Neural Implants Research Articles

Comparative analysis of energy transfer mechanisms for neural implants.

As neural implant technologies advance rapidly, a nuanced understanding of their powering mechanisms becomes indispensable, especially given the long-term biocompatibility risks like oxidative stress and inflammation, which can be aggravated by recurrent surgeries, including battery replacements. This review delves into a comprehensive analysis, starting with biocompatibility considerations for both energy storage units and transfer methods. The review focuses on four main mechanisms for powering neural implants: Electromagnetic, Acoustic, Optical, and Direct Connection to the Body. Among these, Electromagnetic Methods include techniques such as Near-Field Communication (RF). Acoustic methods using high-frequency ultrasound offer advantages in power transmission efficiency and multi-node interrogation capabilities. Optical methods, although still in early development, show promising energy transmission efficiencies using Near-Infrared (NIR) light while avoiding electromagnetic interference. Direct connections, while efficient, pose substantial safety risks, including infection and micromotion disturbances within neural tissue. The review employs key metrics such as specific absorption rate (SAR) and energy transfer efficiency for a nuanced evaluation of these methods. It also discusses recent innovations like the Sectored-Multi Ring Ultrasonic Transducer (S-MRUT), Stentrode, and Neural Dust. Ultimately, this review aims to help researchers, clinicians, and engineers better understand the challenges of and potentially create new solutions for powering neural implants.

Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant.

Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.

Flexible switch matrix addressable electrode arrays with organic electrochemical transistor and pn diode technology

Due to their effective ionic-to-electronic signal conversion and mechanical flexibility, organic neural implants hold considerable promise for biocompatible neural interfaces. Current approaches are, however, primarily limited to passive electrodes due to a lack of circuit components to realize complex active circuits at the front-end. Here, we introduce a p-n organic electrochemical diode using complementary p- and n-type conducting polymer films embedded in a 15-μm -diameter vertical stack. Leveraging the efficient motion of encapsulated cations inside this polymer stack and the opposite doping mechanisms of the constituent polymers, we demonstrate high current rectification ratios (105\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${10}^{5}$$\\end{document}) and fast switching speeds (230 μs). We integrate p-n organic electrochemical diodes with organic electrochemical transistors in the front-end pixel of a recording array. This configuration facilitates the access of organic electrochemical transistor output currents within a large network operating in the same electrolyte, while minimizing crosstalk from neighboring elements due to minimized reverse-biased leakage. Furthermore, we use these devices to fabricate time-division-multiplexed amplifier arrays. Lastly, we show that, when fabricated in a shank format, this technology enables the multiplexing of amplified local field potentials directly in the active recording pixel (26-μm diameter) in a minimally invasive form factor with shank cross-sectional dimensions of only 50×8 μm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mu m}^{2}$$\\end{document}.

Ultra‐Soft Neural Probe with a Temporary High‐Strength U‐Section Coating by Picosecond Laser Micromachining

This paper reports an ultra‐soft neural probe with a temporary high‐strength U‐section coating of polyethylene glycol (PEG) for the first time. Its fabrication is compatible with MEMS processes, and an ultrathin U‐section coating over the probe's back and sidewall is precisely formed by spinning and cold laser cutting. With this novel coating, the probe has both minimized cross‐sectional area and sufficient mechanical strength for low‐invasive penetration into the brain. Besides, the remained ultra‐soft deformable probe after PEG dissolution is expected to be the next generation of neural implants for chronic recording. © 2024 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.

Neural Implants without Active Implanted Electronics: Possibilities and Limitations of Transcutaneous Coupling in Miniaturized Active Implants

Neural Implants without Active Implanted Electronics: Possibilities and Limitations of Transcutaneous Coupling in Miniaturized Active Implants

78.8 pJ/b, 100 Mb/s Noncoherent IR-UWB Receiver for Multichannel Neurorecording Implants.

In this article, we present a novel approach for designing a low-power, low-area impulse radio ultra-wideband (IR-UWB) noncoherent receiver capable of achieving a data rate of 100 Mbps. Our proposed receiver demonstrates the ability to demodulate ON-OFF keying pulse streams across the entire lower frequency band defined by the Federal Communication Commission for UWB applications. The key components of the proposed receiver include a reconfigurable differential two-stage low-noise amplifier, a fully differential squarer, narrow-band interface rejection filters, and variable gain baseband amplifiers. These circuits work cohesively to ensure efficient signal reception and processing. To validate the performance of the proposed receiver, we implemented the design using TSMC 40-nm CMOS process technology. A short-range communication including a 1.5 cm tissue layer is tested utilizing a typical upconversion UWB transmitter fabricated in the same technology. Remarkably, the proposed receiver achieves a data rate of 100 Mbps with an impressively low energy efficiency of 78.8 pJ/b and occupies an area of 0.705 mm2. The compact size, remarkable energy efficiency, and high data rate capabilities of the proposed receiver meet the stringent requirements of neural recording implants.

Investigation of a chondroitin sulfate-based bioactive coating for neural interface applications.

Invasive neural implants allow for high-resolution bidirectional communication with the nervous tissue and have demonstrated the ability to record neural activity, stimulate neurons, and sense neurochemical species with high spatial selectivity and resolution. However, upon implantation, they are exposed to a foreign body response which can disrupt the seamless integration of the device with the native tissue and lead to deterioration in device functionality for chronic implantation. Modifying the device surface by incorporating bioactive coatings has been a promising approach to camouflage the device and improve integration while maintaining device performance. In this work, we explored the novel application of a chondroitin sulfate (CS) based hydrophilic coating, with anti-fouling and neurite-growth promoting properties for neural recording electrodes. CS-coated samples exhibited significantly reduced protein-fouling in vitro which was maintained for up to 4-weeks. Cell culture studies revealed a significant increase in neurite attachment and outgrowth and a significant decrease in microglia attachment and activation for the CS group as compared to the control. After 1-week of in vivo implantation in the mouse cortex, the coated probes demonstrated significantly lower biofouling as compared to uncoated controls. Like the in vitro results, increased neuronal population (neuronal nuclei and neurofilament) and decreased microglial activation were observed. To assess the coating's effect on the recording performance of silicon microelectrodes, we implanted coated and uncoated electrodes in the mouse striatum for 1 week and performed impedance and recording measurements. We observed significantly lower impedance in the coated group, likely due to the increased wettability of the coated surface. The peak-to-peak amplitude and the noise floor levels were both lower in the CS group compared to the controls, which led to a comparable signal-to-noise ratio between the two groups. The overall single unit yield (% channels recording a single unit) was 74% for the CS and 67% for the control group on day 1. Taken together, this study demonstrates the effectiveness of the polysaccharide-based coating in reducing biofouling and improving biocompatibility for neural electrode devices.

Design of a Low-Power, High-Data-Rate, and Crystal-Less All-Digital IR-UWB Transmitter for High-Density Neural Implants

Design of a Low-Power, High-Data-Rate, and Crystal-Less All-Digital IR-UWB Transmitter for High-Density Neural Implants

BrainForest: Neuromorphic Multiplier-Less Bit-Serial Weight-Memory-Optimized 1024-Tree Brain-State Classification Processor.

Personalized brain implants have the potential to revolutionize the treatment of neurological disorders and augment cognition. Medical implants that deliver therapeutic stimulation in response to detected seizures have already been deployed for the treatment of epilepsy. These devices require low-power integrated circuits for life-long operation. This constraint impedes the integration of machine-learning driven classifiers that could improve treatment outcomes. This paper introduces BrainForest, a neuromorphic multiplier-less bit-serial weight-memory-optimized brain-state classification processor. The architecture achieves state-of-the-art energy efficiency using two layers of neuron models to implement the spectral and temporal functions needed for classification: 1) resonate-and-fire neurons are used to extract physiological signal band energy EEG biomarkers 2) leaky integrator neurons are used to build multi-timescale representations for classification. Sparse neural model firing activity is used to clock-gate device logic, thereby decreasing power consumption by 93%. An energy-optimized 1024-tree boosted decision forest performs the classification used to trigger stimulation in response to detected pathological brain states. The IC is implemented in 65nm CMOS with state-of-the-art power consumption (best case: 9.6μW, typical: 118μW), achieving a seizure sensitivity of 97.5% with a false detection rate of 2.08 per hour.

Neuralink and Brain-Computer Interface-Exciting Times for Artificial Intelligence.

Purvish Mahendra ParikhBrain-computer interfaces are becoming a tangible reality, capable of significantly aiding patients in real-world scenarios. The recent approval by the U.S. Food and Drug Administration for clinical human trials of Neuralink marks a monumental stride, comparable to Mr. Armstrong's moonwalk. Numerous other companies are also pioneering innovative solutions in this domain. Presently, over 150,000 patients in the United States possess brain implants. As technology advances, it holds the potential to alleviate various conditions, notably motor paralysis, cerebral palsy, and involuntary movements.

Phase Transition Liquid Metal Enabled Emerging Biomedical Technologies and Applications.

Phase change materials that can absorb or release large amounts of heat during phase transition, play a critical role in many important processes, including heat dissipation, thermal energy storage, and solar energy utilization. In general, phase change materials are usually encapsulated in passive modules to provide assurance for energy management. The shape and mechanical changes of these materials are greatly ignored. An emerging class of phase change materials, liquid metals (LMs) have attracted significant interest beyond thermal management, including in transformable robots, flexible electronics, soft actuators, and biomedicine. Interestingly, the melting point of LM is highly tunable around body temperature, allowing it to experience considerable stiffness change when interacting with human organisms during solid-liquid change, which brings about novel phenomena, applied technologies, and therapeutic methods, such as mechanical destruction of tumors, neural electrode implantation technique, and embolization therapy. This review focuses on the technology, regulation, and application of the phase change process along with diverse changes of LM to facilitate emerging biomedical applications based on the influences of mechanical stiffness change and versatile regulation strategies. Typical applications will also be categorized and summarized. Lastly, the advantages and challenges of using the unique and reversible process for biomedicine will be discussed.

The differential effects of psychiatrists' and patients’ prior experiences on views about psychiatric electroceutical interventions

The aim of this study is to examine ways in which prior experiences and familiarity with psychiatric electroceutical interventions (PEI) shape psychiatrists' and patients’ views about these interventions. We administered a national survey, with an embedded experiment, to psychiatrists (n = 505) and adults diagnosed with depression (n = 1050). We randomly assigned respondents to one of 8 conditions using a full factorial experimental design: 4 PEI modalities [ECT, rTMS, DBS, or adaptive brain implants (ABIs)] by 2 depression severity levels [moderate or severe]. We analyzed the survey data with ANOVA and OLS linear regression models. Patients having experience with any PEI reported more positive affect toward, but also greater perceived risk from, their assigned PEI than did patients with no such experience. Psychiatrists who referred or administered any PEI reported more positive affect toward and greater perceived influence on self and perceived benefit from their assigned PEI than did psychiatrists with no such familiarity. Limitations of our study include that our participants were randomly assigned to a PEI, not necessarily to the one they had experience with. Moreover, our study did not directly ask about the kind of experiences participants had with a given PEI.Overall, our survey data shows that greater experience with PEIs elicits more positive affect in both stakeholder groups. Beyond this, prior PEI experience shapes attitudes towards these interventions in complex ways. Further research linking different types of experience with a given PEI would help better understand factors shaping attitudes about specific PEIs.

Head-mounted central venous access during optical recordings and manipulations of neural activity in mice.

Establishing reliable intravenous catheterization in mice with optical implants allows the combination of neural manipulations and recordings with rapid, time-locked delivery of pharmacological agents. Here we present a procedure for handmade jugular vein catheters designed for head-mounted intravenous access and provide surgical and postoperative guidance for improved survival and patency. A head-mounted vascular access point eliminates the need for a back-mounted button in animals already receiving neural implants, thereby reducing sites of implantation. This protocol, which is readily adoptable by experimenters with previous training and experience in mouse surgery, enables repeated fiber photometry recordings or optogenetic manipulation during drug delivery in adult mice that are awake and behaving, whether head fixed or freely moving. With practice, an experienced surgeon requires ~30 min to perform catheterization on each mouse. Altogether, these techniques facilitate the reliable and repeated delivery of pharmacological agents in mouse models while simultaneously recording at high temporal resolution and/or manipulating neural populations.

Brain implants help people to recover after severe head injury

Brain implants help people to recover after severe head injury

The Longevity of Neural Interfaces—Mechanical Oscillation of Thin Film Metal‐Based Neural Electrodes Determine Stability During Electrical Stimulation

AbstractThe success of bioelectronics medicine with neural implants inevitably depends on the longevity of neural interfaces where a full understanding of the associated risks serves as the first step, to begin with. Until now, failure of neural electrodes is primarily explained by extreme electrochemical reactions, whereas no direct link between electrical stimulation and mechanical deformation of microelectrodes can be proved. The research provides new quantitative evidence of electrically induced mechanical vibrations in thin film neural interfaces. This study investigates the dynamic changes in intrinsic mechanical stress in clinically used neural electrodes under electrical stimulation. Via live imaging of the electrode plane, the deformation and progressive adhesion loss of the thin film during stimulation is for the first time approved. The results reveal nano‐oscillations in the interfaces under alternating current. This hints at a direct link between electrochemical charge transfer and mechanical stability. Considering neural interfaces as resonating actuators serves as a key to assessing the stability of neural interfaces and a valuable input to a longstanding question on the associated failure mechanisms of thin film microelectrodes. It is believed, that the outcome of this work may significantly contribute to improving the future design of thin film neural interfaces and better conditioning them for life‐long reliability.

Piezoelectricity, Pyroelectricity, and Ferroelectricity in Biomaterials and Biomedical Applications.

Piezoelectric, pyroelectric, and ferroelectric materials are considered unique biomedical materials due to their dielectric crystals and asymmetric centers that allow them to directly convert various primary forms of energy in the environment, such as sunlight, mechanical energy, and thermal energy, into secondary energy, such as electricity and chemical energy. These materials possess exceptional energy conversion ability and excellent catalytic properties, which have led to their widespread usage within biomedical fields. Numerous biomedical applications have demonstrated great potential with these materials, including disease treatment, biosensors, and tissue engineering. For example, piezoelectric materials are used to stimulate cell growth in bone regeneration, while pyroelectric materials are applied in skin cancer detection and imaging. Ferroelectric materials have even found use in neural implants that record and stimulate electrical activity in the brain. This paper reviews the relationship between ferroelectric, piezoelectric, and pyroelectric effects and the fundamental principles of different catalytic reactions. It also highlights the preparation methods of these three materials and the significant progress made in their biomedical applications. The review concludes by presenting key challenges and future prospects for efficient catalysts based on piezoelectric, pyroelectric, and ferroelectric nanomaterials for biomedical applications.

Breakthroughs in Brain Implants.

In 2023, Brain implants got a big boost. Neuralink, Elon Musk's startup, began recruiting for its first clinical trial for paralysis patients; Precision Neuroscience received breakthrough designation from the Food and Drug Administration (FDA), allowing it to fast-track its own trials. Meanwhile, scientific advances are revealing promising new applications for such devices, including more comprehensive restoration of speech, sight, hearing, and movement to people who have lost those abilities, as well as help for psychiatric conditions, such as eating disorders and depression.

Activation of mechanoluminescent nanotransducers by focused ultrasound enables light delivery to deep-seated tissue in vivo.

Light is used extensively in biological and medical research for optogenetic neuromodulation, fluorescence imaging, photoactivatable gene editing and light-based therapies. The major challenge to the in vivo implementation of light-based methods in deep-seated structures of the brain or of internal organs is the limited penetration of photons in biological tissue. The presence of light scattering and absorption has resulted in the development of invasive techniques such as the implantation of optical fibers, the insertion of endoscopes and the surgical removal of overlying tissues to overcome light attenuation and deliver it deep into the body. However, these procedures are highly invasive and make it difficult to reposition and adjust the illuminated area in each animal. Here, we detail a noninvasive approach to deliver light (termed 'deLight') in deep tissue via systemically injected mechanoluminescent nanotransducers that can be gated by using focused ultrasound. This approach achieves localized light emission with sub-millimeter resolution and millisecond response times in any vascularized organ of living mice without requiring invasive implantation of light-emitting devices. For example, deLight enables optogenetic neuromodulation in live mice without a craniotomy or brain implants. deLight provides a generalized method for applications that require a light source in deep tissues in vivo, such as deep-brain fluorescence imaging and photoactivatable genome editing. The implementation of the entire protocol for an in vivo application takes ~1-2 weeks.

MRI‐Compatible, Transparent PEDOT:PSS Neural Implants for the Alleviation of Neuropathic Pain with Motor Cortex Stimulation

AbstractSimultaneous monitoring of electrophysiology and magnetic resonance imaging (MRI) could guide the innovative diagnosis and treatment of various neurodegenerative diseases that are previously impossible. However, this technique is difficult because the existing metal‐based implantable neural interface for electrophysiology is not free from signal distortions from its intrinsic magnetic susceptibility while performing an MRI of the implanted area of the neural interface. Moreover, brain tissue heating from neural implants generated by the radiofrequency field from MRI poses potential hazards for patients. Previous studies with soft polymer‐based electrode arrays provide relatively suitable MRI compatibility but does not guarantee high‐resolution electrophysiological signal acquisition and stimulation performance. Here, MRI compatible, optically transparent flexible implantable device capable of electrophysiological multichannel mapping and electrical stimulation is introduced. Using the device, neuropathic pain (NP) relief with a 30‐channel electrophysiological mapping of the somatosensory area before and after motor cortex stimulation (MCS) in allodynia rats after noxious stimulation is confirmed. Additionally, artifact‐free manganese‐enhanced MRI of dramatic relief of pain‐related region activity by MCS is demonstrated. Furthermore, artifact‐free optogenetics with transgenic mice is also investigated by recording light‐evoked potentials. These results suggest a promising neuro‐prosthetic for analyzing and modulating spatiotemporal neurodynamic without MRI or optical modality resolution constraints.

Brain-implanted conductors amplify radiofrequency fields in rodents: Advantages and risks.

Over the past few decades, daily exposure to radiofrequency (RF) fields has been increasing due to the rapid development of wireless and medical imaging technologies. Under extreme circumstances, exposure to very strong RF energy can lead to heating of body tissue, even resulting in tissue injury. The presence of implanted devices, moreover, can amplify RF effects on surrounding tissue. Therefore, it is important to understand the interactions of RF fields with tissue in the presence of implants, in order to establish appropriate wireless safety protocols, and also to extend the benefits of medical imaging to increasing numbers of people with implanted medical devices. This study explored the neurological effects of RF exposure in rodents implanted with neuronal recording electrodes. We exposed freely moving and anesthetized rats and mice to 950 MHz RF energy while monitoring their brain activity, temperature, and behavior. We found that RF exposure could induce fast onset firing of single neurons without heat injury. In addition, brain implants enhanced the effect of RF stimulation resulting in reversible behavioral changes. Using an optical temperature measurement system, we found greater than tenfold increase in brain temperature in the vicinity of the implant. On the one hand, our results underline the importance of careful safety assessment for brain-implanted devices, but on the other hand, we also show that metal implants may be used for neurostimulation if brain temperature can be kept within safe limits.