Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation... more Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation. Severe TBI is commonly treated by a two-stage surgical intervention, where decompressive craniectomy is first conducted to remove a large portion of calvarial bone and allow unimpeded brain swelling. In the second surgery, spaced weeks to months after the first, cranioplasty is performed to restore the cranial bone. Hydrogels with paste-like precursor solutions for surgical placement may potentially revolutionize TBI treatment by permitting a single-stage surgical intervention, capable of being implanted with the initial surgery, remaining pliable during brain swelling, and tuned to regenerate calvarial bone after brain swelling has subsided. The current study evaluated the use of photocrosslinkable pentenoate-functionalized hyaluronic acid (PHA) and non-crosslinking hyaluronic acid (HA) hydrogels encapsulating naturally derived tissue particles of demineralized bone matrix (DBM), devi...
IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society, Jul 5, 2016
Brain-machine-body interfaces (BMBIs) aim to create an artificial connection in the nervous syste... more Brain-machine-body interfaces (BMBIs) aim to create an artificial connection in the nervous system by converting neural activity recorded from one cortical region to electrical stimuli delivered to another cortical region, spinal cord, or muscles in real-time. In particular, conditioning-mode BMBIs utilize such activity-dependent stimulation strategies to induce functional re-organization in the nervous system and promote functional recovery after injury by exploiting mechanisms underlying neuroplasticity. This paper reports on reconfigurable, field-programmable gate array (FPGA)-based implementation of a translation algorithm to extract multichannel stimulus trigger signals from intracortical neural spike activity. The approach features digital spike discrimination based on user-set thresholding and time-amplitude windowing, decision making to support different triggering patterns for various stimulation scenarios, as well as trigger-pattern-dependent blanking schemes for robust op...
Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement... more Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement are promising for filling complex geometries in craniofacial bone regeneration applications. Colloidal materials have demonstrated modest clinical outcomes as bone substitutes in orthopedic applications, but limited success in craniofacial applications. As such, development of a novel colloidal gel will fill a void in commercially available products for use in craniofacial reconstruction. One likely application for this technology is cranial reconstruction. Currently, traumatic brain injury (TBI) is often treated with a hemi-craniectomy, a procedure in which half the cranium is removed to allow the injured brain to swell and herniate beyond the enclosed cranial vault. The use of colloidal gels would allow for the design of a pliable material capable of expansion during brain swelling and facilitate cranial bone regeneration alleviating the need for a second surgery to replace the previo...
1) Determine if higher doses of motor therapy in chronic post-stroke hemiparesis result in better... more 1) Determine if higher doses of motor therapy in chronic post-stroke hemiparesis result in better outcomes compared to lower doses, and 2) Evaluate potential modifiers of the dose-response relationship. Eighty-five adults with UE paresis ≥ 6 months after stroke were randomized to one of four dose groups in this single-blind, parallel, RCT. The dosing parameter manipulated was amount of task-specific training, as indexed by the number of task repetitions. Groups received 3200, 6400, 9600, or Individualized Maximum (IM) repetitions, during 1 hr sessions, 4 days/week for 8 weeks. The intervention was an individualized, progressive task-specific upper limb training program designed to improve upper limb functional motor capacity. The primary outcome was the slope of the Action Research Arm Test (ARAT) during the intervention. Effects of dose and potential modifiers of the dose-response relationship were evaluated with hierarchical linear models. ARAT scores for the 3200, 9600, and IM ...
Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability... more Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynapti...
While adaptive processes in the cerebral cortex have long been thought to contribute to functiona... more While adaptive processes in the cerebral cortex have long been thought to contribute to functional recovery after stroke, the precise neuronal structures and mechanisms underlying these processes have been difficult to identify. Over the past 15 years, a large number of studies conducted in human stroke patients and in experimental animal models have contributed to a more coherent picture of the brain's adaptive capacity after injury. These studies suggest that the cerebral cortex undergoes significant and functional structural plasticity for at least several weeks to months following injury. Adaptive changes have been demonstrated in the intact tissue surrounding the lesion, as well as in other cortical motor areas remote from the site of injury. Recent results from non-human primate studies of cortical reorganization after stroke demonstrate marked functional changes in the intact cortical tissue adjacent to the infarct in the weeks following an ischemic lesion. Further, intensive task-specific practice with the impaired limb has a modulatory effect on the inevitable cortical plasticity. Taken together with parallel studies of forced use in human stroke patients, it is likely that use of the impaired limb can influence adaptive reorganizational mechanisms in the intact cerebral cortex, and thus, promote functional recovery.
ABSTRACT Background and Objectives: Reaching is one of the arm major functions and has poor recov... more ABSTRACT Background and Objectives: Reaching is one of the arm major functions and has poor recovery after stroke. Although kinematic metrics of reaching reflect “true” impairment after stroke, these metrics are largely ignored in functional MRI studies. In this study, we examined the relationship between motor–related activation of the primary motor cortex (or M1) and clinical and kinematic measures of arm motor impairment in chronic stage of stroke. We hypothesized that patients would show i) increased handgrip-related M1 activation, particularly for those with poor outcome, ii) decreased active range of elbow extension, and iii) M1 activation would be negatively related to clinical/kinematic metrics of arm motor impairment. We also hypothesized that M1 activation would be stronger correlated with kinematic than clinical metrics. Methods: Nineteen survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and twelve age-sex matched healthy participants underwent functional MRI assessment (TR=2000ms; TE=50ms; FOV=240mm; matrix=64x64; slice thickness=5mm; 0 skip; resolution=5x5mm2; 100 time points) during the impaired hand (dominant hand in controls) grip and kinematic assessment of elbow extension during a reach-to-gasp task (Vicon system). In patients, arm motor impairment was also evaluated using Fugl-Meyer Upper Extremity (FMUE) scale. Percentage change of blood oxygen level-dependent response (or activation) was measured in M1 contralateral to the tested hand (ipsilesional in patients). We focused on M1 given the strong previous evidences for its involvement in motor recovery after stroke and which should not be confused with the location of the subcortical lesion. Relationships between M1 activation and clinical and kinematic measures were determined. Results: Compared to controls, significant increase in activation of M1 contralateral to the tested hand (p=0.006) along with decrease in elbow extension (p<0.001) was observed in patients, particularly in those with poor outcome. In patients, M1 activation was negatively and significantly correlated with elbow extension (p=0.02) and tended to be negatively correlated with FMUE (p=0.06). Conclusions: Our preliminary results demonstrated that Kinematic metrics of reaching play a complementary role to the current clinical assessments and might increase our understanding of the neural mechanisms underlying altered reaching ability after stroke. Although kinematic analysis is time-consuming, we suggest that when an intervention appears to enhance recovery, the use of a combined approach, including fMRI and kinematic measures, will facilitate the distinction between recovery and compensation at both levels, neural and behavioral. This approach will be also extremely helpful to control for the effect of the possible variations in the task execution on the resulting cortical maps. This work was supported by American Heart Association (AHA Grant 0860041Z to CMC).
Current research in brain computer interface (BCI) technology is advancing beyond preclinical stu... more Current research in brain computer interface (BCI) technology is advancing beyond preclinical studies, with trials beginning in human patients. To date, these trials have been carried out with several different types of recording interfaces. The success of these devices has varied widely, but different factors such as the level of invasiveness, timescale of recorded information, and ability to maintain stable functionality of the device over a long period of time all must be considered in addition to accuracy in decoding intent when assessing the most practical type of device moving forward. Here, we discuss various approaches to BCIs, distinguishing between devices focusing on control of operations extrinsic to the subject (e.g., prosthetic limbs, computer cursors) and those focusing on control of operations intrinsic to the brain (e.g., using stimulation or external feedback), including closed-loop or adaptive devices. In this discussion, we consider the current challenges facing ...
The morphology of the somata originating the corticospinal tract was examined in 24 species of ma... more The morphology of the somata originating the corticospinal tract was examined in 24 species of mammals to identify commonalities and major sources of variation among the different species. Horseradish peroxidase was applied to a hemisection of the spinal cord at the C1-C2 junction. After tetramethylbenzidine processing, the labeled somata throughout the cerebral cortex were plotted and counted. Then, 23 morphological characteristics of the corticospinal somata were examined, including their number, size, and density across the cortical surface. The results show that morphological characteristics of corticospinal somata are closely related to an animal's body, brain, and cerebral cortex size. That is, mammals with large neocortical surfaces tend to have larger as well as more corticospinal somata; mammals with large bodies tend to have corticospinal somata that are less densely distributed. Moreover, the probable increase in the ratio of local noncorticospinal somata to corticospinal somata implies that the evolution of the corticospinal tract was accomplished by an increase in "support" or "server" cells as well as an increase in the size of the tract itself. The results also show that several characteristics are reliably related to an animal's taxonomic classification and hence its ancestry. Comparisons among three mammalian lineages indicate that some characteristics may have changed uniquely in the anthropoid primate lineage, and thus, presumably, in the human lineage. The results suggest that if morphological characteristics of the corticospinal tract important in the evolution of the specialized motor abilities in anthropoid primates are sought, then examination of the role of changes in soma diameter, rostral (motor)/caudal (sensory) ratios of density, concentration, surface density, and volume density may be more instructive than examination of the total number of corticospinal neurons alone.
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.
The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor c... more The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.
Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation... more Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation. Severe TBI is commonly treated by a two-stage surgical intervention, where decompressive craniectomy is first conducted to remove a large portion of calvarial bone and allow unimpeded brain swelling. In the second surgery, spaced weeks to months after the first, cranioplasty is performed to restore the cranial bone. Hydrogels with paste-like precursor solutions for surgical placement may potentially revolutionize TBI treatment by permitting a single-stage surgical intervention, capable of being implanted with the initial surgery, remaining pliable during brain swelling, and tuned to regenerate calvarial bone after brain swelling has subsided. The current study evaluated the use of photocrosslinkable pentenoate-functionalized hyaluronic acid (PHA) and non-crosslinking hyaluronic acid (HA) hydrogels encapsulating naturally derived tissue particles of demineralized bone matrix (DBM), devi...
IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society, Jul 5, 2016
Brain-machine-body interfaces (BMBIs) aim to create an artificial connection in the nervous syste... more Brain-machine-body interfaces (BMBIs) aim to create an artificial connection in the nervous system by converting neural activity recorded from one cortical region to electrical stimuli delivered to another cortical region, spinal cord, or muscles in real-time. In particular, conditioning-mode BMBIs utilize such activity-dependent stimulation strategies to induce functional re-organization in the nervous system and promote functional recovery after injury by exploiting mechanisms underlying neuroplasticity. This paper reports on reconfigurable, field-programmable gate array (FPGA)-based implementation of a translation algorithm to extract multichannel stimulus trigger signals from intracortical neural spike activity. The approach features digital spike discrimination based on user-set thresholding and time-amplitude windowing, decision making to support different triggering patterns for various stimulation scenarios, as well as trigger-pattern-dependent blanking schemes for robust op...
Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement... more Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement are promising for filling complex geometries in craniofacial bone regeneration applications. Colloidal materials have demonstrated modest clinical outcomes as bone substitutes in orthopedic applications, but limited success in craniofacial applications. As such, development of a novel colloidal gel will fill a void in commercially available products for use in craniofacial reconstruction. One likely application for this technology is cranial reconstruction. Currently, traumatic brain injury (TBI) is often treated with a hemi-craniectomy, a procedure in which half the cranium is removed to allow the injured brain to swell and herniate beyond the enclosed cranial vault. The use of colloidal gels would allow for the design of a pliable material capable of expansion during brain swelling and facilitate cranial bone regeneration alleviating the need for a second surgery to replace the previo...
1) Determine if higher doses of motor therapy in chronic post-stroke hemiparesis result in better... more 1) Determine if higher doses of motor therapy in chronic post-stroke hemiparesis result in better outcomes compared to lower doses, and 2) Evaluate potential modifiers of the dose-response relationship. Eighty-five adults with UE paresis ≥ 6 months after stroke were randomized to one of four dose groups in this single-blind, parallel, RCT. The dosing parameter manipulated was amount of task-specific training, as indexed by the number of task repetitions. Groups received 3200, 6400, 9600, or Individualized Maximum (IM) repetitions, during 1 hr sessions, 4 days/week for 8 weeks. The intervention was an individualized, progressive task-specific upper limb training program designed to improve upper limb functional motor capacity. The primary outcome was the slope of the Action Research Arm Test (ARAT) during the intervention. Effects of dose and potential modifiers of the dose-response relationship were evaluated with hierarchical linear models. ARAT scores for the 3200, 9600, and IM ...
Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability... more Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynapti...
While adaptive processes in the cerebral cortex have long been thought to contribute to functiona... more While adaptive processes in the cerebral cortex have long been thought to contribute to functional recovery after stroke, the precise neuronal structures and mechanisms underlying these processes have been difficult to identify. Over the past 15 years, a large number of studies conducted in human stroke patients and in experimental animal models have contributed to a more coherent picture of the brain's adaptive capacity after injury. These studies suggest that the cerebral cortex undergoes significant and functional structural plasticity for at least several weeks to months following injury. Adaptive changes have been demonstrated in the intact tissue surrounding the lesion, as well as in other cortical motor areas remote from the site of injury. Recent results from non-human primate studies of cortical reorganization after stroke demonstrate marked functional changes in the intact cortical tissue adjacent to the infarct in the weeks following an ischemic lesion. Further, intensive task-specific practice with the impaired limb has a modulatory effect on the inevitable cortical plasticity. Taken together with parallel studies of forced use in human stroke patients, it is likely that use of the impaired limb can influence adaptive reorganizational mechanisms in the intact cerebral cortex, and thus, promote functional recovery.
ABSTRACT Background and Objectives: Reaching is one of the arm major functions and has poor recov... more ABSTRACT Background and Objectives: Reaching is one of the arm major functions and has poor recovery after stroke. Although kinematic metrics of reaching reflect “true” impairment after stroke, these metrics are largely ignored in functional MRI studies. In this study, we examined the relationship between motor–related activation of the primary motor cortex (or M1) and clinical and kinematic measures of arm motor impairment in chronic stage of stroke. We hypothesized that patients would show i) increased handgrip-related M1 activation, particularly for those with poor outcome, ii) decreased active range of elbow extension, and iii) M1 activation would be negatively related to clinical/kinematic metrics of arm motor impairment. We also hypothesized that M1 activation would be stronger correlated with kinematic than clinical metrics. Methods: Nineteen survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and twelve age-sex matched healthy participants underwent functional MRI assessment (TR=2000ms; TE=50ms; FOV=240mm; matrix=64x64; slice thickness=5mm; 0 skip; resolution=5x5mm2; 100 time points) during the impaired hand (dominant hand in controls) grip and kinematic assessment of elbow extension during a reach-to-gasp task (Vicon system). In patients, arm motor impairment was also evaluated using Fugl-Meyer Upper Extremity (FMUE) scale. Percentage change of blood oxygen level-dependent response (or activation) was measured in M1 contralateral to the tested hand (ipsilesional in patients). We focused on M1 given the strong previous evidences for its involvement in motor recovery after stroke and which should not be confused with the location of the subcortical lesion. Relationships between M1 activation and clinical and kinematic measures were determined. Results: Compared to controls, significant increase in activation of M1 contralateral to the tested hand (p=0.006) along with decrease in elbow extension (p<0.001) was observed in patients, particularly in those with poor outcome. In patients, M1 activation was negatively and significantly correlated with elbow extension (p=0.02) and tended to be negatively correlated with FMUE (p=0.06). Conclusions: Our preliminary results demonstrated that Kinematic metrics of reaching play a complementary role to the current clinical assessments and might increase our understanding of the neural mechanisms underlying altered reaching ability after stroke. Although kinematic analysis is time-consuming, we suggest that when an intervention appears to enhance recovery, the use of a combined approach, including fMRI and kinematic measures, will facilitate the distinction between recovery and compensation at both levels, neural and behavioral. This approach will be also extremely helpful to control for the effect of the possible variations in the task execution on the resulting cortical maps. This work was supported by American Heart Association (AHA Grant 0860041Z to CMC).
Current research in brain computer interface (BCI) technology is advancing beyond preclinical stu... more Current research in brain computer interface (BCI) technology is advancing beyond preclinical studies, with trials beginning in human patients. To date, these trials have been carried out with several different types of recording interfaces. The success of these devices has varied widely, but different factors such as the level of invasiveness, timescale of recorded information, and ability to maintain stable functionality of the device over a long period of time all must be considered in addition to accuracy in decoding intent when assessing the most practical type of device moving forward. Here, we discuss various approaches to BCIs, distinguishing between devices focusing on control of operations extrinsic to the subject (e.g., prosthetic limbs, computer cursors) and those focusing on control of operations intrinsic to the brain (e.g., using stimulation or external feedback), including closed-loop or adaptive devices. In this discussion, we consider the current challenges facing ...
The morphology of the somata originating the corticospinal tract was examined in 24 species of ma... more The morphology of the somata originating the corticospinal tract was examined in 24 species of mammals to identify commonalities and major sources of variation among the different species. Horseradish peroxidase was applied to a hemisection of the spinal cord at the C1-C2 junction. After tetramethylbenzidine processing, the labeled somata throughout the cerebral cortex were plotted and counted. Then, 23 morphological characteristics of the corticospinal somata were examined, including their number, size, and density across the cortical surface. The results show that morphological characteristics of corticospinal somata are closely related to an animal's body, brain, and cerebral cortex size. That is, mammals with large neocortical surfaces tend to have larger as well as more corticospinal somata; mammals with large bodies tend to have corticospinal somata that are less densely distributed. Moreover, the probable increase in the ratio of local noncorticospinal somata to corticospinal somata implies that the evolution of the corticospinal tract was accomplished by an increase in "support" or "server" cells as well as an increase in the size of the tract itself. The results also show that several characteristics are reliably related to an animal's taxonomic classification and hence its ancestry. Comparisons among three mammalian lineages indicate that some characteristics may have changed uniquely in the anthropoid primate lineage, and thus, presumably, in the human lineage. The results suggest that if morphological characteristics of the corticospinal tract important in the evolution of the specialized motor abilities in anthropoid primates are sought, then examination of the role of changes in soma diameter, rostral (motor)/caudal (sensory) ratios of density, concentration, surface density, and volume density may be more instructive than examination of the total number of corticospinal neurons alone.
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.
The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor c... more The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.
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