Guest Editorial: Implantable bioelectronics.

The realm of implantable bioelectronics represents a frontier in medical science, merging technology, biology, and medicine to innovate treatments that enhance, restore, or monitor physiological functions. This field has yielded devices like cochlear implants, cardiac pacemakers, deep brain stimulators, and vagus nerve stimulators, each designed to address a specific health condition, ranging from sensorineural hearing loss to chronic pain, neurological disorders, and heart rhythm irregularities. Such devices underscore the potential of bioelectronics to significantly improve patient outcomes and quality of life. Recent technological breakthroughs in materials science, nanotechnology, and microfabrication have enabled the development of more sophisticated, smaller, and biocompatible bioelectronic devices. However, the field also encounters challenges, particularly in extending the capabilities of devices such as retinal prostheses, which aim to restore vision but currently offer limited visual acuity. Research in implantable bioelectronics is highly timely, driven by an aging global population with a growing prevalence of chronic diseases that could benefit from these technologies. The convergence of societal health needs, advancing technological capabilities, and a supportive ecosystem for innovation marks this era as pivotal for bioelectronic research.

Soft electrodes for simultaneous bio-potential and bio-impedance study of the face.

The human body's vascular system is a finely regulated network: blood vessels can change in shape (i.e. constrict, or dilate), their elastic response may shift and they may undergo temporary and partial blockages due to pressure applied by skeletal muscles in their immediate vicinity. Simultaneous measurement of muscle activation and the corresponding changes in vessel diameter, in particular at anatomical regions such as the face, is challenging, and how muscle activation constricts blood vessels has been experimentally largely overlooked. Here we report on a new electronic skin technology for facial investigations to address this challenge. The technology consists of screen-printed dry carbon electrodes on soft polyurethane substrate. Two dry electrode arrays were placed on the face: One array for bio-potential measurements to capture muscle activity and a second array for bio-impedance. For the bio-potential signals, independent component analysis (ICA) was used to differentiate different muscle activations. Four-contact bio-impedance measurements were used to extract changes (related to artery volume change), as well as beats per minute (BPM). We performed concurrent bio-potential and bio-impedance measurements in the face. From the simultaneous measurements we successfully captured fluctuations in the superficial temporal artery diameter in response to facial muscle activity, which ultimately changes blood flow. The observed changes in the face, following muscle activation, were consistent with measurements in the forearm and were found to be notably more intricate. Both at the arm and the face, a clear increase in the baseline impedance was recorded during muscle activation (artery narrowing), while the impedance changes signifying the pulse had a clear repetitive trend only at the forearm. These results reveal the direct connection between muscle activation and the blood vessels in their vicinity and start to unveil the complex mechanisms through which facial muscles might modulate blood flow and possibly affect human physiology.

Facial electromyography during exercise using soft electrode array: A feasibility study.

The use of wearable sensors for real-time monitoring of exercise-related measures has been extensively studied in recent years (e.g., performance enhancement, optimizing athlete's training, and preventing injuries). Surface electromyography (sEMG), which measures muscle activity, is a widely researched technology in exercise monitoring. However, due to their cumbersome nature, traditional sEMG electrodes are limited. In particular, facial EMG (fEMG) studies in physical training have been limited, with some scarce evidence suggesting that fEMG may be used to monitor exercise-related measurements. Altogether, sEMG recordings from facial muscles in the context of exercise have been examined relatively inadequately. In this feasibility study, we assessed the ability of a new wearable sEMG technology to measure facial muscle activity during exercise. Six young, healthy, and recreationally active participants (5 females), performed an incremental cycling exercise test until exhaustion, while facial sEMG and vastus lateralis (VL) EMG were measured. Facial sEMG signals from both natural expressions and voluntary smiles were successfully recorded. Stable recordings and high-resolution facial muscle activity mapping were achieved during different exercise intensities until exhaustion. Strong correlations were found between VL and multiple facial muscles' activity during voluntary smiles during exercise, with statistically significant coefficients ranging from 0.80 to 0.95 (p<0.05). This study demonstrates the feasibility of monitoring facial muscle activity during exercise, with potential implications for sports medicine and exercise physiology, particularly in monitoring exercise intensity and fatigue.

Bio-potential noise of dry printed electrodes: physiology versus the skin-electrode impedance.

Objective. To explore noise characteristics and the effect physiological activity has on the link between impedance and noise.Approach. Dry-printed electrodes are emerging as a new and exciting technology for skin electro-physiology. Such electrode arrays offer many advantages including user convenience, quick placement, and high resolution. Here we analyze extensive electro-physiological data recorded from the arm and the face to study and quantify the noise of dry electrodes, and to characterize the link between noise and impedance. In particular, we studied the effect of the physiological state of the subject (e.g. rapid eye movement sleep) on noise.Main results. We show that baseline noise values extracted from dry electrodes in the arm are in agreement with the Nyquist equation. In the face, on the other hand, the measured noise values were higher than the values predicted by the Nyquist equation. In addition, we studied how different electrode properties affect performances, including electrode size, shape, and material properties.Significance. Altogether, the results presented here provide a basis for understanding dry electrode performances and substantiate their great potential in electro-physiological investigations.

Monitoring sleep stages with a soft electrode array: Comparison against vPSG and home-based detection of REM sleep without atonia.

Sleep disorders are symptomatic hallmarks of a variety of medical conditions. Accurately identifying the specific stage in which these disorders occur is particularly important for the correct diagnosis of non-rapid eye movement and rapid eye movement parasomnias. In-lab polysomnography suffers from limited availability and does not reflect habitual sleep conditions, which is especially important in older adults and those with neurodegenerative diseases. We aimed to explore the feasibility and validity of a new wearable system for accurately measuring sleep at home. The system core technology is soft, printed dry electrode arrays and a miniature data acquisition unit with a cloud-based data storage for offline analysis. The positions of the electrodes allow manual scoring following the American Association of Sleep Medicine guidelines. Fifty participants (21 healthy subjects, mean age 56.6 ± 8.4 years; and 29 patients with Parkinson's disease, 65.4 ± 7.6 years) underwent a polysomnography evaluation with parallel recording with the wearable system. Total agreement between the two systems reached Cohen's kappa (k) of 0.688 with agreement in each stage of: wake k = 0.701; N1 = 0.224; N2 = 0.584; N3 = 0.410; and rapid eye movement = 0.723. Moreover, the system reliably detected rapid eye movement sleep without atonia with a sensitivity of 85.7%. Additionally, a comparison between sleep as measured in the sleep lab with data collected from a night at home showed significantly lower wake after sleep onset at home. The results demonstrate that the system is valid, accurate and allows for the exploration of sleep at home. This new system offers an opportunity to help detect sleep disorders on a larger scale than possible today, fostering better care.

Bi-directional electrical recording and stimulation of the intact retina with a screen-printed soft probe: a feasibility study.

Introduction: Electrophysiological investigations of intact neural circuits are challenged by the gentle and complex nature of neural tissues. Bi-directional electrophysiological interfacing with the retina, in its intact form, is particularly demanding and currently there is no feasible approach to achieve such investigations. Here we present a feasibility study of a novel soft multi-electrode array suitable for bi-directional electrophysiological study of the intact retina. Methods: Screen-printed soft electrode arrays were developed and tested. The soft probes were designed to accommodate the curvature of the retina in the eye and offer an opportunity to study the retina in its intact form. Results: For the first time, we show both electrical recording and stimulation capabilities from the intact retina. In particular, we demonstrate the ability to characterize retina responses to electrical stimulation and reveal stable, direct, and indirect responses compared with ex-vivo conditions. Discussion: These results demonstrate the unique performances of the new probe while also suggesting that intact retinas retain better stability and robustness than ex-vivo retinas making them more suitable for characterizing retina responses to electrical stimulation.

High efficiency coupling to metal-insulator-metal plasmonic waveguides.

A periodic array of dual-Vivaldi antennas integrated with metal-insulator-metal (MIM) plasmonic waveguides was designed and investigated for its infrared light absorbance efficiency. Full-wave analysis was used to optimize MIM waveguides compatible with parallel and series connected DC leads without sacrificing radiation efficiency. Free-space to MIM waveguide in-coupling efficiency as high as 41% has been obtained in a sub-wavelength unit cell geometry at a wavelength of 1373 nm. Higher efficiency, up to 85%, is predicted with a modified design including a backplane reflector. A nanofabrication process was developed to realize test devices and far-field optical spectroscopy was used as experimental evidence for antenna-waveguide matching.

In the Eye of the Storm: Bi-Directional Electrophysiological Investigation of the Intact Retina.

Electrophysiological investigations reveal a great deal about the organization and function of the retina. In particular, investigations of explanted retinas with multi electrode arrays are widely used for basic and applied research purposes, offering high-resolution and detailed information about connectivity and structure. Low-resolution, non-invasive approaches are also widely used. Owing to its delicate nature, high-resolution electrophysiological investigations of the intact retina until now are sparse. In this Mini Review, we discuss progress, challenges and opportunities for electrode arrays suitable for high-resolution, multisite electrophysiological interfacing with the intact retina. In particular, existing gaps in achieving bi-directional electrophysiological investigation of the intact retina are discussed.

Similarities and disparities between visual analysis and high-resolution electromyography of facial expressions.

Computer vision (CV) is widely used in the investigation of facial expressions. Applications range from psychological evaluation to neurology, to name just two examples. CV for identifying facial expressions may suffer from several shortcomings: CV provides indirect information about muscle activation, it is insensitive to activations that do not involve visible deformations, such as jaw clenching. Moreover, it relies on high-resolution and unobstructed visuals. High density surface electromyography (sEMG) recordings with soft electrode array is an alternative approach which provides direct information about muscle activation, even from freely behaving humans. In this investigation, we compare CV and sEMG analysis of facial muscle activation. We used independent component analysis (ICA) and multiple linear regression (MLR) to quantify the similarity and disparity between the two approaches for posed muscle activations. The comparison reveals similarity in event detection, but discrepancies and inconsistencies in source identification. Specifically, the correspondence between sEMG and action unit (AU)-based analyses, the most widely used basis of CV muscle activation prediction, appears to vary between participants and sessions. We also show a comparison between AU and sEMG data of spontaneous smiles, highlighting the differences between the two approaches. The data presented in this paper suggests that the use of AU-based analysis should consider its limited ability to reliably compare between different sessions and individuals and highlight the advantages of high-resolution sEMG for facial expression analysis.

Electrophysiological investigation of intact retina with soft printed organic neural interface.

Objective.Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities.Ex vivo, the retina can be readily investigated using multi electrode arrays (MEAs). However, MEA recording and stimulation from an intact retina (in the eye) has been so far insufficient.Approach.In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20µm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40µm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50µm) PU film. Plasma polymerized 3.4-ethylenedioxythiophene was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both explanted and intact inside an enucleated eye, were used.Main results.A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate.Ex vivoelectrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed.Significance.Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissuein vivo.

Lie to my face: An electromyography approach to the study of deceptive behavior.

BACKGROUND: Deception is present in all walks of life, from social interactions to matters of homeland security. Nevertheless, reliable indicators of deceptive behavior in real-life scenarios remain elusive. METHODS: By integrating electrophysiological and communicative approaches, we demonstrate a new and objective detection approach to identify participant-specific indicators of deceptive behavior in an interactive scenario of a two-person deception task. We recorded participants' facial muscle activity using novel dry screen-printed electrode arrays and applied machine-learning algorithms to identify lies based on brief facial responses. RESULTS: With an average accuracy of 73%, we identified two groups of participants: Those who revealed their lies by activating their cheek muscles and those who activated their eyebrows. We found that the participants lied more often with time, with some switching their telltale muscle groups. Moreover, while the automated classifier, reported here, outperformed untrained human detectors, their performance was correlated, suggesting reliance on shared features. CONCLUSIONS: Our findings demonstrate the feasibility of using wearable electrode arrays in detecting human lies in a social setting and set the stage for future research on individual differences in deception expression.

The Home-Based Sleep Laboratory.

Sleep disturbances are prevalent in neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular. Recent evidence points to the clinical value of sleep in disease progression and improving quality of life. Therefore, monitoring sleep quality in an ongoing manner at the convenience of one's home has the potential to improve clinical research and to contribute to significantly better personalized treatment. Further, precise mapping of sleep patterns of each patient can contribute to a better understanding of the disease, its progression and the appropriate medical treatment. Here we review selective, state-of-the-art, home-based devices for assessing sleep and sleep related disorders. We highlight the large potential as well as the main challenges. In particular, we discuss medical validity, standardization and regulatory concerns that currently impede widespread clinical adoption of existing devices. Finally, we propose a roadmap with the technological and scientific steps that are required to impact PD research and treatment.

Soft Devices for High-Resolution Neuro-Stimulation: The Interplay Between Low-Rigidity and Resolution.

The field of neurostimulation has evolved over the last few decades from a crude, low-resolution approach to a highly sophisticated methodology entailing the use of state-of-the-art technologies. Neurostimulation has been tested for a growing number of neurological applications, demonstrating great promise and attracting growing attention in both academia and industry. Despite tremendous progress, long-term stability of the implants, their large dimensions, their rigidity and the methods of their introduction and anchoring to sensitive neural tissue remain challenging. The purpose of this review is to provide a concise introduction to the field of high-resolution neurostimulation from a technological perspective and to focus on opportunities stemming from developments in materials sciences and engineering to reduce device rigidity while optimizing electrode small dimensions. We discuss how these factors may contribute to smaller, lighter, softer and higher electrode density devices.

Untangling Photofaradaic and Photocapacitive Effects in Organic Optoelectronic Stimulation Devices.

Light, as a versatile and non-invasive means to elicit a physiological response, offers solutions to problems in basic research as well as in biomedical technologies. The complexity and limitations of optogenetic methods motivate research and development of optoelectronic alternatives. A recently growing subset of approaches relies on organic semiconductors as the active light absorber. Organic semiconductors stand out due to their high optical absorbance coefficients, mechanical flexibility, ability to operate in a wet environment, and potential biocompatibility. They could enable ultrathin and minimally invasive form factors not accessible with traditional inorganic materials. Organic semiconductors, upon photoexcitation in an aqueous medium, can transduce light into (1) photothermal heating, (2) photochemical/photocatalytic redox reactions, (3) photocapacitive charging of electrolytic double layers, and (4) photofaradaic reactions. In realistic conditions, different effects may coexist, and understanding their role in observed physiological phenomena is an area of critical interest. This article serves to evaluate the emerging picture of photofaradaic vs. photocapacitive effects in the context of our group's research efforts and that of others over the past few years. We present simple experiments which can be used to benchmark organic optoelectronic stimulation devices.

Multi-channel electromyography-based mapping of spontaneous smiles.

OBJECTIVE: Human facial muscle activation underlies highly sophisticated signaling mechanisms that are critically important for healthy physiological function. Accordingly, the necessity to analyze facial muscle activation at high-resolution and in a non-invasive manner is important for the diagnosis and treatment of many medical conditions. However, current clinical examination methods are neither precise nor quantitative. APPROACH: Wearable, multi-channel surface electromyography can provide a solution to this yet unmet challenge. Here, we present the design and testing of a customized surface electromyography electrode array for facial muscle mapping. MAIN RESULTS: Muscle activation maps were derived from repeated voluntary facial muscle activations. A customized independent component analysis algorithm and a clustering algorithm were developed to identify consistent building block activation patterns within and between participants. Finally, focusing on spontaneous smile analysis and relying on the building block mapping, we classified muscle activation sources, revealing a consistent intra-subject activation and an inter-subject variability. SIGNIFICANCE: The herein described approach can be readily used for automated and objective mapping of facial expressions in general and in the assessment of normal and abnormal smiling in particular.

Home monitoring of sleep with a temporary-tattoo EEG, EOG and EMG electrode array: a feasibility study.

OBJECTIVE: Circadian and sleep dysfunction have long been symptomatic hallmarks of a variety of devastating neurodegenerative conditions. The gold standard for sleep monitoring is overnight sleep in a polysomnography (PSG) laboratory. However, this method has several limitations such as availability, cost and being labour-intensive. In recent years there has been a heightened interest in home-based sleep monitoring via wearable sensors. Our objective was to demonstrate the use of printed electrode technology as a novel platform for sleep monitoring. APPROACH: Printed electrode arrays offer exciting opportunities in the realm of wearable electrophysiology. In particular, soft electrodes can conform neatly to the wearer's skin, allowing user convenience and stable recordings. As such, soft skin-adhesive non-gel-based electrodes offer a unique opportunity to combine electroencephalography (EEG), electromyography (EMG), electrooculography (EOG) and facial EMG capabilities to capture neural and motor functions in comfortable non-laboratory settings. In this investigation temporary-tattoo dry electrode system for sleep staging analysis was designed, implemented and tested. MAIN RESULTS: EMG, EOG and EEG were successfully recorded using a wireless system. Stable recordings were achieved both at a hospital environment and a home setting. Sleep monitoring during a 6 h session shows clear differentiation of sleep stages. SIGNIFICANCE: The new system has great potential in monitoring sleep disorders in the home environment. Specifically, it may allow the identification of disorders associated with neurological disorders such as rapid eye movement (REM) sleep behavior disorder.

Calcium imaging, MEA recordings, and immunostaining images dataset of neuron-astrocyte networks in culture under the effect of norepinephrine.

Background: Monitoring the activity and morphology of neuron-astrocyte networks in culture is a powerful tool for studying dynamics, structure, and communication in neuron-astrocyte networks independently or as a model of the sub-brain network. These cultures are known to produce stereotypical patterns of activity, e.g., highly synchronized network bursts resembling sleep or seizure states, thus it enables the exploration of behaviors that can relate to brain function and disease. High-resolution microscopy of calcium imaging combined with simultaneous electrical recording provides a comprehensive overview on the network's dynamics. This setup makes it possible to apply global perturbations of electrical and chemical stimulation on the cultures during the recording task and to record the effects on network activity on-line. Morphological changes in the cultures can be obtained to have a complete dataset for structure-function study of neuron-astrocyte networks in vitro. Findings: The 4 TB of data presented here was recorded and imaged as part of an accompanying study looking at in vitro structure-function of neuron-astrocyte networks. Simultaneous optical (calcium imaging) and electrical (micro-electrode array) recordings lasted 5-12 minutes and included spontaneous activity recording, electrical and chemical stimulation of neuron-astrocyte, and isolated astrocyte cultures. The data include activity recordings of 58 different cultures, with 1-2 regions of interest recorded for each culture. Production procedures, experimental protocols, and reuse options are included. The data have been suitable to reveal changes in the activity and morphology of the cultures and enabled observation and analysis of neuron-astrocyte and isolated astrocyte culture behaviors under the applied perturbations. Conclusions: Our dataset is sufficient to show significant changes in activity and morphology of neuron-astrocyte networks in culture under the applied stimulations. More than 100 recordings of 58 different cultures give insight of the observation's significance and led to conclusions about astrocyte activity and neuron-astrocyte network communication. Making it available here will allow others to test new tools for calcium imaging analysis and extracellular neuronal voltage recordings.

In situ real-time beam monitoring with dielectric meta-holograms.

A novel approach for performing in situ and real-time beam monitoring, based on dielectric meta-hologram, is proposed and demonstrated. The ultrathin dielectric meta-hologram projects a portion of the beam power onto a screen to provide a visual indicator of the spatial intensity distribution of a Gaussian laser beam, as well as its waist position along the optical axis. Specifically, we demonstrate simple monitoring of the spot size, astigmatism, lateral position, and position along the optical axis of the beam. Good agreement is found with both theory and conventional knife-edge beam profiler measurements. This in situ beam monitoring approach could provide a highly useful tool for numerous optical applications.

Activity changes in neuron-astrocyte networks in culture under the effect of norepinephrine.

The concerted activity of neuron-glia networks is responsible for the fascinating dynamics of brain functions. Although these networks have been extensively investigated using a variety of experimental (in vivo and in vitro) and theoretical models, the manner by which neuron-glia networks interact is not fully understood. In particular, how neuromodulators influence network-level signaling between neurons and astrocytes was poorly addressed. In this work, we investigated global effects of the neuromodulator norepinephrine (NE) on neuron-astrocyte network communication in co-cultures of neurons and astrocytes and in isolated astrocyte networks. Electrical stimulation was used to activate the neuron-astrocyte glutamate-mediated pathway. Our results showed dramatic changes in network activity under applied global perturbations. Under neuromodulation, there was a marked rise in calcium signaling in astrocytes, neuronal spontaneous activity was reduced, and the communication between neuron-astrocyte networks was perturbed. Moreover, in the presence of NE, we observed two astrocyte behaviors based on their coupling to neurons. There were also morphological changes in astrocytes upon application of NE, suggesting a physical cause underlies the change in signaling. Our results shed light on the role of NE in controlling sleep-wake cycles.

Direct Electrical Neurostimulation with Organic Pigment Photocapacitors.

An efficient nanoscale semiconducting optoelectronic system is reported, which is optimized for neuronal stimulation: the organic electrolytic photocapacitor. The devices comprise a thin (80 nm) trilayer of metal and p-n semiconducting organic nanocrystals. When illuminated in physiological solution, these metal-semiconductor devices charge up, transducing light pulses into localized displacement currents that are strong enough to electrically stimulate neurons with safe light intensities. The devices are freestanding, requiring no wiring or external bias, and are stable in physiological conditions. The semiconductor layers are made using ubiquitous and nontoxic commercial pigments via simple and scalable deposition techniques. It is described how, in physiological media, photovoltage and charging behavior depend on device geometry. To test cell viability and capability of neural stimulation, photostimulation of primary neurons cultured for three weeks on photocapacitor films is shown. Finally, the efficacy of the device is demonstrated by achieving direct optoelectronic stimulation of light-insensitive retinas, proving the potential of this device platform for retinal implant technologies and for stimulation of electrogenic tissues in general. These results substantiate the conclusion that these devices are the first non-Si optoelectronic platform capable of sufficiently large photovoltages and displacement currents to enable true capacitive stimulation of excitable cells.