Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.

Outcomes of Transvenous Lead Extraction in a Referral Center in Northern Israel.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are increasingly being used; thus, there is an increasing need for transvenous lead extraction (TLE). OBJECTIVES: To summarize our experience with TLE at single referral center in northern Israel. METHODS: The study included all patients who underwent TLE at our center between 2019 and 2022, regardless of the indication. RESULTS: The cohort included 50 patients. The mean age was 69 ± 10.36 years; 78% were males. A total of 99 electrodes were targeted. The mean number of electrodes was 1.96 (range 1-4) per patient. The time between lead implantation and extraction ranged between 1.1 and 34 years with an average of 8.14 ± 5.71 years (median of 7.5 years). Complete lead removal was achieved in 98% of patients and in 98.99% of leads. The complete procedural success rate as well as the clinical procedural success rate was 96%. The procedural failure rate was 4% (1 patient died 2 days after the index procedure and 1 patient remained with large portion of lead). The indication for TLE was infection in 78% of the cohort group. Powered mechanical sheaths were used in 36 patients (72%), laser sheaths in 27 (54%), and a combination of laser and mechanical sheaths in 16 (32%). CONCLUSIONS: The clinical and procedural success rates of TLE, primarily for CEID-related infection, were high. A combination of laser and mechanical sheaths was needed in one-third of patients.

The TD Drive: A Parametric, Open-Source Implant for Multi-Area Electrophysiological Recordings in Behaving and Sleeping Rats.

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as the formation and consolidation of memories, are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD Drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and mediolateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze using two different commercial recording systems and headstages. Thus, presented here is the adaptable design and assembly of a new electrophysiological implant, facilitating fast preparation and implantation.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

Structural, Functional, and Genetic Changes Surrounding Electrodes Implanted in the Brain.

ConspectusImplantable neurotechnology enables monitoring and stimulating of the brain signals responsible for performing cognitive, motor, and sensory tasks. Electrode arrays implanted in the brain are increasingly used in the clinic to treat a variety of sources of neurological diseases and injuries. However, the implantation of a foreign body typically initiates a tissue response characterized by physical disruption of vasculature and the neuropil as well as the initiation of inflammation and the induction of reactive glial states. Likewise, electrical stimulation can induce damage to the surrounding tissue depending on the intensity and waveform parameters of the applied stimulus. These phenomena, in turn, are likely influenced by the surface chemistry and characteristics of the materials employed, but further information is needed to effectively link the biological responses observed to specific aspects of device design. In order to inform improved design of implantable neurotechnology, we are investigating the basic science principles governing device-tissue integration. We are employing multiple techniques to characterize the structural, functional, and genetic changes that occur in the cells surrounding implanted electrodes. First, we have developed a new "device-in-slice" technique to capture chronically implanted electrodes within thick slices of live rat brain tissue for interrogation with single-cell electrophysiology and two-photon imaging techniques. Our data revealed several new observations of tissue remodeling surrounding devices: (a) there was significant disruption of dendritic arbors in neurons near implants, where losses were driven asymmetrically on the implant-facing side. (b) There was a significant loss of dendritic spine densities in neurons near implants, with a shift toward more immature (nonfunctional) morphologies. (c) There was a reduction in excitatory neurotransmission surrounding implants, as evidenced by a reduction in the frequency of excitatory postsynaptic currents (EPSCs). Lastly, (d) there were changes in the electrophysiological underpinnings of neuronal spiking regularity. In parallel, we initiated new studies to explore changes in gene expression surrounding devices through spatial transcriptomics, which we applied to both recording and stimulating arrays. We found that (a) device implantation is associated with the induction of hundreds of genes associated with neuroinflammation, glial reactivity, oligodendrocyte function, and cellular metabolism and (b) electrical stimulation induces gene expression associated with damage or plasticity in a manner dependent upon the intensity of the applied stimulus. We are currently developing computational analysis tools to distill biomarkers of device-tissue interactions from large transcriptomics data sets. These results improve the current understanding of the biological response to electrodes implanted in the brain while producing new biomarkers for benchmarking the effects of novel electrode designs on responses. As the next generation of neurotechnology is developed, it will be increasingly important to understand the influence of novel materials, surface chemistries, and implant architectures on device performance as well as the relationship with the induction of specific cellular signaling pathways.

Designing next-generation subscalp devices for seizure monitoring: A systematic review and meta-analysis of established extracranial hardware.

Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.

Implantable Neural Microelectrodes: How to Reduce Immune Response.

Implantable neural microelectrodes exhibit the great ability to accurately capture the electrophysiological signals from individual neurons with exceptional submillisecond precision, holding tremendous potential for advancing brain science research, as well as offering promising avenues for neurological disease therapy. Although significant advancements have been made in the channel and density of implantable neural microelectrodes, challenges persist in extending the stable recording duration of these microelectrodes. The enduring stability of implanted electrode signals is primarily influenced by the chronic immune response triggered by the slight movement of the electrode within the neural tissue. The intensity of this immune response increases with a higher bending stiffness of the electrode. This Review thoroughly analyzes the sequential reactions evoked by implanted electrodes in the brain and highlights strategies aimed at mitigating chronic immune responses. Minimizing immune response mainly includes designing the microelectrode structure, selecting flexible materials, surface modification, and controlling drug release. The purpose of this paper is to provide valuable references and ideas for reducing the immune response of implantable neural microelectrodes and stimulate their further exploration in the field of brain science.

Text and image generation from intracranial electroencephalography using an embedding space for text and images.

Objective.Invasive brain-computer interfaces (BCIs) are promising communication devices for severely paralyzed patients. Recent advances in intracranial electroencephalography (iEEG) coupled with natural language processing have enhanced communication speed and accuracy. It should be noted that such a speech BCI uses signals from the motor cortex. However, BCIs based on motor cortical activities may experience signal deterioration in users with motor cortical degenerative diseases such as amyotrophic lateral sclerosis. An alternative approach to using iEEG of the motor cortex is necessary to support patients with such conditions.Approach. In this study, a multimodal embedding of text and images was used to decode visual semantic information from iEEG signals of the visual cortex to generate text and images. We used contrastive language-image pretraining (CLIP) embedding to represent images presented to 17 patients implanted with electrodes in the occipital and temporal cortices. A CLIP image vector was inferred from the high-γpower of the iEEG signals recorded while viewing the images.Main results.Text was generated by CLIPCAP from the inferred CLIP vector with better-than-chance accuracy. Then, an image was created from the generated text using StableDiffusion with significant accuracy.Significance.The text and images generated from iEEG through the CLIP embedding vector can be used for improved communication.

Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.

Brain-computer interfaces (BCIs) that reconstruct and synthesize speech using brain activity recorded with intracranial electrodes may pave the way toward novel communication interfaces for people who have lost their ability to speak, or who are at high risk of losing this ability, due to neurological disorders. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a man with impaired articulation due to ALS, participating in a clinical trial (ClinicalTrials.gov, NCT03567213) exploring different strategies for BCI communication. The 3-stage approach reported here relies on recurrent neural networks to identify, decode and synthesize speech from electrocorticographic (ECoG) signals acquired across motor, premotor and somatosensory cortices. We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the participant from a vocabulary of 6 keywords previously used for decoding commands to control a communication board. Evaluation of the intelligibility of the synthesized speech indicates that 80% of the words can be correctly recognized by human listeners. Our results show that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words while preserving the participant's voice profile, and provide further evidence for the stability of ECoG for speech-based BCIs.

Development of a Low-cost Epimysial Electromyography Electrode: A Simplified Workflow for Fabrication and Testing.

Electromyography (EMG) is a valuable diagnostic tool for detecting neuromuscular abnormalities. Implantable epimysial electrodes are commonly used to measure EMG signals in preclinical models. Although classical resources exist describing the principles of epimysial electrode fabrication, there is a sparsity of illustrative information translating electrode theory to practice. To remedy this, we provide an updated, easy-to-follow guide on fabricating and testing a low-cost epimysial electrode. Electrodes were made by folding and inserting two platinum-iridium foils into a precut silicone base to form the contact surfaces. Next, coated stainless steel wires were welded to each contact surface to form the electrode leads. Lastly, a silicone mixture was used to seal the electrode. Ex vivo testing was conducted to compare our custom-fabricated electrode to an industry standard electrode in a saline bath, where high levels of signal agreement (sine [intraclass correlation - ICC= 0.993], square [ICC = 0.995], triangle [ICC = 0.958]), and temporal-synchrony (sine [r = 0.987], square [r = 0.990], triangle [r= 0.931]) were found across all waveforms. Low levels of electrode impedance were also quantified via electrochemical impedance spectroscopy. An in vivo performance assessment was also conducted where the vastus lateralis muscle of a rat was surgically instrumented with the custom-fabricated electrode and signaling was acquired during uphill and downhill walking. As expected, peak EMG activity was significantly lower during downhill walking (0.008 ± 0.005 mV) than uphill (0.031 ± 0.180 mV, p = 0.005), supporting the validity of the device. The reliability and biocompatibility of the device were also supported by consistent signaling during level walking at 14 days and 56 days post implantation (0.01 ± 0.007 mV, 0.012 ± 0.007 mV respectively; p > 0.05) and the absence of histological inflammation. Collectively, we provide an updated workflow for the fabrication and testing of low-cost epimysial electrodes.

An automated algorithm for stereoelectroencephalography electrode localization and labelling.

PURPOSE: Stereoelectroencephalography (sEEG) is increasingly utilized for localization of seizure foci, functional mapping, and neurocognitive research due to its ability to target deep and difficult to reach anatomical locations and to study in vivo brain function with a high signal-to-noise ratio. The research potential of sEEG is constrained by the need for accurate localization of the implanted electrodes in a common template space for group analyses. METHODS: We present an algorithm to automate the grouping of sEEG electrodes by trajectories, labelled by target and insertion point. This algorithm forms the core of a pipeline that fully automates the entire process of electrode localization in standard space, using raw CT and MRI images to produce atlas labelled MNI coordinates. RESULTS: Across 196 trajectories from 20 patients, the pipeline successfully processed 190 trajectories with localizations within 0.25±0.55 mm of the manual annotation by two reviewers. Six electrode trajectories were not directly identified due to metal artifacts and locations were interpolated based on the first and last contact location and the number of contacts in that electrode as listed in the surgical record. CONCLUSION: We introduce our algorithm and pipeline for automatically localizing, grouping, and classifying sEEG electrodes from raw CT and MRI. Our algorithm adds to existing pipelines and toolboxes for electrode localization by automating the manual step of marking and grouping electrodes, thereby expedites the analyses of sEEG data, particularly in large datasets.

Monolithically Defined Wireless Fully Implantable Nervous System Interfaces.

ConspectusEvolution of implantable neural interfaces is critical in addressing the challenges in understanding the fundamental working principles and therapeutic applications for central and peripheral nervous systems. Traditional approaches utilizing hermetically sealed, rigid electronics and detached electrodes face challenges in power supply, encapsulation, channel count, dispersed application location, and modality. Employing thin-film, wirelessly powered devices is promising to expand capabilities. Devices that forego bulky power supplies, favoring a configuration where electronics are integrated directly onto thin films, reduce displacement volumes for seamless, fully implantable interfaces with high energy availability and soft mechanics to conform to the neuronal target. We discuss 3 device architectures: (1) Highly miniaturized devices that merge electronics and neural interfaces into a single, injectable format; (2) Interfaces that consolidate power, computation, and neural connectivity on a thin sheet applied directly to the target area; (3) A spatially dislocated approach where power and computation are situated subdermally, connected via a thin interconnect to the neural interface.Each has advantages and constraints in terms of implantation invasiveness, power capturing efficiency, and directional sensitivity of power delivery. In powering these devices, near-field power delivery emerges as the most implemented technique. Key parameters are size and volume of primary and secondary antennas, which determine coupling efficiency and power delivery. Based on application requirements, ranging from small to large animal models, subjects require system level designs. Material strategies play a crucial role; monolithic designs, with materials like polyimide substrates, enable scalability with high performance. This contrasts with established hermetic encapsulation approaches that use a stainless steel or titanium box with passthroughs that result in large tissue displacements and prohibit intimate integration with target organ systems. Encapsulation, particularly with parylene, enables longevity and effectiveness; more research is needed to enable human lifetime operation. Implant-to-ambient device communication, focusing on strategies compatible with well-established standards and off-the-shelf electronics, is discussed with the goal of enabling seamless system integration, reliability, and scalability. The interface with the central nervous system is explored through various wireless, battery-free devices capable of both stimulation (electrical and optogenetic) and recording (photometric and electrochemical). These devices show advanced capabilities for chronic studies and insights into neural dynamics. In the peripheral nervous system, stimulation devices for applications, such as spinal and muscle stimulation, are discussed. The challenges lie in the mechanical and electrochemical durability. Examples that successfully navigate these challenges offer solutions for chronic studies in this domain. The potential of wireless, fully implantable nervous system interfaces using near field resonant power transfer is characterized by monolithically defined device architecture, providing a significant leap toward seamless access to the central and peripheral nervous systems. New avenues for research and therapeutic applications supporting a multimodal and multisite approach to neuromodulation with a high degree of connectivity and a holistic approach toward deciphering and supplementing the nervous system may enable recovery and treatment of injury and chronic disease.

Considerations for implanting speech brain computer interfaces based on functional magnetic resonance imaging.

Objective.Brain-computer interfaces (BCIs) have the potential to reinstate lost communication faculties. Results from speech decoding studies indicate that a usable speech BCI based on activity in the sensorimotor cortex (SMC) can be achieved using subdurally implanted electrodes. However, the optimal characteristics for a successful speech implant are largely unknown. We address this topic in a high field blood oxygenation level dependent functional magnetic resonance imaging (fMRI) study, by assessing the decodability of spoken words as a function of hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal-axis.Approach.Twelve subjects conducted a 7T fMRI experiment in which they pronounced 6 different pseudo-words over 6 runs. We divided the SMC by hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal axis. Classification was performed on in these SMC areas using multiclass support vector machine (SVM).Main results.Significant classification was possible from the SMC, but no preference for the left or right hemisphere, nor for the precentral or postcentral gyrus for optimal word classification was detected. Classification while using information from the cortical surface was slightly better than when using information from deep in the central sulcus and was highest within the ventral 50% of SMC. Confusion matrices where highly similar across the entire SMC. An SVM-searchlight analysis revealed significant classification in the superior temporal gyrus and left planum temporale in addition to the SMC.Significance.The current results support a unilateral implant using surface electrodes, covering the ventral 50% of the SMC. The added value of depth electrodes is unclear. We did not observe evidence for variations in the qualitative nature of information across SMC. The current results need to be confirmed in paralyzed patients performing attempted speech.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 2.

The field of neuromodulation has evolved significantly over the past decade. Developments include novel indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapeutic interventions. In this review, which is the second part of an effort to document and integrate the basic fundamentals and recent successful developments in the field, we will focus on classic paradigms for electrode placement as well as new exploratory targets, mechanisms of neuromodulation using this technique and new developments, including focused ultrasound driven ablative procedures.

O campo da neuromodulação evoluiu significativamente na última década. Esse progresso inclui novas indicações e inovações de hardware, software e técnicas de estimulação, levando a uma expansão das áreas clínicas cobertas e no papel dessas técnicas como intervenções terapêuticas eficazes. Nesta revisão, que é a segunda parte de um esforço para documentar e integrar os fundamentos básicos e os desenvolvimentos recentes e bem-sucedidos no campo, vamos nos concentrar em paradigmas clássicos para colocação de eletrodos, bem como em novos alvos exploratórios, mecanismos de neuromodulação usados por esta técnica e novos desenvolvimentos, incluindo procedimentos ablativos orientados por ultrassom focalizado.

A scoping review on the clinical effectiveness of Trans-Impedance Matrix (TIM) measurements in detecting extracochlear electrodes and tip fold overs in Cochlear Ltd devices.

BACKGROUND: Extrusion of electrodes outside the cochlea and tip fold overs may lead to suboptimal outcomes in cochlear implant (CI) recipients. Intraoperative measures such as Trans-Impedance Matrix (TIM) measurements may enable clinicians to identify electrode malposition and direct surgeons to correctly place the electrode array during surgery. OBJECTIVES: To assess the current literature on the effectiveness of TIM measurements in identifying extracochlear electrodes and tip fold overs. METHODS: A scoping review of studies on TIM-based measurements were carried out using the Databases-Medline/PubMed, AMED, EMBASE, CINAHL and the Cochrane Library following PRISMA guidelines. Eleven full texts articles met the inclusion criteria. Only human studies pertaining to TIM as a tool used in CI were included in the review. Further, patient characteristics, electrode design, and TIM measurement outcomes were reported. RESULTS: TIM measurements were available for 550 implanted ears with the subjects age ranged between 9 months to 89 years. Abnormal TIM measurements were reported for 6.55% (36). Tip fold over was detected in 3.64% (20) of the cases, extracochlear electrodes in 1.45% (8), and 1.45% (8) were reported as buckling. Slim-modiolar electrode array designs were more common (54.71%) than pre-curved (23.34%) or lateral wall (21.95%) electrode array. Abnormal cochlear anatomy was reported for five ears (0.89%), with normal cochlear anatomy for all other patients. CONCLUSION: TIM measurement is a promising tool for the intraoperative detection of electrode malposition. TIM measurement has a potential to replace intraoperative imaging in future. Though, TIM measurement is in its early stages of clinical utility, intuitive normative data sets coupled with standardised criteria for detection of abnormal electrode positioning would enhance its sensitivity.

Feasibility and safety of stereoelectroencephalography in young children.

PURPOSE: Stereoelectroencephalography (SEEG) is a diagnostic surgery that implants electrodes to identify areas of epileptic onset in patients with drug-resistant epilepsy (DRE). SEEG is effective in identifying the epileptic zone; however, placement of electrodes in very young children has been considered contraindicated due to skull thinness. The goal of this study was to evaluate if SEEG is safe and accurate in young children with thin skulls. METHODS: Four children under the age of two years old with DRE underwent SEEG to locate the region of seizure onset. Presurgical planning and placement of electrodes were performed using ROSA One Brain. Preoperative electrode plans were merged with postoperative CT scans to determine accuracy. Euclidean distance between the planned and actual trajectories was calculated using a 3D coordinate system at both the entry and target points for each electrode. RESULTS: Sixty-three electrodes were placed among four patients. Mean skull thickness at electrode entry sites was 2.34 mm. The mean difference between the planned and actual entry points was 1.12 mm, and the mean difference between the planned and actual target points was 1.73 mm. No significant correlation was observed between planned and actual target points and skull thickness (Pearson R = - 0.170). No perioperative or postoperative complications were observed. CONCLUSIONS: This study demonstrates that SEEG can be safe and accurate in children under two years of age despite thin skulls. SEEG should be considered for young children with DRE, and age and skull thickness are not definite contraindications to the surgery.

Depletion of complement factor 3 delays the neuroinflammatory response to intracortical microelectrodes.

The neuroinflammatory response to intracortical microelectrodes (IMEs) used with brain-machine interfacing (BMI) applications is regarded as the primary contributor to poor chronic performance. Recent developments in high-plex gene expression technologies have allowed for an evolution in the investigation of individual proteins or genes to be able to identify specific pathways of upregulated genes that may contribute to the neuroinflammatory response. Several key pathways that are upregulated following IME implantation are involved with the complement system. The complement system is part of the innate immune system involved in recognizing and eliminating pathogens - a significant contributor to the foreign body response against biomaterials. Specifically, we have identified Complement 3 (C3) as a gene of interest because it is the intersection of several key complement pathways. In this study, we investigated the role of C3 in the IME inflammatory response by comparing the neuroinflammatory gene expression at the microelectrode implant site between C3 knockout (C3-/-) and wild-type (WT) mice. We have found that, like in WT mice, implantation of intracortical microelectrodes in C3-/- mice yields a dramatic increase in the neuroinflammatory gene expression at all post-surgery time points investigated. However, compared to WT mice, C3 depletion showed reduced expression of many neuroinflammatory genes pre-surgery and 4 weeks post-surgery. Conversely, depletion of C3 increased the expression of many neuroinflammatory genes at 8 weeks and 16 weeks post-surgery, compared to WT mice. Our results suggest that C3 depletion may be a promising therapeutic target for acute, but not chronic, relief of the neuroinflammatory response to IME implantation. Additional compensatory targets may also be required for comprehensive long-term reduction of the neuroinflammatory response for improved intracortical microelectrode performance.

Long-term outcomes with abandoning versus extracting sterile leads: A 10-year population-based study.

BACKGROUND: Long-term outcomes of sterile lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) remain unclear. METHODS: We performed a retrospective study of a population residing in southeastern Minnesota with follow-up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE of sterile leads from January 1, 2000, to January 1, 2011, and had follow-up for at least 10 years or until their death were included. RESULTS: A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. Indications for subsequent lead extraction arose in 9.1% (n = 14) of patients with initial LA and 5.3% (n = 1) in patients with initial TLE, after an average of 7 years. Moreover, 28.6% of patients in the LA cohort who required subsequent extraction did not proceed with the extraction, and among those who proceeded, 60% had clinical success and 40% had a clinical failure. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges (5.2% vs. 5.3%). There was no difference in 10-year survival probability among the LA group and the TLE group (p = .64). CONCLUSION: An initial lead abandonment strategy was associated with more complicated subsequent extraction procedures compared to patients with an initial transvenous lead extraction strategy. However, there was no difference in 10-year survival probability between both lead management approaches.

Transvenous lead advancement in pediatric pacing to overcome growth-induced lead straightening and stretching.

BACKGROUND: The stretching of the lead caused by somatic growth may lead to complications (dislodgement, fracture, failure) of transvenous leads implanted in pediatric patients. Atrial loop and absorbable ligatures may prevent it. Periodical lead advancement with lead pushing from the pocket may be an option to growth-induced stretching. Our aim was to analyze retrospectively the outcome of periodical transvenous lead advancement in children with pacemaker (PM). METHODS: A procedure of lead advancement was performed in patients with a single-chamber PM implanted for isolated congenital complete atrioventricular block or sinus node dysfunction with growth-induced lead straightening/stretching. The PM pocket was opened, the lead was released from subcutaneous adherences and was gently advanced to shape again a loop/semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are described as median (25th-75th centiles). RESULTS: 14 patients with 13 VVIR and 1 AAIR PM implanted at 6.8 (5.9-8.0) years of age, 23 (19-26) kg, 118 (108-124) cm, underwent 30 advancement procedures, 1.5 (1.0-2.3) per patient, during follow-up [45 (35-63) months]. Delta between procedures was: 18 (14-25) months, 11 (7-13) cm, 6 (4-9) kg; 90% of leads were successfully advanced without complications. Three unsuccessful procedures occurred with longer times [30 (14-37) months]. Electrical lead parameters did not show significant differences pre-/post-procedures. CONCLUSION: the advancement of transvenous leads in children seems safe and effective. This procedure may be another possible choice to preserve transvenous lead position and function until growth has completed.

Is the Position of the Basal-Most Electrode Depending on Electrode Array Design and Influencing Postoperative Speech Perception? A Retrospective Analysis of 495 Ears.

OBJECTIVE: The objective of this study is to examine the influence of electrode array design on the position of the basal-most electrode in cochlear implant (CI) surgery and therefore the stimulability of the basal cochlea. Specifically, we evaluated the angular insertion depth of the basal-most electrode in perimodiolar and straight electrode arrays in relation to postoperative speech perception. MATERIALS AND METHODS: We conducted a retrospective analysis of 495 patients between 2013 and 2018 using the Cochlear™ Contour Advance® (CA), Cochlear™ Slim Straight® (SSA), or Cochlear™ Slim Modiolar® (SMA) electrode arrays, as well as the MED-EL Flex24 (F24), MED-EL Flex28 (F28), and MED-EL FlexSoft (F31.5) electrode arrays. Cochlear size and the position of the basal-most electrode were measured using rotational tomography or cone beam computed tomography, and the results were compared with postoperative speech perception in monosyllables and numbers. RESULTS: The straight electrode arrays, specifically the F31.5 (31.5 mm length) and the F28 (28 mm length), exhibited a significantly greater angular insertion depth of the basal-most electrode. No significant correlation was found between cochlear morphology measurements and the position of the basal-most electrode artifact. Cochleostomy-inserted electrode arrays showed a significantly higher insertion depth of the basal-most electrode. Nevertheless, the position of the basal-most electrode did not have a significant impact on postoperative speech perception. CONCLUSION: Straight electrode arrays with longer lengths achieved deeper angular insertion depths of the basal-most electrode. Cochlear morphology does not have a substantial influence on the position of basal-most electrode. The study confirms that the basal area of the cochlea, responsible for high-frequency range during acoustic stimulation, is not the primary region for speech understanding via electrical stimulation with CI.