{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:29:08Z","timestamp":1787077748734,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,14]]},"group-title":"Neuroscience","reference-count":19,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH-NCATS CTSA","award":["KL2 TR002379"],"award-info":[{"award-number":["KL2 TR002379"]}]},{"name":"NIH","award":["U01-NS128612"],"award-info":[{"award-number":["U01-NS128612"]}]},{"name":"NIH","award":["R01-MH122258"],"award-info":[{"award-number":["R01-MH122258"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Our approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - \u03b8 (axial) and \u03c6 (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate system\u2019s origin along the insular axis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17\u00b0 to 17\u00b0 in the axial plane (\u03b8) and 31\u00b0 to 69\u00b0 in the sagittal plane (\u03c6). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>As stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>SIGNIFICANCE STATEMENT<\/jats:title>\n                  <jats:p>\n                    The insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry \u2014 into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation \u2014 much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present \u201c\n                    <jats:italic>Insulotaxy<\/jats:italic>\n                    ,\u201d a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insula\u2019s unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.08.739317","type":"posted-content","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:20:11Z","timestamp":1786742411000},"source":"Crossref","is-referenced-by-count":0,"title":["Insulotaxy: Navigating the Human Insula with a Novel Stereotactic Framework"],"prefix":"10.64898","author":[{"given":"Panagiotis","family":"Kerezoudis","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA"},{"name":"Division of Neuroscience, Mayo Graduate School of Biomedical Sciences, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5191-7244","authenticated-orcid":false,"given":"Michael A","family":"Jensen","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan T.","family":"Klassen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Worrell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Gregg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuri F.","family":"Ince","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Mayo Graduate School of Biomedical Sciences, Rochester, MN, USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie J.","family":"Van Gompel","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Mayo Graduate School of Biomedical Sciences, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Mayo Graduate School of Biomedical Sciences, Rochester, MN, USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081811051217000_2026.08.08.739317v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.05.010"},{"key":"2026081811051217000_2026.08.08.739317v1.2","doi-asserted-by":"crossref","unstructured":"Vetkas A , Germann J , Boutet A , et al. 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