Training Paradigms on the Locomotor Recovery of Adult Spinal Mice", "book_title": "Proceedings of the First IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics BioRob 2006", "author": [ { "family_name": "Cai", "given_name": "Lance L.", "clpid": "Cai-Lance-L" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Liang", "given_name": "Yongqiang", "clpid": "Liang-Yongqiang" }, { "family_name": "Burdick", "given_name": "Joel", "clpid": "Burdick-J-W" }, { "family_name": "Otoshi", "given_name": "Chad K.", "clpid": "Otoshi-Chad-K" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "This paper introduces a new \"assist-as needed\"\n(AAN) training paradigm for rehabilitation\nof spinal cord injuries via robotic training devices. In\nthe pilot study reported in this paper, nine female\nadult Swiss-Webster mice were divided into three\ngroups, each experiencing a different robotic training\ncontrol strategy: a fixed training trajectory (Fixed\nGroup, A), an AAN training method without inter-limb\ncoordination (Band Group, B), and an AAN\ntraining method with bilateral hindlimb coordination\n(Window Group, C). Fourteen days after complete\ntransection at the mid-thoracic level, the mice were\nrobotically trained to step in the presence of an\nacutely administered serotonin agonist, quipazine, for\na period of six weeks. The mice that received AAN\ntraining (Groups B and C) show higher levels of recovery\nthan Group A mice, as measured by the number,\nconsistency, and periodicity of steps realized during\ntesting sessions. Group C displays a higher incidence\nof alternating stepping than Group B. These\nresults indicate that this training approach may be\nmore effective than fixed trajectory paradigms in promoting\nrobust post-injury stepping behavior. Furthermore,\nthe constraint of inter-limb coordination\nappears to be an important contribution to successful\ntraining. Presented in this paper are also some preliminary\nresults from a recent full-scale study that\ncomplements the conclusions from this pilot study.", "doi": "10.1109/BIOROB.2006.1639061", "isbn": "1-4244-0040-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-02", "pages": "62-67" }, { "id": "authors:jpnss-mks27", "collection": "authors", "collection_id": "jpnss-mks27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190614-161544893", "type": "article", "title": "Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training", "author": [ { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Cai", "given_name": "Lance L.", "clpid": "Cai-Lance-L" }, { "family_name": "Otoshi", "given_name": "Chad K.", "clpid": "Otoshi-Chad-K" }, { "family_name": "Reinkensmeyer", "given_name": "David J.", "clpid": "Reikensmeyer-D-J" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "abstract": "In the present study, concurrent treatment with robotic step training and a serotonin agonist, quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7\u2013T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, quipazine treatment, or a combination of robotic training with quipazine treatment, to examine the mechanisms by which training and quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.", "doi": "10.1523/JNEUROSCI.1523-05.2005", "pmcid": "PMC6726027", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2005-12-14", "series_number": "50", "volume": "25", "issue": "50", "pages": "11738-11747" }, { "id": "authors:0zm4b-fzg74", "collection": "authors", "collection_id": "0zm4b-fzg74", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140611-081051132", "type": "book_section", "title": "Effects of consistency vs. variability in robotically controlled training of stepping in adult spinal mice", "author": [ { "family_name": "Cai", "given_name": "L. L.", "clpid": "Cai-Lance-L" }, { "family_name": "Fong", "given_name": "A. J.", "clpid": "Fong-Andy-J" }, { "family_name": "Otoshi", "given_name": "C. K.", "clpid": "Otoshi-C-K" }, { "family_name": "Liang", "given_name": "Y. Q.", "clpid": "Liang-Yongqiang" }, { "family_name": "Cham", "given_name": "J. G.", "clpid": "Cham-J-G" }, { "family_name": "Zhong", "given_name": "H.", "clpid": "Zhong-Hui" }, { "family_name": "Roy", "given_name": "R. R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. R.", "clpid": "Edgerton-V-R" }, { "family_name": "Burdick", "given_name": "J. W.", "clpid": "Burdick-J-W" } ], "abstract": "This paper studies the possible benefit that can be obtained by introducing variability into the robotic control of trajectories used to train hindlimb locomotion in adult spinal mice. The spinal cords of adult female Swiss-Webster mice were completely transected at a mid-thoracic level. Fourteen days post-transection, the spinal mice were robotically trained to step in the presence of a 5-HT agonist, quipazine, for a period of six weeks. In this pilot study nine animals were divided into three groups, each receiving a different control strategy: a fixed training trajectory (Group A), a variable training trajectory without interlimb coordination imposed (Group B) and a variable training trajectory with hindlimb bilateral coordination imposed (Group C). Preliminary results indicate that Group A recovers more slowly than the two groups receiving variable modes of robotic training. Groups B and C show higher levels of recovery than Group A in terms of the number of steps performed during testing sessions, as well as in their step periodicity and shape consistency. Group C displays a higher incidence of alternating stepping than Group B. These results indicate that variable trajectory robotic training paradigms may be more effective than fixed trajectory paradigms in promoting robust post-injury stepping behavior. Furthermore, it appears that the inclusion of interlimb coordination is an important contribution to successful training.", "doi": "10.1109/ICORR.2005.1502028", "publisher": "IEEE", "publication_date": "2005-06" } ]