An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results

The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35 mu m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7 mu V-rms, and to selectively elicit the tibial and plantar muscles using different active sites of the electrode.

Soft multimodal neural interfaces for unravelling sensory neurological circuits

Frédéric Pierre Gérald Michoud

Diseases or injuries affecting the nervous system can dramatically disrupt the quality of life. Despite extensive efforts towards treating dysfunctional nervous systems, the pharmacological and electrical approaches generally involved lack the temporal and spatial resolutions needed to selectively modulate neural activity. The somatosensory system intertwines numerous neural populations with distinct functionalities, whose specific neuromodulation would be beneficial for the alleviation of chronic pain and the restoration of locomotion after spinal cord injury. This thesis aims to develop a new generation of electrical and optical neural interfaces to selectively parse the somatosensory system. At the peripheral nerve level, we proposed an optical cuff and a wireless optoelectronic system to deliver epineural optogenetic stimulations in freely-behaving mice. The former consists of a soft elastomeric cuff wrapped around the sciatic nerve and integrated into a thin optic fiber. We demonstrated consistent orderly recruitment of motor units with optical stimulations in Thy1::ChR2 mice. This optocuff represents a simple, yet efficient, solution to probe the peripheral nervous system using optogenetics. However, untethered experimentation offers more versatility for fine neuromodulation applications. Within this framework, we developed a system comprising an ultra-miniaturized wireless stimulator and a soft circumneural ÎŒ-LED array to deliver optogenetic stimulations to the sciatic nerve. This optoelectronic implant conformed to the nerveâs morphology and complied with its dynamic motion. We demonstrated the systemâs efficacy via optogenetic activation of nociceptors in TRPV1::ChR2 mice. Both the optocuff and the wireless optoelectronic system exhibited seamless bio-integration after chronic implantation, thus highlighting the benefits of soft neurotechnology for interfacing with peripheral nerves. At the spinal level, we introduced a transversal electrode array for multipolar epidural stimulation of the spinal cord. The silicone materials used for its fabrication conferred this implant with mechanical properties matching the dura mater, allowing for remarkable biocompatibility following long-term implantation. Based on the spinal cord anatomy, this implant displayed a wide distribution of neural electrodes at a single spinal level, which enabled selective recruit- ment of posterior spinal roots. This novel paradigm was implemented to a spatio-temporal stimulation protocol and demonstrated potential in restoring locomotion after spinal cord injury. Finally, we reported a soft ÎŒ-LED array to deliver optogenetic stimulations in deep spinal structures. Insertion of this thin (< 100 ÎŒm) optoelectronic implant in the mouse epidural space did not provoke tissue damages while maintaining its functionality with normal dynamic motion. As a proof-of-principle, we showed concomitant electromyographic activity with epidural optical stimulations in Thy1::ChR2 mice. This premise offers a large range of opportunities to probe the spinal circuits involved in sensory processing and locomotion. In conclusion, these selective neural interfaces are proposed as innovative tools to unravel peripheral and spinal neural circuits. This venue will support the development of relevant clinical treatments for tackling dysfunctional neural systems. Eventually, these implant concepts pave the way for the translation of fine neuromodulation therapies in humans.

EPFL2019

Low-Power Circuits and Systems Design for Data Acquisition and Transmission in a Wireless Cortical Implant

Vahid Majidzadeh Bafar

Minimally invasive monitoring of the electrical activity of specific cortical areas using implantable microsystems offers the promise of diagnosing neurological diseases, as well as detecting and identifying neural activity patterns which are specific to a behavioral phenomenon. Multi-channel recording in-vivo impose critical constraints on circuits and systems design in order to comply with severe safety requirements. The system power consumption should be sufficiently small in order to enable autonomous and battery-less operation as well as to limit the temperature increase due to operation of the implant. Moreover, small area and volume of the implant are critical constraints to minimize issues associated with surgery operation and implantation. In this research, low-power circuits and systems techniques for data acquisition and transmission in wireless multi-channel cortical implants are presented. Wireless power transmission is carried out using an inductive coupling technique along with fully on-chip low-drop-out (LDO) voltage regulation. Stable operation over a wide range of load conditions, and fast load and line regulation are the main design issues of LDO regulators, which are addressed by proposing a novel compensation methodology, and a power supply rejection ratio (PSRR) boosting technique. Low-noise operation of the analog front-end is obtained by introducing new design techniques at circuit and system levels. The partial OTA sharing technique is proposed as a circuit-level approach which results in a significant reduction of power dissipation as well as silicon area, in addition to a very low noise efficiency factor (NEF). The effect of mismatch on crosstalk between channels, trade-off between noise and crosstalk, and nonlinearity of the amplifiers are theoretically analyzed and confirmed by measurement results. Three different system architectures are presented, which preserve the temporal information of the recording sites by avoiding channel multiplexing. A 16-channel neural recording system is presented, which uses an oversampling delta modulator as a dedicated ADC per channel. The oversampling delta modulator not only improves the system level NEF, but also provides in-site compression of the slow varying neural signal. The fabricated prototype consumes 220 μW from a 1.2 V power supply and achieves an input-referred noise equal to 2.8 μVrms. The application of algebraic Walsh-Hadamard coding in multi-channel recording systems is investigated by developing a 16-channel prototype. The linear and orthogonal combination of channels provided by coding, maps the spacial information of the channels to the temporal information of a superposed signal, and enables parallel recording from multiple channels using a single ADC. Moreover, this technique improves the spacial resolution of the recording sites by moving the shared signal processing hardware to the outside of the sensor plane. A fabricated chip supports a sensor pitch equal to 250 μm, consumes 359 μW from a 1.2 V power supply, and achieves an input-referred noise equal 4.1 μVrms. Finally, a system on a package (SoP) is presented which consists of a 64-channel neural recording system named Neuro+II, and an impulse radio ultra wideband (IR-UWB) transmitter. Neuro+II hosts the power conversion and voltage regulation blocks, the analog/mixed-mode front-end unit, and the digital baseband processing module. A dynamic power scaling technique is presented which enables 20.4% reduction in power consumtion of the analog/mixed-mode front-end. Neuro+II consumes 3.26 mW and achieves a power dissipation density equal to 13 mW/cm2. An IR-UWB transmitter is presented as an up-link communication module of the Neuro+II. An eight pulse-position modulation (8-PPM) scheme is implemented using a novel all-digital delayed-locked-loop (DLL) circuit, which offers better spectral compliance with USA Federal Communication Commision (FCC) regulations. A symmetric pulse combining technique is proposed to reduce the number of power amplifier elements by half, which enhances the tuning range capability of the transmitter. The fabricated transmiter consumes 540 μW and achieves an energy efficiency of 45 pJ/bit with an output power measured at -26 dBm. Continuous improvements in the field not only support research in the life science do- main, but also enables the clinical treatment of some diseases and extends the application field of such systems from clinical experiments to in-house treatments and ambulatory monitoring.

EPFL2012

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

Lin Jin, Sylvain Eric Lengacher, Pierre Magistretti, Luc Pellerin

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. (C) 2014 Elsevier Inc. All rights reserved.

Elsevier2015