Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> A method is described for the manufacture of a three-dimensional electrode array geometry for chronic intracortical stimulation. This silicon based array consists of a 4.2*4.2*0.12 mm thick monocrystalline substrate, from which project 100 conductive, silicon needles sharpened to facilitate cortical penetration. Each needle is electrically isolated from the other needles, and is about 0.09 mm thick at its base and 1.5 mm long. The sharpened end of each needle is coated with platinum to facilitate charge transfer into neural tissue. The following manufacturing processes were used to create this array: thermomigration of 100 aluminum pads through an n-type silicon block, creating trails of highly conductive p/sup +/ silicon isolated from each other by opposing pn junctions; a combination of mechanical and chemical micromachining which creates individual penetrating needles of the p/sup +/ silicon trails; metal deposition to create active electrode areas and electrical contact pads; and array encapsulation with polyimide. > <s> BIB001 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> A number of research groups are developing electrical implants that can be attached directly to the retina in an attempt to restore vision to patients suffering from retinal degeneration. However, despite promising results in animal experiments, there are still several major obstacles to overcome before retinal prostheses can be used clinically. <s> BIB002 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants, making the biocompatibility of implanted electrodes a primary concern in device design. This review presents the biological components and time course of the acute and chronic tissue reaction in brain tissue, analyses the brain tissue response of current electrode systems, and comments on the various material science and bioactive strategies undertaken by electrode designers to enhance electrode performance. <s> BIB003 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Deep brain stimulation (DBS) was developed to treat movement disorders, but translational research has revealed new targets for this procedure. Aziz and colleagues elucidate the neurophysiological and translational principles of DBS and provide a model for its underlying mechanisms. <s> BIB004 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> This paper presents a review of wearable EEG technology: the evolution of ambulatory EEG units from the bulky, limited lifetime devices available today to small devices present only on the head that can record the EEG for days, weeks or months at a time. The EEG requirements, application areas and research challenges are highlighted. A survey of neurologists is also carried out clearly indicating the medical desire for such devices. <s> BIB005 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Although there have been substantial innovations in antiepileptic drug therapy over the past 15 years, the proportion of patients with medically refractory epilepsy has remained largely unchanged, highlighting the need for new therapeutic strategies. In this article, Stacey and Litt review recent progress in the development of implantable devices designed to detect, predict and extinguish seizures, and consider the challenges that lie ahead, including improvements in seizure prediction and personalized control. <s> BIB006 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Regaining motor function is of high priority to patients with spinal cord injury (SCI). A variety of electronic devices that interface with the brain or spinal cord, which have applications in neural prosthetics and neurorehabilitation, are in development. Owing to our advancing understanding of activity-dependent synaptic plasticity, new technologies to monitor, decode and manipulate neural activity are being translated to patient populations, and have demonstrated clinical efficacy. Brain-machine interfaces that decode motor intentions from cortical signals are enabling patient-driven control of assistive devices such as computers and robotic prostheses, whereas electrical stimulation of the spinal cord and muscles can aid in retraining of motor circuits and improve residual capabilities in patients with SCI. Next-generation interfaces that combine recording and stimulating capabilities in so-called closed-loop devices will further extend the potential for neuroelectronic augmentation of injured motor circuits. Emerging evidence suggests that integration of closed-loop interfaces into intentional motor behaviours has therapeutic benefits that outlast the use of these devices as prostheses. In this Review, we summarize this evidence and propose that several known plasticity mechanisms, operating in a complementary manner, might underlie the therapeutic effects that are achieved by closing the loop between electronic devices and the nervous system. <s> BIB007 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic in vivo data (133–189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array. <s> BIB008 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Wireless power delivery and telemetry have enabled completely implantable neural devices. Current day implants are controlled, monitored, and powered wirelessly, eliminating the need for batteries and prolonging the lifetime. A brief overview of wireless platforms for such implantable devices is presented in this paper alongside an in-depth discussion of wireless platform for peripheral nerve implants covering design requirements, link design, and safety. Initial acute studies on the performance of the wireless power and data links in rodents are also presented. <s> BIB009 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> This work reports an ear-EEG acquisition system with dry-contact active electrodes for future wearable applications. Employing dedicated chopper buffer in the active electrodes, a prototype fabricated in a 0.18-µm CMOS demonstrates input impedance as large as 18GΩ@DC and 6.7GΩ@50Hz, and 3.03fA/vHz input current noise, and a total input-referred noise (IRN) of 0.67µV rms in 0.5–100Hz bandwidth. System's CMRR in combination with active electrodes is higher than 100dB@DC. Under large source impedance imbalance of 1MΩ, a 78-dB@50Hz CMRR is still obtained. To validate the system's ability to record EEG, an auditory stead-state response was measured, showing same SNR with wet electrodes and a commercial EEG amplifier. <s> BIB010 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> For patients with bilateral cochlear implants (BiCIs), understanding a target talker in a noisy situation can be difficult. Current efforts for improving speech-in-noise understanding have focused on improving signal-to-noise ratio by using multiple microphones or signal processing, with only moderate improvements in speech understanding performance. However, BiCI users typically report having a better ear for listening which can lead to an asymmetry in speech unmasking performance. This work proposes a novel listening strategy for improving speech-in-noise understanding by combining (a) a priori knowledge of a better ear and having a BiCI user selectively attend to a target talker in that ear with (b) signal processing that delivers the target talker to the better ear and the noisy background to the opposite ear. This strategy is different from traditional noise reduction strategies because it maintains situational awareness (background sounds are delivered to the ear contralateral to the better ear) while improving speech understanding. Speech recognition performance was evaluated with and without the better ear strategy in a speech-in-noise listening test using a virtual auditory space created from individualized head-related transfer functions. Listeners showed an average improvement of 4.4 dB signal-to-noise ratio in their speech reception threshold when using the better ear strategy with no listener showing a decrement in performance. This implies that the strategy has the potential to boost speech-in-noise recognition in BiCI users and may be useful in other hearing assistance devices such as hearing aids. <s> BIB011 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> The ability to decipher brain functions and understand the neuronal communication networking properties to develop innovative solutions to treat neurodegenerative diseases remains one of the biggest challenges in biomedicine. Since the early days, numerous solutions have been proposed for BMI, largely concentrating on the use of tethered electrodes that are inserted into the brain to either stimulate or suppress neural activities. In recent years, the field of optogenetics has provided a new alternative of utilizing light to stimulate genetically engineered neurons. While the original approach proposed the use of tethered optical cables inserted into the skull to transfer light into the brain for stimulation, numerous advances have been made to incorporate wireless technologies that will allow these devices to be attached to the skull or implanted in the brain. This article presents a review on the current technologies that have been proposed for different wireless optogenetics solutions, ranging from devices that are head mounted to miniature devices that can be embedded deep in the brain. We focus on a comparative analysis of the architecture and structure of the devices, the wireless technology used for signaling to the unit, as well as the energy consumption profile for each of the devices. Finally, the article presents future challenges to further miniaturize wireless optogenetic devices, concentrating specifically on the communication properties. <s> BIB012 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Abstract Recently developed classes of ultraminiaturized wireless devices provide powerful capabilities in neuroscience research, as implantable light sources for simulation/inhibition via optogenetics, as integrated microfluidic systems for programmed pharmacological delivery and as multimodal sensors for physiological measurements. These platforms leverage basic advances in biocompatible materials, semiconductor device designs and systems engineering concepts to afford modes of operation that are qualitatively distinct from those of conventional approaches that tether animals to external hardware by means of optical fibers, electrical cables and/or fluidic tubing. Neuroscience studies that exploit the unique features of these technologies enable insights into neural function through targeted stimulation, inhibition and recording, with spatially and genetically precise manipulation of neural circuit activity. Experimental possibilities include studies in naturalistic, three dimensional environments, investigations of pair-wise or group related social interactions and many other scenarios of interest that cannot be addressed using traditional hardware. <s> BIB013 </s> Biointegrated and Wirelessly Powered Implantable Brain Devices: A Review <s>  <s> Neural recording electrode technologies have contributed considerably to neuroscience by enabling the extracellular detection of low-frequency local field potential oscillations and high-frequency action potentials of single units. Nevertheless, several long-standing limitations exist, including low multiplexity, deleterious chronic immune responses and long-term recording instability. Driven by initiatives encouraging the generation of novel neurotechnologies and the maturation of technologies to fabricate high-density electronics, novel electrode technologies are emerging. Here, we provide an overview of recently developed neural recording electrode technologies with high spatial integration, long-term stability and multiple functionalities. We describe how these emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future. <s> BIB014
In contrary, portable surface electroencephalography (EEG) permits the uninterrupted monitoring and evaluation of brain activity macroscopically for a long period of time BIB005 , BIB010 . However, same as with fMRI, the low spatiotemporal resolution of EEG sabotages the accuracy of measurement and is incompatible with neuroscience studies on scenarios such as single-neuron resolution. Individual neurons constitute the morphological as well as operational units of the brain and their spatiotemporal recordings are key to properly understand the brain function. Nowadays, to record extracellular activities, including action potentials and local field potentials (LFPs), implantable neural devices are most commonly used BIB014 , BIB001 . These invasive and implantable neural interfacing devices are widely applied in different clinical scenarios for example, peripheral, and spinal nerve interfaces for monitoring epilepsy, cochlear and retinal implants, and as deep brain stimulators BIB007 BIB011 BIB004 BIB006 BIB002 . Like most of the implantable devices, the exceedingly dynamic and corrosive condition of the biological tissue is antagonistic to implants. The vulnerability originates due to mechanical and physical mismatch linking the implants and brain tissues which causes scar formation and introduces neuroinflammatory response, thus, gradually degrades the recorded neural signal BIB008  BIB003 . As a result, implantable neural devices are required to be bioinert, physically soft and small enough to complement those of brain tissues. The goal is then developing neuron-like, multifunctional neural engineering platforms or neuroprostheses interfaces that enforce significantly low constraints on the normal environments of the brain and incites negligible inflammatory responses. Implantable neural devices based on tethered and rigid devices initiate considerable tissue damage and disturbance with the normal behaviour of animals, thereby hampering chronic in vivo operations BIB012 BIB013 BIB009  . The mechanical mismatch and micromotion introduced by the interconnection that links the neural implant placed near the brain and skull-mounted connector (i.e., tether), can be minimized by using a wireless power system. The most commonly used wireless power technologies used are electromagnetic, photovoltaic, and ultrasound BIB012 ,  . The ultrasound-based power transfer method uses ultrasound to vibrate an energy harvester based on implantable piezoelectric. On the other hand, photovoltaic wireless power harvesting is based on the conversion of light into electricity by using photovoltaic cells. Although innovative, these wireless solutions are limited due to the complex circuitry and low power transfer distance. As a result, the electromagnetic based wireless power transfer, which working principle is the electromagnetic induction, This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see http://creativecommons.org/licenses/by/4.0/ still the most popular choice to realize the fully implantable, wirelessly powered, and miniaturized neural devices for chronic implantation BIB012 , BIB013 ,  . This paper studies novel design approaches for developing soft, flexible and wireless interfaces of implantable neural devices by manifesting physical and mechanical consistency with brain tissues. The review starts by considering different neural interfaces, incorporating key parameters to consider for implantable neural probes. Following sections highlights the challenges and progress in implantable probe biointegration using circuit analysis of the probe/tissue interface. In Section III, most of the common wireless power modalities for implantable neural interface have been addressed including electromagnetic, ultrasound, and solar. Finally, there is a conclusion section, followed by the discussion on the state of the implantable neural interface suggesting scopes for future studies.