A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies

Abstract

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method.

High Efficiency Power Management Unit for Implantable Optical-Electrical Stimulators

“…1.8 V, RV: 3.3 V and HV: 12 V) from an input ac voltage within the ISM frequency band 6.78-13.56 MHz received from the inductive link. As shown in FIGURE 1, the system has four hybrid optical-electrical stimulator units, control logic, and EMG sensor [11] in a single chip for a fully implantable solution. The proposed regulating rectifier features singlestage rectification and regulation with PWM control, an LDO with internal bandgap reference, and a high voltage latch CP with a two-phase non-overlapping clock generator [23].…”

“…The analog PWM controller is shown in FIGURE 6. It consists of an error amplifier (EA) as shown in FIGURE 11 which senses the error between a reference voltage 𝑉 >)H , and 𝑅𝑉 • (𝑅 ! + 𝑅 " )/(𝑅 # + 𝑅 !…”

“…This work is an expansion of [10] and provides further details on the circuit design topology; it includes measured results from the fabricated chip of the PMU highlighted in FIGURE 1. Further circuit details on the stimulator unit and EMG sensor can be found in [11]. The rest of the paper is organized as follows.…”

An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of amyotrophic lateral sclerosis

“…The aim of this neural replacement strategy is therefore to provide a biological interface capable of rendering any target muscle receptive to control signals transmitted by optical stimulation to engrafted motor neurons ( Bryson et al, 2016 ). Importantly, we have recently developed a prototype 64-channel stimulation and recording device capable of controlling multiple independent intraneural graft sites that could be used to elicit coordinated function of large numbers of muscles, in order to restore useful motor functions ( Liu et al, 2022 ).…”

“…The aim of this neural replacement strategy is therefore to provide a biological interface capable of rendering any target muscle receptive to control signals transmitted by optical stimulation to engrafted motor neurons Bryson et al (2016) . Importantly, we have recently developed a prototype 64-channel stimulation and recording device capable of controlling multiple independent intraneural graft sites that could be used to elicit coordinated function of large numbers of muscles, in order to restore useful motor functions Liu et al (2022) . This novel approach to restore control of paralyzed muscles in ALS patients, using a combination of cell replacement and optical stimulation, has several key advantages over existing cell replacement and electrical stimulation strategies, including: i) the ability to engraft motor neurons peripherally, in close proximity to targeted muscles, which greatly accelerates the rate of reinnervation and reduces the period of denervation, consequently ameliorating denervationinduced muscle atrophy; ii) avoidance of engrafting replacement cells into the neurotoxic environment that exists within the CNS of ALS patients and the necessity for reinnervating axons of CNS-engrafted motor neurons to overcome the inhibitory CNS:PNS barrier in order to exit the CNS and grow the often long distances to target muscles; iii) specificity of optical stimulation to the engrafted ChR2 + motor neurons avoids painful off-target activation of sensory afferents or aberrant activation of endogenous motor axons associated with electrical nerve stimulation (ENS); and critically, iv) the ability to recruit motor units in correct physiological order using optical nerve stimulation (ONS) Llewellyn et al ( 2010) , avoids the problem of rapid muscle fatigue associated with ENS and incorrect, non-physiological motor unit recruitment.…”