Decoding Information From Neural Signals Recorded Using Intraneural Electrodes: Toward the Development of a Neurocontrolled Hand Prosthesis

The possibility of controlling dexterous hand prostheses by using a direct connection with the nervous system is particularly interesting for the significant improvement of the quality of life of patients, which can derive from this achievement. Among the various approaches, peripheral nerve based intrafascicular electrodes are excellent neural interface candidates, representing an excellent compromise between high selectivity and relatively low invasiveness. Moreover, this approach has undergone preliminary testing in human volunteers and has shown promise. In this paper, we investigate whether the use of intrafascicular electrodes can be used to decode multiple sensory and motor information channels with the aim to develop a finite state algorithm that may be employed to control neuroprostheses and neurocontrolled hand prostheses. The results achieved both in animal and human experiments show that the combination of multiple sites recordings and advanced signal processing techniques (such as wavelet denoising and spike sorting algorithms) can be used to identify both sensory stimuli (in animal models) and motor commands (in a human volunteer). These findings have interesting implications, which should be investigated in future experiments. © 2006 IEEE

A model for selection of eyespots on butterfly wings

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell

Separability of neural responses to standardised mechanical stimulation of limbs

Abstract Considerable scientific and technological efforts are currently being made towards the development of neural prostheses. Understanding how the peripheral nervous system responds to electro-mechanical stimulation of the limb, will help to inform the design of prostheses that can restore function or accelerate recovery from injury to the sensory motor system. However, due to differences in experimental protocols, it is difficult, if not impossible, to make meaningful comparisons between different peripheral nerve interfaces. Therefore, we developed a low-cost electronic system to standardise the mechanical stimulation of a rat’s hindpaw. Three types of mechanical stimulations, namely, proprioception, touch and nociception were delivered to the limb and the electroneurogram signals were recorded simultaneously from the sciatic nerve with a 16-contact cuff electrode. For the first time, results indicate separability of neural responses according to stimulus type as well as intensity. Statistical analysis reveal that cuff contacts placed circumferentially, rather than longitudinally, are more likely to lead to higher classification rates. This flexible setup may be readily adapted for systematic comparison of various electrodes and mechanical stimuli in rodents. Hence, we have made its electro-mechanical design and computer programme available onlin

Bringing sensation to prosthetic hands—chronic assessment of implanted thin-film electrodes in humans

Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses. Longevity of the electrodes is key to success, which we have improved for the polyimide-based transverse intrafascicular multichannel electrode (TIME). The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months. We present a comprehensive assessment of the electrical properties of the thin-film metallization as well as material status post explantationem. The TIMEs stayed within the electrochemical safe limits while enabling consistent and precise amplitude modulation. This lead to a reliable performance in terms of eliciting sensation. No signs of corrosion or morphological change to the thin-film metallization of the probes was observed by means of electrochemical and optical analysis. The presented longevity demonstrates that thin-film electrodes are applicable in permanent implant systems

The neural basis of perceived intensity in natural and artificial touch

Electrical stimulation of sensory nerves is a powerful tool for studying neural coding because it can activate neural populations in ways that natural stimulation cannot. Electrical stimulation of the nerve has also been used to restore sensation to patients who have suffered the loss of a limb. We have used long-term implanted electrical interfaces to elucidate the neural basis of perceived intensity in the sense of touch. To this end, we assessed the sensory correlates of neural firing rate and neuronal population recruitment independently by varying two parameters of nerve stimulation: pulse frequency and pulse width. Specifically, two amputees, chronically implanted with peripheral nerve electrodes, performed each of three psychophysical tasks-intensity discrimination, magnitude scaling, and intensity matching-in response to electrical stimulation of their somatosensory nerves. We found that stimulation pulse width and pulse frequency had systematic, cooperative effects on perceived tactile intensity and that the artificial tactile sensations could be reliably matched to skin indentations on the intact limb. We identified a quantity we termed the activation charge rate (ACR), derived from stimulation parameters, that predicted the magnitude of artificial tactile percepts across all testing conditions. On the basis of principles of nerve fiber recruitment, the ACR represents the total population spike count in the activated neural population. Our findings support the hypothesis that population spike count drives the magnitude of tactile percepts and indicate that sensory magnitude can be manipulated systematically by varying a single stimulation quantity

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

Elective amputation and bionic substitution restore functional hand use after critical soft tissue injuries

Critical soft tissue injuries may lead to a non-functional and insensate limb. In these cases standard reconstructive techniques will not suffice to provide a useful outcome, and solutions outside the biological arena must be considered and offered to these patients. We propose a concept which, after all reconstructive options have been exhausted, involves an elective amputation along with a bionic substitution, implementing an actuated prosthetic hand via a structured tech-neuro-rehabilitation program. Here, three patients are presented in whom this concept has been successfully applied after mutilating hand injuries. Clinical tests conducted before, during and after the procedure, evaluating both functional and psychometric parameters, document the benefits of this approach. Additionally, in one of the patients, we show the possibility of implementing a highly functional and natural control of an advanced prosthesis providing both proportional and simultaneous movements of the wrist and hand for completing tasks of daily living with substantially less compensatory movements compared to the traditional systems. It is concluded that the proposed procedure is a viable solution for re-gaining highly functional hand use following critical soft tissue injuries when existing surgical measures fail. Our results are clinically applicable and can be extended to institutions with similar resources

An orphan gene is necessary for preaxial digit formation during salamander limb development

Limb development in salamanders differs from other tetrapods in that the first digits to form are the two most anterior (preaxial dominance). This has been proposed as a salamander novelty and its mechanistic basis is unknown. Salamanders are the only adult tetrapods able to regenerate the limb, and the contribution of preaxial dominance to limb regeneration is unclear. Here we show that during early outgrowth of the limb bud, a small cohort of cells express the orphan gene Prod1 together with Bmp2, a critical player in digit condensation in amniotes. Disruption of Prod1 with a gene-editing nuclease abrogates these cells, and blocks formation of the radius and ulna, and outgrowth of the anterior digits. Preaxial dominance is a notable feature of limb regeneration in the larval newt, but this changes abruptly after metamorphosis so that the formation of anterior and posterior digits occurs together within the autopodium resembling an amniote-like pattern