Elizabeth C. Tyler-Kabara

High-performance neuroprosthetic control by an individual with tetraplegia.

BACKGROUND Paralysis or amputation of an arm results in the loss of the ability to orient the hand and grasp, manipulate, and carry objects, functions that are essential for activities of daily living. Brain-machine interfaces could provide a solution to restoring many of these lost functions. We therefore tested whether an individual with tetraplegia could rapidly achieve neurological control of a high-performance prosthetic limb using this type of an interface. METHODS We implanted two 96-channel intracortical microelectrodes in the motor cortex of a 52-year-old individual with tetraplegia. Brain-machine-interface training was done for 13 weeks with the goal of controlling an anthropomorphic prosthetic limb with seven degrees of freedom (three-dimensional translation, three-dimensional orientation, one-dimensional grasping). The participants ability to control the prosthetic limb was assessed with clinical measures of upper limb function. This study is registered with ClinicalTrials.gov, NCT01364480. FINDINGS The participant was able to move the prosthetic limb freely in the three-dimensional workspace on the second day of training. After 13 weeks, robust seven-dimensional movements were performed routinely. Mean success rate on target-based reaching tasks was 91·6% (SD 4·4) versus median chance level 6·2% (95% CI 2·0-15·3). Improvements were seen in completion time (decreased from a mean of 148 s [SD 60] to 112 s [6]) and path efficiency (increased from 0·30 [0·04] to 0·38 [0·02]). The participant was also able to use the prosthetic limb to do skilful and coordinated reach and grasp movements that resulted in clinically significant gains in tests of upper limb function. No adverse events were reported. INTERPRETATION With continued development of neuroprosthetic limbs, individuals with long-term paralysis could recover the natural and intuitive command signals for hand placement, orientation, and reaching, allowing them to perform activities of daily living. FUNDING Defense Advanced Research Projects Agency, National Institutes of Health, Department of Veterans Affairs, and UPMC Rehabilitation Institute.

An electrocorticographic brain interface in an individual with tetraplegia.

Brain-computer interface (BCI) technology aims to help individuals with disability to control assistive devices and reanimate paralyzed limbs. Our study investigated the feasibility of an electrocorticography (ECoG)-based BCI system in an individual with tetraplegia caused by C4 level spinal cord injury. ECoG signals were recorded with a high-density 32-electrode grid over the hand and arm area of the left sensorimotor cortex. The participant was able to voluntarily activate his sensorimotor cortex using attempted movements, with distinct cortical activity patterns for different segments of the upper limb. Using only brain activity, the participant achieved robust control of 3D cursor movement. The ECoG grid was explanted 28 days post-implantation with no adverse effect. This study demonstrates that ECoG signals recorded from the sensorimotor cortex can be used for real-time device control in paralyzed individuals.

Neural constraints on learning

Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain–computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain–computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess.

Neural Interface Technology for Rehabilitation: Exploiting and Promoting Neuroplasticity

This article reviews neural interface technology and its relationship with neuroplasticity. Two types of neural interface technology are reviewed, highlighting specific technologies that the authors directly work with: (1) neural interface technology for neural recording, such as the micro-ECoG BCI system for hand prosthesis control, and the comprehensive rehabilitation paradigm combining MEG-BCI, action observation, and motor imagery training; (2) neural interface technology for functional neural stimulation, such as somatosensory neural stimulation for restoring somatosensation, and non-invasive cortical stimulation using rTMS and tDCS for modulating cortical excitability and stroke rehabilitation. The close interaction between neural interface devices and neuroplasticity leads to increased efficacy of neural interface devices and improved functional recovery of the nervous system. This symbiotic relationship between neural interface technology and the nervous system is expected to maximize functional gain for individuals with various sensory, motor, and cognitive impairments, eventually leading to better quality of life.

Ten-dimensional anthropomorphic arm control in a human brain−machine interface: difficulties, solutions, and limitations

OBJECTIVE In a previous study we demonstrated continuous translation, orientation and one-dimensional grasping control of a prosthetic limb (seven degrees of freedom) by a human subject with tetraplegia using a brain-machine interface (BMI). The current study, in the same subject, immediately followed the previous work and expanded the scope of the control signal by also extracting hand-shape commands from the two 96-channel intracortical electrode arrays implanted in the subjects left motor cortex. APPROACH Four new control signals, dictating prosthetic hand shape, replaced the one-dimensional grasping in the previous study, allowing the subject to control the prosthetic limb with ten degrees of freedom (three-dimensional (3D) translation, 3D orientation, four-dimensional hand shaping) simultaneously. MAIN RESULTS Robust neural tuning to hand shaping was found, leading to ten-dimensional (10D) performance well above chance levels in all tests. Neural unit preferred directions were broadly distributed through the 10D space, with the majority of units significantly tuned to all ten dimensions, instead of being restricted to isolated domains (e.g. translation, orientation or hand shape). The addition of hand shaping emphasized object-interaction behavior. A fundamental component of BMIs is the calibration used to associate neural activity to intended movement. We found that the presence of an object during calibration enhanced successful shaping of the prosthetic hand as it closed around the object during grasping. SIGNIFICANCE Our results show that individual motor cortical neurons encode many parameters of movement, that object interaction is an important factor when extracting these signals, and that high-dimensional operation of prosthetic devices can be achieved with simple decoding algorithms. ClinicalTrials.gov Identifier: NCT01364480.

Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients

OBJECT The proximity of craniopharyngiomas to vital neurovascular structures and their high recurrence rates make them one of the most challenging and controversial management dilemmas in neurosurgery. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for both pediatric and adult craniopharyngiomas. The object of the present study was to present the results of EES and analyze outcome in both the pediatric and the adult age groups. METHODS The authors retrospectively reviewed the records of patients with craniopharyngioma who had undergone EES in the period from June 1999 to April 2011. RESULTS Sixty-four patients, 47 adults and 17 children, were eligible for this study. Forty-seven patients had presented with primary craniopharyngiomas and 17 with recurrent tumors. The mean age in the adult group was 51 years (range 28-82 years); in the pediatric group, 9 years (range 4-18 years). Overall, the gross-total resection rate was 37.5% (24 patients); near-total resection (> 95% of tumor removed) was 34.4% (22 patients); subtotal resection (≥ 80% of tumor removed) 21.9% (14 patients); and partial resection (< 80% of tumor removed) 6.2% (4 patients). In 9 patients, EES had been combined with radiation therapy (with radiosurgery in 6 cases) as the initial treatment. Among the 40 patients (62.5%) who had presented with pituitary insufficiency, pituitary function remained unchanged in 19 (47.5%), improved or normalized in 8 (20%), and worsened in 13 (32.5%). In the 24 patients who had presented with normal pituitary function, new pituitary deficit occurred in 14 (58.3%). Nineteen patients (29.7%) suffered from diabetes insipidus at presentation, and the condition developed in 21 patients (46.7%) after treatment. Forty-four patients (68.8%) had presented with impaired vision. In 38 (86.4%) of them, vision improved or even normalized after surgery; in 5, it remained unchanged; and in 1, it temporarily worsened. One patient without preoperative visual problems showed temporary visual deterioration after treatment. Permanent visual deterioration occurred in no one after surgery. The mean follow-up was 38 months (range 1-135 months). Tumor recurrence after EES was discovered in 22 patients (34.4%) and was treated with repeat surgery (6 patients), radiosurgery (1 patient), combined repeat surgery and radiation therapy (8 patients), interferon (1 patient), or observation (6 patients). Surgical complications included 15 cases (23.4%) with CSF leakage that was treated with surgical reexploration (13 patients) and/or lumbar drain placement (9 patients). This leak rate was decreased to 10.6% in recent years after the introduction of the vascularized nasoseptal flap. Five cases (7.8%) of meningitis were found and treated with antibiotics without further complications. Postoperative hydrocephalus occurred in 7 patients (12.7%) and was treated with ventriculoperitoneal shunt placement. Five patients experienced transient cranial nerve palsies. There was no operative mortality. CONCLUSIONS With the goal of gross-total or maximum possible safe resection, EES can be used for the treatment of every craniopharyngioma, regardless of its location, size, and extension (excluding purely intraventricular tumors), and can provide acceptable results comparable to those for traditional craniotomies. Endoscopic endonasal surgery is not limited to adults and actually shows higher resection rates in the pediatric population.

Intracortical microstimulation of human somatosensory cortex

Tactile percepts were consistently elicited in the hand of a person with cervical spinal cord injury using intracortical microstimulation of the somatosensory cortex. A sense of touch Touch is essential for hand use. Yet, brain-controlled prosthetic limbs have not been endowed with this critical sense. In a new study by Flesher et al., microelectrode arrays were implanted into the primary somatosensory cortex of a person with spinal cord injury and, by delivering current through the electrodes, generated sensations of touch that were perceived as coming from his own paralyzed hand. These sensations often felt like pressure, could be graded in intensity, and were stable for months. The authors suggest that this approach could be used to convey information about contact location and pressure necessary for prosthetic hands to interact with objects. Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation.

Human motor cortical activity recorded with Micro-ECoG electrodes, during individual finger movements

In this study human motor cortical activity was recorded with a customized micro-ECoG grid during individual finger movements. The quality of the recorded neural signals was characterized in the frequency domain from three different perspectives: (1) coherence between neural signals recorded from different electrodes, (2) modulation of neural signals by finger movement, and (3) accuracy of finger movement decoding. It was found that, for the high frequency band (60–120 Hz), coherence between neighboring micro-ECoG electrodes was 0.3. In addition, the high frequency band showed significant modulation by finger movement both temporally and spatially, and a classification accuracy of 73% (chance level: 20%) was achieved for individual finger movement using neural signals recorded from the micro-ECoG grid. These results suggest that the micro-ECoG grid presented here offers sufficient spatial and temporal resolution for the development of minimally-invasive brain-computer interface applications.

Slit-ventricle syndrome secondary to shunt-induced suture ossification.

OBJECTIVETo report five children with slit-ventricle syndrome who were found to have increased intracranial pressure despite functioning cerebrospinal fluid shunts. METHODSComputed tomographic scans demonstrated erosion of the inner table of the cranium and sclerosis of the cranial sutures, particularly the coronal suture. Magnetic resonance imaging scans demonstrated no cerebrospinal fluid over the convexities. The patients were treated with cranial expansion operations that included removal of the sclerotic sutures, which were examined histologically. RESULTSPostoperatively, symptoms resolved for all children. Sutures were abnormal and contained foci of cartilage and bone within abnormally arranged fibrous tissue. CONCLUSIONWe postulate that chronic overdrainage of cerebrospinal fluid via shunts dampens the normal cerebral pressure waves; growth of the calvarium is thus understimulated, and this leads to ossification of the sutures, which become unable to expand to allow normal brain growth. Shunt-induced craniostenosis should be considered for children with symptoms of slit-ventricle syndrome for whom shunts are functional but intracranial pressure is increased. Cranial expansion operations may be more appropriate treatments than subtemporal decompressions for such children, given the diffuseness of the suture pathological features.

Relationship Between Hyperglycemia and Outcome in Children with Severe Traumatic Brain Injury

Objective: To determine the relationship between hyperglycemia and outcome in infants and children after severe traumatic brain injury. Design: Retrospective review of a prospectively collected Pediatric Neurotrauma Registry. Setting and Patients: Children admitted after severe traumatic brain injury (postresuscitation Glasgow Coma Scale ⩽8) were studied (1999–2004). A subset of children (n = 28) were concurrently enrolled in a randomized, controlled clinical trial of early hypothermia for neuroprotection. Interventions: Demographic data, serum glucose concentrations, and outcome assessments were collected. Methods and Main Results: Children (n = 57) were treated with a standard traumatic brain injury protocol. Exogenous glucose was withheld for 48 hrs after injury unless hypoglycemia was observed (blood glucose <70 mg/dL). Early (first 48 hrs) and Late (49–168 hrs) time periods were defined and mean blood glucose concentrations were calculated. Additionally, children were categorized based on peak blood glucose concentrations during each time period (normal, blood glucose <150 mg/dL; mild hyperglycemia, blood glucose ⩽200 mg/dL; severe hyperglycemia, blood glucose >200 mg/dL). In the Late period, an association between elevated mean serum glucose concentration and outcome was observed (133.5 ± 5.6 mg/dL in the unfavorable group vs. 115.4 ± 4.1 mg/dL in favorable group, p = .02). This association continued to be significant after correcting for injury severity, age, and exposure to insulin (p = .03). Similarly, in the Late period, children within the severe hyperglycemia group had decreased incidence of good outcome compared to children within the other glycemic groups (% good outcome: normal, 61.9%; mild hyperglycemia, 73.7%; severe hyperglycemia, 33.3%; p = .05). However, when adjusted for exposure to insulin, this relationship was no longer statistically significant. Conclusions: In children with severe traumatic brain injury, hyperglycemia beyond the initial 48 hrs is associated with poor outcome. This relationship was observed in both our analysis of mean blood glucose concentrations as well as among the patients with episodic severe hyperglycemia. This observation suggests a relationship between hyperglycemia and outcome from traumatic brain injury. However, only a prospective study can answer the important question of whether manipulating serum glucose concentration can improve outcome after traumatic brain injury in children.