# Advances in endovascular brain computer interface: Systematic review and future implications

Julien Ognard, Gerard El Hajj, Onam Verma, Sherief Ghozy, Ramanathan

Kadirvel, David F Kallmes, Waleed Brinjikji

► To cite this version:

Julien Ognard, Gerard El Hajj, Onam Verma, Sherief Ghozy, Ramanathan Kadirvel, et al.. Advances in endovascular brain computer interface: Systematic review and future implications. Journal of Neuroscience Methods, 2025, 420, pp.110471. 10.1016/j.jneumeth.2025.110471. hal-05115294

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# Advances in endovascular brain computer interface: Systematic review and future implications

Julien Ognard<sup>a,b,*</sup>, Gerard El Hajj<sup>a</sup>, Onam Verma<sup>c</sup>, Sherief Ghozy<sup>a,d</sup>, Ramanathan Kadirvel<sup>a,d</sup>, David F. Kallmes<sup>a</sup>, Waleed Brinjikji<sup>a,d</sup>

## ABSTRACT

**Background:** Brain-computer interfaces (BCIs) translate neural activity into real-world commands. While traditional invasive BCIs necessitate craniotomy, endovascular BCIs offer a minimally invasive alternative using the venous system for electrode placement.

**New method:** This systematic review evaluates the technical feasibility, safety, and clinical outcomes of endovascular BCIs, discussing their future implications. A systematic review was conducted per PRISMA guidelines. The search spanned PubMed, Web of Science, and Scopus databases using keywords related to neural interfaces and endovascular approaches. Studies were included if they reported on endovascular BCIs in preclinical or clinical settings. Dual independent screening and extraction focused on electrode material, recording capabilities, safety parameters, and clinical efficacy.

**Results:** From 1385 initial publications, 26 met the inclusion criteria. Seventeen studies investigated the Stentrode device. Among the 24 preclinical studies, 16 used ovine or rodent models, and 9 addressed engineering or simulation aspects. Two clinical studies reported six ALS patients successfully using an endovascular BCI for digital communication. Preclinical data established the endovascular ovine model, demonstrating stable neural recordings and vascular changes with long-term implantation. Key challenges include thrombosis risk, long-term electrode stability, and anatomical variability.

**Comparison with existing methods:** Endovascular BCI reduced invasiveness, improved safety profiles, with comparable neural recording fidelity to invasive methods, and promising preliminary clinical outcomes in severely paralyzed patients.

**Conclusions:** Early results are promising, but clinical data remain scarce. Further research is needed to optimize signal processing, enhance electrode biocompatibility, and refine endovascular procedures for broader clinical applications.

## 1. Introduction

Brain-computer interfaces (BCIs) enable direct communication between neural activity and external devices. BCIs encompass a spectrum of technologies, ranging from non-invasive (e.g., electroencephalography EEG) to invasive (e.g., intracranial implants), aimed primarily at recording or delivering stimulation.

Traditional invasive BCIs require craniotomy for electrode implantation, with inherent surgical risks, whereas non-invasive methods are limited by low signal resolution due to attenuation.

Endovascular neural recording has evolved significantly over the past decades. Early devices, such as the Seeker guidewire (0.2–0.6 mm diameter) and the POD catheter (Penn et al., 1973; Stoeter et al., 1995), repurposed vascular tools with exposed metal tips to record intracranial intravascular EEG, demonstrating 2–5 × higher amplitude signals than scalp electrodes in epilepsy monitoring (He et al., 2016). Kennedy et al.

first reported an implantable BCI device in a human (Kennedy and Bakay, 1998). These single-electrode systems, while minimally invasive, focused on recording spontaneous and evoked potentials (e.g., somatosensory, auditory) in humans and animals.

By the early 2000s, the development of multi-electrode probes (Bower et al., 2013) marked a significant advancement. These probes enabled higher-resolution recordings in vessels like the Superior Sagittal Sinus (SSS). Endovascular electrocorticography (ECOG), captured epileptiform spikes and microspikes comparable to subdural grids in porcine models. Further technological miniaturization led to micro- and nanowire electrodes, with diameters ranging from 0.6 to 20 µm. Notably, Llinás et al. introduced platinum/iridium arrays capable of recording spinal cord and sciatic nerve activity with low noise levels (Llinás et al., 2005). Upcoming BCIs approach cortical anatomy through contiguous venous sinuses using endovascular techniques similar to venous sinus stent deployment, which are ubiquitously used to treat

<footnote><sup>a</sup> Department of Radiology, Mayo Clinic, Rochester, MN, USA</footnote>

<footnote><sup>b</sup> Univ Brest, LATIM, INSERM UMR1101, CHU Brest, France</footnote>

<footnote><sup>c</sup> Post-Graduate Institute of Medical Education and Research, Chandigarh, India</footnote>

<footnote><sup>d</sup> Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA</footnote>

<footnote>* Correspondence to: Alfred Building 9-446 200 First St. SW, Rochester, MN 55905, USA.</footnote>

<footnote>E-mail address: julien.ognard@chu-brest.fr (J. Ognard).</footnote>
idiopathic intracranial hypertension and pulsatile tinnitus. (Oxley, 2025). Endovascularly deployed BCIs, while minimally invasive, come with distinct complications and challenges as compared to traditional open surgery. This may represent a transformative approach in neuroprosthetics with potential to restore autonomy in severely impaired patients (Abbasi and Suran, 2023).

This systematic review aims to synthesize evidence from preclinical and early human experiences, providing a comprehensive evaluation of technical feasibility, safety considerations, and preliminary clinical outcomes associated with endovascular BCIs. Through examining these early-stage results, we aim to clarify the technology's current role, identify knowledge gaps, and inform the future clinical positioning and developmental pathways for endovascular BCIs.

# 2. Material and methods

## 2.1. Standard protocol approvals

No ethical approval was required as the current study involved analyzing and synthesizing previously published data and information from secondary use of deidentified electronic databases (Code of Federal Regulations, 45 CFR 46.102). No protocol was registered. The study was not funded. All data to conduct or reproduce the study are available online. It was conducted and reported per the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 recommendations (Page et al., 2021).

## 2.2. Search strategy

We used Nested Knowledge® (NK) AutoLit® software, version 1.89 (NK, St Paul, Minnesota, USA) for literature search, duplicate removal, article screening and evaluation processes. We performed a systematic review of the English-language literature using the following databases: PubMed/Medline, Web of Science, Scopus. The search included a combination of keywords: ("neural interface*" OR "brain computer interface*" OR "transcortical stimulation" OR "brain stimulation" OR "stentrode*" OR "BCI" OR "TCS" OR "electrode array") AND ("transvenous" OR "brain vein*" OR "cort* vein*" OR "venous sinus" OR "endovascular" OR "venous"). In addition to the database search, we searched through unpublished results of ongoing/just terminated clinical trials. We also reviewed the bibliographies of included studies and consulted field experts to identify missed articles.

## 2.3. Eligibility criteria and study selection

We used NK AutoLit® software for the study selection process. Initially, two authors (JO, GEH) independently screened titles and abstracts to identify potentially eligible studies. Subsequently, the full-text articles of the selected studies were thoroughly assessed against the predetermined criteria. Any discrepancies in study selection were resolved through consensus. We included all studies providing reports on endovascular BCIs. All publications from the inception to December 31, 2024, were screened. Exclusion criteria consisted of no statement endovascular BCIs, conference abstracts not reporting substantial results, and review articles.

## 2.4. Data extraction and study outcomes

This review systematically evaluates the feasibility, safety, and clinical applications of endovascular BCIs, while identifying current challenges and future research directions. A predefined data extraction form was employed. Extracted data encompassed study characteristics, and included study type, animal model, BCI device used, device design, recording features and results, safety parameters, and indicators of clinical efficacy and patient characteristics (if clinical). Any discrepancies or conflicts were resolved through discussion and consensus. As

no meta-analysis was performed, no risk of bias was assessed.

# 3. Results

## 3.1. Study selection and inclusion

From the initial pool of 1385 publications identified, 210 duplicates were removed. Of the remaining articles, 56 were found to be potentially eligible based on their titles and abstracts. Ultimately, 26 studies met the inclusion criteria and provided sufficient information for this systematic review. Table 1 reports the summary of included studies, and Fig. 1 reports the PRISMA flow chart.

## 3.2. Characteristics of included studies

The 26 included studies were published between 2016 and 2024. Among the included studies: 17 manuscripts mentioned Stentrode device. The majority of manuscripts (24/26) addressed preclinical data, including 16 studies on animals, the ovine model initially described by (Oxley et al., 2016) were mostly used totaling 185 sheep across studies. Only two studies (Wang et al., 2024; Zhang et al., 2023) used a rodent model. Nine studies provided engineering or simulation details. Two studies were dedicated to clinical applications, including 6 patients conducted among patients with severe motor palsy and amyotrophic lateral sclerosis (ALS). Details and key findings are reported in Table 1.

## 3.3. Endovascular BCIs systems

A brain-computer interface is a system designed to establish direct communication between the brain and external devices by translating neural activity into actionable commands. In essence, BCIs record neural signals (typically electrical activity from neurons), process these signals to decode intended actions, and translate them into functional outputs such as computer cursor movement, or digital communication (Fig. 2). Endovascular BCIs offer an innovative approach. It uses the brain vasculature to place the array as close as possible to a target area to interact (mainly record) with the brain activity. Such approaches are mostly represented by an electrode array-stent trans-venous placement (mainly, Stentrode) (Oxley, 2025).

At the cellular level, neurons produce signals that form local field potentials. Electrodes are positioned within blood vessels and pick up faint microvolt signals that are subsequently amplified, filtered, and converted into digital form. The data then undergoes a series of signal processing steps, including preprocessing to remove noise, feature extraction to highlight critical elements and dimensionality reduction to streamline the information for analysis (Deshpande et al., 2025; Combrisson et al., 2024). Kacker el al. recently published (Kacker et al., 2025) motor activity in gamma and high gamma bands recorded with a Stentrode from the human motor cortex in two people with ALS In the frequency domain. Power spectral density plots were computed from single-channel recordings to compare the average power during rest and movement epochs. To quantify these differences, the area under the curve of the power spectral density were calculated across key motor-related frequency bands and visualized using kernel density estimates. In the time domain, raw broadband signals were filtered into specific frequency bands to isolate oscillatory components. Mainly machine learning techniques decode the user's intentions from this processed data, with calibration and feedback mechanisms refining the system's precision over time (Kardam et al., 2023; Llorella et al., 2021).

In stimulation mode, BCIs may deliver electrical impulses to modulate neural activity, for example to treat movement disorders (Zhang et al., 2024). Endovascular BCIs like the Stentrode are optimized for recording, though their potential for stimulation remains under investigation. Preclinical studies have shown that the Stentrode's electrodes can activate the cortex (Gerboni et al., 2018), suggesting potential for stimulation applications.
<table><caption>**Table 1**
Included studies. NA: Not applicable. NR: Not reported.</caption><thead><tr><th>First Author</th><th>Journal</th><th>Year</th><th>Reference</th><th>Device</th><th>Study type</th><th>Number of subjects</th><th>Contribution</th></tr></thead><tbody><tr><td>Oxley TJ</td><td>Nat Biotechnol</td><td>2016</td><td>(Oxley et al., 2016)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>33 sheep</td><td>Endovascular Stentrode implants demonstrated stable neural signal recording in sheep, matching epidural arrays and detecting somatosensory evoked potentials in 98% of channels over 28 days, offering a less invasive alternative to subdural electrodes with comparable efficacy for chronic BCIs</td></tr><tr><td>Wong Y</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2016</td><td>(Wong et al., 2016)</td><td>NR - Stentrode design</td><td>Preclinical (Engineering)</td><td>NA</td><td>Nitinol electrodes, despite higher impedance, demonstrated comparable neural signal recording to platinum/stainless steel in sheep models, with self-expanding properties enhancing vessel wall contact, offering a promising minimally invasive alternative for endovascular brain-computer interfaces pending long-term stability validation</td></tr><tr><td>Opie NL</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2016</td><td>(Opie et al., 2016c)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>10 sheep</td><td>Feasibility of a stable endovascular neural interface, with electrode impedance stable over 91 days, neural bandwidth around 193 Hz for six months, and no vessel occlusion.</td></tr><tr><td>Opie NL</td><td>J Neural Eng</td><td>2016</td><td>(Opie et al., 2016a)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>15 sheep</td><td>Stent-electrode arrays revealed stable 1 kHz impedances, a shift in 100 Hz phase angles stabilizing after 8 days, and histological confirmation of neointimal integration</td></tr><tr><td>Opie NL</td><td>IEEE Trans Biomed Eng</td><td>2017</td><td>(Opie et al., 2017)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>12 sheep</td><td>Endovascular stent-electrode arrays achieve > 85% neointimal coverage by 4 weeks with no vascular occlusion, validated by micro-CT/histology correlation</td></tr><tr><td>Oxley TJ</td><td>J Neurosurg</td><td>2018</td><td>(Oxley et al., 2018)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>39 sheep</td><td>Ovine model and venous pathway description, 4-Fr catheter was successful in accessing the SSS in 100% of cases</td></tr><tr><td>John SE</td><td>Sci Rep</td><td>2018</td><td>(John et al., 2018b)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>6 sheep</td><td>Stentrode endovascular neural interface achieved comparable bandwidth, SNR, spatial resolution, and decoding accuracy to traditional subdural and epidural arrays,</td></tr><tr><td>Gerboni G</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2018</td><td>(Gerboni et al., 2018)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>1 sheep</td><td>Characterization of endovascular cortical stimulation measured using cortical subdural surface recordings</td></tr><tr><td>Opie NL</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2018</td><td>(Opie et al., 2018a)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>12 sheep</td><td>Stentrode implanted in the superior sagittal sinus over the motor cortex consistently recorded high-frequency neural signals over 6 + months regardless of electrode position or orientation</td></tr><tr><td>Opie NL</td><td>Nat Biomed Eng</td><td>2018</td><td>(Opie et al., 2018b)</td><td>Stentrode</td><td>Preclinical (Engineering)</td><td>25 sheep</td><td>Deployment of a Stentrode via the jugular vein elicited motor responses similar to invasive electrode</td></tr><tr><td>Forsyth IA</td><td>Int. IEEE/EMBS Conf. Neural Eng., NER</td><td>2019</td><td>(Forsyth et al., 2019)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>2 sheep</td><td>Cortical movement-related signals were recorded using a Stentrode placed in the superior sagittal sinus adjacent to the motor cortex. Recorded brain signal was used to train a support vector machine classifier.</td></tr><tr><td>John SE</td><td>IEEE Trans Biomed Eng</td><td>2019</td><td>(John et al., 2019)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>5 sheep</td><td>Electrode location did not significantly affect impedance magnitude, but both location and size influenced phase angles in a frequency-dependent manner, with subdural and epidural electrodes showing stronger capacitive behavior, and intravascular placement affecting phase responses below 10 kHz.</td></tr><tr><td>Opie NL</td><td>Int. Winter Conf. Brain-Comput. Interface, BCI</td><td>2020</td><td>(Opie et al., 2020)</td><td>Stentrode</td><td>Preclinical (Engineering)</td><td>NA</td><td>Mechanical properties of the Stentrode are similar to commercially available neurovascular stents used to access cortical vessels for clot retrieval and coil placement</td></tr><tr><td>Oxley TJ</td><td>J Neurointerv Surg</td><td>2021</td><td>(Oxley et al., 2021)</td><td>Stentrode</td><td>Clinical</td><td>2 patients (ALS)</td><td>First-in-human report of experience of an ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocardiography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis</td></tr><tr><td>Fanelli A</td><td>ADVANCED MATERIALS TECHNOLOGIES</td><td>2022</td><td>(Fanelli et al., 2022)</td><td>Poymeric material</td><td>Preclinical (Engineering)</td><td>NA</td><td>Transient neurovascular interface for neural recording and stimulation has been developed, fabricated entirely from polymeric materials using straightforward molding technique</td></tr><tr><td>John SE</td><td>J Neural Eng</td><td>2022</td><td>(John et al., 2022)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>15 sheep</td><td>Endovascular neural interfaces triggered a foreign body response with extracellular matrix buildup, macrophages, and vascular remodeling without occluding blood flow. Despite lumen narrowing, the ENI successfully recorded epileptiform activity.</td></tr></tbody></table>

(continued on next page)
<table><caption>Table 1 (continued)</caption><thead><tr><th>First Author</th><th>Journal</th><th>Year</th><th>Reference</th><th>Device</th><th>Study type</th><th>Number of subjects</th><th>Contribution</th></tr></thead><tbody><tr><td>Tarigoppula VSA</td><td>Int. IEEE/EMBS Conf. Neural Eng., NER</td><td>2023</td><td>(Tarigoppula et al., 2023)</td><td>Stentrode</td><td>Preclinical (Animal)</td><td>2 sheep</td><td>Stentrode was safely retrieved from a dural sinus after an implantation period of seven days</td></tr><tr><td>Wen B</td><td>Int. Winter Conf. Brain-Comput. Interface, BCI</td><td>2023</td><td>(Wen et al., 2023)</td><td>Stentrode</td><td>Preclinical (Engineering)</td><td>NA</td><td>Three-electrode configuration may be the most effective design for intravascular stent electrode arrays in neural interface applications</td></tr><tr><td>Mitchell P</td><td>JAMA Neurol</td><td>2023</td><td>(Mitchell et al., 2023)</td><td>Stentrode</td><td>Clinical</td><td>4 patients (ALS)</td><td>Four patients successfully used the Stentrode BCI for computer control with stable signal bandwidth and no serious adverse events over 12 months</td></tr><tr><td>Zhang A</td><td>Science</td><td>2023</td><td>(Zhang et al., 2023)</td><td>Flexible probe</td><td>Preclinical (Animal)</td><td>3 rats</td><td>Ultra-small flexible endovascular neural probe that can be implanted into sub-100-micron vessels</td></tr><tr><td>Mahoney TB</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2023</td><td>(Mahoney et al., 2023)</td><td>NR - Stentrode design</td><td>Preclinical (Animal)</td><td>1 sheep</td><td>Comparison between sub-scalp and stent electrode array signals</td></tr><tr><td>Qi W</td><td>Annu Int Conf IEEE Eng Med Biol Soc</td><td>2023</td><td>(Qi et al., 2023)</td><td>NR -Stentrode design</td><td>Preclinical (Simulation)</td><td>NA</td><td>In a CFD simulation stent struts created recirculation zones and reduced Time-Averaged Wall Shear Stress to 0</td></tr><tr><td>Qi W</td><td>Sci Rep</td><td>2024</td><td>(Qi et al., 2024)</td><td>NR -Stentrode design</td><td>Preclinical (Animal & Simulation)</td><td>3 sheep</td><td>Stent-mounted neural interfaces alter venous hemodynamics, with vessel deformation affecting lumen geometry and neointimal proliferation in sheep negatively correlating with mean Wall Shear Stress</td></tr><tr><td>Wang X</td><td>Nat Commun</td><td>2024</td><td>(Wang et al., 2024)</td><td>uFINE-I</td><td>Preclinical (Animal)</td><td>4 rats, 4 sheep</td><td>The ultra flexible intravascular neural electrode (uFINE-I) enabled high-resolution neural recording in sheep with minimal tissue damage, successfully capturing local field potentials and single-unit activity</td></tr><tr><td>Xu Z</td><td>J Neural Eng</td><td>2024</td><td>(Xu et al., 2024)</td><td>NR -Telemetry module</td><td>Preclinical (Engineering)</td><td>NA</td><td>Optical wireless telemetry module designed for integration within a smart stent</td></tr><tr><td>Wen</td><td>Micromachines</td><td>2024</td><td>(Wen et al., 2024)</td><td>NR -Stentrode design</td><td>Preclinical (Engineering and Simulation)</td><td>NA</td><td>Laser welding technique enables the fabrication of smaller endovascular stent electrodes</td></tr></tbody></table>

<figure><img src="image_3.png" /><figcaption>Fig. 1. Flow diagram of the patients included in this study. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram summarizing the selection process of studies included in the review. A total of 1625 records were identified through database searches, with 210 duplicates removed. After screening 1385 records, 56 full-text reports were assessed for eligibility. Of these, 27 were excluded for reasons including being letters, reviews, congress abstracts, or non-endovascular BCI-related content. A total of 26 studies met inclusion criteria. No additional records were identified through other sources.</figcaption></figure>
<figure><img src="image_4.png" /><figcaption>**Fig. 2.** Schematic illustration of an endovascular brain-computer interface (BCI) system. The endovascular BCI, featuring a Stentrode design with an integrated electrode array (depicted in yellow), is implanted within the superior sagittal sinus of the cerebral venous system (shown in blue overlay), positioned adjacent to the primary motor cortex (highlighted in deep blue) to capture neural activity. The electrode array records broadband neural signals that gather cellular-level activities, as illustrated in the inset. The lead extends through the lateral sinus and jugular vein, connecting to a subcutaneous thoracic implantable receiver-transmitter. This device wirelessly transmits the recorded neural signals to an external unit, which interfaces with a computer. The processed neural data are translated into actionable visual commands ("Tasks") displayed on the computer interface, enabling brain-to-device communication. *This figure was created using BioRender* (https://BioRender.com).</figcaption></figure>

## 3.4. Preclinical feasibility and safety

### 3.4.1. Animal experiments

The ovine (sheep) model is a cornerstone in preclinical studies of endovascular BCIs due to its anatomical and physiological parallels with humans. The ovine model for cerebral catheter venography was described by Oxley et al. (2018). Table 2 compares venous anatomy between human and sheep. Sheep possess large brains (approximately 100–140 g) and a venous architecture suitable for testing catheter-based delivery systems. Multiple studies in ovine models have provided evidence that endovascular BCIs can reliably record neural activity over chronic implantation periods (Table 1). Oxley et al. (2016) implanted Stentrode devices via the jugular vein into the SSS of multiple sheep cohorts to record local field potentials near the motor cortex.

Electrochemical impedance is the measure of opposition encountered by an electrical current when passing through the electrode-tissue interface. Lower impedance indicates improved signal quality and device-tissue integration. In these studies, electrodes maintained stable impedance values, and recordings of somatosensory evoked potentials were achieved in a high percentage of channels (≈98 %) over the study duration (Opie et al., 2018a; Oxley et al., 2016). High-frequency neural signals (up to 245 Hz) were consistently recorded up to 192 days without significant degradation, and variations in electrode position or orientation had a minimal impact on signal quality. Over 6 months,

electrochemical impedance decreased from 3.99 kΩ to 2.28 kΩ at 1 kHz, with phase angles stabilizing after 8 days.

Initial evidence that endovascular electrical stimulation can reliably elicit cortical activation was presented by Opie et al. (2018b) and Gerboni et al. (2018), via Stentrode measured using cortical subdural surface recordings in an adult sheep.

By day 45, Stentrodes were enveloped by neointimal growth, primarily composed of fibroblasts, leading to vessel wall thickening, a typical response to stenting, causing the device become permanently embedded in tissue. Stentrode endothelialization makes it theoretically irretrievable but a team reported the feasibility of an endovascular retrieval from a dural sinus after an implantation period of seven days with no vascular damages (Tarigoppula et al., 2023).

Over a period of up to 190 days, this progressive endothelialization was associated with improved electrical coupling without causing vessel occlusion or significant adverse events (Opie et al., 2017; Oxley et al., 2016).

The safety profile was further supported by histopathological examinations showing neointimal growth that secured the stent without provoking significant inflammation or thrombosis (John et al., 2019; Opie et al., 2017; Opie et al., 2016b). Neointimal coverage increased from 12.6 % (7 days) to 96 % (100 + days), while vessel lumen area decreased slightly from 5.48 mm² to 4.06 mm². Notably, one animal experienced implantation failure due to anatomical challenges when
<caption>**Table 2**</caption>

Comparative venous anatomy between human and sheep for BCI ovine model. Reported in Wang et al. (2024) an adapted, using data from Altafulla et al. (2020), Andrews et al. (1989), Hoffmann et al. (2014), Kong et al. (2023), Neudorfer et al. (2020), Oxley et al. (2016), Santoreneos et al. (1998), Tubbs et al. (2009).

<table><thead><tr><th>Venous Structure</th><th>Sheep anatomy</th><th>Human anatomy</th><th>Sheep Diameter (mm)</th><th>Human Diameter (mm)</th><th>Comparison</th><th>Nearby Functional Areas</th></tr></thead><tbody><tr><td>Dorsal sagittal sinus</td><td>Begins at crista galli, drains fine ethmoidal veins (EV), and merges into TrS</td><td>Superior sagittal sinus, anterior part may be absent, replaced functionally by two superior cerebral veins; terminates in transverse sinus</td><td>1-2.5 (distal-proximal)</td><td>4-10</td><td>Similar, human sinus is larger</td><td>Motor, prefrontal, somatosensory, visual cortex</td></tr><tr><td>Dorsal cerebral veins</td><td>Drains hemisphere surfaces, enters DSS</td><td>Superior cerebral veins drain hemisphere surfaces, enter superior sagittal sinus</td><td>Not described</td><td>1-5 (distal-proximal)</td><td>Similar morphology</td><td>Motor, somatosensory cortex</td></tr><tr><td>Great cerebral vein (Galen)</td><td>Formed by ICV at "confluence venous caudalis"</td><td>Formed by ICV and basal veins of Rosenthal at "confluence venous posterior"</td><td>1.5</td><td>4</td><td>Similar, human veins are larger</td><td>Pineal gland</td></tr><tr><td>Internal cerebral veins (ICV)</td><td>Formed by thalamostriate vein (TSV) and vein of the septum pellucidum (VSP)</td><td>Formed by TSV and anterior septal veins</td><td>Not described</td><td>1.5-2</td><td>Similar morphology</td><td>Ventral capsule, ventral striatum, lateral habenula</td></tr><tr><td>Choroidal vein (ChV)</td><td>Brush-like with numerous short branches, drains TSV</td><td>Brush-like with numerous short branches, drains TSV</td><td>Not described</td><td>1</td><td>Similar morphology</td><td>Hippocampus</td></tr><tr><td>Lateral vein (LV)</td><td>Formed by central vein (CeV), dorsomedial basilar cerebral vein (DMBCV), rostral ventral cerebellar vein (RVCrV), and drains into GCV</td><td>Lateral vein of lateral ventricle drains into ICV, called 'lateral vein of lateral ventricle'</td><td>Not described</td><td>2-3</td><td>Different morphology</td><td>-</td></tr><tr><td>Caudate nucleus veins (VCN)</td><td>Drains into TSV from rostral and lateral directions</td><td>Anterior and transverse caudate veins drain into TSV</td><td>Not described</td><td>1</td><td>Similar morphology</td><td>Caudate nucleus</td></tr><tr><td>Straight sinus (SS)</td><td>Formed by confluence of GCV (ventrally) and vein of the corpus callosum (VCC) (dorsally); drains into confluence of sinus or TrS</td><td>Receives inferior sagittal sinus, great vein of Galen, and superior cerebellar veins; drains into confluence of sinus or TrS</td><td>2-2.5</td><td>2-5</td><td>Similar, human sinus is larger</td><td>Visual cortex</td></tr><tr><td>Sigmoid sinus (SiS)</td><td>Continues caudoventrally as caudal TrS branch, draining into ventral occipital sinus (VOS); connects dorsal and ventral sinus system</td><td>Continuation of TrS at occipitopetrosal junction, draining into internal jugular vein</td><td>Not described</td><td>7-8</td><td>Similar, human sinus is larger</td><td>-</td></tr><tr><td>Temporal sinus (TeS)</td><td>Larger than SiS, merges with two emissary veins, drains into maxillary vein (MV) and profundal temporal vein (PTV)</td><td>-</td><td>Not described</td><td>2.5</td><td>Different morphology</td><td>-</td></tr><tr><td>Transverse sinus (TrS)</td><td>Continuation of DSS, part of the confluence of sinus</td><td>Caudal continuation of superior sagittal sinus, part of confluence of sinus</td><td>2.5</td><td>6</td><td>Similar, human sinus is larger</td><td>-</td></tr><tr><td>Internal jugular vein (IJV)</td><td>Major venous return pathway, draining into the brachiocephalic vein</td><td>Main venous drainage of the head, merging into the brachiocephalic vein</td><td>3.5-6</td><td>10-15</td><td>Human is larger and carries more venous return</td><td>-</td></tr><tr><td>Common jugular vein (CJV)</td><td>Drains into the subclavian vein, merging with the IJV</td><td>Merges with the subclavian vein to form the brachiocephalic vein</td><td>6-8</td><td>15-20</td><td>Human is significantly larger</td><td>-</td></tr></tbody></table>

navigating the torcular Herophili.

Technical issues included electrode shorting, observed in 5–10 % of electrodes excluded post-mortem, primarily due to fluid ingress into percutaneous leads, though this did not compromise overall device functionality (Oxley et al., 2018). Concerning the safety of the intervention to implant the Stentrode, a telescoping coaxial catheter system was developed to navigate the tortuous venous anatomy. Using a 2-Fr and 4-Fr catheters, the team achieved 100 % SSS access with zero complications, in contrast to 5-Fr and 6-Fr systems which recorded complication rates of 33 % and 36 %, respectively (including venous dissection, subdural hemorrhage, thrombus formation).

High-frequency neural signals refer to neural oscillations recorded at higher frequency bands (above 70–100 Hz), typically associated with local neuronal firing. These signals, often in the gamma band, encode detailed information about motor intent or cognitive states. Other pre-clinical studies compared endovascular arrays with traditional subdural or epidural arrays: although high-frequency power was slightly lower in endovascular recordings compared to subdural electrodes, the spatial resolution and overall signal stability were comparable (John et al., 2018a, 2018b; Opie et al., 2016b).

Signal bandwidth refers to the range of frequencies within which the neural interface can effectively record and interpret neural signals. A broader bandwidth allows capturing a more extensive range of neuronal

activities. Neural recordings maintained an average maximum bandwidth of 193.4 Hz, comparable to invasive arrays, without degradation over time. (John et al., 2019). Endovascular electrodes showed higher phase angles at low frequencies (≤1 kHz), indicating a more resistive interface from nearby blood vessels, while SD/ED arrays exhibited capacitive effects from fibrous encapsulation. Although impedance was similar across arrays except at high frequencies (>10 kHz), IV arrays had lower impedance overall which suggested reduced voltage stimulation requirements. Notably, mechanical failures led to significant electrode dropouts (40–60 % for IV, 33–73 % for SD/ED), and signal attenuation correlated more with electrode-brain distance than vascular placement. Forsyth et al. (2019) reported that the Stentrode achieved classification accuracies comparable to SD arrays and superior to ED arrays in differentiating movement from rest states (>70 %), although it was less effective at distinguishing left from right movements.

### 3.5. Device engineering and design

Stentrode (patent/US20220323241A1) was built on intracranial stent technology currently in clinical use to facilitate easy transfer from animal models to humans (Oxley et al., 2016). It employs a commercially available, self-expanding stent (Solitaire SAB, Covidien, (Campbell et al., 2015)) as a scaffold for the attachment of 750 µm
was punctured, and a 6-French sheath was then introduced after administration of 5000 units of heparin. A coaxial catheter system comprising a 0.36 mm Transend microwire, 2 F microcatheter, and 4 F delivery catheter (1.1 mm internal diameter)—was navigated into the SSS overlying the motor cortex. The Stentrode, preloaded in a custom 4-French delivery sheath with a radio-opaque tip, was advanced to 10 mm beyond the target marker and deployed. Deployment was confirmed by repeat angiography, which confirmed symmetric wall apposition and unimpaired blood flow. Following deployment, the transmission lead was then tunneled subcutaneously to a chest pocket, and the patient was extubated and discharged two days later.

Preclinical studies further reported insight on the conditions under which the stent was studied. Oxley et al. (2018) described the ovine model and key vascular parameters: the common jugular vein (median 7.4 mm), internal jugular vein (median 4.4 mm), transverse sinus (median 2.5 mm), and the SSS narrowing from 2.4 mm proximally to 1.2 mm distally, with the cortical cruciate sulcal vein (CSV; median diameter 1.1 mm) bifurcating at ~39–40 mm and accurately delin-eating the motor area. Opie et al. (2018b) electrodes implanted in front of the CSVs using endovascular (91 %), subdural (86 %), and pen-e-trating (91 %) arrays that consistently elicited repeatable, localized motor responses, whereas only 23 % of electrodes placed behind this landmark produced responses. These findings underscore the critical importance of positioning electrodes anterior to the CSVs for effective motor cortex stimulation.

### 3.7. Additional devices and innovation

Recent advances in ultra-flexible micro-endovascular probes offer a promising solution to the trade-off between invasiveness and spatial resolution in neural interfaces (Zhang et al., 2023).

One innovative alternative to the Stentrode is the uFINE-I, (Wang et al., 2024). This ultra flexible implantable neural electrode (uFINE-I) is designed for minimally invasive, intravascular delivery, enabling high-resolution single-unit recording in large animal models. Fabricated via advanced lithography, the uFINE-I measures 50 cm in length, 5 µm in thickness, and 120 µm width. It incorporates 30 IrOx/PEDOT: PSS-coated electrode sites (each 30 µm in diameter, with 40 µm spacing), achieving impedances below 100 kΩ. Designed for trans-cerebral venous implantation, the electrode integrates with a custom intravascular system that includes a nickel-titanium microneedle (puncture force: 1.65 N), 1.7 F microcatheter, and a balloon catheter for directional control.

Other studies have addressed challenges associated with long lead wires and battery requirements by integrating optical telemetry modules and focused ultrasound power transfer systems (Xu et al., 2024).

Fanelli et al. (2022) proposed a fully polymeric transient neuro-vascular interface fabricated via replica molding. This device utilizes a poly-ε-caprolactone scaffold with PEDOT:PSS conductive ele-ments—comprising four 600 µm electrodes, 200 µm feedlines, and overall dimensions of 44 mm × 7.6 mm × 77 µm, demonstrated tunable degradation; for instance, a 70:30 PCL:PLGA blend losing half its weight by day 120 under accelerated conditions. This design offers a dual advantage: it leverages the cerebrovascular system to access neural tis-sue without the need for invasive surgery, and its transient design may reduce inflammatory responses and eliminate the need for additional surgeries to remove or replace the device.

Trans-arterial approach for neural recording and stimulation are less studied and represented than trans-venous approach (Liu et al., 2025). The WEB device implanted within cerebral aneurysms of awake patients can capture task-specific brain electrical activities (Li et al., 2023). Future studies are warranted to establish the efficacy of and support for endovascular EEG as a tool for brain recording, brain stimulation, and brain-machine interface applications.

A recent study (Wen et al., 2024) demonstrated the fabrication of endovascular micro-wire stent electrodes using laser welding and

ablation techniques. Their optimized laser parameters created elec-trodes that ensure both mechanical and electrochemical performance in narrow vascular environments.

Traditional neural recording and stimulation devices face significant limitations due to their invasive implantation, which risks neuronal injury, blood-brain barrier disruption, and inflammatory reactions that impair device performance (Thielen et al., 2023). Opie and O'Brien's analysis (Opie and O'Brien, 2022) highlights the trade-off between ef-ficacy and safety: direct cortical stimulation, while highly effective (83.3 % responder rate), carries greater risks (12.5 % complications) due to craniotomy, whereas vagus nerve stimulation (VNS) is safer (7.8 % risk) but less effective (49.7 % responder rate).

## 4. Discussion

### 4.1. Current achievement and remaining challenges

The reviewed evidence demonstrates that endovascular BCIs can provide stable, high-fidelity neural recordings while minimizing the risks associated with craniotomy. Preclinical studies have established the feasibility of chronic implantation with favorable electrode-tissue integration and minimal adverse vascular events (Oxley et al., 2016; Opie et al., 2017). Early human trials further corroborate these findings, reporting reliable signal acquisition and effective control of digital de-vices in patients with severe paralysis (Majidi et al., 2023; Mitchell et al., 2023).

Despite these promising results, several technical challenges persist. High-frequency neural recordings (>100 Hz) offer detailed neural ac-tivity insights but are susceptible to attenuation and noise interference, highlighting the importance of optimized electrode materials and signal processing techniques. Electrochemical impedance measurements inform electrode-tissue interface stability; however, variability and drift over prolonged implantation may necessitate improved electrode coat-ings, yet tissue encapsulation can increase it over time, degrading per-formance. Signal processing must balance real-time decoding demands with computational complexity. BCIs target specific bands (e.g., mu [8–12 Hz], gamma [30–100 Hz]), but hardware may limit high-frequency detection, which further constrain applications.

#### 4.1.1. Long-term durability and biocompatibility

Data beyond 12–18 months are sparse, limiting our understanding of chronic biocompatibility and electrode durability (Fernández-Villegas et al., 2023). Current electrode materials, typically platinum-iridium alloys, may exhibit signal drift or degradation over time, prompting investigation into novel coatings for improved longevity (Wong et al., 2016).

#### 4.1.2. Advancements in signal processing

While early decoding algorithms have demonstrated adequate per-formance, enhanced computational models—potentially incorporating AI and machine learning—are needed to support real-time neural signal processing under varied environmental conditions (Einizade et al., 2022; Llorella et al., 2021).

#### 4.1.3. Antithrombotic management

A balance must be refined between minimizing thrombosis risk (especially in-stent thrombosis) and reducing the risk of pocket hema-toma associated with the sub clavicular pocket housing the internal telemetry unit (Brannigan and McClanahan, 2024). Current practice adapted from intracranial venous stenting protocols, involves prophy-lactic dual antiplatelet therapy (DAPT) for 3 months post-implantation, followed by aspirin monotherapy for one year. However, evidence suggests that antiplatelet agents may not be optimal for venous stenting due to the platelet-independent nature of venous thrombosis, which is primarily driven by the clotting cascade (Cheddad El Aouni et al., 2022). A review of 96 articles indicated that DAPT is associated with a higher
risk of hematoma compared to anticoagulant therapies, with the lowest risk observed with direct oral anticoagulants (DOACs).

### 4.1.4. Anatomical variability, device deployment, and complex vasculature

Literature on stents deployed permanently within cerebral veins for the treatment of idiopathic intracranial hypertension reports a technical success rate of 99.3% and an adverse event rate of only 2.09% (Puffer et al., 2013). Primary risks associated with cardiac pacemakers and the associated lead wires being mechanical failure (0.98%) and infection (0.56–0.68%), relating to surgical procedures and device sterility (Klug et al., 2007).

The review of J. (Brannigan et al., 2024) revealed substantial heterogeneity in key anatomical features of the superior cortical veins. This variability complicates the standardized deployment of electrode arrays, particularly for cortical vein implantation, which could enhance signal quality compared to SSS placement but requires precise alignment with functional brain regions. While current human deployments focus on the SSS, capturing lower limb motor cortex activity, recent preclinical advances demonstrate the feasibility of implanting electrode arrays in smaller cerebral vessels, such as the middle cerebral artery in rats (Zhang et al., 2023). However, translating this to human cortical veins faces anatomical hurdles, including acute vessel confluence angles (>100°), hairpin turns, and drainage into lacunae, which complicate device navigation (J. Brannigan et al., 2024; Brockmann et al., 2011). Additionally, cortical veins exhibit fragility due to thin, less muscular walls and lack of structural support in the subdural space, raising risks of perforation, a concern highlighted in subdural hematoma studies (Monea et al., 2014). The vein of Trolard, the largest cortical tributary (2.1–3.3 mm diameter), is a pragmatic initial target for existing stent-sized devices, yet its posterior parietal location may shift decoding focus from primary motor cortex (M1) to somatosensory (S1) or posterior parietal regions, which still enable motor intent detection (Fujiwara et al., 2023). Smaller sulcal veins (<1 mm diameter), though closer to the cortex, demand miniaturized electrode arrays and adaptive delivery systems to address anatomical variability, evident in SSS branch counts ranging from 11 to 45 and inconsistent presence of anastomotic veins like Trolard (identified in <65% of cases) (Oka et al., 1985). Current electrode sizes (500–750 µm) provide a balance between effective neural recording and safe vascular deployment, though further miniaturization could enhance spatial resolution and accessibility to deeper cortical regions. However, this miniaturization challenges signal quality, power delivery, and device durability, necessitating advanced materials and microfabrication techniques. Wen et al. recently proposed a laser ablation technology that brings the advantages of endovascular micro-wire electrode and stent, helping make the electrodes smaller and fit into a catheter with an inner diameter of 0.6 mm (Wen et al., 2025).

Age-related vessel diameter reduction and wall thickening further necessitate tailored approaches for younger patients with long-term implantation needs (Naidoo et al., 2022). Myoendothelial sphincters at venous junctions and slit-like SSS openings add procedural complexity, potentially requiring vasodilators during implantation. Future advancements must prioritize high-resolution cortical mapping, sulcal vein accessibility, and hybrid decoding strategies to leverage both motor and sensory signals.

### 4.2. Stentrode vs Neuralink

While the Stentrode is an endovascular device implanted minimally invasively via cerebral veins, Neuralink employs intracortical electrode arrays implanted into the brain cortex. Differences between the two systems are summarized in Table 3. Neuralink's BCI is an ambitious advancement in intracortical neuroprosthetics – utilizing high-density microelectrode arrays' direct interaction with the human cortex. Bettering previous neurostimulation techniques like deep brain stimulation (DBS), which rely on low-resolution macroelectrode (1270 µm/16 electrodes) targeting subcortical structures, Neuralink adopts ultrathin

<caption>**Table 3**</caption>

Comparison between timelines, capabilities and potential applications of Neuralink BCI and Synchron Stentrode.

<table><thead><tr><th>Feature</th><th>Neuralink</th><th>Synchron</th></tr></thead><tbody><tr><td>Company (Founding year)</td><td>Neuralink (2016)</td><td>Synchron (2016)</td></tr><tr><td>BCI Technology</td><td>Intracortical electrode array (Neural Lace)</td><td>Endovascular stent-electrode array (Stentrode)</td></tr><tr><td>Implantation method</td><td>Conventional Craniotomy and robot-assisted electrode implantation at primary motor cortex</td><td>Minimally invasive catheter-based insertion in central sulcus vein via the superior sagittal sinus</td></tr><tr><td>FDA Approval Trials</td><td>May 2023<br>PRIME (September 2023 – Present)</td><td>July 2021<br>SWITCH (May 2019 – Jan 2022) – Australia<br>COMMAND (August 2021 – Jan 2024)</td></tr><tr><td>Device Power and Communication</td><td>Wireless power and communication through an implanted unit behind the ear</td><td>Wireless transmission through an indwelling stent</td></tr><tr><td>Spatial resolution</td><td>~4–6 µm submicron away from neurons – Very high resolution<br>Records individual neuron activity</td><td>3–5 mm from neurons – Lower resolution<br>Records bulk activity from a population of neurons</td></tr><tr><td>Noise to signal ratio (NSR) and Noise interference</td><td>Minimal interference from blood flow, movement, and external sources<br>Low NSR</td><td>Interference from heartbeat, blood flow, and electrical noise from surrounding tissue<br>High NSR</td></tr><tr><td>Neurostimulation and closed loop communication Bandwidth</td><td>Can record and stimulate neurons for real-time adaptive control<br>1024–3072 channels (~100–200 Hz per channel) → High bandwidth (millions of bits per second)</td><td>Only records neural signals, no stimulation possible<br>16 channels (~30–50 Hz per channel) → Lower bandwidth (thousands of bits per second).</td></tr><tr><td>Adaptation</td><td>AI + Real time stimulation</td><td>AI + Repeated user training</td></tr><tr><td>Risks and complications</td><td>Infection, immune response, scarring, brain damage</td><td>Thrombosis, stroke, sinus rupture, need for long term anticoagulation</td></tr><tr><td>Current Capabilities</td><td>Patient 1 – Cursor control, online chess, manage music selection.<br>Patient 2 – 3D design using CAD software, Video games</td><td>SWITCH Trial (4 patients)<br>Compose emails, send text messages, performed online shopping using thought-controlled cursor control combined with eye-tracking COMMAND Trial (6 patients)<br>Unspecified<br>Generalizable though derived expressions of intent translated into digital actions across technology platforms</td></tr><tr><td>Potential clinical applications</td><td>Fine motor control (e.g., robotic limb movement, brain-to-text typing, bidirectional stimulation for cognitive/neuromodulation applications)</td><td>Broad minimally invasive neurorehabilitation (e.g., digital device control for paralyzed patients, early-stage assistive technologies)</td></tr><tr><td>Future results to look out for</td><td>Blindsight (September 2024) visual cortex interface – initial implementations to provide low resolution visuals and aspires to enhance visual fidelity over time</td><td></td></tr></tbody></table>
flexible electrode threads (4–6 µm/3072 electrodes), allowing granular, high bandwidth neural data acquisition at the cost of minimal cortical disruption. Perhaps its most defining innovation is the robot-assisted implantation system with sub-millimeter precision, which autonomously inserts these electrode threads while navigating around the cortical vasculature. Its advanced engineering and implantation system helps overcome complications (e.g., gliosis, fibrotic encapsulation, microvascular damage) associated with conventional rigid electrode arrays. Stentrode, compared to Neuralink BCI, is technologically modest but strategically designed for safer and broader clinical applications. Synchron initiated the first in-human trial of Stentrode (SWITCH trial – Stentrode with Though-Controlled Digital Switch) in Australia in May 2019, subsequently completing the last follow-up and publishing results in January 2022. This laid the groundwork for FDA approval for its US-based COMMAND trial in July 2021, which reported positive 12-month safety and efficacy outcomes in September 2024 – reinforcing the potential of the Stentrode as a viable BCI solution. Neuralink's initial application was denied by the FDA in early 2022 due to significant safety concerns like the device's lead battery, potential migration of device wires and inadvertent brain tissue damage during device removal. The FDA approval came through in May 2023 and the PRIME Study (Precise Robotically Implanted Brain Computer Interface) started recruitment in September 2023. To date, three patients have received Neuralink BCI, with limited clinical outcomes available; it has accomplished cursor control with thought alone with its first implant “telepathy”. While initial studies show comparable clinical outcomes of Stentrode and Neuralink BCI and better safety profile for the former, it would be shortsighted to apply the principle of parsimony (Occam's Razor) and assume that a less invasive approach like stentrode is inherently superior due to its procedural simplicity. Neuralink offers higher spatial resolution, allowing specificity in neuronal recording and a significantly larger bandwidth, allowing larger data transmission per second (millions vs. thousands of bits/second in Stentrode). Neurostimulation and bidirectional closed loop communication are distinct capabilities of Neuralink, which can be potentially leveraged for fine motor and neuro-cognitive prosthesis such as thought controlled robotic exoskeleton, speech and vision prosthesis, etc. The comparison between endovascular and intracortical BCI parallels clinical decision making in pharmacology, where different routes of administration are selected based on therapeutic needs. Just as oral formulations are preferred for ease of use and safety, but intravenous (IV) or intrathecal administration is necessary for rapid or targeted effects: Synchron's endovascular BCI prioritizes safety and accessibility, whereas Neuralink's intracortical design is tailored for high-precision applications requiring millisecond-scale neural decoding and stimulation. Ultimately, the future likely holds distinct roles for the two techniques in neuro-rehabilitative and diagnostic paradigms. Stentrode is capable of early-stage assistive technology such as thought-controlled digital interaction through feedforward-only digital neuron signal translation. On the other hand, possible applications of Neuralink devices remain to be developed and its true potential is yet to be uncovered.

### 4.3. Endovascular BCI market

Synchron has partnered with NVIDIA to advance its endovascular brain-computer interface technology using the NVIDIA Holoscan platform (“NVIDIA Holoscan,”). Holoscan enables low-latency neural signal processing, multi-AI inference, and GPU-accelerated edge computing, thereby enhancing BCI responsiveness and privacy. Real-time edge AI not only improves neural signal decoding but also boosts overall system performance. Furthermore, scalable brain-language models are poised to redefine human-machine interaction, extending beyond medical use to consumer neurotech.

The global brain-computer interface (BCI) market was valued at USD 2.44 billion in 2024 and is projected to grow at a CAGR of 18.15% from 2025 to 2030, driven by an increasing prevalence of neurological disorders, an aging population, and advancements in neurotechnology (“Brain Computer Interface Market Size | Industry Report, 2030,” n.d.). Additionally, the military segment is also growing due to applications like thought-controlled drones and telepathic communication systems. Projects like DARPA's (US Defense Advanced Research Projects Agency) portable neural interface system aiming to enhance national security by 2050. BCIs straddle medical restoration (e.g., paralysis treatment) and augmentation (e.g., cognitive enhancement), a duality exemplified by DARPA's military-focused projects.

### 4.4. Regulatory and ethical considerations

As endovascular BCIs advance toward larger clinical trials, addressing regulatory challenges is paramount. Current FDA guidelines for implanted neural devices require extensive safety and efficacy data from multi-center studies involving larger, diverse patient populations. In parallel, ethical concerns, particularly regarding data privacy and equitable access for vulnerable patient groups, also need careful consideration as the technology moves toward widespread clinical adoption (Khan et al., 2022).

Moreover, technical challenges persist in the world of device miniaturization and integration with external processing units. Existing systems often rely on relatively bulky external receivers and power modules, potentially limiting their practicality for everyday use. Future iterations must prioritize reduced form factors and fully wireless solutions to enhance usability and patient comfort (NVIDIA Holoscan; “Synchron Announces First Use of Amazon’s Alexa with a Brain Computer Interface,” 2024).

Ethical concerns include consent, neural data privacy and the risk of coercive enhancement. DARPA's pursuit of “super soldiers” underscores the potential for misuse, blurring the line between therapy and augmentation.

While Neuralink bridges the tech industry (leveraging robotics, AI) and medical industry (targeting neurological disorders). Its tech-driven approach may raise concerns about commercialization, regulatory rigor, accessibility, data security, and the philosophical implications of human-AI integration, challenging notions of identity and autonomy.

### 4.5. Limitations

First, it only included studies published in English, which may have resulted in the exclusion of relevant scarce preliminary findings reported in other languages. Additionally, study quality and potential biases were not systematically evaluated. Our review heavily relies on preclinical animal studies, primarily in ovine models, with only a few clinical trials available. The translation of findings from animal studies to humans must be founded here as important proof-of-concept data, enabling a critical transition into first-in-human trials, and acknowledging and understanding the difference between the clinical and preclinical setting, as we reported above when comparing venous anatomy, mays brought clue to the human application, when differences will be felt in endovascular navigation, electrode deployment, and long-term device integration. A substantial proportion of included studies originate from the same research group holding patents related to the primary device investigated (Stentrode). This overlap raises the possibility of author-related bias, potentially influencing reported outcomes, emphasizing the need for independent replication of results.

### 4.6. Future directions

In future investigations, standardized outcome measures, uniform reporting guidelines, and long-term follow-up frameworks are essential to enhance comparability across studies and facilitate reliable assessment of clinical effectiveness and device safety. Selection criteria may include clear anatomical parameters such as venous sinus dimensions, branching patterns, and vessel tortuosity evaluated through
preoperative imaging. Disease-specific criteria, such as the degree of motor cortex preservation and functional impairment level measured by scales like the ALS Functional Rating Scale (ALSFRS-R), should be uniformly applied across trials to harmonize patient populations. Outcome measures should also be standardized, utilizing benchmarks like electrochemical impedance spectroscopy to evaluate electrode stability and signal fidelity, predefined adverse event classifications aligned with Common Terminology Criteria for Adverse Events (CTCAE), and standardized clinical efficacy endpoints such as accuracy metrics, bit rates, and typing speeds for digital task performance. Finally, consistent follow-up intervals with predefined imaging and clinical assessments should be mandated, along with standardized antiplatelets management, facilitating robust longitudinal analysis of device safety, biocompatibility, and functional durability.

We acknowledge here a potential bias associated with a majority of studies originating from the same research group, advocating for independent replication studies to validate and extend current findings.

Furthermore, as endovascular BCIs inherently interact with sensitive cognitive data, robust safeguards must be established to protect mental privacy and autonomy. It would become important to implement rigorous data protection protocols, comprehensive informed consent, and create clear regulatory frameworks addressing ethical and legal considerations surrounding cognitive rights and user autonomy.

Long-term, large-scale clinical trials (Phase III studies) are in this way essential to confirm the safety and efficacy of endovascular BCIs in diverse populations, including those with stroke, epilepsy, and other neurological conditions beyond ALS (Mitchell et al., 2023b; He et al., 2024).

Iterative design improvements, such as the development of bioactive electrode coatings and the incorporation of advanced electrode geometries, may reduce adverse tissue responses while enhancing signal quality (Opie et al., 2020; Tarigoppula et al., 2023).

The integration of cloud-based adaptive models could enable real-time patient-specific signal processing, potentially extending device functionality beyond motor control to include cognitive and speech prostheses (Willett et al., 2023).

Although current translational efforts have focused on the superficial cortical veins in the human brain, the arterial system may also provide an avenue to targeting deep brain structures. Deep structures including the nucleus accumbens and subgenual white matter are known to lie immediately adjacent to the anterior cerebral artery, with a diameter of 1.9 – 2.6 mm40. Furthermore, structures currently only accessible only via craniotomy such as the subthalamic nucleus, hippocampus and internal capsule, could potentially be reached through via deep arteries in the human brain (Oxley et al., 2016).

Alternative methods of non-invasive but non endovascular BCIs should also be considered (Mahoney et al., 2023), including sub-scalp EEG systems that offer advantages in removability, spatial flexibility, and chronic usability via replacement, addressing key endovascular BCI limitations.

Endocisternal neural interfaces leverage cerebrospinal fluid-filled spaces to reach the entire brain convexity, deep ventricular regions, and the spinal cord; when combined with wireless, magnetoelectrically powered bioelectronics that allow percutaneous navigation, flexible electrode repositioning, and safe explantation after chronic implantation, these systems not only parallel the minimally invasive appeal of endovascular BCIs but also overcome their limitations by expanding the range of accessible neural targets for potential therapies in stroke rehabilitation and epilepsy monitoring (Yang et al., 2024; Chen et al., 2025, 2024). Also, this endovascular technique could be of interest in interfacing with peripheral nerves and spinal cord. Nicolai et al. (2023) showed that endovascular stimulation electrode within the internal jugular vein could activate the vagus nerve.

Further studies are needed to determine the most effective electrode materials for long-term stability. Improved computational models are required for enhanced neural signal decoding and real-time processing

(Einizade et al., 2022; Llorella et al., 2021).

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), modulates brain activity externally without surgical intervention. Endovascular BCIs, such as the Stentrode, occupy an intermediate position: it records neural signals through the vascular wall, distinguishing it from NIBS, which focuses solely on stimulation. However, an overlap emerges if endovascular BCIs are adapted for stimulation. Gerboni et al. reported the first characterization of endovascular cortical stimulation measured using cortical subdural surface recordings (Gerboni et al., 2018). This potential dual functionality contrasts with NIBS's unidirectional approach, positioning endovascular BCIs as a hybrid technology bridging invasive and non-invasive domain. This method may benefit from technical advances and deeper access capability to match the efficacy of traditional DBS in modulating deep brain circuits to treat movement disorders like Parkinson's disease, or the spatial precision of stereo EEG to localize epileptogenic zones in patients with refractory epilepsy (Herff et al., 2020).

## 5. Conclusion

Endovascular BCIs represent a transformative approach to neural interfacing by combining the safety of minimally invasive vascular access with the potential for high-resolution, chronic neural recording.

Preclinical studies and early human trials confirm that devices such as the Stentrode can achieve stable performance while mitigating the risks inherent to open-brain surgery; however, challenges related to long-term material stability, decoding precision, and regulatory approval remain. Future work should prioritize advancements in electrode materials, optimization of antithrombotic regimens, and integration of next-generation AI to broaden the clinical applications of these systems, from motor control to cognitive prostheses. With continued interdisciplinary innovation, endovascular BCIs are poised to redefine neuroprosthetic technologies and expand therapeutic options for patients with severe neurological disorders.

## Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

## CRediT authorship contribution statement

**Kallmes David F.:** Validation, Supervision, Software. **Brinjikji Waleed:** Writing – review & editing, Validation, Project administration. **El Hajj Gerard:** Writing – review & editing, Validation, Methodology, Investigation, Data curation. **Verma Onam:** Writing – review & editing, Visualization, Formal analysis. **Ghozy Sherief:** Writing – review & editing, Validation, Software, Project administration, Formal analysis. **Kadirvel Ramanathan:** Writing – review & editing, Validation, Supervision, Resources. **Ognard Julien:** Writing – review & editing, Writing – original draft, Validation, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

## Declaration of Competing Interest

J.O. received research grants from SFNR, GIRCI-GO, INNOVEO-Chu De Brest, Medtronic, Phenox, Institut Servier, Philippe Foundation, Philips, and receives consulting fees from Balt; G.E. reports no disclosures relevant to the manuscript; S.G. reports no disclosures relevant to the manuscript; OV. reports no disclosures relevant to the manuscript; R. K. received research support from Cerenovus Inc, Medtronic, Endovascular Engineering, Frontier Bio, Sensome Inc, Endomimetics, Ancure LLC, Neurogami Medical, MIVI Biosciences, Monarch Biosciences, Stryker, Conway Medical, Piraeus Medical, and Bionaut Labs. He holds the following research grants: NIH (R01NS076491, R44NS107111,
R43NS110114 and R21NS128199) and NSF (081215707); D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic; W.B. holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN.

## Acknowledgement

Authors thank Worrell, Gregory A., M.D., Ph.D. for his review of the manuscript.

## Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.jneumeth.2025.110471.

## Data availability

No data was used for the research described in the article.

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