Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements. Main Outcome Measures: Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES. Results: With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects. Conclusions: Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics

Models of Traumatic Cerebellar Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective

Dexterous Control of Seven Functional Hand Movements Using Cortically-Controlled Transcutaneous Muscle Stimulation in a Person With Tetraplegia

Individuals with tetraplegia identify restoration of hand function as a critical, unmet need to regain their independence and improve quality of life. Brain-Computer Interface (BCI)-controlled Functional Electrical Stimulation (FES) technology addresses this need by reconnecting the brain with paralyzed limbs to restore function. In this study, we quantified performance of an intuitive, cortically-controlled, transcutaneous FES system on standardized object manipulation tasks from the Grasp and Release Test (GRT). We found that a tetraplegic individual could use the system to control up to seven functional hand movements, each with >95% individual accuracy. He was able to select one movement from the possible seven movements available to him and use it to appropriately manipulate all GRT objects in real-time using naturalistic grasps. With the use of the system, the participant not only improved his GRT performance over his baseline, demonstrating an increase in number of transfers for all objects except the Block, but also significantly improved transfer times for the heaviest objects (videocassette (VHS), Can). Analysis of underlying motor cortex neural representations associated with the hand grasp states revealed an overlap or non-separability in neural activation patterns for similarly shaped objects that affected BCI-FES performance. These results suggest that motor cortex neural representations for functional grips are likely more related to hand shape and force required to hold objects, rather than to the objects themselves. These results, demonstrating multiple, naturalistic functional hand movements with the BCI-FES, constitute a further step toward translating BCI-FES technologies from research devices to clinical neuroprosthetics

Extracting wavelet based neural features from human intracortical recordings for neuroprosthetics applications

Abstract Background Understanding the long-term behavior of intracortically-recorded signals is essential for improving the performance of Brain Computer Interfaces. However, few studies have systematically investigated chronic neural recordings from an implanted microelectrode array in the human brain. Methods In this study, we show the applicability of wavelet decomposition method to extract and demonstrate the utility of long-term stable features in neural signals obtained from a microelectrode array implanted in the motor cortex of a human with tetraplegia. Wavelet decomposition was applied to the raw voltage data to generate mean wavelet power (MWP) features, which were further divided into three sub-frequency bands, low-frequency MWP (lf-MWP, 0–234 Hz), mid-frequency MWP (mf-MWP, 234 Hz–3.75 kHz) and high-frequency MWP (hf-MWP, >3.75 kHz). We analyzed these features using data collected from two experiments that were repeated over the course of about 3 years and compared their signal stability and decoding performance with the more standard threshold crossings, local field potentials (LFP), multi-unit activity (MUA) features obtained from the raw voltage recordings. Results All neural features could stably track neural information for over 3 years post-implantation and were less prone to signal degradation compared to threshold crossings. Furthermore, when used as an input to support vector machine based decoding algorithms, the mf-MWP and MUA demonstrated significantly better performance, respectively, in classifying imagined motor tasks than using the lf-MWP, hf-MWP, LFP, or threshold crossings. Conclusions Our results suggest that using MWP features in the appropriate frequency bands can provide an effective neural feature for brain computer interface intended for chronic applications. Trial registration This study was approved by the U.S. Food and Drug Administration (Investigational Device Exemption) and the Ohio State University Medical Center Institutional Review Board (Columbus, Ohio). The study conformed to institutional requirements for the conduct of human subjects and was filed on ClinicalTrials.gov (Identifier NCT01997125)

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification