Stimulation Circuit Research Articles

Highly Photoresponsive Vertically Stacked Silicon Nanowire Photodetector with Biphasic Current Stimulator IC for Retinal Prostheses

This paper presents an integrated approach for a retinal prosthesis that overcomes the scalability challenges and limitations of conventional systems that use external cameras. Silicon nanowires (SiNWs) are utilized as photonic sensors due to their nanoscale dimensions and high surface-to-volume ratio. To enhance these properties and achieve high photoresponsivity, our research team developed a vertically stacked SiNW structure using a fabrication method entirely based on dry etching. The fabricated SiNW photodetector demonstrated excellent electrical and optical characteristics, including linear I–V characteristics that confirmed ohmic contact formation and high photoresponsivity exceeding 105 A/W across the 400–800 nm wavelength range. The SiNW photodetector, following its integration with a switched capacitor stimulator circuit, exhibited a proportional increase in stimulation current in response to higher light intensity and increased SiNW density. In vitro experiments confirmed the efficacy of the integrated system in inducing neural responses from retinal cells, as indicated by an increased number of neural spikes observed at higher light intensities and SiNW densities. This study contributes to sensor technology by demonstrating an approach to integrating nanostructures and electronic components, which enhances control and functionality.

High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS)

BackgroundNumerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke.MethodsThis is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III–V stroke lasting from 3 months to 1 year. Evaluation of patients’ upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology.DiscussionThe high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs.Trial registrationChinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

A full-custom fully implantable cochlear implant system validated in vivo with an animal model

Realizations of fully implantable cochlear implants (FICIs) for providing adequate solution to esthetic concerns and frequent battery replacement have lacked of addressing system level criteria as a complete device. Here, we present a full-custom FICI that considers design of both an implantable sensor for wide range sound sensing and a signal conditioning circuit for electrical stimulation of the auditory nerve. The microelectromechanical system (MEMS)-based acoustic sensor utilizes multiple cantilever beam structures to sense and filter the mechanical vibrations on the ossicular chain. The area optimized bilayer design of the piezoelectric sensor met with the volume limitation in the middle ear while achieving high signal-to-noise-ratio. The sensor outputs are processed by a current mode low-power signal conditioning circuit that stimulates the auditory neurons through intracochlear electrodes. The FICI is validated with an in vivo model where the electrical auditory brainstem response (eABR) of the animal was observed while applying sound excitation. The eABR results demonstrate that the system is able to evoke responses in the auditory nerves of a guinea pig for sound range of 45–100 dB SPL within the selected frequency bands.

A low power frequency-programmable stimulation circuit for small rodent pacemaker

A low power frequency-programmable stimulation circuit for small rodent pacemaker

An Efficient Pulse Circuit Design for Magnetic Stimulation with Diversified Waveforms and Adjustable Parameters.

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) has important applications both in the exploration of mental disorder causes and the treatment of mental disorders. During the stimulation, the TMS system generates the intracranial time-varying induced E-field (E-field), which alters the membrane potential of neurons and subsequently exerts neural regulatory effects. The temporal waveform of the induced E-fields is directly related to the stimulation effect. To meet the needs of scientific research on diversified stimulation waveforms and flexible adjustable stimulation parameters, a novel efficient pulse magnetic stimulation circuit (the EPMS circuit) design based on asymmetric cascaded multilevel technology is proposed in this paper. Based on the transient analysis of the discharge circuit, this circuit makes it possible to convert the physical quantity (the intracranial induced E-field) that needs to be measured after magnetic stimulation into easily analyzable electrical signals (the discharge voltage at both ends of the stimulation coil in the TMS circuit). This EPMS circuit can not only realize monophasic and biphasic cosine-shaped intracranial induced E-fields, which are widely used in the market, but also realize three types of new intracranial induced E-field stimulation waveform with optional amplitude and adjustable pulse width, including monophasic near-rectangular, biphasic near-rectangular and monophasic/biphasic ladder-shaped stimulation waveform, which breaks through the limitation of the stimulation waveform of traditional TMS systems. Among the new waveforms produced by the EPMS circuit, further research was conducted on the dynamic response characteristics of neurons under the stimulation of the biphasic four-level waveform (the BFL waveform) with controllable parameters. The relationship between TMS circuit parameters (discharge voltage level and duration) and corresponding neural response characteristics (neuron membrane potential change and neuronal polarizability ratio) was explained from a microscopic perspective. Accordingly, the biological physical quantities (neuronal membrane potential) that are difficult to measure can be transformed into easily analyzable electrical signals (the discharge voltage level and duration). Results showed that compared with monophasic and biphasic cosine induced E-fields with the same energy loss, the neuron polarization ratio is decreased by 54.5% and 87.5%, respectively, under the stimulation of BFL waveform, which could effectively enhance the neuromodulation effect and improve the stimulation selectivity.

Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs.

In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

Motor Behavior Regulation of Rat Robots Using Integrated Electrodes Stimulated by Micro-Nervous System.

As a cutting-edge technology, animal robots based on living organisms are being extensively studied, with potential for diverse applications in the fields of neuroscience, national security, and civil rescue. However, it remains a significant challenge to reliably control the animal robots with the objective of protecting their long-term survival, and this has seriously hindered their practical implementation. To address this issue, this work explored the use of a bio-friendly neurostimulation system that includes integrated stimulation electrodes together with a remote wireless stimulation circuit to control the moving behavior of rat robots. The integrated electrodes were implanted simultaneously in four stimulation sites, including the medial forebrain bundle (MFB) and primary somatosensory cortex, barrel field (S1BF). The control system was able to provide flexibility in adjusting the following four stimulation parameters: waveform, amplitude, frequency, and duration time. The optimized parameters facilitated the successful control of the rat's locomotion, including forward movement and left and right turns. After training for a few cycles, the rat robots could be guided along a designated route to complete the given mission in a maze. Moreover, it was found that the rat robots could survive for more than 20 days with the control system implanted. These findings will ensure the sustained and reliable operation of the rat robots, laying a robust foundation for advances in animal robot regulation technology.

Multifunctional ultraflexible neural probe for wireless optogenetics and electrophysiology

Electrophysiology and optogenetics are pivotal in neuroscience for probing and modulating neural activities, playing a vital role in unraveling the complexities of brain functionality. Despite their importance, the efficacy of existing devices is hampered by insufficient functional integration, pronounced foreign body reactions, and physical constraints that impede natural animal behaviors. Here, we develop a multifunctional, ultraflexible neural probe designed for simultaneous electrophysiological monitoring and optical neural modulation, along with mechanical properties that are conducive to flexibility and compliance. By integrating a wireless neural signal acquisition and stimulation circuit, we achieved wireless recording of brain signals in mice and wireless optogenetic control over their locomotor behavior. The multifunctional ultraflexible probe presented in this study holds substantial promise for closed-loop brain-machine interfaces and deepening our understanding of neural circuit functions. This innovative approach addresses the aforementioned limitations by a comprehensive solution for in vivo neural interrogation and manipulation, marking a significant advancement in the tools available for neuroscience research.

Double‐Sided, Thin‐Film Microelectrode Array with Hemispheric Electrodes for Subretinal Stimulation

AbstractComponents in neural implants, such as the electrode array and stimulator circuit, are often fabricated discretely. This modular fabrication scheme offers flexibility during development but poses difficulties during assembly, as components must be compactly integrated for implantation. It is particularly difficult in cases where the electrode array is required to have a high number of channels, such as in retinal prostheses. This paper presents the development of a parylene C‐based, double‐sided microelectrode array with 294 hemispheric electrodes for subretinal stimulation. The bonding pads on the bottom side of the double‐sided array are connected with electrodes through vias, eliminating the interconnection lines. The array can be integrated with a stimulator circuit through pad‐to‐pad bonding, resulting in a compact implant. The hemispheric electrodes are fabricated using thermally reflowed photoresist infillings, through which the height and width of the hemispheres can be easily controlled. The long‐term stability and biocompatibility of the materials and methods used to fabricate and package the electrodes are demonstrated in in vitro and in vivo environments over months. Finally, subretinal stimulation by the developed electrodes is successfully demonstrated using in vitro retinal patches from mice and monkeys.

Charge-Mode Neural Stimulator With a Capacitor-Reuse Residual Charge Detector and Active Charge Balancing for Epileptic Seizure Suppression.

This study proposes a charge-mode neural stimulator for electrical stimulation systems that utilizes a capacitor-reuse technique with a residual charge detector and achieves active charge balancing simultaneously. The design is mainly used for epilepsy suppression systems to achieve real-time symptom relief during seizures. A charge-mode stimulator is adopted in consideration of the complexity of circuit design, the high voltage tolerance of transistors, and system integration requirements in the future. The residual charge detector allows users to understand the current stimulus situation, enabling them to make optimal adjustments to the stimulation parameters. On the basis of the information on actual stimulation charge, active charge balancing can effectively prevent the accumulation of mismatched charges on electrode impedance. The capacitor- and phase-reuse techniques help realize high integration of the overall stimulator circuit in consideration of the commonality of the use of a capacitor and charging/discharging phase in the stimulation circuit and charge detector. The proposed charge-mode neural stimulator is implemented in a TSMC 0.18 µm 1P6M CMOS process with a core area of 0.2127 mm2. Measurement results demonstrate the accuracy of the stimulation's functionality and the programmable stimulus parameters. The effectiveness of the proposed charge-mode neural stimulator for epileptic seizure suppression is verified through animal experiments.

Effect of Non-invasive Spinal Stimulation on Self-sustained Firing Motoneuron Model: In-Silico Study Using Human Body Model.

Transcutaneous spinal electrical stimulation (tSCS) is a non-invasive neuromodulation approach using a low intensity direct current. Recent developments in the technique have opened the possibility that tSCS can help restore motor function after spinal cord injury (SCI). However, the exact mechanism of action tSCS has on the spinal circuits is still unknown. Due to the complexity of experimental synthesis in a human model to delineate the mechanisms, models that link the stimulation paradigm and circuit behaviors are advantageous. Thus, this study aims to simulate the underlying changes in motor circuit firing rates in response to external stimuli induced by tSCS. Serial stimulations combining a high-fidelity finite element model with the human torso and spinal cord with a lumped motor neuron model is constructed. The parameters for both components of the model were derived from previous studies. We focused our analysis on a lumped motor neuron model that describes sustained firing behavior of the motor neuron driven primarily by persistent inward current (PIC), a signature behavior of the motor neuron after SCI. Modulation of the PIC behaviors was achieved by stimulating voltage-dependent calcium and sodium channels in the dendrite using a tSCS-induced electric field (E-field) expressed at different a spatial locations of the motor neuron in the gray matter. The PIC behaviors of spinal motor neurons in the left ventral horn were suppressed, while for the most part invariant in the right ventral horn. These initial simulations will provide a steppingstone for future examinations that incorporate additional neuronal models of inhibitory and excitatory interneurons to access the circuit-level effect of spinal stimulation.

Wireless Device with Energy Management for Closed-Loop Deep Brain Stimulation (CLDBS)

Deep brain stimulation (DBS) is an effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases, and has been consolidated as a first-line tool in the last two decades. Closed-loop deep brain stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real time. The main contribution of this paper is a low-size/power-controlled, compact and complete CLDBS system with two simultaneous acquisition channels, two simultaneous neurostimulation channels and wireless communication. Each channel has a low-noise amplifier (LNA) buffer in differential configuration to eliminate the DC signal component of the input. Energy management is efficiently done by the control and communication unit. The battery supports almost 9 h with both the acquisition and stimulation circuits active. If only the stimulation circuit is used as an Open Loop DBS, the battery can hold sufficient voltage for 24 h of operation. The whole system is low-cost and portable and therefore it could be used as a wearable device.

Rattractor-Instant guidance of a rat into a virtual cage using the deep brain stimulation.

We developed "Rattractor" (rat attractor), a system to apply electrical stimuli to the deep brain of a rat as it stays in a specified region or a virtual cage to demonstrate an instant electrophysiological feedback guidance for animals. Two wire electrodes were implanted in the brains of nine rats. The electrodes targeted the medial forebrain bundle (MFB), which is a part of the reward system in the deep brain. Following the recovery period, the rats were placed in a plain field where they could move freely, but wired to a stimulation circuit. An image sensor installed over the field detected the subject's position, which triggered the stimulator such that the rat remained within the virtual cage. We conducted a behavioral experiment to evaluate the sojourn ratio of rats residing in the region. Thereafter, a histological analysis of the rat brain was performed to confirm the position of the stimulation sites in the brain. Seven rats survived the surgery and the recovery period without technical failures such as connector breaks. We observed that three of them tended to stay in the virtual cage during stimulation, and this effect was maintained for two weeks. Histological analysis revealed that the electrode tips were correctly placed in the MFB region of the rats. The other four subjects showed no apparent preference for the virtual cage. In these rats, we did not find electrode tips in the MFB, or could not determine their positions. Almost half of the rats tended to remain inside the virtual cage when position-related reward stimuli were triggered in the MFB region. Notably, our system did not require previous training or sequential interventions to affect the behavioral preferences of subjects. This process is similar to the situation in which sheep are chased by a shepherd dog in the desired direction.

A Current Monitoring and Over-Current Detection Circuit for Safe Electrical Stimulation

This brief presents an integrated solution to over-current protection in neuromuscular stimulators. The proposed approach provides fast detection of a single-fault condition, i.e., unintentional electrode short circuit or malfunction of the stimulator, thereby preventing prolonged high-intensity currents from flowing into tissues. In addition, a programmable current threshold enables the system to be also used for monitoring the stimulation intensity. The proposed solution was designed in a 180 nm high-voltage CMOS technology, and its functionality was verified by post-layout simulations in which the safety mechanisms were tested under fault conditions. The implementation only occupies an area of 0.286 mm, making it feasible to be embedded in fully integrated NMES stimulators while providing the required patient safety.

Active charge balancer for CMOS integration of an array of neural stimulators

Neuromorphic engineering, wherein the structure of a neural system is reconstructed and its applications are exploited on CMOS integrated circuits, presents various developments. This study focuses on interface technology that can adapt CMOS integrated circuits to a neural system. Existing neural stimulators are designed to accurately transmit signals and accurately stimulate the nerves; however, embedding them into the brain is challenging owing to their size and power [1]. One solution is to reduce the circuit area and power consumption at the expense of certain precision. This study successfully induces nerve activity using a designed circuit that is connected to the brain of rat; the proposed circuit demonstrates a good effect of charge balance. Moreover, this paper proposes CMOS neural stimulating circuits with low power consumption and a small area.

Signal generation and regulation of implantable nerve stimulator

In the treatment of nervous system diseases, implantable nerve stimulators have attracted more and more attention because of their obvious therapeutic efficacy and high safety. The generation and regulation of stimulus signals are the most important step in the design of an implantable nerve stimulator. The stimulation signals from the implanted nerve stimulator act directly on nerve cells. If the stimulus signal is not delivered accurately according to the set parameters, it will not only affect the therapeutic effect but also cause unpredictable malignant consequences. To generate stimulus signals that meet certain requirements, the different circuit structures need to be designed to be applied to the stimulators with different function types. In this paper, five types of stimulator circuits are introduced, and their strengths and weaknesses are analyzed based on the detailed introduction of the working principles of the different stimulator circuits, which might provide a theoretical and practical reference for future research.

Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing.

'Smart' bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies. Additionally, while adhesive electrodes are essential for robust signal transduction, detachment of existing adhesive dressings can lead to secondary damage to delicate wound tissues without switchable adhesion. Here we overcome these issues by developing a flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with skin-interfacing hydrogel electrodes capable of on-demand adhesion and detachment. In mice, we demonstrate that our wound care system can continuously monitor skin impedance and temperature and deliver electrical stimulation in response to the wound environment. Across preclinical wound models, the treatment group healed ~25% more rapidly and with ~50% enhancement in dermal remodeling compared with control. Further, we observed activation of proregenerative genes in monocyte and macrophage cell populations, which may enhance tissue regeneration, neovascularization and dermal recovery.

An ASIC System for Closed-Loop Blood Pressure Modulation Through Right Cervical Vagus Nerve Stimulation.

Heart disease is the leading cause of death worldwide. Hypertension is an important precursor and the most common risk factor to heart failure. While some patients can control their high blood pressure with pharmaceuticals, many suffer from resistant hypertension, where antihypertensive medications do not achieve the desired outcome. Electrical stimulation is an emerging therapy to modulate blood pressure and integrating it with closed-loop feedback can improve blood pressure control. We design and fabricate two application-specific integrated circuits (ASICs) for stimulation and pressure sensing using TSMC's 180 nm MS RF G process. We create a closed-loop system by integrating the ASICs with a microscale pressure sensor and a custom-built Python script and test the full system in six Long Evans rats using vagus nerve stimulation. After calibration and benchtop verification, we prove the functionality of the system in lowering, and maintaining a desired blood pressure in vivo. The system effectively monitors pressure and stimulates when that pressure exceeds the user-determined threshold. By combining this stimulation therapy with a pressure sensor, we present a novel closed-loop, electroceutical system that has the potential to monitor and modulate blood pressure. We present a drug-free, potentially side-effect-free electroceutical therapeutic for managing resistant hypertension.

Energy efficiency of pulse shaping in electrical stimulation: the interdependence of biophysical effects and circuit design losses

Power efficiency in electrical stimulator circuits is crucial for developing large-scale multichannel applications like bidirectional brain-computer interfaces and neuroprosthetic devices. Many state-of-the-art papers have suggested that some non-rectangular pulse shapes are more energy-efficient for exciting neural excitation than the conventional rectangular shape. However, additional losses in the stimulator circuit, which arise from employing such pulses, were not considered. In this work, we analyze the total energy efficiency of a stimulation system featuring non-rectangular stimuli, taking into account the losses in the stimulator circuit. To this end, activation current thresholds for different pulse shapes and durations in cortical neurons are modeled, and the energy required to generate the pulses from a constant voltage supply is calculated. The proposed calculation reveals an energy increase of 14%–51% for non-rectangular pulses compared to the conventional rectangular stimuli, instead of the decrease claimed in previous literature. This result indicates that a rectangular stimulation pulse is more power-efficient than the tested alternative shapes in large-scale multichannel electrical stimulation systems.