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Biomedical subjects

Jiping He

Publications and source records attributed to Jiping He.

18 recordsLinked to original sources

Recent developments in biofeedback for neuromotor rehabilitation.

The original use of biofeedback to train single muscle activity in static positions or movement unrelated to function did not correlate well to motor function improvements in patients with central nervous system injuries. The concept of task-oriented repetitive training suggests that biofeedback therapy should be delivered during functionally related dynamic movement to optimize motor function improvement. Current, advanced technologies facilitate the design of novel biofeedback systems that possess diverse parameters, advanced cue display, and sophisticated control systems for use in task-oriented biofeedback. In light of these advancements, this article: (1) reviews early biofeedback studies and their conclusions; (2) presents recent developments in biofeedback technologies and their applications to task-oriented biofeedback interventions; and (3) discusses considerations regarding the therapeutic system design and the clinical application of task-oriented biofeedback therapy. This review should provide a framework to further broaden the application of task-oriented biofeedback therapy in neuromotor rehabilitation.

Journal Article↗

Selection and parameterization of cortical neurons for neuroprosthetic control.

When designing neuroprosthetic interfaces for motor function, it is crucial to have a system that can extract reliable information from available neural signals and produce an output suitable for real life applications. Systems designed to date have relied on establishing a relationship between neural discharge patterns in motor cortical areas and limb movement, an approach not suitable for patients who require such implants but who are unable to provide proper motor behavior to initially tune the system. We describe here a method that allows rapid tuning of a population vector-based system for neural control without arm movements. We trained highly motivated primates to observe a 3D center-out task as the computer played it very slowly. Based on only 10-12 s of neuronal activity observed in M1 and PMd, we generated an initial mapping between neural activity and device motion that the animal could successfully use for neuroprosthetic control. Subsequent tunings of the parameters led to improvements in control, but the initial selection of neurons and estimated preferred direction for those cells remained stable throughout the remainder of the day. Using this system, we have observed that the contribution of individual neurons to the overall control of the system is very heterogeneous. We thus derived a novel measure of unit quality and an indexing scheme that allowed us to rate each neuron's contribution to the overall control. In offline tests, we found that fewer than half of the units made positive contributions to the performance. We tested this experimentally by having the animals control the neuroprosthetic system using only the 20 best neurons. We found that performance in this case was better than when the entire set of available neurons was used. Based on these results, we believe that, with careful task design, it is feasible to parameterize control systems without any overt behaviors and that subsequent control system design will be enhanced with cautious unit selection. These improvements can lead to systems demanding lower bandwidth and computational power, and will pave the way for more feasible clinical systems.

Action Potentials↗

Cooperation of spike timing-dependent and heterosynaptic plasticities in neural networks: a Fokker-Planck approach.

It is believed that both Hebbian and homeostatic mechanisms are essential in neural learning. While Hebbian plasticity selectively modifies synaptic connectivity according to activity experienced, homeostatic plasticity constrains this change so that neural activity is always within reasonable physiological limits. Recent experiments reveal spike timing-dependent plasticity (STDP) as a new type of Hebbian learning with high time precision and heterosynaptic plasticity (HSP) as a new homeostatic mechanism acting directly on synapses. Here, we study the effect of STDP and HSP on randomly connected neural networks. Despite the reported successes of STDP to account for neural activities at the single-cell level, we find that, surprisingly, at the network level, networks trained using STDP alone cannot seem to generate realistic neural activities. For instance, STDP would stipulate that past sensory experience be maintained forever if it is no longer activated. To overcome this difficulty, motivated by the fact that HSP can induce strong competition between sensory experiences, we propose a biophysically plausible learning rule by combining STDP and HSP. Based on the Fokker-Planck theory and extensive numerical computations, we demonstrate that HSP and STDP operated on different time scales can complement each other, resulting in more realistic network activities. Our finding may provide fresh insight into the learning mechanism of the brain.

Action Potentials↗

Modulation effects of epidural spinal cord stimulation on muscle activities during walking.

Epidural spinal cord stimulation (ESCS) combined with partial weight bearing therapy (PWBT) has been reported to facilitate recovery of functional walking for individuals after chronic incomplete spinal cord injury (ISCI). Muscle activities were analyzed in this report to examine the modulation effect of ESCS on muscle recruitment during gait training. Two ISCI individuals participated in the study and both are classified as ASIA C with low motor scores in the lower limbs. Stimulating electrodes were placed at the epidural space over T10-L2 spinal segments, along the midline in participant 1 (S1), and off-midline in participant 2 (S2). Surface electromyograms (EMGs) from leg muscles under both ESCS ON and OFF conditions recorded during treadmill gait were analyzed in time-frequency domains. ESCS application produced acute modulations in muscle activities in both participants, but the observed pattern, magnitude, and spectral content of the EMGs differed. In S1, ESCS induced a significant shift in the temporal pattern of muscle activity toward normal comparing with that when ESCS was OFF, though without eliciting noticeable change in frequency distribution between ESCS ON and OFF conditions. When ESCS was applied in S2, a modulation of EMG magnitude was observed and, consequently, improved joint kinematics during walking. In this case, a stimulation entrainment appeared in time-frequency analysis. The results suggest that ESCS activates neural structures in the dorsal aspect of the spinal cord and facilitates gait-related muscle recruitment. The exact effects of ESCS depend on the electrode placement and possibly injury history and residual functions, but in general ESCS produces a positive effect on improved walking speed, endurance, and reduced sense of effort in both ISCI subjects.

Adult↗

Control of hand orientation and arm movement during reach and grasp.

We studied the coordination of arm and wrist motion in a task requiring fine control of hand orientation. Subjects were instructed to reach and grasp one of two targets positioned in the frontal plane at various orientations. The task was performed under three target conditions: fixed orientation, predictably perturbed orientation, and randomly perturbed orientation. For fixed target orientations, the hand began to rotate to the required orientation from the beginning of the reach. Hand peak supination angles scaled linearly with target orientations. The trajectories of hand/arm joint angles also had a one-to-one relationship with different target orientations. These demonstrate that target orientation is a constraint on the hand/arm final orientation, a control variable to be specified in advance by the central nervous system (CNS). Under perturbation conditions, subjects were still able to complete the task smoothly. In the early trials of the predictable perturbation, the hand rotated first to the original target orientation and then corrected for the final target orientation. Initial corrections occurred about 200 ms after the onset of perturbation. This latency decreased as the subjects adapted to the perturbation, and the hand orientation trajectory shifted to match the unperturbed trajectory for the final orientation. By contrast, we observed no clear changes in orientation trajectory under the randomly perturbed conditions. These suggest that feedback control is important to the execution of the movement, but that the CNS tends to optimize feedforward planning rather than feedback correction when the disturbance information is predictable.

Adult↗

Determining natural arm configuration along a reaching trajectory.

Owing to the flexibility and redundancy of neuromuscular and skeletal systems, humans can trace the same hand trajectory in space with various arm configurations. However, the joint trajectories of typical unrestrained movements tend to be consistent both within and across subjects. In this paper we propose a method to solve the 3-D inverse kinematics problem based on minimizing the magnitude of total work done by joint torques. We examined the fit of the joint-space trajectories against those observed from human performance in a variety of movement paths in 3-D workspace. The results showed that the joint-space trajectories produced by the method are in good agreement with the subjects' arm movements (r2>0.98), with the exception of shoulder adduction/abduction (where, in the worst case, r2 approximately 0.8). Comparison of humeral rotation predicted by our algorithm with other models showed that the correlation coefficient r2) between actual data and our predictions is extremely high (mostly >0.98, 11 out of 15 cases, with a few exceptions, 4 of 15, in the range of 0.8-0.9) and the slope of linear regression is much closer to one (<0.05 distortion in 12 out of 15 cases, with only one case >0.15). However, the discrepancy in shoulder adduction/abduction indicated that when only the hand path is known, additional constraint(s) may be required to generate a complete match with human performance.

Algorithms↗

Closed-loop cortical control of direction using support vector machines.

Motor neuroprosthetics research has focused on reproducing natural limb motions by correlating firing rates of cortical neurons to continuous movement parameters. We propose an alternative system where specific spatial-temporal spike patterns, emerging in tasks, allow detection of classes of behavior with the aid of sophisticated nonlinear classification algorithms. Specifically, we attempt to examine ensemble activity from motor cortical neurons, not to reproduce the action this neural activity normally precedes, but rather to predict an output supervisory command to potentially control a vehicle. To demonstrate the principle, this design approach was implemented in a discrete directional task taking a small number of motor cortical signals (8-10 single units) fed into a support vector machine (SVM) to produce the commands Left and Right. In this study, rats were placed in a conditioning chamber performing a binary paddle pressing task mimicking the control of a wheelchair turning left or right. Four animal subjects (male Sprague-Dawley rats) were able to use such a brain-machine interface (BMI) with an average accuracy of 78% on their first day of exposure. Additionally, one animal continued to use the interface for three consecutive days with an average accuracy over 90%.

Algorithms↗

Feature detection in motor cortical spikes by principal component analysis.

Principal component analysis was performed on recorded neural spike trains in rats' motor cortices when rats were involved in real-time control tasks using brain-machine interfaces. The rat with implanted microelectrode array was placed in a conditioning chamber, but freely moving, to decide which one of the two paddles should be activated to shift the cue light to the center. It is found that the principal component feature vectors revealed the importance of individual neurons and windows of time in the decision making process. In addition, one of the first principal components has much higher discriminative capability than others, although it represents only a small percentage of the total variance in the data. Using one to six principal components with a Bayes classifier achieved classification accuracy comparable to that obtained by a more sophisticated high performance support vector classifier.

Action Potentials↗

Millisecond-accurate synchronization of visual stimulus displays for cognitive research.

A widely adopted approach in cognitive psychology research is to analyze changes in the response time to a stimulus onset in order to infer information about the cognitive functioning of a subject being tested. But current techniques have inherent variations in the timing between stimulus activation and stimulus display of up to tens of milliseconds, thereby introducing significant errors when response time or the latency of neural responses is measured. This article presents a novel yet easy-to-implement solution for improving resolution in the synchronizing of stimulus activation and stimulus display. Unlike traditional methods in which the stimulus onset is set as the time at which the routine for displaying the stimulus is called, this approach uses DirectX to monitor the scan line of CRTs and sets the stimulus onset to the time at which the scan line arrives at the position where the stimulus is to be drawn. This approach removes the uncertainty involved in having a time delay between the activation of the display routine and the actual time at which the display occurs, improving the accuracy of response time and latency period measurements to within 200 microsec. With a specially developed driver, this solution can generate a trigger signal synchronized precisely with the stimulus onset in all popular Windows systems (including Windows 2000/XP).

Cognition↗

Biocompatible benzocyclobutene (BCB)-based neural implants with micro-fluidic channel.

Poly-benzocyclobutene (BCB)-based intracortical neural implant was fabricated, in which micro-fluidic channel was embedded to deliver drug solutions. BCB presents several attractive features for chronic applications: flexibility, biocompatibility, desirable chemical and electrical properties, and can be easily manufactured using existing batch micro-fabrication technology. The fabricated implants have single shank with three recording sites (20 microm x 20 microm) and two reserviors (inlet and outlet). The channel had large volume (40 microm width and 10 microm height), and hydrophobic surface to provide a high degree of chemical inertness. All the recording sites were positioned near the end of the shank in order to increase the probability of recording neural signals from a target volume of tissue. In vitro cytotoxicity tests of prototype implants revealed no adverse toxic effects on cultured cells. The implant with a silicon backbone layer of 5-10 microm was robust enough to penetrate rat's pia without buckling, a major drawback of polymer alone. The averaged impedance value at 1 KHz was approximately 1.2 MOmega. Simultaneous recordings of neural signals from barrel cortex of a rat were successfully demonstrated.

3T3 Cells↗

An ex vivo method for evaluating the biocompatibility of neural electrodes in rat brain slice cultures.

Failure of neural recording electrodes implanted in the brain is often attributed to the formation of glial scars around the implant. A leading cause of scar formation is the electrode material. Described below is an approach to evaluate the biocompatibility of novel electrode materials in a representative three-dimensional model. The model, brain slice culture, accounts for the response of the neural tissue in the absence of the systemic response. While limitations of any in vitro model exist, brain slice culture provides an indication of the response of neurons and glia in an environment more indicative of the in vivo environment than two-dimensional cell culture of glia or neurons alone. Polybenzylcyclobutene (BCB) electrodes were developed as test materials for flexible electrodes due to ease of processing, low water uptake, and inherent flexibility when formed in thin sheets. Biocompatibilty of the BCB neural electrodes was evaluated using living brain slices derived from the hippocampal regions of 100 g CD rats. Importantly, fewer animals can be used in brain slice culture to evaluate the neural tissue response than when using live animals, since several slices can be obtained per animal. Cellular response to the electrodes was evaluated at 0, 7, and 14 days. At all time points living cells, both neurons and glia, were observed in the vicinity of the electrode. In addition, cells were observed migrating out from the brain slices onto the shank of the BCB electrode. Brain slice culture is shown to be a viable alternative to in vivo evaluation, in that the response of both neurons and glia can be evaluated in a native three-dimensional state, while sacrificing fewer animals. Future in vivo evaluation with BCB will provide definitive answers on the degree of glial scarring in response to this new and biocompatible electrode material.

Animals↗

A novel model of motor learning capable of developing an optimal movement control law online from scratch.

A computational model of a learning system (LS) is described that acquires knowledge and skill necessary for optimal control of a multisegmental limb dynamics (controlled object or CO), starting from "knowing" only the dimensionality of the object's state space. It is based on an optimal control problem setup different from that of reinforcement learning. The LS solves the optimal control problem online while practicing the manipulation of CO. The system's functional architecture comprises several adaptive components, each of which incorporates a number of mapping functions approximated based on artificial neural nets. Besides the internal model of the CO's dynamics and adaptive controller that computes the control law, the LS includes a new type of internal model, the minimal cost (IM(mc)) of moving the controlled object between a pair of states. That internal model appears critical for the LS's capacity to develop an optimal movement trajectory. The IM(mc) interacts with the adaptive controller in a cooperative manner. The controller provides an initial approximation of an optimal control action, which is further optimized in real time based on the IM(mc). The IM(mc) in turn provides information for updating the controller. The LS's performance was tested on the task of center-out reaching to eight randomly selected targets with a 2DOF limb model. The LS reached an optimal level of performance in a few tens of trials. It also quickly adapted to movement perturbations produced by two different types of external force field. The results suggest that the proposed design of a self-optimized control system can serve as a basis for the modeling of motor learning that includes the formation and adaptive modification of the plan of a goal-directed movement.

Adaptation, Physiological↗

Adaptive behavior of cortical neurons during a perturbed arm-reaching movement in a nonhuman primate.

This chapter provides evidence of spatial and temporal changes in the behavior of neurons within Areas 5 and 4 of the sensorimotor cortex of a nonhuman primate while it was executing a perturbed arm-reaching task. Chronically implanted electrode arrays were used to record simultaneously from 37 to 58 neurons. Also measured were the trajectory of arm movement, EMG activity in selected arm muscles and the perturbation force applied to the arm. The adaptation in Area 4 neurons' behavior usually involved a reduction in the latency from the onset of the perturbation to the peak-firing rate of the cell. In contrast, Area 5 neurons exhibited no such adaptive change in this latency. In each cortical area, the adaptation was not uniform across all neurons, and the spatial pattern of neuronal population behavior changed over the period of behavioral adaptation. We also found that the direction of arm movement and its configuration were important in determining which control strategy (predictive trajectory compensation or stiffness control) the animal used to overcome the externally applied perturbation for an improved performance of the reaching task.

Adaptation, Physiological↗

Epidural spinal-cord stimulation facilitates recovery of functional walking following incomplete spinal-cord injury.

We investigated a novel treatment paradigm for developing functional ambulation in wheelchair-dependent individuals with chronic, incomplete spinal-cord injury. By coordinating epidural stimulation of the dorsal structures of the spinal cord with partial weight bearing treadmill therapy, we observed improvement in treadmill and over-ground ambulation in an individual with chronic incomplete tetraplegia. The application of partial weight-bearing therapy alone was not sufficient to achieve functional ambulation over ground, though treadmill ambulation improved significantly. Combining epidural spinal-cord stimulation (ESCS, T10-T12 vertebral levels) with partial weight-bearing therapy resulted in further improvement during treadmill ambulation. Moreover, the combination of therapies facilitated the transfer of the learned gait into over ground ambulation. Performance improvements were elicited by applying continuous, charge-balanced, monophasic pulse trains at a frequency of 40-60 Hz, a pulse duration of 800 micros, and an amplitude determined by the midpoint (50%) between the sensory and motor threshold values. The participant initially reported a reduction in sense of effort for over ground walking from 8/10 to 3/10 (Borg scale), and was able to double his walking speed. After several weeks of over ground training, he reached maximum walking speeds of 0.35 m/s, and was able to ambulate over 325 m. We propose that ESCS facilitated locomotor recovery in this patient by augmenting the use-dependent plasticity created by partial weight bearing therapy. Confirmation of these promising results in a controlled study of groups of spinal-cord-injured subjects is warranted.

Adaptation, Physiological↗

Glial cell and fibroblast cytotoxicity study on plasma-deposited diamond-like carbon coatings.

Diamond-like carbon films have been evaluated as coatings to improve biocompatibility of orthopedic and cardiovascular implants. This study initiates a series of investigations that will evaluate diamond-like carbon (DLC) as a coating for improved biocompatibility in chronic neuroprosthetic implants. Studies in this report assess the cytotoxicity and cell adhesion behavior of DLC coatings exposed to glial and fibroblast cell lines in vitro. It can be concluded from these studies that DLC coatings do not adversely affect 3T3 fibroblast and T98-G glial cell function in vitro. We also successfully rendered DLC coatings non-adhesive (no significant fibroblast or glial cell adhesion) with surface immobilized dextran using methods developed for other biomaterials and applications. Future work will further develop DLC coatings on prototype microelectrode devices for chronic neural implant applications.

3T3 Cells↗

Probing changes in neural interaction during adaptation.

A procedure is developed to probe the changes in the functional interactions among neurons in primary motor cortex of the monkey brain during adaptation. A monkey is trained to learn a new skill, moving its arm to reach a target under the influence of external perturbations. The spike trains of multiple neurons in the primary motor cortex are recorded simultaneously. We utilize the methodology of directed transfer function, derived from a class of linear stochastic models, to quantify the causal interactions between the neurons. We find that the coupling between the motor neurons tends to increase during the adaptation but return to the original level after the adaptation. Furthermore, there is evidence that adaptation tends to affect the topology of the neural network, despite the approximate conservation of the average coupling strength in the network before and after the adaptation.

Action Potentials↗

Glial cell and fibroblast cytotoxicity study on 4026-cyclotene photosensitive benzocyclobutene (BCB) polymer films.

Photosensitive benzocyclobutene (photo-BCB) is a class of polymers with the trade name Cyclotene. The photoimagable property of Cyclotene makes it suitable for the manufacture of microelectronic devices. The motivation behind this study is that we see an exciting application of photo-BCB as substrates in implantable microelectronic biomedical devices due to several desirable properties distinctive from other polymer materials. To our knowledge, however, photo-BCB has never been tested for biomedical implant applications, as evidenced by the lack reported data on its biocompatibility. This study takes the first step towards assessing photo-BCB biocompatibility by evaluating the cytotoxicity and cell adhesion behavior of Cyclotene 4026 coatings exposed to monolayers of glial and fibroblast cells in vitro. It can be concluded from these studies that photo-BCB films deposited on silicon wafers using microfabrication processes did not adversely affect 3T3 fibroblast and T98-G glial cell function in vitro. We also successfully rendered photo-BCB films non-adhesive (no significant fibroblast or glial cell adhesion) with surface immobilized dextran using methods developed for other biomaterials and applications. Future work will further develop prototype photo-BCB microelectrode devices for chronic neural implant applications.

3T3 Cells↗

Perception threshold and electrode position for spinal cord stimulation.

The perception threshold for epidural spinal cord stimulation in chronic pain management was analyzed on 3,923 testing data obtained from 136 implanted patients. The initial areas of paresthesiae due to stimulation were recorded and reported as the stimulation map according to the location of electrodes. Measurement of dorsal thickness of the cerebrospinal fluid (CSF) layer was obtained from 26 subjects using magnetic resonance imaging (MRI). The results indicate that the perception threshold is a function of the spinal level of the implanted electrodes, of the mediolateral position in the spinal canal and the contact separation of electrode. Differences in perception threshold at various vertebral levels are mainly due to varying depths of the dorsal CSF layer. The medially placed electrodes caudal to the mid-cervical levels have a higher perception threshold than more laterally placed ones. The electrodes at high and mid-cervical levels, however, have a smaller perception threshold if placed medially. The information obtained from this investigation has important implications for the design of a new-generation stimulation system and clinical application to maximize the longevity of the power source.

Adult↗