Printable microscale interfaces for long-term peripheral nerve mapping and precision control

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying advanced peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high-resolution recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation can achieve a high degree of functionally-relevant modulatory specificity within the small scale of the device. These results highlight the potential of new microscale design and fabrication techniques for the realization of viable implantable devices for long-term peripheral interfacing.https://www.biorxiv.org/node/801468.fullFirst author draf

Perspectives on the Neuroscience of Cognition and Consciousness

The origin and current use of the concepts of computation, representation and information in Neuroscience are examined and conceptual flaws are identified which vitiate their usefulness for addressing problems of the neural basis of Cognition and Consciousness. In contrast, a convergence of views is presented to support the characterization of the Nervous System as a complex dynamical system operating in the metastable regime, and capable of evolving to configurations and transitions in phase space with potential relevance for Cognition and Consciousness

Wireless Neuromodulation: From Bench to Bedside

Spinal cord stimulation (SCS), as a neuromodulation therapy, has rapidly evolved over the past few decades to become the treatment of choice for many chronic pain syndromes. However, many equipment-related limitations such as the bulk of the equipment, an implantable pulse generator (IPG), the limited therapeutic stimulation frequency utilized, and the potential adverse events have restricted SCS applications. Recently, advanced nanotechnology and minimally invasive surgical techniques have shown promising options to expand the indications due to reduced surgical trauma/hospital time/costs. We describe the basis for nanotechnology neuromodulation and the preliminary experience with wireless SCS in the treatment of chronic pain conditions. The equipment utilizes a miniature stimulator with microelectronics, percutaneously placed at the appropriate stimulation target, with wireless control to provide the desired stimulation, and then moderated by the clinician and the patient. The wireless device reduces the bulk of the SCS equipment to a single electrode (with embedded sensors), using the new improved neural-electric interface. This wireless neuromodulation (WNM) has been clinically used in several chronic pain conditions, including failed back surgery syndrome, facial pain, chronic regional pain syndrome, and postherpetic neuralgia, with encouraging outcome, without the complications of a traditional SCS resulting from the IPG or its accessories

Neuromorphic hardware for somatosensory neuroprostheses

In individuals with sensory-motor impairments, missing limb functions can be restored using neuroprosthetic devices that directly interface with the nervous system. However, restoring the natural tactile experience through electrical neural stimulation requires complex encoding strategies. Indeed, they are presently limited in effectively conveying or restoring tactile sensations by bandwidth constraints. Neuromorphic technology, which mimics the natural behavior of neurons and synapses, holds promise for replicating the encoding of natural touch, potentially informing neurostimulation design. In this perspective, we propose that incorporating neuromorphic technologies into neuroprostheses could be an effective approach for developing more natural human-machine interfaces, potentially leading to advancements in device performance, acceptability, and embeddability. We also highlight ongoing challenges and the required actions to facilitate the future integration of these advanced technologies

Wireless Simultaneous Stimulation-and-Recording Device (SRD) to Train Cortical Circuits in Rat Somatosensory Cortex

The primary goal of this project is to develop a wireless system for simultaneous recording-and-stimulation (SRD) to deliver low amplitude current pulses to the primary somatosensory cortex (SI) of rats to activate and enhance an interhemispheric cortical pathway. Despite the existence of an interhemispheric connection between similar forelimb representations of SI cortices, forelimb cortical neurons respond only to input from the contralateral (opposite side) forelimb and not to input from the ipsilateral (same side) forelimb. Given the existence of this interhemispheric pathway we have been able to strengthen/enhance the pathway through chronic intracortical microstimulation (ICMS) in previous acute experiments of anesthetized rats. In these acute experiments strengthening the interhemispheric pathway also brings about functional reorganization whereby cortical neurons in forelimb cortex respond to new input from the ipsilateral forelimb. Having the ability to modify cortical circuitry will have important applications in stroke patients and could serve to rescue and/or enhance responsiveness in surviving cells around the stroke region. Also, the ability to induce functional reorganization within the deafferented cortical map, which follows limb amputation, will also provide a vehicle for modulating maladaptive cortical reorganization often associated with phantom limb pain leading to reduced pain. In order to increase our understanding of the observed functional reorganization and enhanced pathway, we need to be able to test these observations in awake and behaving animals and eventually study how these changes persist over a prolonged period of time. To accomplish this a system was needed to allow simultaneous recording and stimulation in awake rats. However, no such commercial or research system exists that meets all requirements for such an experiment. In this project we describe the (1) system design, (2) system testing, (3) system evaluation, and (4) system implementation of a wireless simultaneous stimulation-and-recording device (SRD) to be used to modulate cortical circuits in an awake rodent animal model

Distributed Sensing and Stimulation Systems Towards Sense of Touch Restoration in Prosthetics

Modern prostheses aim at restoring the functional and aesthetic characteristics of the lost limb. To foster prosthesis embodiment and functionality, it is necessary to restitute both volitional control and sensory feedback. Contemporary feedback interfaces presented in research use few sensors and stimulation units to feedback at most two discrete feedback variables (e.g. grasping force and aperture), whereas the human sense of touch relies on a distributed network of mechanoreceptors providing high-fidelity spatial information. To provide this type of feedback in prosthetics, it is necessary to sense tactile information from artificial skin placed on the prosthesis and transmit tactile feedback above the amputation in order to map the interaction between the prosthesis and the environment. This thesis proposes the integration of distributed sensing systems (e-skin) to acquire tactile sensation, and non-invasive multichannel electrotactile feedback and virtual reality to deliver high-bandwidth information to the user. Its core focus addresses the development and testing of close-loop sensory feedback human-machine interface, based on the latest distributed sensing and stimulation techniques for restoring the sense of touch in prosthetics. To this end, the thesis is comprised of two introductory chapters that describe the state of art in the field, the objectives and the used methodology and contributions; as well as three studies distributed over stimulation system level and sensing system level. The first study presents the development of close-loop compensatory tracking system to evaluate the usability and effectiveness of electrotactile sensory feedback in enabling real-time close-loop control in prosthetics. It examines and compares the subject\u2019s adaptive performance and tolerance to random latencies while performing the dynamic control task (i.e. position control) and simultaneously receiving either visual feedback or electrotactile feedback for communicating the momentary tracking error. Moreover, it reported the minimum time delay needed for an abrupt impairment of users\u2019 performance. The experimental results have shown that electrotactile feedback performance is less prone to changes with longer delays. However, visual feedback drops faster than electrotactile with increased time delays. This is a good indication for the effectiveness of electrotactile feedback in enabling close- loop control in prosthetics, since some delays are inevitable. The second study describes the development of a novel non-invasive compact multichannel interface for electrotactile feedback, containing 24 pads electrode matrix, with fully programmable stimulation unit, that investigates the ability of able-bodied human subjects to localize the electrotactile stimulus delivered through the electrode matrix. Furthermore, it designed a novel dual parameter -modulation (interleaved frequency and intensity) and compared it to conventional stimulation (same frequency for all pads). In addition and for the first time, it compared the electrotactile stimulation to mechanical stimulation. More, it exposes the integration of virtual prosthesis with the developed system in order to achieve better user experience and object manipulation through mapping the acquired real-time collected tactile data and feedback it simultaneously to the user. The experimental results demonstrated that the proposed interleaved coding substantially improved the spatial localization compared to same-frequency stimulation. Furthermore, it showed that same-frequency stimulation was equivalent to mechanical stimulation, whereas the performance with dual-parameter modulation was significantly better. The third study presents the realization of a novel, flexible, screen- printed e-skin based on P(VDF-TrFE) piezoelectric polymers, that would cover the fingertips and the palm of the prosthetic hand (particularly the Michelangelo hand by Ottobock) and an assistive sensorized glove for stroke patients. Moreover, it developed a new validation methodology to examine the sensors behavior while being solicited. The characterization results showed compatibility between the expected (modeled) behavior of the electrical response of each sensor to measured mechanical (normal) force at the skin surface, which in turn proved the combination of both fabrication and assembly processes was successful. This paves the way to define a practical, simplified and reproducible characterization protocol for e-skin patches In conclusion, by adopting innovative methodologies in sensing and stimulation systems, this thesis advances the overall development of close-loop sensory feedback human-machine interface used for restoration of sense of touch in prosthetics. Moreover, this research could lead to high-bandwidth high-fidelity transmission of tactile information for modern dexterous prostheses that could ameliorate the end user experience and facilitate it acceptance in the daily life

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

Neuro-electronic technology in medicine and beyond

This dissertation looks at the technology and social issues involved with interfacing electronics directly to the human nervous system, in particular the methods for both reading and stimulating nerves. The development and use of cochlea implants is discussed, and is compared with recent developments in artificial vision. The final sections consider a future for non-medicinal applications of neuro-electronic technology. Social attitudes towards use for both medicinal and non-medicinal purposes are discussed, and the viability of use in the latter case assessed

A compact system for simultaneous stimulation and recording for closed-loop myoelectric control

Background.Despite important advancements in control and mechatronics of myoelectric prostheses, the communication between the user and his/her bionic limb is still unidirectional, as these systems do not provide somatosensory feedback. Electrotactile stimulation is an attractive technology to close the control loop since it allows flexible modulation of multiple parameters and compact interface design via multi-pad electrodes. However, the stimulation interferes with the recording of myoelectric signals and this can be detrimental to control.The work in this study was supported by the project ROBIN (8022-00243A and 8022-00226B) funded by the Independent Research Fund Denmark