Our goal is to obtain stable multielectrode recordings from spinal cord below a spinal transection in rats and follow the neural changes that occur after spinal cord injury and as a result of rehabilitation processes. To do this we will use multielectrode neural recordings and microstimulation. The data will be unique and novel with major potential impacts on our understanding of spinal cord injury, and possible technology transfer to clinical applications. We will use and further develop novel electrode designs initiated in our laboratory to achieve our objectives.
Specific Aim 1 : We will further develop a chronic intraspinal multielectrode probe with recording sites along its length, using novel braided composite electrodes. We will add recording sites distributed along the inserted probe length in order to sample neural activity across laminae. To do this we will add laser ablation techniques to our existing construction. We also plan to reduce component wire diameter by a factor of 2-3 (from current 13 micron wire plus insulation components), increasing wire and probe compliance by a factor of 16 to 81 times beyond current values.
Specific Aim 2 : We will use our electrodes to record activity patterns in spinal cord throughout the process of robot assisted rehabilitation in T9/10 spinalized (ST) rats (both neonatal and adult ST rat injuries). We hypothesize that robot rehabilitation after SCI causes within session dynamic alterations in neural activity, which persist day to day, and correlate with improving functional recovery and weight support. These experiments will provide completely novel data and insights into the rehabilitation process at spinal levels and new measures for assessing rehabilitation and neuroplasticity.
Specific Aim 3 : We will perform intraspinal microstimulation tests in T9/10 spinalized rats (both neonatal and adult ST rat injuries), either throughout, or after, robot assisted rehabilitation. Our hypothesis is that differences in microstimulation between the groups early and late in training will correlate to functional recovery and robot training effects. These new stimulation data are also expected to provide a set of novel outcome measures and circuit test tools for assessing the interaction of focal spinal stimulation, rehabilitation and neuroplasticity. This project has the potential to have enormous and possibly transformative impacts on our understanding of spinal cord function, injury, and rehabilitation processes using standard animal models. Further, the technologies being tuned in Aim 1 may have broad applicability in neural recording and stimulation in many brain areas, and thus enable new generations of neural recording tools and neuroprosthetics.

Public Health Relevance

This project makes improvements in new electrodes useful for basic scientific and clinical applications, and uses these for recordings from spinal cord during rehabilitation that have never been made before. The information gained may help design better rehabilitation and therapies for spinal cord injury and help understand disease progression. The electrodes developed may have numerous basic and clinical applications beyond this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS072651-04
Application #
8508094
Study Section
Neurotechnology Study Section (NT)
Program Officer
Ludwig, Kip A
Project Start
2010-08-20
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$319,617
Indirect Cost
$112,745
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F (2016) Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence. J Neurosci 36:8341-55
Oza, Chintan S; Giszter, Simon F (2015) Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats. J Neurosci 35:7174-89
Giszter, Simon F (2015) Motor primitives--new data and future questions. Curr Opin Neurobiol 33:156-65
Udoekwere, Ubong Ime; Oza, Chintan S; Giszter, Simon F (2014) A pelvic implant orthosis in rodents, for spinal cord injury rehabilitation, and for brain machine interface research: construction, surgical implantation and validation. J Neurosci Methods 222:199-206
Oza, Chintan S; Giszter, Simon F (2014) Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training. Exp Neurol 256:57-69
Hart, Corey B; Giszter, Simon F (2013) Distinguishing synchronous and time-varying synergies using point process interval statistics: motor primitives in frog and rat. Front Comput Neurosci 7:52
Kim, Taegyo; Branner, Almut; Gulati, Tanuj et al. (2013) Braided multi-electrode probes: mechanical compliance characteristics and recordings from spinal cords. J Neural Eng 10:045001
Giszter, Simon F; Hart, Corey B (2013) Motor primitives and synergies in the spinal cord and after injury--the current state of play. Ann N Y Acad Sci 1279:114-26
Song, Weiguo; Giszter, Simon F (2011) Adaptation to a cortex-controlled robot attached at the pelvis and engaged during locomotion in rats. J Neurosci 31:3110-28
Hsieh, F H; Giszter, S F (2011) Robot-driven spinal epidural stimulation compared with conventional stimulation in adult spinalized rats. Conf Proc IEEE Eng Med Biol Soc 2011:5807-10

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