Background: Closed-loop neuromodulation systems have received increased attention in recent years... more Background: Closed-loop neuromodulation systems have received increased attention in recent years as potential therapeutic approaches for treating neurological injury and disease. Objective: The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). Methods: Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecut...
Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on ... more Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation. Approach. Adult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At 4 weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles. Main results. In healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10–12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ∼20 and 60 ms, generally following a Gaussian distribution, rising above baseline a...
The purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS)... more The purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS) results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). Experiments were carried out in adult male Sprague Dawley rats with 175 kdyn moderate T8 contusion injury. Rats were randomly assigned to one of two groups: Control or Activity Dependent Stimulation (ADS) therapy. Four weeks post-SCI, all rats were implanted with a recording electrode in the left hindlimb motor cortex and a fine-wire, custom-made stimulating electrode in the contralateral lumbar spinal cord. Intracortical and intraspinal microstimulation were used to find sites of similar hip representation areas, which were paired together for ADS therapy. In the ADS therapy group, spike-stimulus conditioning was administered for 4 hours/day, 4 days/week, for 4 weeks via a tethered cable in a testing chamber. During therapy sessions, single-unit spikes were discriminated in real time in the hi...
ObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on sp... more ObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LO...
The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), trigg... more The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using intracortical microstimulation (ICMS) to examine the number...
Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 ... more Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to deter...
Neurorehabilitation and neural repair, Jan 23, 2015
Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enh... more Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing poststroke functional recovery in rats, but human clinical trials have had mixed outcomes. To assess the efficacy of CS/RT versus RT in a nonhuman primate model of cortical ischemic stroke. Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex. A subdural monopolar electrode was implanted over the spared DFL representation in dorsal premotor cortex (PMD). Seven weeks postinfarct, monkeys underwent 4 to 6 weeks of RT (n = 8) or CS/RT (n = 7; 100 Hz, cathodal current) therapy. Behavioral performance was assessed before and after infarct, prior to therapy, and 1 and 12 weeks posttherapy (follow-up). The primary outcome measure was motor performance at 1 week posttherapy. Secondary outcomes included follow-up performance at 12 weeks and treatment-related changes in neurophysiological maps of spare...
2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2015
Approximately 6 million people in the United States are currently living with paralysis in which ... more Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat.
New insights into the brain's ability to reorganize after injury are beginning to suggest nov... more New insights into the brain's ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage. Using a between-groups repeated-measures design, squirrel monkeys were randomized to 1 of 2 groups: an experimental group received intravenous GSK249320 beginning 24 hours after an ischemic infarct in motor cortex with repeated dosages given at 1-week intervals for 6 weeks and a control group received only the vehicle at matched time periods. The primary end point was a motor performance index based on a distal forelimb reach-and-retrieval task. Neurophysiological mapping techniques were used to...
Both dl-α-difluoromethylornithine (DFMO) and ethanol have been reported to inhibit the growth of ... more Both dl-α-difluoromethylornithine (DFMO) and ethanol have been reported to inhibit the growth of fibroblasts in cell culture. The objectives of the present study were to determine whether these compounds could be used to inhibit the growth of fibroblasts in vivo, with a bleomycin-induced mouse model of pulmonary fibrosis. DBA2J mice were given a single endotracheal injection of bleomycin, 10 nmol. In addition to bleomycin (BLM), groups of animals received 2% DFMO in drinking water for 4 days prior to BLM and 18 days after (BLM DFMO), 6% ethanol in drinking water for 7 days prior to BLM and 21 days after (BLM E7), 6% ethanol in drinking water for 21 days initiated on the day of BLM intubation (BLM E), or DFMO, E7, and BLM in combination (BLM DFMO E7). Animals died or were killed 21 days after bleomycin treatment and lungs were evaluated by histopathologic criteria. DFMO failed to alter the incidence or severity of fibrotic lesions, increased the severity of epithelial metaplasia (p < 0.05), and reduced the lung disease index (from 56.3 to 42.1%, p < 0.05) and mortality from 83.3 to 41.7% (p < 0.025). In contrast to the unsatisfactory response to DFMO, pretreatment with ethanol (BLM E7) reduced the incidence of interstitial fibrosis from 91.3 to 71.4% (p < 0.05) and confluent fibrosis from 73.9 to 20.0% (p < 0.005). The severity of lesions was also reduced by ethanol, resulting in an 18.5% decrease in interstitial fibrosis, a 25.9% decrease in epithelial metaplasia, and a 55.4% reduction in the lung disease index (all p < 0.01). However, when ethanol and DFMO were administered in combination, the beneficial effects of ethanol alone were not observed, and only the lung disease index was decreased.
All mammals, including the egg-laying mono-tremes, possess an auditory cortex—that is, an auditor... more All mammals, including the egg-laying mono-tremes, possess an auditory cortex—that is, an auditory area in their cerebral neocortex. In contrast, no reptile or bird possesses even neocortex itself let alone an auditory area within it. Therefore, the question of the evolutionary origin of auditory cortex is entangled in the larger question of the origin of mammalian neocortex. Because there are no animals now extant that serve as an unarguable witness to the transition from the reptilian to the mammalian form of cerebral cortex the question of the origin of mammalian cortex is an old and persistent one. We now have but two snapshots of the forebrain through geological time—a reptilian stage without neocortex and a later mammalian stage with a relatively large amount of neocortex and an auditory area already within it.
2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2014
Nearly 6 million people in the United States are currently living with paralysis in which 23% of ... more Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.
Background. There is growing interest in the use of d-amphetamine (d-AMPH) as a pharmacological t... more Background. There is growing interest in the use of d-amphetamine (d-AMPH) as a pharmacological treatment to supplement rehabilitative therapy following stroke. Based on the success of earlier animal models, several clinical studies have demonstrated beneficial effects of applying physical rehabilitation while stroke patients are under the influence of d-AMPH. To begin to understand the neural mechanisms underlying this promising adjuvant therapy, the authors examined the effects of a single pairing of d-AMPH and rehabilitative training on motor performance after cortical infarct in squirrel monkeys. Methods. Microelectrode stimulation techniques were used to delineate hand movement areas in the primary motor cortex prior to delivering a unilateral infarct to the complete hand representation. Postinfarct recovery was assessed for 3 groups of monkeys: d-AMPH + training, saline + training, and spontaneous recovery (SR). Postinfarct training groups received 14 consecutive days of motor...
Background: Closed-loop neuromodulation systems have received increased attention in recent years... more Background: Closed-loop neuromodulation systems have received increased attention in recent years as potential therapeutic approaches for treating neurological injury and disease. Objective: The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). Methods: Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecut...
Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on ... more Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation. Approach. Adult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At 4 weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles. Main results. In healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10–12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ∼20 and 60 ms, generally following a Gaussian distribution, rising above baseline a...
The purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS)... more The purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS) results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). Experiments were carried out in adult male Sprague Dawley rats with 175 kdyn moderate T8 contusion injury. Rats were randomly assigned to one of two groups: Control or Activity Dependent Stimulation (ADS) therapy. Four weeks post-SCI, all rats were implanted with a recording electrode in the left hindlimb motor cortex and a fine-wire, custom-made stimulating electrode in the contralateral lumbar spinal cord. Intracortical and intraspinal microstimulation were used to find sites of similar hip representation areas, which were paired together for ADS therapy. In the ADS therapy group, spike-stimulus conditioning was administered for 4 hours/day, 4 days/week, for 4 weeks via a tethered cable in a testing chamber. During therapy sessions, single-unit spikes were discriminated in real time in the hi...
ObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on sp... more ObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LO...
The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), trigg... more The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using intracortical microstimulation (ICMS) to examine the number...
Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 ... more Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to deter...
Neurorehabilitation and neural repair, Jan 23, 2015
Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enh... more Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing poststroke functional recovery in rats, but human clinical trials have had mixed outcomes. To assess the efficacy of CS/RT versus RT in a nonhuman primate model of cortical ischemic stroke. Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex. A subdural monopolar electrode was implanted over the spared DFL representation in dorsal premotor cortex (PMD). Seven weeks postinfarct, monkeys underwent 4 to 6 weeks of RT (n = 8) or CS/RT (n = 7; 100 Hz, cathodal current) therapy. Behavioral performance was assessed before and after infarct, prior to therapy, and 1 and 12 weeks posttherapy (follow-up). The primary outcome measure was motor performance at 1 week posttherapy. Secondary outcomes included follow-up performance at 12 weeks and treatment-related changes in neurophysiological maps of spare...
2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2015
Approximately 6 million people in the United States are currently living with paralysis in which ... more Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat.
New insights into the brain's ability to reorganize after injury are beginning to suggest nov... more New insights into the brain's ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage. Using a between-groups repeated-measures design, squirrel monkeys were randomized to 1 of 2 groups: an experimental group received intravenous GSK249320 beginning 24 hours after an ischemic infarct in motor cortex with repeated dosages given at 1-week intervals for 6 weeks and a control group received only the vehicle at matched time periods. The primary end point was a motor performance index based on a distal forelimb reach-and-retrieval task. Neurophysiological mapping techniques were used to...
Both dl-α-difluoromethylornithine (DFMO) and ethanol have been reported to inhibit the growth of ... more Both dl-α-difluoromethylornithine (DFMO) and ethanol have been reported to inhibit the growth of fibroblasts in cell culture. The objectives of the present study were to determine whether these compounds could be used to inhibit the growth of fibroblasts in vivo, with a bleomycin-induced mouse model of pulmonary fibrosis. DBA2J mice were given a single endotracheal injection of bleomycin, 10 nmol. In addition to bleomycin (BLM), groups of animals received 2% DFMO in drinking water for 4 days prior to BLM and 18 days after (BLM DFMO), 6% ethanol in drinking water for 7 days prior to BLM and 21 days after (BLM E7), 6% ethanol in drinking water for 21 days initiated on the day of BLM intubation (BLM E), or DFMO, E7, and BLM in combination (BLM DFMO E7). Animals died or were killed 21 days after bleomycin treatment and lungs were evaluated by histopathologic criteria. DFMO failed to alter the incidence or severity of fibrotic lesions, increased the severity of epithelial metaplasia (p < 0.05), and reduced the lung disease index (from 56.3 to 42.1%, p < 0.05) and mortality from 83.3 to 41.7% (p < 0.025). In contrast to the unsatisfactory response to DFMO, pretreatment with ethanol (BLM E7) reduced the incidence of interstitial fibrosis from 91.3 to 71.4% (p < 0.05) and confluent fibrosis from 73.9 to 20.0% (p < 0.005). The severity of lesions was also reduced by ethanol, resulting in an 18.5% decrease in interstitial fibrosis, a 25.9% decrease in epithelial metaplasia, and a 55.4% reduction in the lung disease index (all p < 0.01). However, when ethanol and DFMO were administered in combination, the beneficial effects of ethanol alone were not observed, and only the lung disease index was decreased.
All mammals, including the egg-laying mono-tremes, possess an auditory cortex—that is, an auditor... more All mammals, including the egg-laying mono-tremes, possess an auditory cortex—that is, an auditory area in their cerebral neocortex. In contrast, no reptile or bird possesses even neocortex itself let alone an auditory area within it. Therefore, the question of the evolutionary origin of auditory cortex is entangled in the larger question of the origin of mammalian neocortex. Because there are no animals now extant that serve as an unarguable witness to the transition from the reptilian to the mammalian form of cerebral cortex the question of the origin of mammalian cortex is an old and persistent one. We now have but two snapshots of the forebrain through geological time—a reptilian stage without neocortex and a later mammalian stage with a relatively large amount of neocortex and an auditory area already within it.
2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2014
Nearly 6 million people in the United States are currently living with paralysis in which 23% of ... more Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.
Background. There is growing interest in the use of d-amphetamine (d-AMPH) as a pharmacological t... more Background. There is growing interest in the use of d-amphetamine (d-AMPH) as a pharmacological treatment to supplement rehabilitative therapy following stroke. Based on the success of earlier animal models, several clinical studies have demonstrated beneficial effects of applying physical rehabilitation while stroke patients are under the influence of d-AMPH. To begin to understand the neural mechanisms underlying this promising adjuvant therapy, the authors examined the effects of a single pairing of d-AMPH and rehabilitative training on motor performance after cortical infarct in squirrel monkeys. Methods. Microelectrode stimulation techniques were used to delineate hand movement areas in the primary motor cortex prior to delivering a unilateral infarct to the complete hand representation. Postinfarct recovery was assessed for 3 groups of monkeys: d-AMPH + training, saline + training, and spontaneous recovery (SR). Postinfarct training groups received 14 consecutive days of motor...
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