<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD with MathML3 v1.3 20210610//EN"  "JATS-archivearticle1-3-mathml3.dtd"><article xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.3"><front><journal-meta><journal-id journal-id-type="nlm-ta">elife</journal-id><journal-id journal-id-type="publisher-id">eLife</journal-id><journal-title-group><journal-title>eLife</journal-title></journal-title-group><issn publication-format="electronic" pub-type="epub">2050-084X</issn><publisher><publisher-name>eLife Sciences Publications, Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">106452</article-id><article-id pub-id-type="doi">10.7554/eLife.106452</article-id><article-id pub-id-type="doi" specific-use="version">10.7554/eLife.106452.3</article-id><article-version article-version-type="publication-state">version of record</article-version><article-categories><subj-group subj-group-type="display-channel"><subject>Research Advance</subject></subj-group><subj-group subj-group-type="heading"><subject>Neuroscience</subject></subj-group></article-categories><title-group><article-title>Material damage to multielectrode arrays after electrolytic lesioning is insignificant</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tor</surname><given-names>Alice</given-names></name><contrib-id authenticated="true" contrib-id-type="orcid">https://orcid.org/0009-0008-7688-2018</contrib-id><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="con1"/><xref ref-type="fn" rid="conf1"/></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Stephen E</given-names></name><contrib-id authenticated="true" contrib-id-type="orcid">https://orcid.org/0000-0002-3871-0185</contrib-id><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="fn" rid="con2"/><xref ref-type="fn" rid="conf1"/></contrib><contrib contrib-type="author"><name><surname>Bray</surname><given-names>Iliana E</given-names></name><contrib-id authenticated="true" contrib-id-type="orcid">https://orcid.org/0000-0002-3029-8309</contrib-id><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="other" rid="fund4"/><xref ref-type="fn" rid="con3"/><xref ref-type="fn" rid="conf1"/></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name><contrib-id authenticated="true" contrib-id-type="orcid">https://orcid.org/0000-0001-7778-5473</contrib-id><email>26elife@pn.stanford.edu</email><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="other" rid="fund9"/><xref ref-type="other" rid="fund10"/><xref ref-type="fn" rid="con4"/><xref ref-type="fn" rid="conf1"/></contrib><on-behalf-of>for the Brain Interfacing Laboratory</on-behalf-of><aff id="aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ror">https://ror.org/00f54p054</institution-id><institution>Electrical Engineering Department, Stanford University</institution></institution-wrap><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff><aff id="aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ror">https://ror.org/00f54p054</institution-id><institution>Bioengineering Department, Stanford University</institution></institution-wrap><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff><aff id="aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ror">https://ror.org/00f54p054</institution-id><institution>Neurosurgery Department, Stanford University</institution></institution-wrap><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff><aff id="aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ror">https://ror.org/00f54p054</institution-id><institution>Wu Tsai Neurosciences Institute, Stanford University</institution></institution-wrap><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff></contrib-group><contrib-group content-type="section"><contrib contrib-type="editor"><name><surname>Chen</surname><given-names>Xiaomo</given-names></name><role>Reviewing Editor</role><aff><institution-wrap><institution-id institution-id-type="ror">https://ror.org/05rrcem69</institution-id><institution>University of California, Davis</institution></institution-wrap><country>United States</country></aff></contrib><contrib contrib-type="senior_editor"><name><surname>Behrens</surname><given-names>Timothy E</given-names></name><role>Senior Editor</role><aff><institution-wrap><institution-id institution-id-type="ror">https://ror.org/052gg0110</institution-id><institution>University of Oxford</institution></institution-wrap><country>United Kingdom</country></aff></contrib></contrib-group><pub-date publication-format="electronic" date-type="publication"><day>19</day><month>06</month><year>2026</year></pub-date><volume>14</volume><elocation-id>RP106452</elocation-id><history><date date-type="sent-for-review" iso-8601-date="2025-03-26"><day>26</day><month>03</month><year>2025</year></date></history><pub-history><event><event-desc>This manuscript was published as a preprint.</event-desc><date date-type="preprint" iso-8601-date="2025-03-30"><day>30</day><month>03</month><year>2025</year></date><self-uri content-type="preprint" xlink:href="https://doi.org/10.1101/2025.03.26.645429"/></event><event><event-desc>This manuscript was published as a reviewed preprint.</event-desc><date date-type="reviewed-preprint" iso-8601-date="2025-06-09"><day>09</day><month>06</month><year>2025</year></date><self-uri content-type="reviewed-preprint" xlink:href="https://doi.org/10.7554/eLife.106452.1"/></event><event><event-desc>The reviewed preprint was revised.</event-desc><date date-type="reviewed-preprint" iso-8601-date="2026-03-04"><day>04</day><month>03</month><year>2026</year></date><self-uri content-type="reviewed-preprint" xlink:href="https://doi.org/10.7554/eLife.106452.2"/></event></pub-history><permissions><copyright-statement>© 2025, Tor et al</copyright-statement><copyright-year>2025</copyright-year><copyright-holder>Tor et al</copyright-holder><ali:free_to_read/><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref><license-p>This article is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use and redistribution provided that the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="elife-106452-v1.pdf"/><self-uri content-type="figures-pdf" xlink:href="elife-106452-figures-v1.pdf"/><related-article related-article-type="article-reference" ext-link-type="doi" xlink:href="10.7554/eLife.84385" id="ra1"/><abstract><p>The quality of stable long-term recordings from chronically implanted electrode arrays is essential for experimental neuroscience and brain-computer interfaces. This work uses scanning electron microscopy (SEM) to image and analyze eight 96-channel Utah arrays previously implanted in motor cortical regions of four subjects (subject H = 2242 days implanted, F = 1875, U = 2680, C = 594), providing important contributions to a growing body of long-term implant research leveraging this imaging technology. Four of these arrays have been used in electrolytic lesioning experiments (H = 10 lesions, F = 1, U = 4, C = 1), a recently developed electrolytic perturbation technique demonstrated compatible with continued neuroelectrophysiology using small direct currents. Previously, our group showed that electrolytic lesioning can be used as a technique to create regions of controlled neuron loss without significantly changing recording quality (Bray, Clarke et al., 2024). Here, by surveying physical damage such as biological debris and material deterioration, we show that electrolytic lesioning causes no statistically significant material damage to the implanted electrode arrays. In addition to surveying physical damage, such as biological debris and material deterioration, this work also analyzes whether electrolytic lesioning created damage beyond what is typical for these arrays. These findings also indicate that there are no statistically significant differences between the damage observed on normal electrodes versus those used for electrolytic lesioning, yielding no evidence that electrolytic lesioning significantly affects the material quality of chronically implanted electrode arrays. Finally, this work also includes the largest collection of single-electrode SEM images for previously implanted multielectrode Utah arrays, spanning 11 different intact arrays and one broken array. As the clinical relevance of chronically implanted electrodes with single-neuron resolution continues to grow, these images may be used to provide the foundation for a larger public database and inform further electrode design and analyses.</p></abstract><kwd-group kwd-group-type="author-keywords"><kwd>electron microscopy</kwd><kwd>multielectrode array</kwd><kwd>electrolytic lesion</kwd></kwd-group><kwd-group kwd-group-type="research-organism"><title>Research organism</title><kwd>Rhesus macaque</kwd></kwd-group><funding-group><award-group id="fund1"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/0447fe631</institution-id><institution>United States Department of Defense</institution></institution-wrap></funding-source><award-id>National Defense Science and Engineering Graduate</award-id><principal-award-recipient><name><surname>Tor</surname><given-names>Alice</given-names></name></principal-award-recipient></award-group><award-group id="fund2"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/021nxhr62</institution-id><institution>National Science Foundation</institution></institution-wrap></funding-source><award-id>1828993</award-id><principal-award-recipient><name><surname>Tor</surname><given-names>Alice</given-names></name></principal-award-recipient></award-group><award-group id="fund3"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/03mtd9a03</institution-id><institution>Stanford School of Medicine</institution></institution-wrap></funding-source><award-id>Dean's Postdoctoral Fellowship</award-id><principal-award-recipient><name><surname>Clarke</surname><given-names>Stephen E</given-names></name></principal-award-recipient></award-group><award-group id="fund4"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/013kjyp64</institution-id><institution>American Heart Association</institution></institution-wrap></funding-source><award-id>828653</award-id><principal-award-recipient><name><surname>Bray</surname><given-names>Iliana E</given-names></name></principal-award-recipient></award-group><award-group id="fund5"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/021nxhr62</institution-id><institution>National Science Foundation</institution></institution-wrap></funding-source><award-id>Graduate Research Fellowship Program 1656518</award-id><principal-award-recipient><name><surname>Bray</surname><given-names>Iliana E</given-names></name></principal-award-recipient></award-group><award-group id="fund6"><funding-source><institution-wrap><institution>Stanford Human-Centered AI Seed Research Grant</institution></institution-wrap></funding-source><principal-award-recipient><name><surname>Clarke</surname><given-names>Stephen E</given-names></name><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name></principal-award-recipient></award-group><award-group id="fund7"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/01cwqze88</institution-id><institution>National Institutes of Health</institution></institution-wrap></funding-source><award-id>R01NS123517</award-id><principal-award-recipient><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name></principal-award-recipient></award-group><award-group id="fund8"><funding-source><institution-wrap><institution>Stanford Wu Tsai Neurosciences Institute</institution></institution-wrap></funding-source><principal-award-recipient><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name></principal-award-recipient></award-group><award-group id="fund9"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/01cwqze88</institution-id><institution>National Institutes of Health</institution></institution-wrap></funding-source><award-id>R01NS130789</award-id><principal-award-recipient><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name></principal-award-recipient></award-group><award-group id="fund10"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/01cwqze88</institution-id><institution>National Institutes of Health</institution></institution-wrap></funding-source><award-id>U19NS118284</award-id><principal-award-recipient><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name></principal-award-recipient></award-group><award-group id="fund11"><funding-source><institution-wrap><institution-id institution-id-type="ror">https://ror.org/021nxhr62</institution-id><institution>National Science Foundation</institution></institution-wrap></funding-source><award-id>ECCS-2026822</award-id></award-group><funding-statement>The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.</funding-statement></funding-group><custom-meta-group><custom-meta specific-use="meta-only"><meta-name>Author impact statement</meta-name><meta-value>An analysis of the largest publicly available collection of scanning electron microscopy images of explanted multielectrode arrays reveals that electrolytic lesioning causes no significant additional damage to array electrodes.</meta-value></custom-meta><custom-meta specific-use="meta-only"><meta-name>publishing-route</meta-name><meta-value>prc</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>In the past two decades, the advancement of implanted electrode arrays has drastically shifted the field of neuroscience from theories based on individually recorded neurons to those based on the systems-level activity of neuron populations (<xref ref-type="bibr" rid="bib16">Cunningham and Yu, 2014</xref>; <xref ref-type="bibr" rid="bib40">Vyas et al., 2020</xref>; <xref ref-type="bibr" rid="bib18">Ebitz and Hayden, 2021</xref>). Specifically, the 96-channel Utah array (Blackrock Neurotech, Salt Lake City, UT) has been used to make pivotal discoveries in motor systems neuroscience and develop clinically impactful brain-computer interfaces (<xref ref-type="bibr" rid="bib24">Maynard et al., 1997</xref>; <xref ref-type="bibr" rid="bib32">Serruya et al., 2002</xref>; <xref ref-type="bibr" rid="bib20">Gilja et al., 2012</xref>; <xref ref-type="bibr" rid="bib14">Churchland et al., 2012</xref>; <xref ref-type="bibr" rid="bib19">Gallego et al., 2020</xref>; <xref ref-type="bibr" rid="bib40">Vyas et al., 2020</xref>). These electrode arrays are widely used in neuroprosthetics research for patients with motor disorders and have been used for a variety of purposes, such as movement and speech decoding (<xref ref-type="bibr" rid="bib21">Gilja et al., 2015</xref>; <xref ref-type="bibr" rid="bib41">Willett et al., 2023</xref>). Much of this work in humans relies on the translation of results discovered in non-human primates (NHPs), a crucial animal model in neuroscience research (<xref ref-type="bibr" rid="bib30">Roelfsema and Treue, 2014</xref>; <xref ref-type="bibr" rid="bib25">Mitchell et al., 2018</xref>). One useful application of these arrays in animal studies is microstimulation and electrolytic lesion experiments (<xref ref-type="bibr" rid="bib38">Tehovnik et al., 2006</xref>). Electrolytic lesioning results in small, controllable, and precise amounts of neuron loss. This makes it a helpful technique to study damage to targeted areas of the brain, serving as a causal tool for basic scientific inquiry and as a model for clinical injury-based neuron loss events at a small scale.</p><p>Electrolytic lesioning has been experimented with since the 19th century (<xref ref-type="bibr" rid="bib23">Kline, 2007</xref>), and methods have been researched in many species, including rodents, cats, dogs, monkeys, and humans (<xref ref-type="bibr" rid="bib22">Horsley and Clarke, 1908</xref>; <xref ref-type="bibr" rid="bib37">Sweet, 1953</xref>; <xref ref-type="bibr" rid="bib10">Chen et al., 2009</xref>). In electrolytic lesion experiments, researchers pass current through implanted electrodes in order to mark the position of electrodes or create lesions in brain tissue (<xref ref-type="bibr" rid="bib10">Chen et al., 2009</xref>; <xref ref-type="bibr" rid="bib39">Townsend et al., 2002</xref>). These electrolytic lesions can be created using one electrode (unipolar) or by using two electrodes (bipolar) (<xref ref-type="bibr" rid="bib37">Sweet, 1953</xref>; <xref ref-type="bibr" rid="bib9">Chehrazi and Collins, 1981</xref>). In particular, recent work has established a novel lesioning technique to create consistent, controllable electrolytic lesions in NHPs using already-implanted Utah arrays, without damaging the ability to record from the array (<xref ref-type="bibr" rid="bib6">Bray et al., 2024</xref>). However, while recording capabilities seem to remain stable, the physical effect of electrolytic lesioning on the recording array needs further characterization.</p><p>Previous studies have shown temporally decreasing performance of collected signals from long-term implanted arrays, thought to be a consequence of the immune response, mechanical movement of the array relative to surrounding tissue, and physical degradation of the array (<xref ref-type="bibr" rid="bib36">Suner et al., 2005</xref>; <xref ref-type="bibr" rid="bib35">Simeral et al., 2011</xref>; <xref ref-type="bibr" rid="bib17">Downey et al., 2018</xref>). This is also reflected in studies that specifically examine the damages that occur to electrode arrays while they are implanted in NHPs (<xref ref-type="bibr" rid="bib13">Chestek et al., 2011</xref>; <xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>). In particular, the use of scanning electrode microscopy (SEM) has been used to visually examine and analyze the effect of neural implantation on arrays with extremely high definition (<xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>; <xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>; <xref ref-type="bibr" rid="bib27">Patel et al., 2023</xref>; <xref ref-type="bibr" rid="bib2">Barrese et al., 2016</xref>; <xref ref-type="bibr" rid="bib42">Woeppel et al., 2021</xref>). These studies, which span both NHPs and humans, provide direct evidence that the observable physical damage incurred by implanted arrays has direct impact on the array’s performance.</p><p>The Utah array is a silicon-based array manufactured with several layers of different materials (<xref ref-type="bibr" rid="bib43">Yi et al., 2022</xref>). Silicon electrodes are first etched out of a glass and silicon base. Each individual electrode is then metallized at the tip. Finally, a layer of parylene C coats all but these metallized tips to help isolate and insulate each electrode (<xref ref-type="bibr" rid="bib8">Campbell et al., 1991</xref>; <xref ref-type="bibr" rid="bib3">Bhandari et al., 2010</xref>). Both in vitro and in vivo testing of electrode arrays revealed environmental damage to these materials, such as cracking, textural defects, and degradation in response to the brain’s temperature and salinity (<xref ref-type="bibr" rid="bib7">Caldwell et al., 2020</xref>; <xref ref-type="bibr" rid="bib1">Barrese et al., 2013</xref>). The immune response of the brain also damages the electrodes due to effects like glial scarring (gliosis) and inflammation (<xref ref-type="bibr" rid="bib28">Polikov et al., 2005</xref>; <xref ref-type="bibr" rid="bib1">Barrese et al., 2013</xref>; <xref ref-type="bibr" rid="bib31">Salatino et al., 2017</xref>). This damage may be exacerbated by the surgical techniques used during implantation, which include pushing the electrode array into cortex and tethering the implant to the skull (<xref ref-type="bibr" rid="bib28">Polikov et al., 2005</xref>; <xref ref-type="bibr" rid="bib4">Biran et al., 2007</xref>; <xref ref-type="bibr" rid="bib29">Potter et al., 2012</xref>). These results are confirmed in the previously mentioned SEM analyses (<xref ref-type="bibr" rid="bib2">Barrese et al., 2016</xref>; <xref ref-type="bibr" rid="bib42">Woeppel et al., 2021</xref>; <xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>; <xref ref-type="bibr" rid="bib27">Patel et al., 2023</xref>; <xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>).</p><p>Additionally, the Utah array is available with both platinum and iridium oxide-based coatings. Aggressive electrical stimulation is known to dissolve platinum-based electrodes (<xref ref-type="bibr" rid="bib34">Shepherd et al., 2021</xref>; <xref ref-type="bibr" rid="bib33">Shah et al., 2024</xref>). Other studies have shown iridium oxide to be more resistant to stimulation-related damage, but not completely insusceptible (<xref ref-type="bibr" rid="bib15">Cogan et al., 2004</xref>; <xref ref-type="bibr" rid="bib26">Negi et al., 2010</xref>; <xref ref-type="bibr" rid="bib11">Chen et al., 2014</xref>; <xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>). However, the physical electrode damage associated with electrolytic lesioning remains to be studied.</p><p>This work comprises images of 11 different multielectrode Utah arrays (ten 96-channel, one 64-channel). Of these imaged arrays, eight arrays chronically implanted in regions of the motor cortex for varying amounts of time were analyzed further (Monkey H = 2242 days, F = 1875, U = 2680, C = 594). Four out of eight of these arrays were used to perform electrolytic lesioning experiments (<italic>n</italic> = 4 monkeys; H = 10 lesions, F = 1, U = 4, C = 1). Additionally, the image set includes images of a broken 96-channel Utah array, which was shattered during explant but remained intact while implanted. This set of images represents the largest publicly available collection of high-quality, single-electrode SEM images of explanted multielectrode Utah arrays. A total of 938 individual electrodes are available to view, along with 11 additional images from the broken array. Specific details for each imaged array are available in <xref ref-type="supplementary-material" rid="supp1">Supplementary file 1</xref>.</p></sec><sec id="s2" sec-type="results"><title>Results</title><p>All collected images, along with their associated scores, are available in interactive <xref ref-type="video" rid="video1">Video 1</xref>. Each of the 12 arrays and individual electrodes may be selected and viewed. Representative electrodes for each category and damage score, as well as electrodes used for lesioning, are also viewable for each array in an additional drop-down menu when available. Rough anatomical layouts of the array’s implant location are also included. Electrode numbering maps are available in <xref ref-type="supplementary-material" rid="video1sdata2">Video 1—source data 2</xref>.</p><media mimetype="video" mime-subtype="mp4" xlink:href="elife-106452-video1.mp4" id="video1"><label>Video 1.</label><caption><title><ext-link ext-link-type="uri" xlink:href="https://stacks.stanford.edu/file/dz983xf0632/data/raw/fig1/index.html">Interactive display</ext-link>: Video demonstrates how to use the interactive display of all captured scanning electron microscopy (SEM) array images, available through the provided <ext-link ext-link-type="uri" xlink:href="https://stacks.stanford.edu/file/dz983xf0632/data/raw/fig1/index.html">link</ext-link>.</title><p>Once an array has been selected, a diagram of each array’s anatomical position (derived from surgical drawings and notes) appears, along with an SEM image of the array. All array images are displayed with the wire bundle to the right side and with electrode tips facing the viewer. Specific electrodes may be selected from the array image; SEM images of each electrode and their scores in each of the five damage categories will appear along with any additional notes. Furthermore, examples of specific scores for each damage type are selectable through an additional drop-down menu for each array. Similarly, electrodes used for electrolytic lesioning are also selectable through an additional drop-down menu for each array.</p><p><supplementary-material id="video1sdata1"><label>Video 1—source data 1.</label><caption><title>Tutorial video for interactive display.</title></caption><media mimetype="application" mime-subtype="zip" xlink:href="elife-106452-video1-data1-v1.zip"/></supplementary-material></p><p><supplementary-material id="video1sdata2"><label>Video 1—source data 2.</label><caption><title>Numbering layout of the electrodes as imaged (pins facing outwards, towards the reader).</title><p>Wire bundle is arranged to the right. Each radial section of the array is also color-coded and labeled. R1 refers to the innermost core electrodes of the array, R2 refers to the next outer ring of the array, and so on.</p></caption><media mimetype="application" mime-subtype="pdf" xlink:href="elife-106452-video1-data2-v1.pdf"/></supplementary-material></p></caption></media><p>The first set of analyses specifically considers the four arrays used in electrolytic lesioning experiments. Scores for each damage category, along with total scores, are visualized as heatmaps in <xref ref-type="fig" rid="fig1">Figure 1</xref>. Median total scores for each radial section of the array show that the outermost electrodes tend to have the greatest total observed damage across all four arrays. Generally, electrode damage decreases when moving to the center of the array. Shank fractures tend to be spatially close on each array, suggesting that shared mechanical trauma caused these sections of fracture. As mentioned in the Methods section, these fractures may have reasonably occurred during explantation and handling, as no diminished recording performance of these fractured electrodes was observed while the array was actively implanted. Additional heatmaps are available for the four additional arrays implanted in NHP but not used for lesioning in <xref ref-type="fig" rid="fig1s1">Figure 1—figure supplement 1</xref>.</p><fig-group><fig id="fig1" position="float"><label>Figure 1.</label><caption><title>Heatmaps of damage scores (0–3) across the five identified types of damage and across the four imaged lesioning arrays.</title><p>Electrodes are displayed using the orientation in <xref ref-type="video" rid="video1">Video 1</xref> (electrode tips facing viewer, wire bundle on the right). Second-to-rightmost column displays summed damage scores for each array across the five types of damage. Electrodes used for electrolytic lesioning are denoted with blue dots. Median summed scores for each radial section of the array are plotted in the bar charts to the right of the heatmaps. Ring layout and numbering information are available in <xref ref-type="supplementary-material" rid="video1sdata2">Video 1—source data 2</xref>. Unwired electrodes (electrodes not wire bonded at time of manufacture) and electrodes with shank fractures are ignored and displayed in black, as they are not scored.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig1-v1.tif"/></fig><fig id="fig1s1" position="float" specific-use="child-fig"><label>Figure 1—figure supplement 1.</label><caption><title>Heatmaps of damage scores (0–3) across the five identified types of damage and across all eight intact, imaged non-human primate (NHP) arrays.</title><p>Electrodes are displayed using the orientation in <xref ref-type="video" rid="video1">Video 1</xref> (electrode tips facing viewer, wire bundle on the right). Second-to-rightmost column displays summed damage scores for each array across the five types of damage. Electrodes used for electrolytic lesioning are denoted with blue dots. Median summed scores for each radial section of the array are plotted in the bar charts to the right of the heatmaps. Ring layout and numbering information is available in <xref ref-type="supplementary-material" rid="video1sdata2">Video 1—source data 2</xref>. Unwired electrodes (electrodes not wire bonded at time of manufacture) and electrodes with shank fractures are ignored and displayed in black, as they are not scored.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig1-figsupp1-v1.tif"/></fig></fig-group><p>Histograms of damage scores in each category, along with average score distributions per array, are shown in <xref ref-type="fig" rid="fig2">Figure 2</xref>. For each category, histograms of electrodes used for lesioning (black) are stacked on top of histograms of normal electrodes (gray). Additionally, the average distribution of scores is shown for each array. These plots indicate that there is no observable difference in the distribution of scores given to electrodes used for lesioning versus those not. Additional histograms are available for the four additional arrays implanted in NHP but not used for lesioning in <xref ref-type="fig" rid="fig2s1">Figure 2—figure supplement 1</xref>.</p><fig-group><fig id="fig2" position="float"><label>Figure 2.</label><caption><title>Stacked histograms of damage scores (0–3) across the five identified types of damage and across the four imaged lesioning arrays.</title><p>Gray indicates normal electrodes, and black indicates lesioning electrodes. The rightmost column displays the average distribution of damage scores across the five types of damage. Electrodes with shank fractures (SF) are ignored, as they are not scored.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig2-v1.tif"/></fig><fig id="fig2s1" position="float" specific-use="child-fig"><label>Figure 2—figure supplement 1.</label><caption><title>Stacked histograms of damage scores (0–3) across the five identified types of damage and across all eight intact, non-human primate (NHP) imaged arrays.</title><p>Gray indicates normal electrodes, and black indicates lesioning electrodes. Rightmost column displays the average distribution of damage scores across the five types of damage. Electrodes with shank fractures (SF) are ignored, as they are not scored.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig2-figsupp1-v1.tif"/></fig></fig-group><p>The Shapiro–Wilk test for normality returned a significant p-value for almost all sets of scores for each array and type of damage. Similarly, the Shapiro–Wilk test for normality returned a significant p-value for almost all sets of scores for each array and type of damage when split into populations used and not used for lesioning, but was not performed where electrode count was too small to carry out the test (C and F; lesioning electrodes = 2). In the majority of cases that returned an insignificant p-value, certain types of damage were not present on the array and thus scores were uniformly zero (Monkey U’s M1 tip breakage, parylene C delamination, and parylene C cracking scores; Monkey C’s PMd parylene C delamination scores and M1 parylene C cracking scores). In all other cases where the Shapiro–Wilk test returned an insignificant p-value (Monkey H’s total damage scores on lesioning electrodes, Monkey U’s coating cracks scores), low electrode counts may reduce the statistical power of the test (H = 18 lesioning electrodes, U = 8). This indicates that scores are largely not normally distributed and that nonparametric statistical tests should be used to evaluate differences between populations. All Shapiro–Wilk test p-values are available in <xref ref-type="supplementary-material" rid="supp2">Supplementary file 2</xref>.</p><p>For each category of damage, as well as the total damage score, no statistically significant difference was identified between lesioning and non-lesioning electrodes on the same array. Similarly, for each category of damage, as well as the total damage score, no statistically significant difference was identified between lesioning and non-lesioning electrodes pooled across all four arrays. This indicates that the electrode populations used for lesioning and those not used for recording only do not have statistically different sample means or variances, suggesting they are samples of the same underlying population. These p-values are included in <xref ref-type="supplementary-material" rid="supp3">Supplementary file 3</xref>. However, again, it is important to note that these tests done on individual arrays have limited power due to low electrode counts (H = 18 lesioning electrodes, F = 2, U = 8, C = 2).</p><p>This next set of analyses compares entire population statistics of all eight NHP arrays. Both the Mann–Whitney <italic>U</italic> and Levene tests resulted in inconsistently significant/non-significant p-values when comparing lesioning arrays against non-lesioning arrays within the same implanted animal. This indicates inconsistency in overall distribution and variance of data. This suggests that there are likely large differences between the amount and intensity of material damage dealt to implanted arrays even when implanted in the same subject. These results do not determine whether or not electrolytic lesioning experiments contribute to the magnitude of these differences, but the inconsistency in the significance of the above results may indicate that other factors, such as the brain’s varied immune response, differences in mechanical forces, and disparities in external handling, may play a large role in damage to these arrays. These p-values are included in <xref ref-type="supplementary-material" rid="supp4">Supplementary file 4</xref>.</p><p>The Pearson correlation matrix across all four arrays for the five different damage types is shown in <xref ref-type="fig" rid="fig3">Figure 3</xref>. This plot demonstrates that there is overall low pairwise correlation between each type of damage, with the exception of coating cracks and tip breakage, which display moderate positive correlation (<inline-formula><alternatives><mml:math id="inf1"><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mn>0.47</mml:mn></mml:math><tex-math id="inft1">\begin{document}$r=0.47$\end{document}</tex-math></alternatives></inline-formula>, Bonferroni-corrected <inline-formula><alternatives><mml:math id="inf2"><mml:mstyle><mml:mrow><mml:mstyle displaystyle="false"><mml:mi mathvariant="normal">p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mstyle></mml:mrow></mml:mstyle></mml:math><tex-math id="inft2">\begin{document}$\rm p \lt 0.05$\end{document}</tex-math></alternatives></inline-formula>). These results align with previous comparisons on the distribution of damage scores, which showed that damage scores tended to vary across the five different types. Additional correlation plots for each of the five array layout rings are available in Supplemental Materials. Raw <inline-formula><alternatives><mml:math id="inf3"><mml:mi>r</mml:mi></mml:math><tex-math id="inft3">\begin{document}$r$\end{document}</tex-math></alternatives></inline-formula> and p-values for each test are also available in <xref ref-type="supplementary-material" rid="supp5">Supplementary file 5</xref>.</p><fig-group><fig id="fig3" position="float"><label>Figure 3.</label><caption><title>Correlation plot (Pearson’s R) across the five different damage types.</title><p>AD = abnormal debris, TB = tip breakages, CC = metal coating cracks, PC = parylene C cracks, PD = parylene C delamination. Results demonstrate overall low correlation (magnitude &lt; 0.25) across different damage types, with the exception of coating cracks and tip breakage, with a correlation coefficient of 0.47. Test values with Bonferroni-corrected p &lt; 0.05 are displayed with asterisks. Raw p-values are separately available in <xref ref-type="supplementary-material" rid="supp2">Supplementary file 2</xref>. Electrodes with shank fractures are ignored, as they are not scored.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig3-v1.tif"/></fig><fig id="fig3s1" position="float" specific-use="child-fig"><label>Figure 3—figure supplement 1.</label><caption><title>Correlation plots (Pearson’s <italic>R</italic>) for each of the five rings across all four imaged lesioning arrays.</title><p>(Row 1, right to left: R1 and R2; row 2: R3 and R4; bottom row: R5). Test values with Bonferroni-corrected p &lt; 0.05 are displayed with asterisks. Raw <inline-formula><alternatives><mml:math id="inf4"><mml:mi>r</mml:mi></mml:math><tex-math id="inft4">\begin{document}$r$\end{document}</tex-math></alternatives></inline-formula> and p-values are separately available in <xref ref-type="supplementary-material" rid="supp5">Supplementary file 5</xref>.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig3-figsupp1-v1.tif"/></fig><fig id="fig3s2" position="float" specific-use="child-fig"><label>Figure 3—figure supplement 2.</label><caption><title>Scatterplots of the lesion electrodes’ damage scores over the target current for each lesion.</title><p>A best-fit line is also plotted along with regression results. In cases where only one target current was used (ie. subjects with only one lesion), linear regression was not performed. No best-fit lines were statistically significant at p = 0.05.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig3-figsupp2-v1.tif"/></fig><fig id="fig3s3" position="float" specific-use="child-fig"><label>Figure 3—figure supplement 3.</label><caption><title>Scatterplots of the lesion electrodes’ damage scores over the target lesioning procedure duration for each lesion.</title><p>A best-fit line is also plotted along with regression results. In cases where only one duration was used (ie. subjects with only one lesion, subjects with the same duration across all lesions), linear regression was not performed. Scatterplots with statistically significant lines of best fit are starred in yellow.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig3-figsupp3-v1.tif"/></fig><fig id="fig3s4" position="float" specific-use="child-fig"><label>Figure 3—figure supplement 4.</label><caption><title>Histograms of the lesion electrodes’ damage scores, separated by array material.</title><p>Blue bars are IrOx arrays and orange bars are Pt arrays. The first row shows scores across all eight scored non-human primate (NHP) arrays (<italic>n</italic> = 384 IrOx electrodes, <italic>n</italic> = 384 Pt electrodes). The second row shows scores for only the four NHP arrays used for lesioning (<italic>n</italic> = 192 IrOx electrodes, <italic>n</italic> = 192 Pt electrodes). The third row shows scores for only the subset of electrodes used for NHP lesioning (<italic>n</italic> = 10 IrOx electrodes, <italic>n</italic> = 20 Pt electrodes). Notably, it appears that platinum arrays imaged in this work generally appear to report less damage than iridium oxide arrays when considering all arrays. Additionally, the imaged platinum arrays appear to always report less parylene C damage. However, platinum arrays generally appear to report more other types of damage (abnormal debris, tip breakage, coating cracks) when used for lesioning. This supports previous literature that indicates IrOx may be more resistant to stimulation-related damage than Pt (<xref ref-type="bibr" rid="bib15">Cogan et al., 2004</xref>; <xref ref-type="bibr" rid="bib26">Negi et al., 2010</xref>; <xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>; <xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>). It is important to note that many other factors, such as time in tissue, explant surgery, and immune response of the specific implant subject, all impact the conclusions of this analysis.</p></caption><graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-106452-fig3-figsupp4-v1.tif"/></fig></fig-group></sec><sec id="s3" sec-type="discussion"><title>Discussion</title><p>Overall, these results collectively demonstrate that there is no obvious, statistically significant difference between observed damage to electrodes used versus not used for electrolytic lesioning. This indicates that any material effects potentially caused by electrolytic lesioning are indistinguishable from the typical damage seen in long-term implanted arrays. Because this method of lesioning involves passing weak direct current into the brain over relatively short time periods, its physical effects on the array electrodes are similar to alternating current stimulation. A recent study found that SEM-visible damage caused by stimulation on iridium oxide electrodes is highly variable between arrays, where one imaged array demonstrated noticeable stimulation-related damage and the other array had no such damage (<xref ref-type="bibr" rid="bib42">Woeppel et al., 2021</xref>). Furthermore, the study found that array recording quality was not compromised by stimulation. Similarly, other work did not show significant differences in SEM-visible degradation between platinum electrodes used for stimulation and iridium oxide electrodes used for stimulation (<xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>; <xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>). All of these previous studies used different stimulation protocols: a pulse train delivered at 20–300 Hz at amplitudes 1–100 μA (<xref ref-type="bibr" rid="bib42">Woeppel et al., 2021</xref>), a pulse train delivered at 300 Hz at amplitudes 1–210 μA (<xref ref-type="bibr" rid="bib12">Chen et al., 2023</xref>), and an undisclosed low-current stimulation (<xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>). Additionally, dissolution of electrodes due to current is most salient at aggressive levels of stimulation; one study reviewing electrode dissolution delivered variable amplitudes of current at 50 Hz for 7 hr <xref ref-type="bibr" rid="bib26">Negi et al., 2010</xref>; another study utilized currents at least one order of magnitude greater than the above protocols (<xref ref-type="bibr" rid="bib34">Shepherd et al., 2021</xref>). The electrolytic lesioning in this work primarily used direct currents delivered at around 150 μA for 45 s, though parameters ranged between 50–450 μA and 12–600 s. Thus, despite the differences between specific lesioning and stimulation protocols, the findings presented here are consistent with previous studies that found no unusual damage to the electrodes used for stimulation. This aligns with previous findings that electrolytic lesioning does not significantly impact the recording ability of electrodes (<xref ref-type="bibr" rid="bib6">Bray et al., 2024</xref>).</p><p>The patterns of damage found in this work also largely reflect previous SEM analyses of explanted arrays. A prior study also found that the electrodes closest to the perimeter of the array suffered the most damage (<xref ref-type="bibr" rid="bib5">Bjånes et al., 2024</xref>). This pattern is also visually observable in other published results (<xref ref-type="bibr" rid="bib27">Patel et al., 2023</xref>; <xref ref-type="bibr" rid="bib42">Woeppel et al., 2021</xref>). This is likely because the edges of the arrays serve as a physical shield for the innermost electrodes. Edge electrodes are subject to greater access to brain tissue, as well as to mechanical damage incurred during surgery and handling.</p><p>The frequency of damage types identified in this work differs from previous studies, but is not unusual. In this work, the most common damage type within arrays used for lesioning is abnormal debris (<italic>n</italic> = 276, 71.9%), followed by metal coating cracks (<italic>n</italic> = 214, 55.7%), tip breakage (<italic>n</italic> = 102, 26.6%), parylene C cracks (<italic>n</italic> = 95, 24.7%), and parylene C delamination (<italic>n</italic> = 48, 12.5%). On these lesioning arrays, there were <italic>n</italic> = 53, or 13.8%, shank fractures. Similarly, across all eight NHP arrays imaged, the most common damage type is abnormal debris (<italic>n</italic> = 518, 67.4%), followed by metal coating cracks (<italic>n</italic> = 480, 62.5%), tip breakage (<italic>n</italic> = 233, 30.3%), parylene C cracks (<italic>n</italic> = 224, 29.2%), and parylene C delamination (<italic>n</italic> = 60, 7.8%). Across all eight NHP arrays, there were <italic>n</italic> = 117, or 15.2%, shank fractures. However, a prior study found that coating cracks were the most common type of observed damage, followed closely by parylene C cracks, then tip breakage, abnormal debris, and parylene C delamination (<xref ref-type="bibr" rid="bib27">Patel et al., 2023</xref>). While the frequency of damage types is not exactly aligned, previous work included a cleaning step during array preparation for SEM imaging; this work does not explicitly attempt to remove excess brain tissue from imaged arrays, which likely led to the relative increase we observed in abnormal debris. Additionally, variation in individual researchers’ scoring standards may also contribute to differences. As mentioned above, the overall spatial pattern of damage between these two studies is consistent. Finally, this study also found a moderate positive correlation between coating cracks and tip breakage. This reflects the fact that damage to the silicon core of an electrode often occurs in tandem with cracking and flaking of the surrounding metal coating; the silicon cannot break without also breaking its coating. This correlation is visible in the collected images presented in <xref ref-type="video" rid="video1">Video 1</xref>.</p><p>This work analyzed high-definition SEM images of previously implanted electrode arrays used for electrolytic lesioning. Across all eight arrays previously implanted in NHPs, damage disproportionately occurred to the outer edges of arrays. Additionally, no statistically significant difference was found between the damage experienced by normal and lesioning electrodes within the same array. Furthermore, statistical testing between arrays used and not used for lesioning experiments did not indicate consistent, significant differences. Finally, this work also presents the largest publicly available set of SEM images of explanted arrays, consisting of 11 different multielectrode Utah arrays (ten 96-channel, one 64-channel) and one broken 96-channel array. These results from this dataset align with previous SEM studies of chronically implanted arrays used for both recording and stimulation, while providing further evidence for electrolytic lesioning as a safe and useful technique for experimental neuroscience.</p></sec><sec id="s4" sec-type="methods"><title>Methods</title><sec id="s4-1"><title>Electrolytic lesioning</title><p>All lesions were performed following previously described procedures (<xref ref-type="bibr" rid="bib6">Bray et al., 2024</xref>). To summarize, each lesion is created by passing around 150 μA of direct current for approximately 45 s between two adjacent electrodes (one anode and one cathode) on the array. Thus, each lesion is bipolar, not unipolar, and is produced without a pulse/frequency-based protocol. Exact parameters, ranging between 50–450 μA and 12–600 s for each lesion, are available in <xref ref-type="supplementary-material" rid="supp6">Supplementary file 6</xref>.</p></sec><sec id="s4-2"><title>Array preparation</title><p>Nine explanted NHP arrays were utilized for this study. Monkey H, F, and C were each implanted with two 96-channel Utah arrays in M1 (primary motor cortex) and PMd (dorsal premotor cortex). H’s M1 array was used for electrolytic lesioning experiments. F’s and C’s PMd arrays were used for electrolytic lesioning experiments. Monkey U was implanted with three 96-channel arrays; two in M1, and one in PMd. U’s lateral M1 array was used for electrolytic lesioning experiments. U’s medial M1 array was not used for recording, and was damaged during extraction. Monkey H’s arrays were implanted for 2242 days (electrolytic lesions on days 2088, 2129, 2136, 2164, 2172, 2180, 2187, 2192, 2221, and 2228). Monkey F’s arrays were implanted for 1875 days (electrolytic lesion on day 1875). Monkey U’s arrays were implanted for 2680 days (electrolytic lesions on days 1215, 1250, 1264, and 1286). Monkey C’s arrays were implanted for 594 days (electrolytic lesion on day 304). To produce each electrolytic lesion, current was passed between two electrodes on the array. Further details on each monkey’s arrays, as well as any additional imaged arrays, are available in <xref ref-type="supplementary-material" rid="supp1">Supplementary file 1</xref>. All monkeys were male rhesus macaques. Further details on animal and lesioning procedures are available in a prior report (<xref ref-type="bibr" rid="bib6">Bray et al., 2024</xref>). All animal procedures and protocols were approved by the Stanford University Institutional Animal Care and Use Committee (#D16-00134).</p><p>All arrays used in this work were 10 × 10 multielectrode Utah arrays (Blackrock Neurotech, Salt Lake City, UT). Monkey C was implanted with an array with electrode shank lengths of 1.5 mm, while Monkeys H, F, and U were implanted with arrays with electrode shank lengths of 1 mm. Monkey U and C’s arrays were manufactured with an iridium oxide metal coating, while H and F’s arrays were manufactured with platinum coatings.</p><p>Arrays were first soaked in either a 0.9% saline or 10% formalin solution immediately following explant surgery, then stored separately in either water, formalin, ethanol, or dry in a closed container. Prior to imaging, all arrays were allowed to dry without any further cleaning or preparation.</p></sec><sec id="s4-3"><title>Scanning electron microscopy</title><p>SEM images were collected using a Hitachi TM4000+ Tabletop SEM (Hitachi Ltd, Tokyo, Japan). Arrays were mounted on PELCO SEMClip Pin Mounts (Ted Pella, Redding, CA) using conductive copper tape, carbon tape, and included clip mounts. Arrays were not sputter-coated for imaging. Due to the amount of organic material left on the arrays, images were collected in low-vacuum mode to avoid distortion from accumulated electrical charge of the non-conductive material. Full array images were collected with the arrays flat on the mount surface, while single-electrode images were collected with the arrays positioned at an approximate 45°angle. Most images were collected using a mixed backscatter/secondary electron (BSE/SE) mode with a low accelerating voltage of 5 kV, although modes and voltage values were adjusted for certain electrodes to optimize image clarity. Specific settings for each collected image are included in <xref ref-type="video" rid="video1">Video 1</xref>.</p></sec><sec id="s4-4"><title>Damage scoring</title><p>A prior study categorized damage observable with SEM into six distinct types: abnormal debris, tip breakage, coating cracks (cracking of the metal coating around the silicon core of an electrode), parylene C cracks, parylene C delamination, and shank fracture (<xref ref-type="bibr" rid="bib27">Patel et al., 2023</xref>). Similarly, damage to the arrays in this study were scored in five categories: abnormal debris (AB), silicon tip breakage (TB), platinum coating cracks (CC), parylene C coating cracks (PC), and parylene C coating delamination (PD). Each recording electrode was scored from 0 to 3 in five different categories, as described above. Electrodes with shank fractures (SF) were not scored, as these fractures may have reasonably occurred during explantation and handling of the arrays separate from the damage incurred while in the brain. Each electrode was scored between 0–3, where 0 indicated no visible effects, 1 indicated visible effects but likely no impact on recording ability, 2 indicated possible impact on recording ability, and 3 indicated likely impact on recording ability. Scores were given without prior knowledge of which electrodes had been used for electrolytic lesioning. Although this scoring system is subjective and based on visual observation, all images used to compute these scores are publicly available in <xref ref-type="video" rid="video1">Video 1</xref> for independent evaluation.</p></sec><sec id="s4-5"><title>Statistical tests</title><p>First, the Pearson’s correlation coefficient was calculated between each subcategory of damage to determine whether any types of damage were related. To explore potential spatial relationships, this analysis was repeated for each radial ring of electrodes, as shown in <xref ref-type="fig" rid="fig3s1">Figure 3—figure supplement 1</xref>.</p><p>Statistical significance was also assessed between electrodes used in the electrolytic lesion experiments versus those which had not. The Shapiro–Wilk test indicated that scores did not follow a normal distribution; therefore, nonparametric methods such as the Mann–Whitney <italic>U</italic> test and the Levene test were used to compare the underlying statistics of each array’s electrode population. The null hypothesis of the Mann–Whitney <italic>U</italic> test is that sample distributions of two sets of scores are the same. The null hypothesis of the Levene test is that the sample variance of two sets of scores are the same.</p><p>Similarly, statistical significance was assessed as described above between lesioning versus normal electrodes, which were pooled across all four arrays used for electrolytic lesioning. Finally, this analysis was repeated between electrode scores across pairs of lesioning and non-lesioning arrays implanted in the same subject for the same length of time.</p></sec></sec></body><back><sec sec-type="additional-information" id="s5"><title>Additional information</title><fn-group content-type="competing-interest"><title>Competing interests</title><fn fn-type="COI-statement" id="conf1"><p>No competing interests declared</p></fn></fn-group><fn-group content-type="author-contribution"><title>Author contributions</title><fn fn-type="con" id="con1"><p>Data curation, Software, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing – original draft, Writing – review and editing</p></fn><fn fn-type="con" id="con2"><p>Conceptualization, Data curation, Supervision, Validation, Writing – original draft, Writing – review and editing</p></fn><fn fn-type="con" id="con3"><p>Conceptualization, Writing – review and editing</p></fn><fn fn-type="con" id="con4"><p>Conceptualization, Resources, Supervision, Funding acquisition, Methodology, Writing – original draft, Project administration</p></fn></fn-group><fn-group content-type="ethics-information"><title>Ethics</title><fn fn-type="other"><p>All animal procedures and protocols were approved by the Stanford University Institutional Animal Care and Use Committee (IACUC) of Stanford University.</p></fn></fn-group></sec><sec sec-type="supplementary-material" id="s6"><title>Additional files</title><supplementary-material id="mdar"><label>MDAR checklist</label><media xlink:href="elife-106452-mdarchecklist1-v1.pdf" mimetype="application" mime-subtype="pdf"/></supplementary-material><supplementary-material id="supp1"><label>Supplementary file 1.</label><caption><title>Details and characteristics for all imaged and analyzed devices in this work.</title></caption><media xlink:href="elife-106452-supp1-v1.pdf" mimetype="application" mime-subtype="pdf"/></supplementary-material><supplementary-material id="supp2"><label>Supplementary file 2.</label><caption><title>Shapiro-Wilk p-values.</title></caption><media xlink:href="elife-106452-supp2-v1.csv" mimetype="application" mime-subtype="octet-stream"/></supplementary-material><supplementary-material id="supp3"><label>Supplementary file 3.</label><caption><title>Mann-Whitney U and Levene p-values when comparing damage scores given to lesioning/non-lesioning electrodes.</title></caption><media xlink:href="elife-106452-supp3-v1.csv" mimetype="application" mime-subtype="octet-stream"/></supplementary-material><supplementary-material id="supp4"><label>Supplementary file 4.</label><caption><title>Mann-Whitney U and Levene p-values when comparing total damage scores given to arrays used for lesioning/non-lesioning.</title></caption><media xlink:href="elife-106452-supp4-v1.csv" mimetype="application" mime-subtype="octet-stream"/></supplementary-material><supplementary-material id="supp5"><label>Supplementary file 5.</label><caption><title>Correlation r and p-values.</title></caption><media xlink:href="elife-106452-supp5-v1.pdf" mimetype="application" mime-subtype="pdf"/></supplementary-material><supplementary-material id="supp6"><label>Supplementary file 6.</label><caption><title>Details for electrolytic lesions referenced in this manuscript.</title></caption><media xlink:href="elife-106452-supp6-v1.csv" mimetype="application" mime-subtype="octet-stream"/></supplementary-material></sec><sec sec-type="data-availability" id="s7"><title>Data availability</title><p>All images and data used in this analysis have been deposited at the Stanford Data Repository (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.25740/dz983xf0632">https://doi.org/10.25740/dz983xf0632</ext-link>). All data for this manuscript are embedded into the source code of Video 1.</p><p>The following dataset was generated:</p><p><element-citation publication-type="data" specific-use="isSupplementedBy" id="dataset1"><person-group person-group-type="author"><name><surname>Tor</surname><given-names>A</given-names></name><name><surname>Clarke</surname><given-names>S</given-names></name><name><surname>Bray</surname><given-names>I</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name></person-group><year iso-8601-date="2025">2025</year><data-title>Materials associated with Tor, et al., eLife 2025</data-title><source>Stanford Data Repository</source><pub-id pub-id-type="doi">10.25740/dz983xf0632</pub-id></element-citation></p></sec><ack id="ack"><title>Acknowledgements</title><p>We thank S Baker for veterinary support, and K Chin and M Truong for administrative support. The members of the Brain Interfacing Laboratory who supported this work were Michelle S Wechsler, Mackenzie Risch, Alexandra Paraskevopoulou, Stephen I Ryu, Alissa S Ling, Elizabeth Jun, Michael P Silvernagel, Yuxin Wu, Kenji Y Marshall, Muhammad Abdulla, and Sydney Hunt. MS Wechsler, A Paraskevopoulou, K Lebedev, and MJ Risch were responsible for animal care and surgical support. SI Ryu was responsible for nonhuman primate array implantation. AS Ling, E Jun, MP Silvernagel, Y Wu, K Marshall, MU Abdulla, and S Hunt assisted in animal care. Part of this work was performed at the Stanford Nano Shared. Facilities (SNSF), supported by the National Science Foundation under award ECCS-2026822. A Tor was supported by the Department of Defense (DoD) through the National Defense Science &amp; Engineering Graduate (NDSEG) Fellowship Program and by a training grant from the National Science Foundation (1828993). SE Clarke was supported by a Stanford School of Medicine’s Dean’s Postdoctoral Fellowship. IE Bray was supported by an American Heart Association Predoctoral Fellowship (828653) and the National Science Foundation GRFP (1656518). This work was supported by a Stanford Human-Centered. AI Seed Research Grant to SE Clarke and P Nuyujukian. This work was additionally supported by the following to P Nuyujukian: the National Institutes of Health (R01NS123517, R01NS130789, U19NS118284) and the Stanford Wu Tsai Neurosciences Institute.</p></ack><ref-list><title>References</title><ref id="bib1"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barrese</surname><given-names>JC</given-names></name><name><surname>Rao</surname><given-names>N</given-names></name><name><surname>Paroo</surname><given-names>K</given-names></name><name><surname>Triebwasser</surname><given-names>C</given-names></name><name><surname>Vargas-Irwin</surname><given-names>C</given-names></name><name><surname>Franquemont</surname><given-names>L</given-names></name><name><surname>Donoghue</surname><given-names>JP</given-names></name></person-group><year iso-8601-date="2013">2013</year><article-title>Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates</article-title><source>Journal of Neural Engineering</source><volume>10</volume><elocation-id>066014</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/10/6/066014</pub-id><pub-id pub-id-type="pmid">24216311</pub-id></element-citation></ref><ref id="bib2"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barrese</surname><given-names>JC</given-names></name><name><surname>Aceros</surname><given-names>J</given-names></name><name><surname>Donoghue</surname><given-names>JP</given-names></name></person-group><year iso-8601-date="2016">2016</year><article-title>Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates</article-title><source>Journal of Neural Engineering</source><volume>13</volume><elocation-id>026003</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/13/2/026003</pub-id><pub-id pub-id-type="pmid">26824680</pub-id></element-citation></ref><ref id="bib3"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bhandari</surname><given-names>R</given-names></name><name><surname>Negi</surname><given-names>S</given-names></name><name><surname>Solzbacher</surname><given-names>F</given-names></name></person-group><year iso-8601-date="2010">2010</year><article-title>Wafer-scale fabrication of penetrating neural microelectrode arrays</article-title><source>Biomedical Microdevices</source><volume>12</volume><fpage>797</fpage><lpage>807</lpage><pub-id pub-id-type="doi">10.1007/s10544-010-9434-1</pub-id><pub-id pub-id-type="pmid">20480240</pub-id></element-citation></ref><ref id="bib4"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Biran</surname><given-names>R</given-names></name><name><surname>Martin</surname><given-names>DC</given-names></name><name><surname>Tresco</surname><given-names>PA</given-names></name></person-group><year iso-8601-date="2007">2007</year><article-title>The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull</article-title><source>Journal of Biomedical Materials Research. Part A</source><volume>82</volume><fpage>169</fpage><lpage>178</lpage><pub-id pub-id-type="doi">10.1002/jbm.a.31138</pub-id><pub-id pub-id-type="pmid">17266019</pub-id></element-citation></ref><ref id="bib5"><element-citation publication-type="preprint"><person-group person-group-type="author"><name><surname>Bjånes</surname><given-names>DA</given-names></name><name><surname>Kellis</surname><given-names>S</given-names></name><name><surname>Nickl</surname><given-names>R</given-names></name><name><surname>Baker</surname><given-names>B</given-names></name><name><surname>Aflalo</surname><given-names>T</given-names></name><name><surname>Bashford</surname><given-names>L</given-names></name><name><surname>Chivukula</surname><given-names>S</given-names></name><name><surname>Fifer</surname><given-names>MS</given-names></name><name><surname>Osborn</surname><given-names>LE</given-names></name><name><surname>Christie</surname><given-names>B</given-names></name><name><surname>Wester</surname><given-names>BA</given-names></name><name><surname>Celnik</surname><given-names>PA</given-names></name><name><surname>Kramer</surname><given-names>D</given-names></name><name><surname>Pejsa</surname><given-names>K</given-names></name><name><surname>Crone</surname><given-names>NE</given-names></name><name><surname>Anderson</surname><given-names>WS</given-names></name><name><surname>Pouratian</surname><given-names>N</given-names></name><name><surname>Lee</surname><given-names>B</given-names></name><name><surname>Liu</surname><given-names>CY</given-names></name><name><surname>Tenore</surname><given-names>F</given-names></name><name><surname>Rieth</surname><given-names>L</given-names></name><name><surname>Andersen</surname><given-names>RA</given-names></name></person-group><year iso-8601-date="2024">2024</year><article-title>Quantifying physical degradation alongside recording and stimulation performance of 980 intracortical microelectrodes chronically implanted in three humans for 956-2246 days</article-title><source>medRxiv</source><pub-id pub-id-type="doi">10.1101/2024.09.09.24313281</pub-id></element-citation></ref><ref id="bib6"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bray</surname><given-names>IE</given-names></name><name><surname>Clarke</surname><given-names>SE</given-names></name><name><surname>Casey</surname><given-names>KM</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name><collab>Brain Interfacing Laboratory</collab></person-group><year iso-8601-date="2024">2024</year><article-title>Neuroelectrophysiology-compatible electrolytic lesioning</article-title><source>eLife</source><volume>12</volume><elocation-id>RP84385</elocation-id><pub-id pub-id-type="doi">10.7554/eLife.84385</pub-id><pub-id pub-id-type="pmid">39259198</pub-id></element-citation></ref><ref id="bib7"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Caldwell</surname><given-names>R</given-names></name><name><surname>Street</surname><given-names>MG</given-names></name><name><surname>Sharma</surname><given-names>R</given-names></name><name><surname>Takmakov</surname><given-names>P</given-names></name><name><surname>Baker</surname><given-names>B</given-names></name><name><surname>Rieth</surname><given-names>L</given-names></name></person-group><year iso-8601-date="2020">2020</year><article-title>Characterization of Parylene-C degradation mechanisms: In vitro reactive accelerated aging model compared to multiyear in vivo implantation</article-title><source>Biomaterials</source><volume>232</volume><elocation-id>119731</elocation-id><pub-id pub-id-type="doi">10.1016/j.biomaterials.2019.119731</pub-id><pub-id pub-id-type="pmid">31918225</pub-id></element-citation></ref><ref id="bib8"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Campbell</surname><given-names>PK</given-names></name><name><surname>Jones</surname><given-names>KE</given-names></name><name><surname>Huber</surname><given-names>RJ</given-names></name><name><surname>Horch</surname><given-names>KW</given-names></name><name><surname>Normann</surname><given-names>RA</given-names></name></person-group><year iso-8601-date="1991">1991</year><article-title>A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array</article-title><source>IEEE Transactions on Bio-Medical Engineering</source><volume>38</volume><fpage>758</fpage><lpage>768</lpage><pub-id pub-id-type="doi">10.1109/10.83588</pub-id><pub-id pub-id-type="pmid">1937509</pub-id></element-citation></ref><ref id="bib9"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chehrazi</surname><given-names>B</given-names></name><name><surname>Collins</surname><given-names>WF</given-names></name></person-group><year iso-8601-date="1981">1981</year><article-title>A comparison of effects of bipolar and monopolar electrocoagulation in brain</article-title><source>Journal of Neurosurgery</source><volume>54</volume><fpage>197</fpage><lpage>203</lpage><pub-id pub-id-type="doi">10.3171/jns.1981.54.2.0197</pub-id><pub-id pub-id-type="pmid">7452334</pub-id></element-citation></ref><ref id="bib10"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>YY</given-names></name><name><surname>Lai</surname><given-names>HY</given-names></name><name><surname>Lin</surname><given-names>SH</given-names></name><name><surname>Cho</surname><given-names>CW</given-names></name><name><surname>Chao</surname><given-names>WH</given-names></name><name><surname>Liao</surname><given-names>CH</given-names></name><name><surname>Tsang</surname><given-names>S</given-names></name><name><surname>Chen</surname><given-names>YF</given-names></name><name><surname>Lin</surname><given-names>SY</given-names></name></person-group><year iso-8601-date="2009">2009</year><article-title>Design and fabrication of a polyimide-based microelectrode array: application in neural recording and repeatable electrolytic lesion in rat brain</article-title><source>Journal of Neuroscience Methods</source><volume>182</volume><fpage>6</fpage><lpage>16</lpage><pub-id pub-id-type="doi">10.1016/j.jneumeth.2009.05.010</pub-id><pub-id pub-id-type="pmid">19467262</pub-id></element-citation></ref><ref id="bib11"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>KH</given-names></name><name><surname>Dammann</surname><given-names>JF</given-names></name><name><surname>Boback</surname><given-names>JL</given-names></name><name><surname>Tenore</surname><given-names>FV</given-names></name><name><surname>Otto</surname><given-names>KJ</given-names></name><name><surname>Gaunt</surname><given-names>RA</given-names></name><name><surname>Bensmaia</surname><given-names>SJ</given-names></name></person-group><year iso-8601-date="2014">2014</year><article-title>The effect of chronic intracortical microstimulation on the electrode-tissue interface</article-title><source>Journal of Neural Engineering</source><volume>11</volume><elocation-id>026004</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/11/2/026004</pub-id><pub-id pub-id-type="pmid">24503702</pub-id></element-citation></ref><ref id="bib12"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Wang</surname><given-names>F</given-names></name><name><surname>Kooijmans</surname><given-names>R</given-names></name><name><surname>Klink</surname><given-names>PC</given-names></name><name><surname>Boehler</surname><given-names>C</given-names></name><name><surname>Asplund</surname><given-names>M</given-names></name><name><surname>Roelfsema</surname><given-names>PR</given-names></name></person-group><year iso-8601-date="2023">2023</year><article-title>Chronic stability of a neuroprosthesis comprising multiple adjacent Utah arrays in monkeys</article-title><source>Journal of Neural Engineering</source><volume>20</volume><elocation-id>036039</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2552/ace07e</pub-id><pub-id pub-id-type="pmid">37386891</pub-id></element-citation></ref><ref id="bib13"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chestek</surname><given-names>CA</given-names></name><name><surname>Gilja</surname><given-names>V</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name><name><surname>Foster</surname><given-names>JD</given-names></name><name><surname>Fan</surname><given-names>JM</given-names></name><name><surname>Kaufman</surname><given-names>MT</given-names></name><name><surname>Churchland</surname><given-names>MM</given-names></name><name><surname>Rivera-Alvidrez</surname><given-names>Z</given-names></name><name><surname>Cunningham</surname><given-names>JP</given-names></name><name><surname>Ryu</surname><given-names>SI</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name></person-group><year iso-8601-date="2011">2011</year><article-title>Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex</article-title><source>Journal of Neural Engineering</source><volume>8</volume><elocation-id>045005</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/8/4/045005</pub-id><pub-id pub-id-type="pmid">21775782</pub-id></element-citation></ref><ref id="bib14"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Churchland</surname><given-names>MM</given-names></name><name><surname>Cunningham</surname><given-names>JP</given-names></name><name><surname>Kaufman</surname><given-names>MT</given-names></name><name><surname>Foster</surname><given-names>JD</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name><name><surname>Ryu</surname><given-names>SI</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name></person-group><year iso-8601-date="2012">2012</year><article-title>Neural population dynamics during reaching</article-title><source>Nature</source><volume>487</volume><fpage>51</fpage><lpage>56</lpage><pub-id pub-id-type="doi">10.1038/nature11129</pub-id><pub-id pub-id-type="pmid">22722855</pub-id></element-citation></ref><ref id="bib15"><element-citation publication-type="confproc"><person-group person-group-type="author"><name><surname>Cogan</surname><given-names>SF</given-names></name><name><surname>Plante</surname><given-names>TD</given-names></name><name><surname>Ehrlich</surname><given-names>J</given-names></name></person-group><year iso-8601-date="2004">2004</year><article-title>Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes</article-title><conf-name>26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society</conf-name><pub-id pub-id-type="doi">10.1109/IEMBS.2004.1404158</pub-id></element-citation></ref><ref id="bib16"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cunningham</surname><given-names>JP</given-names></name><name><surname>Yu</surname><given-names>BM</given-names></name></person-group><year iso-8601-date="2014">2014</year><article-title>Dimensionality reduction for large-scale neural recordings</article-title><source>Nature Neuroscience</source><volume>17</volume><fpage>1500</fpage><lpage>1509</lpage><pub-id pub-id-type="doi">10.1038/nn.3776</pub-id><pub-id pub-id-type="pmid">25151264</pub-id></element-citation></ref><ref id="bib17"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Downey</surname><given-names>JE</given-names></name><name><surname>Schwed</surname><given-names>N</given-names></name><name><surname>Chase</surname><given-names>SM</given-names></name><name><surname>Schwartz</surname><given-names>AB</given-names></name><name><surname>Collinger</surname><given-names>JL</given-names></name></person-group><year iso-8601-date="2018">2018</year><article-title>Intracortical recording stability in human brain-computer interface users</article-title><source>Journal of Neural Engineering</source><volume>15</volume><elocation-id>046016</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2552/aab7a0</pub-id><pub-id pub-id-type="pmid">29553484</pub-id></element-citation></ref><ref id="bib18"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ebitz</surname><given-names>RB</given-names></name><name><surname>Hayden</surname><given-names>BY</given-names></name></person-group><year iso-8601-date="2021">2021</year><article-title>The population doctrine in cognitive neuroscience</article-title><source>Neuron</source><volume>109</volume><fpage>3055</fpage><lpage>3068</lpage><pub-id pub-id-type="doi">10.1016/j.neuron.2021.07.011</pub-id><pub-id pub-id-type="pmid">34416170</pub-id></element-citation></ref><ref id="bib19"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gallego</surname><given-names>JA</given-names></name><name><surname>Perich</surname><given-names>MG</given-names></name><name><surname>Chowdhury</surname><given-names>RH</given-names></name><name><surname>Solla</surname><given-names>SA</given-names></name><name><surname>Miller</surname><given-names>LE</given-names></name></person-group><year iso-8601-date="2020">2020</year><article-title>Long-term stability of cortical population dynamics underlying consistent behavior</article-title><source>Nature Neuroscience</source><volume>23</volume><fpage>260</fpage><lpage>270</lpage><pub-id pub-id-type="doi">10.1038/s41593-019-0555-4</pub-id><pub-id pub-id-type="pmid">31907438</pub-id></element-citation></ref><ref id="bib20"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gilja</surname><given-names>V</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name><name><surname>Chestek</surname><given-names>CA</given-names></name><name><surname>Cunningham</surname><given-names>JP</given-names></name><name><surname>Yu</surname><given-names>BM</given-names></name><name><surname>Fan</surname><given-names>JM</given-names></name><name><surname>Churchland</surname><given-names>MM</given-names></name><name><surname>Kaufman</surname><given-names>MT</given-names></name><name><surname>Kao</surname><given-names>JC</given-names></name><name><surname>Ryu</surname><given-names>SI</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name></person-group><year iso-8601-date="2012">2012</year><article-title>A high-performance neural prosthesis enabled by control algorithm design</article-title><source>Nature Neuroscience</source><volume>15</volume><fpage>1752</fpage><lpage>1757</lpage><pub-id pub-id-type="doi">10.1038/nn.3265</pub-id><pub-id pub-id-type="pmid">23160043</pub-id></element-citation></ref><ref id="bib21"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gilja</surname><given-names>V</given-names></name><name><surname>Pandarinath</surname><given-names>C</given-names></name><name><surname>Blabe</surname><given-names>CH</given-names></name><name><surname>Nuyujukian</surname><given-names>P</given-names></name><name><surname>Simeral</surname><given-names>JD</given-names></name><name><surname>Sarma</surname><given-names>AA</given-names></name><name><surname>Sorice</surname><given-names>BL</given-names></name><name><surname>Perge</surname><given-names>JA</given-names></name><name><surname>Jarosiewicz</surname><given-names>B</given-names></name><name><surname>Hochberg</surname><given-names>LR</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name><name><surname>Henderson</surname><given-names>JM</given-names></name></person-group><year iso-8601-date="2015">2015</year><article-title>Clinical translation of a high-performance neural prosthesis</article-title><source>Nature Medicine</source><volume>21</volume><fpage>1142</fpage><lpage>1145</lpage><pub-id pub-id-type="doi">10.1038/nm.3953</pub-id><pub-id pub-id-type="pmid">26413781</pub-id></element-citation></ref><ref id="bib22"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Horsley</surname><given-names>V</given-names></name><name><surname>Clarke</surname><given-names>RH</given-names></name></person-group><year iso-8601-date="1908">1908</year><article-title>The structure and functions of the cerebellum examined by a new method</article-title><source>Brain</source><volume>31</volume><fpage>45</fpage><lpage>124</lpage><pub-id pub-id-type="doi">10.1093/brain/31.1.45</pub-id></element-citation></ref><ref id="bib23"><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Kline</surname><given-names>MT</given-names></name></person-group><year iso-8601-date="2007">2007</year><source>Chapter 169 - Radiofrequency Techniques</source><publisher-name>W.B. Saunders</publisher-name></element-citation></ref><ref id="bib24"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maynard</surname><given-names>EM</given-names></name><name><surname>Nordhausen</surname><given-names>CT</given-names></name><name><surname>Normann</surname><given-names>RA</given-names></name></person-group><year iso-8601-date="1997">1997</year><article-title>The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces</article-title><source>Electroencephalography and Clinical Neurophysiology</source><volume>102</volume><fpage>228</fpage><lpage>239</lpage><pub-id pub-id-type="doi">10.1016/s0013-4694(96)95176-0</pub-id><pub-id pub-id-type="pmid">9129578</pub-id></element-citation></ref><ref id="bib25"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mitchell</surname><given-names>AS</given-names></name><name><surname>Thiele</surname><given-names>A</given-names></name><name><surname>Petkov</surname><given-names>CI</given-names></name><name><surname>Roberts</surname><given-names>A</given-names></name><name><surname>Robbins</surname><given-names>TW</given-names></name><name><surname>Schultz</surname><given-names>W</given-names></name><name><surname>Lemon</surname><given-names>R</given-names></name></person-group><year iso-8601-date="2018">2018</year><article-title>Continued need for non-human primate neuroscience research</article-title><source>Current Biology</source><volume>28</volume><fpage>R1186</fpage><lpage>R1187</lpage><pub-id pub-id-type="doi">10.1016/j.cub.2018.09.029</pub-id><pub-id pub-id-type="pmid">30352184</pub-id></element-citation></ref><ref id="bib26"><element-citation publication-type="confproc"><person-group person-group-type="author"><name><surname>Negi</surname><given-names>S</given-names></name><name><surname>Bhandari</surname><given-names>R</given-names></name><name><surname>Van Wagenen</surname><given-names>R</given-names></name><name><surname>Solzbacher</surname><given-names>F</given-names></name></person-group><year iso-8601-date="2010">2010</year><article-title>IEEE 23rd International Conference on Micro Electro Mechanical Systems (MEMS)</article-title><conf-name>IEEE Wancha</conf-name><pub-id pub-id-type="doi">10.1109/MEMSYS.2010.5442438</pub-id></element-citation></ref><ref id="bib27"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname><given-names>PR</given-names></name><name><surname>Welle</surname><given-names>EJ</given-names></name><name><surname>Letner</surname><given-names>JG</given-names></name><name><surname>Shen</surname><given-names>H</given-names></name><name><surname>Bullard</surname><given-names>AJ</given-names></name><name><surname>Caldwell</surname><given-names>CM</given-names></name><name><surname>Vega-Medina</surname><given-names>A</given-names></name><name><surname>Richie</surname><given-names>JM</given-names></name><name><surname>Thayer</surname><given-names>HE</given-names></name><name><surname>Patil</surname><given-names>PG</given-names></name><name><surname>Cai</surname><given-names>D</given-names></name><name><surname>Chestek</surname><given-names>CA</given-names></name></person-group><year iso-8601-date="2023">2023</year><article-title>Utah array characterization and histological analysis of a multi-year implant in non-human primate motor and sensory cortices</article-title><source>Journal of Neural Engineering</source><volume>20</volume><elocation-id>014001</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2552/acab86</pub-id><pub-id pub-id-type="pmid">36595323</pub-id></element-citation></ref><ref id="bib28"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Polikov</surname><given-names>VS</given-names></name><name><surname>Tresco</surname><given-names>PA</given-names></name><name><surname>Reichert</surname><given-names>WM</given-names></name></person-group><year iso-8601-date="2005">2005</year><article-title>Response of brain tissue to chronically implanted neural electrodes</article-title><source>Journal of Neuroscience Methods</source><volume>148</volume><fpage>1</fpage><lpage>18</lpage><pub-id pub-id-type="doi">10.1016/j.jneumeth.2005.08.015</pub-id><pub-id pub-id-type="pmid">16198003</pub-id></element-citation></ref><ref id="bib29"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Potter</surname><given-names>KA</given-names></name><name><surname>Buck</surname><given-names>AC</given-names></name><name><surname>Self</surname><given-names>WK</given-names></name><name><surname>Capadona</surname><given-names>JR</given-names></name></person-group><year iso-8601-date="2012">2012</year><article-title>Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses</article-title><source>Journal of Neural Engineering</source><volume>9</volume><elocation-id>046020</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/9/4/046020</pub-id><pub-id pub-id-type="pmid">22832283</pub-id></element-citation></ref><ref id="bib30"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roelfsema</surname><given-names>PR</given-names></name><name><surname>Treue</surname><given-names>S</given-names></name></person-group><year iso-8601-date="2014">2014</year><article-title>Basic neuroscience research with nonhuman primates: a small but indispensable component of biomedical research</article-title><source>Neuron</source><volume>82</volume><fpage>1200</fpage><lpage>1204</lpage><pub-id pub-id-type="doi">10.1016/j.neuron.2014.06.003</pub-id><pub-id pub-id-type="pmid">24945764</pub-id></element-citation></ref><ref id="bib31"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Salatino</surname><given-names>JW</given-names></name><name><surname>Ludwig</surname><given-names>KA</given-names></name><name><surname>Kozai</surname><given-names>TDY</given-names></name><name><surname>Purcell</surname><given-names>EK</given-names></name></person-group><year iso-8601-date="2017">2017</year><article-title>Glial responses to implanted electrodes in the brain</article-title><source>Nature Biomedical Engineering</source><volume>1</volume><fpage>862</fpage><lpage>877</lpage><pub-id pub-id-type="doi">10.1038/s41551-017-0154-1</pub-id><pub-id pub-id-type="pmid">30505625</pub-id></element-citation></ref><ref id="bib32"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Serruya</surname><given-names>MD</given-names></name><name><surname>Hatsopoulos</surname><given-names>NG</given-names></name><name><surname>Paninski</surname><given-names>L</given-names></name><name><surname>Fellows</surname><given-names>MR</given-names></name><name><surname>Donoghue</surname><given-names>JP</given-names></name></person-group><year iso-8601-date="2002">2002</year><article-title>Instant neural control of a movement signal</article-title><source>Nature</source><volume>416</volume><fpage>141</fpage><lpage>142</lpage><pub-id pub-id-type="doi">10.1038/416141a</pub-id><pub-id pub-id-type="pmid">11894084</pub-id></element-citation></ref><ref id="bib33"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shah</surname><given-names>DD</given-names></name><name><surname>Carter</surname><given-names>P</given-names></name><name><surname>Shivdasani</surname><given-names>MN</given-names></name><name><surname>Fong</surname><given-names>N</given-names></name><name><surname>Duan</surname><given-names>W</given-names></name><name><surname>Esrafilzadeh</surname><given-names>D</given-names></name><name><surname>Poole-Warren</surname><given-names>LA</given-names></name><name><surname>Aregueta Robles</surname><given-names>UA</given-names></name></person-group><year iso-8601-date="2024">2024</year><article-title>Deciphering platinum dissolution in neural stimulation electrodes: Electrochemistry or biology?</article-title><source>Biomaterials</source><volume>309</volume><elocation-id>122575</elocation-id><pub-id pub-id-type="doi">10.1016/j.biomaterials.2024.122575</pub-id><pub-id pub-id-type="pmid">38677220</pub-id></element-citation></ref><ref id="bib34"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shepherd</surname><given-names>RK</given-names></name><name><surname>Carter</surname><given-names>PM</given-names></name><name><surname>Dalrymple</surname><given-names>AN</given-names></name><name><surname>Enke</surname><given-names>YL</given-names></name><name><surname>Wise</surname><given-names>AK</given-names></name><name><surname>Nguyen</surname><given-names>T</given-names></name><name><surname>Firth</surname><given-names>J</given-names></name><name><surname>Thompson</surname><given-names>A</given-names></name><name><surname>Fallon</surname><given-names>JB</given-names></name></person-group><year iso-8601-date="2021">2021</year><article-title>Platinum dissolution and tissue response following long-term electrical stimulation at high charge densities</article-title><source>Journal of Neural Engineering</source><volume>18</volume><elocation-id>036021</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2552/abe5ba</pub-id><pub-id pub-id-type="pmid">33578409</pub-id></element-citation></ref><ref id="bib35"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simeral</surname><given-names>JD</given-names></name><name><surname>Kim</surname><given-names>SP</given-names></name><name><surname>Black</surname><given-names>MJ</given-names></name><name><surname>Donoghue</surname><given-names>JP</given-names></name><name><surname>Hochberg</surname><given-names>LR</given-names></name></person-group><year iso-8601-date="2011">2011</year><article-title>Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array</article-title><source>Journal of Neural Engineering</source><volume>8</volume><elocation-id>025027</elocation-id><pub-id pub-id-type="doi">10.1088/1741-2560/8/2/025027</pub-id><pub-id pub-id-type="pmid">21436513</pub-id></element-citation></ref><ref id="bib36"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Suner</surname><given-names>S</given-names></name><name><surname>Fellows</surname><given-names>MR</given-names></name><name><surname>Vargas-Irwin</surname><given-names>C</given-names></name><name><surname>Nakata</surname><given-names>GK</given-names></name><name><surname>Donoghue</surname><given-names>JP</given-names></name></person-group><year iso-8601-date="2005">2005</year><article-title>Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex</article-title><source>IEEE Transactions on Neural Systems and Rehabilitation Engineering</source><volume>13</volume><fpage>524</fpage><lpage>541</lpage><pub-id pub-id-type="doi">10.1109/TNSRE.2005.857687</pub-id><pub-id pub-id-type="pmid">16425835</pub-id></element-citation></ref><ref id="bib37"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sweet</surname><given-names>WH</given-names></name></person-group><year iso-8601-date="1953">1953</year><article-title>Unipolar anodal electrolytic lesions in the brain of man and cat: Report of five human cases with electrically produced bulbar or mesencephalic tractotomies</article-title><source>A.M.A. Archives of Neurology &amp; Psychiatry</source><volume>70</volume><elocation-id>224</elocation-id><pub-id pub-id-type="doi">10.1001/archneurpsyc.1953.02320320090007</pub-id><pub-id pub-id-type="pmid">13795961</pub-id></element-citation></ref><ref id="bib38"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tehovnik</surname><given-names>EJ</given-names></name><name><surname>Tolias</surname><given-names>AS</given-names></name><name><surname>Sultan</surname><given-names>F</given-names></name><name><surname>Slocum</surname><given-names>WM</given-names></name><name><surname>Logothetis</surname><given-names>NK</given-names></name></person-group><year iso-8601-date="2006">2006</year><article-title>Direct and indirect activation of cortical neurons by electrical microstimulation</article-title><source>Journal of Neurophysiology</source><volume>96</volume><fpage>512</fpage><lpage>521</lpage><pub-id pub-id-type="doi">10.1152/jn.00126.2006</pub-id><pub-id pub-id-type="pmid">16835359</pub-id></element-citation></ref><ref id="bib39"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Townsend</surname><given-names>G</given-names></name><name><surname>Peloquin</surname><given-names>P</given-names></name><name><surname>Kloosterman</surname><given-names>F</given-names></name><name><surname>Hetke</surname><given-names>JF</given-names></name><name><surname>Leung</surname><given-names>LS</given-names></name></person-group><year iso-8601-date="2002">2002</year><article-title>Recording and marking with silicon multichannel electrodes</article-title><source>Brain Research. Brain Research Protocols</source><volume>9</volume><fpage>122</fpage><lpage>129</lpage><pub-id pub-id-type="doi">10.1016/s1385-299x(02)00139-3</pub-id><pub-id pub-id-type="pmid">12034331</pub-id></element-citation></ref><ref id="bib40"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vyas</surname><given-names>S</given-names></name><name><surname>Golub</surname><given-names>MD</given-names></name><name><surname>Sussillo</surname><given-names>D</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name></person-group><year iso-8601-date="2020">2020</year><article-title>Computation through neural population dynamics</article-title><source>Annual Review of Neuroscience</source><volume>43</volume><fpage>249</fpage><lpage>275</lpage><pub-id pub-id-type="doi">10.1146/annurev-neuro-092619-094115</pub-id><pub-id pub-id-type="pmid">32640928</pub-id></element-citation></ref><ref id="bib41"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Willett</surname><given-names>FR</given-names></name><name><surname>Kunz</surname><given-names>EM</given-names></name><name><surname>Fan</surname><given-names>C</given-names></name><name><surname>Avansino</surname><given-names>DT</given-names></name><name><surname>Wilson</surname><given-names>GH</given-names></name><name><surname>Choi</surname><given-names>EY</given-names></name><name><surname>Kamdar</surname><given-names>F</given-names></name><name><surname>Glasser</surname><given-names>MF</given-names></name><name><surname>Hochberg</surname><given-names>LR</given-names></name><name><surname>Druckmann</surname><given-names>S</given-names></name><name><surname>Shenoy</surname><given-names>KV</given-names></name><name><surname>Henderson</surname><given-names>JM</given-names></name></person-group><year iso-8601-date="2023">2023</year><article-title>A high-performance speech neuroprosthesis</article-title><source>Nature</source><volume>620</volume><fpage>1031</fpage><lpage>1036</lpage><pub-id pub-id-type="doi">10.1038/s41586-023-06377-x</pub-id><pub-id pub-id-type="pmid">37612500</pub-id></element-citation></ref><ref id="bib42"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Woeppel</surname><given-names>K</given-names></name><name><surname>Hughes</surname><given-names>C</given-names></name><name><surname>Herrera</surname><given-names>AJ</given-names></name><name><surname>Eles</surname><given-names>JR</given-names></name><name><surname>Tyler-Kabara</surname><given-names>EC</given-names></name><name><surname>Gaunt</surname><given-names>RA</given-names></name><name><surname>Collinger</surname><given-names>JL</given-names></name><name><surname>Cui</surname><given-names>XT</given-names></name></person-group><year iso-8601-date="2021">2021</year><article-title>Explant analysis of utah electrode arrays implanted in human cortex for brain-computer-interfaces</article-title><source>Frontiers in Bioengineering and Biotechnology</source><volume>9</volume><elocation-id>759711</elocation-id><pub-id pub-id-type="doi">10.3389/fbioe.2021.759711</pub-id><pub-id pub-id-type="pmid">34950640</pub-id></element-citation></ref><ref id="bib43"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yi</surname><given-names>D</given-names></name><name><surname>Yao</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Chen</surname><given-names>L</given-names></name></person-group><year iso-8601-date="2022">2022</year><article-title>Manufacturing processes of implantable microelectrode array for in vivo neural electrophysiological recordings and stimulation: a state-of-the-art review</article-title><source>Journal of Micro- and Nano-Manufacturing</source><volume>10</volume><elocation-id>041001</elocation-id><pub-id pub-id-type="doi">10.1115/1.4063179</pub-id><pub-id pub-id-type="pmid">37860671</pub-id></element-citation></ref></ref-list></back><sub-article article-type="editor-report" id="sa0"><front-stub><article-id pub-id-type="doi">10.7554/eLife.106452.3.sa0</article-id><title-group><article-title>eLife Assessment</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xiaomo</given-names></name><role specific-use="editor">Reviewing Editor</role><aff><institution>University of California, Davis</institution><country>United States</country></aff></contrib></contrib-group><kwd-group kwd-group-type="evidence-strength"><kwd>Solid</kwd></kwd-group><kwd-group kwd-group-type="claim-importance"><kwd>Useful</kwd></kwd-group></front-stub><body><p>This <bold>useful</bold> manuscript addresses a stability issue for long-term chronically implanted array recordings and electrolytic lesioning, which is relevant to both basic science and translational research. The authors provide a systematic scanning electron microscopy (SEM) of explanted arrays, evaluating electrode damage and sharing extensive datasets accessible through interactive plots. The strength of the evidence is <bold>solid</bold>, but it can be improved by performing additional analyses on complementary neurophysiology, functional, or histological data.</p></body></sub-article><sub-article article-type="referee-report" id="sa1"><front-stub><article-id pub-id-type="doi">10.7554/eLife.106452.3.sa1</article-id><title-group><article-title>Reviewer #1 (Public review):</article-title></title-group><contrib-group><contrib contrib-type="author"><anonymous/><role specific-use="referee">Reviewer</role></contrib></contrib-group></front-stub><body><p>Summary:</p><p>This work presents a GUI with SEM images of 8 Utah arrays (8 of which were explanted, and 4 of which were used for creating cortical lesions).</p><p>Strengths:</p><p>Visual comparison of electrode tips with SEM images, showing that electrolytic lesioning did not appear to cause extra damage to electrodes.</p><p>Weaknesses:</p><p>Given that the analysis was conducted on explanted arrays, and no functional or behavioural in-vivo data or histological data are provided, any damage to the arrays may have occurred after explantation, making the results limited and inconclusive (firstly, that there was no significant relationship between degree of electrode damage and use of electrolytic lesioning, and secondly, that electrodes closer to the edge of the arrays showed more damge than those in the center).</p><p>Overall, these results add new data and reference images to the field, although the insights that can conclusively be drawn are limited due to the low number of electrodes used and lack of in-vivo/ histological/ impedance data.</p></body></sub-article><sub-article article-type="author-comment" id="sa2"><front-stub><article-id pub-id-type="doi">10.7554/eLife.106452.3.sa2</article-id><title-group><article-title>Author response</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tor</surname><given-names>Alice</given-names></name><role specific-use="author">Author</role><aff><institution>Stanford University</institution><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Stephen E</given-names></name><role specific-use="author">Author</role><aff><institution>Stanford University</institution><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff></contrib><contrib contrib-type="author"><name><surname>Bray</surname><given-names>Iliana E</given-names></name><role specific-use="author">Author</role><aff><institution>Stanford University</institution><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff></contrib><contrib contrib-type="author"><name><surname>Nuyujukian</surname><given-names>Paul</given-names></name><role specific-use="author">Author</role><aff><institution>Stanford University</institution><addr-line><named-content content-type="city">Stanford</named-content></addr-line><country>United States</country></aff></contrib><contrib contrib-type="author"><name><surname>Interfacing Laboratory</surname><given-names>Brain</given-names></name><role specific-use="author">Author</role><aff><institution>Stanford University</institution><addr-line><named-content content-type="city">STANFORD</named-content></addr-line><country>United States</country></aff></contrib></contrib-group></front-stub><body><p>The following is the authors’ response to the original reviews.</p><disp-quote content-type="editor-comment"><p><bold>Public Reviews:</bold></p><p><bold>Reviewer #1 (Public review):</bold></p><p>Summary:</p><p>This work presents a GUI with SEM images of 8 Utah arrays (8 of which were explanted, and 4 of which were used for creating cortical lesions).</p><p>Strengths:</p><p>Visual comparison of electrode tips with SEM images, showing that electrolytic lesioning did not appear to cause extra damage to electrodes.</p><p>Weaknesses:</p><p>Given that the analysis was conducted on explanted arrays, and no functional or behavioural in vivo data or histological data are provided, any damage to the arrays may have occurred after explantation. This makes the results limited and inconclusive (firstly, that there was no significant relationship between degree of electrode damage and use of electrolytic lesioning, and secondly, that electrodes closer to the edge of the arrays showed more damage than those in the center).</p></disp-quote><p>We agree insofar as we could not fully control the circumstances of each array during explantation. However, array explantation is potentially damaging, but not universally damaging, as demonstrated by some largely intact arrays in this paper. If electrolytic lesions were damaging to the array, they would be observed. All arrays examined in this paper were carefully stored as described in the paper. All analyses of this type require an explant surgery. Our conclusions remain as strong as any of the results of these analyses.</p><disp-quote content-type="editor-comment"><p>Overall, these results do not add new insight to the field, although they do add more data and reference images.</p></disp-quote><p>We respectfully disagree, as there is no extant SEM analysis on electrode arrays used for lesioning.</p><disp-quote content-type="editor-comment"><p><bold>Reviewer #2 (Public review):</bold></p><p>In this study, the authors used scanning electron microscopy (SEM) to image and analyze eleven Utah multielectrode arrays (including eight chronically implanted in four macaques). Four of the eight arrays had previously been used to deliver electrolytic lesions. Each intact electrode was scored in five damage categories. They found that damage disproportionately occurred to the outer edges of arrays. Importantly, the authors conclude that their electrolytic Lesioning protocol does not significantly increase material degradation compared to normal chronic use without lesion. Additionally, the authors have released a substantial public dataset of single-electrode SEM images of explanted Utah arrays. The paper is well-written and addresses an important stability issue for long-term chronically implanted array recordings and electrolytic lesioning, which is relevant to both basic science and translational research. By comparing lesioning and non-lesioning electrodes on the same array and within the same animal, the study effectively controls for confounds related to the animal and surgical procedures. The shared dataset, accessible via interactive plots, enhances transparency and serves as a valuable reference for future investigations. Below, we outline some major and minor concerns that could help improve the work.</p><p>Major concerns:</p><p>(1) Electrode impedance is a critical measurement to evaluate the performance of recording electrodes. It would be helpful if the authors could provide pre-explant and post-explant impedance values for each electrode alongside the five SEM damage scores. This would allow the readers to assess how well the morphological scores align with functional degradation.</p></disp-quote><p>We agree, electrode impedance is very important in determining electrode performance. However, due to the multi-year, multi-subject nature of this work, we unfortunately do not have this data.</p><disp-quote content-type="editor-comment"><p>(2) The lesion parameters differ across experiments and electrodes. It would be helpful if the authors could evaluate whether damage scores (and/or impedance changes) correlate with total charge, current amplitude, duration, or frequency.</p></disp-quote><p>Thank you for this recommendation. We have included additional analyses in Supplementary Materials.</p><disp-quote content-type="editor-comment"><p><bold>Recommendations for the authors:</bold></p><p><bold>Reviewer #1 (Recommendations for the authors):</bold></p><p>(1) ‘Both in vitro and in vivo testing of electrode arrays revealed environmental damage to these materials, such as cracking, textural defects, and degradation in response to the brain’s temperature and salinity [32]. The immune response of the brain also damages the electrodes due to effects like glial scarring (gliosis) and inflammation [33, 34]. This damage may be exacerbated by the surgical techniques used during implantation, which include pushing the electrode array into cortex and tethering the implant to the skull [33, 35, 36].’</p><p>In the above text, several relevant references have been left out, e.g.:</p><p>Barrese et al., 2013</p><p>Patel et al., 2023</p><p>Woeppel et al, 2021</p><p>Chen et al., 2023</p><p>Bjanes et al., 2025</p></disp-quote><p>Thank you for this recommendation. This section has been updated.</p><disp-quote content-type="editor-comment"><p>(2) ‘Aggressive electrical stimulation is known to dissolve platinum-based electrodes [37, 38]. Other studies have shown iridium oxide to be more resistant to stimulation-related damage, but not completely insusceptible [39, 40].’ Reference number 25 is relevant here.</p></disp-quote><p>Thank you for this recommendation. This section has been updated.</p><disp-quote content-type="editor-comment"><p>(3) ‘F’s and C’s PMd arrays were used for electrolytic lesioning experiments Monkey U was implanted with three 96-channel arrays; two in M1 and one in PMd.’ There seems to be a punctuation mark missing.</p></disp-quote><p>Thank you for this recommendation. This section has been updated.</p><disp-quote content-type="editor-comment"><p>(4) Methods: How much charge was injected via the electrodes that were used for lesioning? What current amplitudes, voltages, durations, and number of pulses were used? If more than 1 pulse was applied, what were the frequencies? Was the pulse cathode-only/ anode/only? What were the electrode impedance values at the time of stimulation? How many electrodes were used for lesioning at any given moment? How long after lesioning did the arrays remain in the tissue?</p></disp-quote><p>Thank you for your questions. An additional supplemental table (Supplemental Table 6) detailing specific NHP lesions parameters has been added. A summary of the lesion procedure (DC, bipolar, two electrodes at a time) has also been included in Methods. All arrays remained in the subject until explant, which ranged between hours (same-day lesion and explant) to several years. Further details on the lesioning procedure are available in citation [?]. Explant dates are available in Supplemental Table 1. Unfortunately, we do not have the impedance values at time of lesioning as this is not a measure we record frequently after implant, though we agree the data would be useful to have.</p><disp-quote content-type="editor-comment"><p>(5) Caption for Figure 1: ‘All array images are displayed with the wire bundle to the right side.’ I recommend adding this text from Figure 2 to the caption of Figure 1: ’electrode tips facing viewer’.</p></disp-quote><p>Thank you for this recommendation. This section has been updated.</p><disp-quote content-type="editor-comment"><p>(6) ‘Electrodes used for electrolytic lesioning are denoted with blue dots.’ Was stimulation carried out across all these electrodes simultaneously?</p></disp-quote><p>No, stimulation was not carried out across all electrode simultaneously. Pairs of electrodes were stimulated at the same time to create lesions. Lesions were performed on different days. We have updated our methods section to reflect this. See the Methods section and citation [?] for more details.</p><disp-quote content-type="editor-comment"><p>(7) For the control array, in Figure 1: ‘Click each column to view a close-up of the 5th row (from top to bottom) of electrodes:’ . It would be clearer to state: ’Click each column to view a close-up of a single electrode in the 5th row (from top to bottom):’.</p></disp-quote><p>Thank you for this recommendation. This section has been updated.</p><disp-quote content-type="editor-comment"><p>(8) Figure 2 caption: ‘Blank electrodes and electrodes with shank fractures are ignored and displayed in black, as they are not scored.’. What is a ‘blank’ electrode?</p></disp-quote><p>A ‘blank’ electrode is an electrode on the array that physically exists but is not wire bonded at time of manufacture to produce recordings. The corner electrodes of the Utah array are all blank electrodes. We have updated this wording to ‘unwired’ for clarity.</p><disp-quote content-type="editor-comment"><p>(9) I recommend incorporating Supplementary Figure 1 into Figure 2, so that the reader can immediately see where the rings are, without referring to the Supplementary Materials.</p></disp-quote><p>Thank you for this recommendation. We have chosen to keep these figures separate for stylistic reasons.</p><disp-quote content-type="editor-comment"><p>(10) Supplementary Figures: The figures should have the word ’Supplementary’ in the title, i.e., ‘Supplementary Figure X,’ not just ‘Figure X.’</p></disp-quote><p>Thank you for this recommendation. These captions have been updated.</p><disp-quote content-type="editor-comment"><p>(11) Throughout the results, the text is overly focused on the type of statistical test used and the p-values, e.g.: ‘When comparing lesioning and non-lesioning electrodes within the same array, each of the two nonparametric statistical tests (Mann-Whitney U-test, Levene Test) returned insignificant p-values for each category of damage as well as for total damage scores for all four arrays used in lesioning experiments.’.</p><p>To make the findings more digestible for the reader, the text should be rephrased in terms of whether the metrics being compared were significantly different or not. E.g.: ‘For each category of damage, as well as for the total damage score, no significant difference was found between electrodes that were or were not used for lesioning (either the mean or the variance of the scores).’.</p></disp-quote><p>Thank you for this recommendation. We have rephrased the text to reflect this note.</p><disp-quote content-type="editor-comment"><p>(12) ‘In Monkey H, the Mann-Whitney U test resulted in an insignificant p-value for coating cracks and parylene C delamination scores, while the Levene test resulted in an insignificant p-value for abnormal debris, coating cracks, and parylene C cracking scores. In Monkey F, the Mann-Whitney U test resulted in an insignificant p-value for parylene C delamination scores, while the Levene test resulted in an insignificant p-value for coating cracks, parylene C delamination, and parylene C cracking scores. In Monkey U, the Mann-Whitney U test resulted in significant p-values for all scores, while the Levene test resulted in an insignificant p-value for abnormal debris, tip breakage, and coating cracks scores. Finally, in Monkey C, the Mann-Whitney U test resulted in an insignificant p-value for parylene C delamination and parylene C cracking scores, while the Levene test resulted in an insignificant p-value for abnormal debris, parylene C delamination, and parylene C cracking scores.’</p><p>To point out another example, this chunk of text is highly repetitive and is unnecessary, as the reader can simply refer to Supplementary Table 4. It should be completely rephrased and summarized, to deliver the key message, i.e. briefly describe what kinds of damage occurred for which arrays. Also, what is the point of the two statistical tests? What are the authors trying to conclude?</p></disp-quote><p>Thank you for this recommendation. We have rephrased and pared down the text to reflect this note.</p><disp-quote content-type="editor-comment"><p>(13) Discussion: ‘Similarly, other work did not show significant differences in SEM-visible degradation between both platinum and iridium oxide coated electrodes used for stimulation [24, 25].’ What differences are being referred to here? Differences in degradation between stimulated Pt versus stimulated IrOx electrodes? Or between stimulated Pt and unstimulated PT electrodes? Stimulated IrOx and unstimulated IrOx? Or something else?</p></disp-quote><p>Thank you for your questions. We are comparing platinum against iridium oxide in this sentence. The wording of our original text has been updated to clarify our intention.</p><disp-quote content-type="editor-comment"><p>(14) Supplementary Tables: P-values lower than .05, .01, and .001 should simply be replaced with ¡.05, ¡.01, and ¡.001. The alpha value after a Bonferroni correction should be stated somewhere in each table or table caption.</p></disp-quote><p>Thank you for this recommendation. We have edited the tables to reflect this note.</p><disp-quote content-type="editor-comment"><p>(15) Title: ‘Material Damage to Multielectrode Arrays after Electrolytic Lesioning is in the Noise’ I don’t understand what the title means. What is in the noise? And what is ‘the noise’?</p></disp-quote><p>“In the noise” is a colloquialism referring to how background information (“noise”) may obscure or distract from other features. This title conveys how material damage to multielectrode arrays due to electrolytic lesioning is largely obscured by the general damage observed on multielectrode arrays after implant and explant.</p><disp-quote content-type="editor-comment"><p>(16) This reference has been left out altogether: Chen et al., 2014. The effect of chronic intracortical microstimulation on the electrode-tissue interface.</p></disp-quote><p>Thank you, this reference is now included.</p><disp-quote content-type="editor-comment"><p><bold>Reviewer #2 (Recommendations for the authors):</bold></p><p>(1) The number of lesion electrodes is low, especially since there are only 2-10 lesion electrodes on three of the four arrays, yielding limited statistical power.</p></disp-quote><p>We agree that the low number of lesioned electrodes limits statistical power. However, due to ethical considerations, it is unlikely for arrays to contain much more than this number of lesion electrodes.</p><disp-quote content-type="editor-comment"><p>(2) The dataset includes both platinum and iridium oxide-coated electrodes. A direct comparison of their damage profiles would be informative.</p></disp-quote><p>Thank you for this recommendation. We have included this additional analysis in Supplementary Materials.</p><disp-quote content-type="editor-comment"><p>(3) It is unclear what “is in the Noise” in the title means without reading the manuscript. It is helpful to improve the clarity of the title.</p></disp-quote><p>Thank you for this recommendation.</p><disp-quote content-type="editor-comment"><p>(4) Please spell out “PMd” and “M1” at first mention to facilitate reading.</p></disp-quote><p>Thank you for this note. The text has been updated to reflect this recommendation.</p></body></sub-article></article>