{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:04:51Z","timestamp":1789362291918,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Integrated molecular profiling has revolutionized brain tumor classification, but its ability to explain preoperative cognitive-emotional phenotypes in glioma patients relative to traditional anatomical factors remains unclear. This study investigated whether molecular features interact with tumor location to influence neuropsychological status, and whether such effects are anatomically context-dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 101 newly diagnosed glioma patients and 52 matched healthy controls. All participants underwent comprehensive neuropsychological assessments. Using a hierarchical strategy, we first stratified patients by tumor location, then examined associations of molecular characteristics and clinical factors with cognitive-emotional measures within each anatomical subgroup. Finally, multivariable regression analyses with formal interaction terms were performed in the entire cohort to test molecular-location interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No significant differences in cognitive or emotional function were observed between patients with deep insular versus superficial frontal-temporal\u2013parietal tumors. However, within the deep insular subgroup, IDH mutation remained associated with distinct patterns of emotional and attentional function after correction for multiple comparisons. Within the superficial frontal subgroup, tumor grade and several specific molecular features showed domain-specific associations with empathy or working memory. Critically, multivariable regression confirmed significant molecular-location interactions: IDH\u202f\u00d7\u202finsular for negative affect and attentional control; grade \u00d7 frontal and TERT \u00d7 frontal for empathy; and 1p\/19q\u202f\u00d7\u202ffrontal for working memory. These findings indicate that molecular features and tumor location interact to explain neuropsychological outcomes more effectively than either factor alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Molecular influences on preoperative cognitive-emotional status in glioma are anatomically context-dependent. Molecular features and tumor location interact to shape neuropsychological outcomes, supporting an integrated framework that incorporates both molecular and anatomical information into preoperative evaluation and personalized management strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1845406","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:36:34Z","timestamp":1789360594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular features and tumor location interact to account for preoperative cognitive-emotional status in glioma"],"prefix":"10.3389","volume":"17","author":[{"given":"Yehong","family":"Fang","sequence":"first","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangsheng","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Psychological and Cognitive Sciences and Mental Health, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Xu","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebral Blood Flow Reconstruction and Head and Neck Tumor New Technology Translation, Tianjin Neurosurgical Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yan","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebral Blood Flow Reconstruction and Head and Neck Tumor New Technology Translation, Tianjin Neurosurgical Institute","place":["Tianjin, China"]},{"name":"The Fourth Central Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41571-019-0177-5","article-title":"Challenges to curing primary brain tumours","volume":"16","author":"Aldape","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1097\/WCO.0000000000001427","article-title":"Characterization, etiology, and management of neurocognitive impairment in patients with glioma: an evidentiary update","volume":"38","author":"Noll","year":"2025","journal-title":"Curr Opin Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"807","DOI":"10.3390\/cancers15030807","article-title":"Presurgical executive functioning in low-grade glioma patients cannot be topographically mapped","volume":"15","author":"Landers","year":"2023","journal-title":"Cancers"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1126\/science.1896849","article-title":"The medial temporal lobe memory system","volume":"253","author":"Squire","year":"1991","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"108599","DOI":"10.1016\/j.neuropsychologia","article-title":"Parietal\/premotor lesions effects on visuomotor cognition in neuro-oncology patients: a multimodal study","volume":"186","author":"Tomasino","year":"2023","journal-title":"Neuropsychologia"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1382380","DOI":"10.3389\/fnhum.2024.1382380","article-title":"What is the cognitive footprint of insular glioma?","volume":"18","author":"Nichols","year":"2024","journal-title":"Front Hum Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1007\/s13311-017-0519-x","article-title":"Glioma subclassifications and their clinical significance","volume":"14","author":"Chen","year":"2017","journal-title":"Neurotherapeutics"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s12031-023-02173-4","article-title":"Molecular determinants of neurocognitive deficits in glioma: based on 2021 WHO classification","volume":"74","author":"Zhang","year":"2024","journal-title":"J Mol Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1093\/nop\/npac077","article-title":"Association between preoperative neurocognitive status and IDH1 mutation status in high-grade gliomas","volume":"10","author":"Liouta","year":"2022","journal-title":"Neuro-oncol Pract"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/s11912-020-00978-9","article-title":"Isocitrate dehydrogenase, patient-reported outcomes, and cognitive functioning of glioma patients: a systematic review","volume":"22","author":"Bunevicius","year":"2020","journal-title":"Curr Oncol Rep"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1093\/nop\/npz008","article-title":"Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a retrospective cohort study prior to antitumor treatment","volume":"6","author":"van Kessel","year":"2019","journal-title":"Neurooncol Pract"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0028-3932(71)90067-4","article-title":"The assessment and analysis of handedness: the Edinburgh inventory","volume":"9","author":"Oldfield","year":"1971","journal-title":"Neuropsychologia"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"10502","DOI":"10.1038\/s41598-022-13739-4","article-title":"Ellipsoid calculations versus manual tumor delineations for glioblastoma tumor volume evaluation","volume":"12","author":"Le Fevre","year":"2022","journal-title":"Sci Rep"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive stateof patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1038\/nprot.2006.390","article-title":"Administration and interpretation of the trail making test","volume":"1","author":"Bowie","year":"2006","journal-title":"Nat Protoc"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1212\/wnl.55.11.1621","article-title":"The FAB: a frontal assessment battery at bedside","volume":"55","author":"Dubois","year":"2000","journal-title":"Neurology"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1037\/h0047235","article-title":"Revised administration and scoring of the digit span test","volume":"21","author":"Blackburn","year":"1957","journal-title":"J Consult Psychol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1037\/\/0021-843x.111.2.225","article-title":"Anxiety-related attentional biases and their regulation by attentional control","volume":"111","author":"Derryberry","year":"2002","journal-title":"J Abnorm Psychol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch Gen Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.20448341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br J Med Psychol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1037\/\/0022-3514.54.6.1063","article-title":"Development and validation of brief measures of positive and negative affect: the PANAS scales","volume":"54","author":"Watson","year":"1988","journal-title":"J Pers Soc Psychol"},{"key":"ref23","first-page":"85","article-title":"A multidimensional approach to individual differences in empathy","volume":"10","author":"Davis","year":"1980","journal-title":"J Pers Soc Psychol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1037\/0022-3514.44.1.113","article-title":"Measuring individual differences in empathy: evidence for a multidimensional approach","volume":"44","author":"Davis","year":"1983","journal-title":"J Pers Soc Psychol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.5498\/wjp.v14.i8.1190","article-title":"Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction","volume":"14","author":"Liang","year":"2024","journal-title":"World J Psychiatry"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/4056436","article-title":"Role of functional imaging techniques to assess motor and language cortical plasticity in glioma patients: a systematic review","volume":"2019","author":"Cirillo","year":"2019","journal-title":"Neural Plast"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"vdae112","DOI":"10.1093\/noajnl\/vdae112","article-title":"Unraveling glioblastoma diversity: insights into methylation subtypes and spatial relationships","volume":"6","author":"Foltyn-Dumitru","year":"2024","journal-title":"Neurooncol Adv"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e01204","DOI":"10.1002\/brb3.1204","article-title":"Understanding cognitive functioning in glioma patients: the relevance of IDH-mutation status and functional connectivity","volume":"9","author":"Derks","year":"2019","journal-title":"Brain Behav"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s11060-023-04289-4","article-title":"Cognitive issues in patients with IDH mutant gliomas: from neuroscience to clinical neuropsychology","volume":"162","author":"Parsons","year":"2023","journal-title":"J Neuro-Oncol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"962","DOI":"10.3758\/s13415-016-0445-0","article-title":"Multidimensional assessment of empathic abilities in patients with insular glioma","volume":"16","author":"Chen","year":"2016","journal-title":"Cogn Affect Behav Neurosci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"636573","DOI":"10.3389\/fneur.2021.636573","article-title":"Contralesional structural plasticity in different molecular pathologic subtypes of insular glioma","volume":"12","author":"Huang","year":"2021","journal-title":"Front Neurol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e2969","DOI":"10.1002\/brb3.2969","article-title":"Structural alterations of the salience network in patients with insular glioma","volume":"13","author":"Hu","year":"2023","journal-title":"Brain Behav"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1017\/S0140525X11000446","article-title":"The brain basis of emotion: a meta-analytic review","volume":"35","author":"Lindquist","year":"2012","journal-title":"Behav Brain Sci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"8755","DOI":"10.2147\/CMAR.S336213","article-title":"Clinical and prognostic implications of 1p\/19q, IDH, BRAF, MGMT promoter, and TERT promoter alterations, and expression of Ki-67 and p53 in human gliomas","volume":"13","author":"Yang","year":"2021","journal-title":"Cancer Manag Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e70358","DOI":"10.1002\/hbm","article-title":"Connectome-based predictive models of general and specific executive functions","volume":"46","author":"Qu","year":"2025","journal-title":"Hum Brain Mapp"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"7110","DOI":"10.1523\/JNEUROSCI.0443-22.2022","article-title":"Common neural mechanisms control attention and working memory","volume":"42","author":"Zhou","year":"2022","journal-title":"J Neurosci"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s00432-021-03536-3","article-title":"Human TERT promoter mutations as a prognostic biomarker in glioma","volume":"147","author":"Powter","year":"2021","journal-title":"J Cancer Res Clin Oncol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"5618","DOI":"10.18632\/aging.205668","article-title":"Predicting the prognosis of glioma patients with TERT promoter mutations and guiding the specific immune profile of immune checkpoint blockade therapy","volume":"16","author":"Cao","year":"2024","journal-title":"Aging"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1544632","DOI":"10.3389\/fpsyt.2025.1544632","article-title":"The neurostructural bases of empathy: morphometric evidence for a multicomponential approach","volume":"16","author":"Arioli","year":"2025","journal-title":"Front Psych"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13293-024-00621-3","article-title":"Differently different?: a commentary on the emerging social cognitive neuroscience of female autism","volume":"15","author":"Rippon","year":"2024","journal-title":"Biol Sex Differ"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s00429-010-0262-0","article-title":"Saliency, switching, attention and control: a network model of insula function","volume":"214","author":"Menon","year":"2010","journal-title":"Brain Struct Funct"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"104736","DOI":"10.1016\/j.neubiorev.2022.104736","article-title":"Anterior insula as a gatekeeper of executive control","volume":"139","author":"Molnar-Szakacs","year":"2022","journal-title":"Neurosci Biobehav Rev"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"103689","DOI":"10.1016\/j.nicl.2024.103689","article-title":"Exploring cognitive landscapes: longitudinal dynamics of left insula gliomas using neuropsychological inquiry, fMRI, and intra-resection real time neuropsychological testing","volume":"44","author":"Cargnelutti","year":"2024","journal-title":"Neuroimage Clin"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"916771","DOI":"10.3389\/fnins.2022.916771","article-title":"Altered structural and functional patterns within executive control network distinguish frontal glioma-related epilepsy","volume":"16","author":"Di","year":"2022","journal-title":"Front Neurosci"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/j.1528-1167.2009.02195.x","article-title":"Patients with epilepsy: cognitively compromised before the start of antiepileptic drug treatment?","volume":"51","author":"Taylor","year":"2010","journal-title":"Epilepsia"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.yebeh.2010.05.007","article-title":"Newly diagnosed epilepsy: cognitive outcome at 5 years","volume":"18","author":"Taylor","year":"2010","journal-title":"Epilepsy Behav"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e2560","DOI":"10.1002\/brb3.2560","article-title":"Presurgical cognitive status in patients with low-grade glioma and epilepsy: testing the effects of seizures, antiseizure medications, and tumor localization","volume":"12","author":"Guarracino","year":"2022","journal-title":"Brain Behav"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s00701-016-2786-4","article-title":"Preoperative neuropsychological presentation of patients with refractory frontal lobe epilepsy","volume":"158","author":"Patrikelis","year":"2016","journal-title":"Acta Neurochir"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fneur.2015.00137","article-title":"Neurological impairment linked with cortico-subcortical infiltration of diffuse low-grade gliomas at initial diagnosis supports early brain plasticity","volume":"6","author":"Smits","year":"2015","journal-title":"Front Neurol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"111415","DOI":"10.1016\/j.jocn.2025.111415","article-title":"Structural and functional connectomic analysis of high-grade gliomas: a systematic review","volume":"139","author":"Burrington","year":"2025","journal-title":"J Clin Neurosci"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"934","DOI":"10.3390\/bs15070934","article-title":"A quantitative review of brain activation maps for Mentalizing, empathy, and social interactions: specifying commonalities and differences","volume":"15","author":"Kranewitter","year":"2025","journal-title":"Behav Sci"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1017\/9781009342919.031","volume-title":"The Cambridge Handbook of Human Affective Neuroscience","author":"Matthaeus","year":"2025"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1845406\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:36:40Z","timestamp":1789360600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1845406\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":52,"alternative-id":["10.3389\/fneur.2026.1845406"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1845406","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]},"article-number":"1845406"}}