Brain function relies on coordinated activity across spatial and temporal scales. Single neurons integrate local and long-range connectivity and reflect activity across brain-wide networks. Understanding integrated brain function requires tools capable of recording from anatomically connected populations in distributed brain areas to bridge local and global dynamics. Here, we present high-density, micro-electrocorticography arrays that facilitate multi-scale studies of brain activity. The hybrid arrays integrate the desirable features of silicone elastomers and polyimide films: silicone provides optical transparency and permits repeated penetration with intracortical arrays, while polyimide enables fine photolithographic feature definition. This combination facilitates high-throughput functional mapping to identify targets and insertion of intracortical arrays for dense local sampling. We demonstrate functional mapping in rats, cats, and marmosets, showing how functional maps guide multi-area laminar recordings. Finally, we demonstrate local and feedforward optogenetic stimulation to investigate cortico-cortical interactions. These capabilities establish the hybrid μECoG as a compelling tool for systems neuroscience.

IntroductionRobust, biocompatible ceramic electrical interconnects are essential for bridging the gap between macro-scale components, such as helically wound leads and connectors, and thin-film polyimide electrodes in neural interfaces. While screen-printed thick-film structures have been utilized for decades, there is a need to broaden the design space and improve reliability through thin-film techniques. This study evaluates various surface configurations to identify the optimal combination of mechanical adhesion, electrical insulation, and functional longevity.MethodsAll samples were fabricated on 96% pure alumina (Al2O3) substrates. Mechanical stability was evaluated via tensile shear tests, comparing thin-film platinum (Pt) with different adhesion promoters (SixNy, SiO2), laser-patterned Pt thin-films, and bare Pt thin-film against reference Al2O3 substrates. Electrical insulation was assessed by performing electrochemical impedance spectroscopy and DC resistance measurements for degradation monitoring. The evaluated layer stacks with PDMS encapsulation included bare thin-film Pt, thick-film Pt/Au with Overglaze, a SiO2 layer, a SixNy layer, and a layer of pulsed laser deposition (PLD) Al2O3. All samples underwent accelerated aging in phosphate buffered saline (PBS) at 60°C (acceleration factor ∼ 4.92 vs. 37°C).ResultsTensile shear strength decreased over the aging period across all groups. However, the integration of adhesion promoters increased mechanical stability compared to bare sputtered Pt, with SixNy coating bringing adhesion levels close to the Al2O3 reference samples. Electrically, SixNy-, PLD-Al2O3, and laser-patterned samples maintained higher insulation impedances over time than PDMS on bare Pt and SiO2. DC resistance measurements indicate good capabilities in protecting the conductors from degradation.DiscussionThe findings demonstrate that the addition of adhesion promoters enhances both the longevity of the mechanical bond and stability of the electrical insulation in ion-rich environments. These results provide guidance for selecting optimal ceramic interconnects for chronic peripheral-nerve implants, balancing reliability, manufacturability, and cost.

Abstract Extracellular matrix (ECM) remodeling is a fundamental determinant of neural tissue repair and implant integration, yet its conserved regulatory architecture remains undefined. While transcriptomic alterations following neural injury and implantation have been described, the ECM-centered programs that unify traumatic injury and neural implant responses remain unclear. Here, integrative systems-level transcriptomic analysis identifies a dominant and conserved ECM regulatory axis linking traumatic brain injury (BI), spinal cord injury (SCI), and neural implant–induced injury. By integrating transcriptomic datasets from brain and spinal cord injury models using weighted gene co-expression network analysis (WGCNA), six conserved ECM-associated gene modules are identified, with hyaluronan (HA)-centered networks emerging as the dominant and conserved regulatory axis across both injury types. Modules enriched for low-molecular-weight HA (LMW-HA) are linked to Toll-like receptor signaling and pro-inflammatory cytokine expression, whereas high-molecular-weight HA (HMW-HA)–associated modules correlate with Cd44 signaling, tissue stabilization and repair. Furthermore, independent validation in thin-film intracortical microelectrode datasets confirms robust activation of HA damage-associated molecular pattern (HA-DAMP) signaling following implantation, with 9/10 injury-derived modules preserved and 88% of transcripts exhibiting resolving temporal dynamics. These findings indicate that neural implants engage conserved trauma-associated ECM programs rather than a conventional foreign-body response, highlighting HA-related metabolisms. Given that HA fragments and HA-modifying enzymes are detectable in cerebrospinal fluid and peripheral circulation, HA-associated signatures may serve as minimally invasive biomarkers of neural injury and implant biocompatibility, enabling longitudinal monitoring and informing next-generation neural interface design.

Successful and responsible innovation in neurotechnology requires clear ethical priorities and a deep understanding of individual and societal needs as well as public concerns. Recent cases of consumer exploitation, misleading claims, and inadequate patient aftercare reveal critical gaps in current practices and underscore the urgent need for more ethical, transparent, and user-centered engagement in this rapidly developing field. This study focuses on four complementary domains: (1) neuroethics and embodiment; (2) the cultural embedding of neurotechnologies; (3) art and culture in relation to neurotechnology; and (4) human enhancement, technovisions, and sociotechnical imaginaries. Across these domains, the manuscript explores user and societal perceptions, highlighting often overlooked asymmetries in communication between scientists and entrepreneurs and those who ultimately receive research outcomes in the form of products. Drawing on the authors’ multidisciplinary expertise and a synthesis of the relevant literature, the manuscript outlines a possible foundation for developing more balanced, inclusive and symmetric communication formats that empower stakeholders regardless of status or expertise. Integrating insights from neurotechnology with applied ethics, the humanities, social sciences, technology assessment and the arts, this work seeks to contribute to a broader understanding of the societal and individual impacts of emerging neurotechnologies and to support the protection and empowerment of users by prioritizing their needs.

OBJECTIVE:High-quality recording of peripheral nerve signals is a critical requirement for implantable neural interfaces, yet the influence of contact configuration and electrical insulation on cuff electrode recording quality remains poorly understood. APPROACH:Using a physical nerve model in vitro, the transfer function of commercially available split-cylinder and spiral cuff electrodes was measured for systematically varied contact configurations, including contact size, spacing, and size ratio of cathode to anode, as well as degree of electrical insulation. To derive single-fiber and compound action potentials, the transfer function was convolved with modeled action currents, enabling direct comparison of recording quality across designs. MAIN RESULTS:Contact edge spacing was found to be more decisive than contact surface area for recording amplitude, regardless of contact segmentation. In quasi-tripolar configurations, common mode suppression additionally reduced sensitivity to geometric variations. Both the length of the longitudinal insulation and the integrity of the electrode seal were found to strongly influence recording amplitude, with complete removal of the seal reducing amplitude by approximately 50%, outweighing all geometric design parameters combined. SIGNIFICANCE:These findings establish electrical insulation integrity as the primary design criterion for cuff electrode recording performance, shifting focus away from contact geometry alone, and provide a practical framework for the development of next-generation peripheral nerve interfaces.

ABSTRACT We present a long‐lasting, multilayered tissue mimicking phantom model that mimics the optical and acoustic properties of the skin and radial artery at the wrist. The silicone‐based phantom is fabricated with tunable properties by varying concentrations of India ink, titanium dioxide, and silicone oil. To assess the longevity of the phantom material, the mechanical, optical, and acoustic properties of the individual layers are characterized over multiple weeks. Comparisons of characterization measurements to physiological reference values demonstrate that the phantom material closely approximates the mechanical properties, while optical properties are also comparable, especially from 700 to 1100 nm. Acoustic properties are less optimally matched, with higher attenuation and lower acoustic velocities than biological tissue. The phantom material exhibits optical and acoustic stability during characterization of the properties over time. A cost analysis of the fabrication technique demonstrates that this is a low‐cost and easily accessible phantom model, which could be implemented at any laboratory. This phantom serves as a validation tool for new optical and acoustic sensors in the first stages of translational research and prototype development. We present a verification of the stability of silicone‐based phantom materials over time, thus enabling long‐term optical and acoustic measurements.

Objective: Decades of studies have enabled a constant optimization of thin-film-based neural implants, with technologies designed to adapt to the biological surroundings through biocompatible and miniaturized materials. Careful assessment of these materials is essential prior to photolithographic fabrication of multilayered devices, as delamination from adhesion mismatches between neighboring layers can compromise recording or stimulation and lead to channel crosstalk or device failure. Multi-layer interactions are therefore closely examined to tailor devices for long-term stability, yet post-implantation examinations still reveal failure modes that are not fully addressed and understood. Here, we propose an in vitro investigation of polyimide (PI), a widely used substrate material, in a simplified single layer configuration, to isolate substrate-related effects and evaluate long-term stability under combined conditions that cover not only the implantation period, but also post-implantation steps. Methods: Accelerated ageing was used to mimic processes occurring in the brain during implantation while aged samples were also exposed to aldehyde-based fixation and storage conditions commonly encountered during post-mortem processing. Surface morphology was assessed using Scanning Electron Microscopy (SEM). Chemical microstructure was analyzed in a dual approach using Time-of-Flight-Secondary-Ion Mass-Spectroscopy (ToF-SIMS) and Fourier Transform Infrared Spectroscopy (FTIR). Conclusion: PI remains morphologically and chemically stable under the harshest conditions, in both implantation scenarios and subsequent post-implantation steps. Significance: These findings provide critical validation for the use of PI as a durable substrate in long-term neural interfaces. They further indicate that damage observed after implantation may arise from factors beyond intrinsic PI degradation, helping prevent misinterpretation during post-implantation analysis.

Limb loss causes severe sensorimotor deficits and often necessitates prosthetic devices, particularly in lower-limb amputees. Although direct neural recording from residual nerves offers a biomimetic route for prosthetic control, low signal amplitudes and challenges in nerve interfacing have limited adoption. Intraneural multichannel electrodes provide a potential solution by enabling access to motor signals from muscles lost after amputation. Here, we report intraneural recordings from two transfemoral amputees using transversal intrafascicular multichannel electrodes implanted in distal branches of the sciatic nerve. We identified multiunit activity associated with volitional phantom movements of the knee, ankle, and toes, exhibiting joint- and direction-specific modulation distributed across electrodes. A Spiking Neural Network-based decoder outperformed conventional methods in predicting attempted movements, with further gains achieved by integrating intraneural and intermuscular signals. Motor and sensory maps showed minimal overlap, indicating early segregation within the sciatic nerve. These findings pave the way for bidirectional, neurally-controlled prosthetic systems.

Morphological and functional properties of vascular stiffness (intima-media thickness, instantaneous diameter, pulse wave velocity, blood pressure) could be monitored solely using ultrasound. Yet, few ultrasound studies estimate both pulse wave velocity and blood pressure. This study presents an in vitro evaluation of a dual-site ultrasound system for the simultaneous estimation of pulse wave velocity and blood pressure from radio-frequency ultrasound data. The circulatory mock-loop incorporating an arm phantom was used as a controlled test environment. Reference pressure and pulse wave velocity values were obtained via a commercial pressure sensor and the PulsePen device (DiaTecne s.r.l., Milano, Italy), respectively. The custom dual-site ultrasound system (6 cm distance between probes) was evaluated across pressures ranging from hypotension to hypertensive crisis. To assess the most accurate estimation strategy, pulse wave velocity was estimated using multiple signal processing approaches, including derivative-based, pulse-feature, cross-correlation, and tangent intersection methods, while blood pressure was derived from linear, exponential, and logarithmic models relating diameter waveforms to pressure. The in vitro mock-loop was improved using a viscous glycerol solution as a blood-mimicking fluid instead of deionized water. The tangent intersection method yielded pulse wave velocity values most consistent with the tonometric reference (0.3 m/s mean error). For blood pressure estimation, the linear equation achieved the best performance, with − 1.8 ± 1.1 mmHg systolic blood pressure mean difference to the reference. Using 40 wt

Neuroprostheses have contributed extensively to humankind's capacity to treat disease and injury. Hearing loss is routinely overcome; pain is controlled; and myriad neurological, sensory, motor, and psychological disorders are managed through interventions involving neuromodulation. Fabrication of active implantable medical devices (AIMDs) often relies on highly skilled operators, leading to high costs, reliability challenges, and limitations to further device miniaturization and manufacturing output. Extending AIMD benefits to other disorders may also require a substantial increase in the number of stimulation or recording channels, exceeding the boundaries of existing fabrication techniques and human dexterity. In one-to-one correspondence, electrical signals must transition between the biological environment and a controlled atmosphere suitable for protecting active electronics-e.g., electrodes interfaced to excitable tissue must ultimately connect to a circuit node, each sensitive to corrosion or shorting when exposed to moisture and ions. Protection is typically achieved by hermetic encapsulation, with each signal crossing the hermetic barrier via a conductive pathway (feedthrough). As the quantity of signals increases, so does the complexity of the encapsulation. Herein, we describe a robust hermetic encapsulation approach with feedthrough densities of around 250 contacts/cm2 and establishment of interconnections to each feedthrough in an all-at-once fashion. The resulting interfaces offer impedances < 5 mΩ between a connection pad of the electronics to the electrode and bond strengths ~10 MPa. An illustrative example is presented as a visual neuroprosthesis for retinal dystrophies with 99 channels of electrical stimulation and associated power and communication interfaces-a device that we call the Phoenix99.

Electrode arrays along peripheral nerves can record sensory, motor and autonomic signals propagating in afferent and efferent direction at different conduction velocities. To extract this temporal information in a delay-and-sum approach, velocity-selective recording (VSR) utilizes summation to amplify time-aligned action potentials and average out noise. This improved contrast subsequently improves the automated detection and classification of action potentials - an essential prerequisite to interface with the peripheral nervous system. In this study, we replaced the summation with multiplication and investigated resulting signal changes. We focused on two derived methods: Lock-IN-Dispersion-Analysis (LINDA) multiplies all recorded signals; Delay-Combinatory-Multiply-And-Sum (DCMAS) multiplies all combinations of an adjustable number of signals and sums the products. Processing simulated neural array recordings, we compared the effects of LINDA and DCMAS on contrast-to-noise ratio (CNR), signal-to-noise-and distortion ratio (SINAD) and AP detectability after thresholding. Compared to VSR, both methods increased CNR, SINAD, and AP detectability but also introduced noise intermodulation distortion which limited SINAD gains. Additionally, LINDA formed a logical AND-gate between signals, suppressing interfering signal peaks. Overall, by increasing CNR, signal multiplication may improve decoding of array recordings, despite increased signal distortion. It may thereby advance neural interfaces for fundamental research, diagnostics or applications in bioelectronic medicine and neuroprostheses.

The loss of hand function is one of the most devastating impairments for individuals with paralysis. While current neurotechnologies can partially restore prehensile control, they fall short of enabling independent finger movements — an essential requirement for full hand dexterity. Achieving this level of precision demands highly selective activation of individual muscles or muscle groups. In this first-in-human study, we explored a novel approach in an individual with chronic tetraplegia. Our method combined targeted surgery to isolate functionally relevant branches of the median and radial nerves with custom intrafascicular electrodes to interface with them. By precisely stimulating motor fibers within these nerves, we successfully restored independent movement in four fingers, including the thumb. The combination of these movements allowed the recreation of the lateral, hook, and palmar grasps with smoothly modulated forces. Furthermore, the participant regained the ability to perform functional tasks, such as pouring water from a bottle. These findings hold significant promise for individuals with hand paralysis, paving the way for neurotechnologies that can bypass spinal cord injuries and restore fine motor control.

Limb loss leads to severe sensorimotor deficits and requires the use of a prosthetic device, especially in lower-limb amputees. While direct recording from residual nerves offers a biomimetic route for an effective prosthetic control, the low amplitude and noisy nature of these neural signals together with the challenge of establishing a reliable nerve interfacing, have hindered its adoption. Intraneural multichannel electrodes could potentially establish an effective interface with the nerve fibers, enabling access to motor signals even from muscles lost after the amputation. In this study, we report the direct neural recordings of two transfemoral amputees using transversal intrafascicular multichannel electrodes (TIME) implanted in the tibial nerves. We observed multiunit activity associated with volitional phantom movements of the knee, ankle and toes flexion and extension, with joint- and direction-specific neural modulation in both participants. The motor signals were distributed across all the electrodes, showing both single-joint and multi-joint selectivity, as well as direction selectivity for limb flexion and extension. After characterizing the neural evoked activity, we developed a Spiking Neural Network (SNN)-based decoder that outperform conventional motor decoders in predicting attempted phantom leg movements. Decoding accuracy improved further by including a broader signal bandwidth that captured both intraneural (ENG) and inter-muscular (imEMG) activity. Finally, comparing motor maps (recording) with sensory maps (stimulation) revealed a minimal overlap, suggesting early segregation of motor and sensory fibers within the tibial nerve before the knee bifurcation. Our findings demonstrate the feasibility to record motor signal and decode lower-limb movements directly from the nerves in amputees using intraneural interfaces. This paves the way for bidirectional, neurally-controlled prosthetic limbs combining natural control with somatosensory feedback through a single implanted interface.

Personalized medicine meets microimplants. Miniaturized, distributed implants may offer treatment options for diseases in which pharmaceuticals do not work for all patients or do not exist at all. In order to supply these implants efficiently with energy combinations of inductive links and ultrasonic transducers were investigated. This methodological review contributes with a comprehensive overview on the energy supply aspects of neural implants and summarizes basic mechanisms, differences and commonalities with the most widespread method, inductive coupling. It is believed that this review as seminal work can guide researchers who are not familiar with the energy supply field as well as neural engineers, neuroscientists, and clinicians to better understand strengths, weaknesses, threats, and opportunities of this methodology in innovative and novel neurotechnological applications. As figure of merit, inductive links are suggested for short distances and to couple energy into the body, while ultrasound is more efficient over larger lengths and in networks inside the body. The authors suggest planar butterfly coils, membrane‐based piezoelectric micromachined ultrasonic transducers and non‐hermetic encapsulation using silicone rubber for these envisioned neural implant networks.

Patients with a lower limb amputation suffer from an impaired balance control and thereby are at a higher risk to fall. To cope with this deficit, they adapt their neuromuscular system by modifying biomechanical and neuromuscular structures. In this study, we investigated changes in corticomuscular coherence between the motor cortex and muscles of the trunk and the intact lower leg. We recorded electroencephalogram (EEG) and electromyogram (EMG) data from 10 unilateral transfemoral amputees and 10 age-matched able-bodied controls during quiet upright stance with eyes open, eyes closed and during dual tasking. To analyse afferent and efferent corticomuscular coherence, directional wavelet coherence between EEG and EMG signals was computed. The corticomuscular coherence analysis showed significant differences between amputees and controls in the afferent and efferent direction and across visual conditions, suggesting differences in the processing of sensory feedback. A power spectral density analysis of the motor cortex contralateral to the amputated leg of amputees showed increased power, as well as a pronounced decrease in alpha frequencies indicating an increased cognitive load. This exploratory study stimulates further hypotheses on how coordination of brain and muscle activity is modulated after a lower limb amputation.

As neural implants become more integrated with human cognition and identity, the risks posed by their sudden discontinuation are unique and demand urgent attention.

Brain movement significantly impacts the biocompatibility of neural probes, primarily due to continuous loading and strain on neural tissue. This study investigates the strain profile at the electrode–tissue interface under various brain displacements—vertical, lateral, diagonal, and torque—across different brain models (linear elastic, hyperelastic, and viscoelastic). The safety margin for tissue damage is assessed by evaluating a 5% strain threshold using two probe widths (30 µm and 100 µm) in tethered and floating configurations. The probe dimensions are informed by previously developed devices implanted in rats for 12 weeks, allowing to correlate the findings with existing immunohistochemical data. A comprehensive simulation studies accounting for various conditions, such as different brain displacements and physics, has not been reported elsewhere. These results challenge the conventional 5% strain threshold for tissue damage, revealing that strains below this critical limit may still pose risks depending on probe geometry and brain model. Furthermore, these simulations underscore the necessity of size‐dependent micromotion models for accurate predictions in untethered conditions. This work highlights the feasibility of integrating immunohistological data into simulation studies, offering valuable insights for researchers while minimizing the need for extensive animal testing during initial probe design phases.