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Word\u2010finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word\u2010finding difficulty in patients, and if so, through which cognitive mechanism(s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010three patients undergoing intracranial monitoring for drug\u2010resistant epilepsy participated in multiple tasks involving word production (auditory naming, short\u2010term verbal free recall, repetition) to probe word\u2010finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed\u2010effects models. We also evaluated for subjective word\u2010finding difficulties through retrospective chart review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Subjective word\u2010finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long\u2010term lexicosemantic memory impairments as indexed by auditory naming (<jats:italic>p<\/jats:italic>\u2009=\u2009.009), in addition to their established impact on short\u2010term verbal memory as indexed by free recall (<jats:italic>p<\/jats:italic>\u2009=\u2009.004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (<jats:italic>p<\/jats:italic>\u2009=\u2009.016 and <jats:italic>p<\/jats:italic>\u2009=\u2009.018), as well as phonological working memory impairments as indexed by repetition reaction time (<jats:italic>p<\/jats:italic>\u2009=\u2009.002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word\u2010finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17781","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T11:15:14Z","timestamp":1695813314000},"page":"3266-3278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Interictal epileptiform discharges contribute to word\u2010finding difficulty in epilepsy through multiple cognitive mechanisms"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-4136","authenticated-orcid":false,"given":"Alexander B.","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Weill Institute of Neurosciences University of California, San Francisco  San Francisco CA USA"},{"name":"Medical Scientist Training Program University of California, San Francisco  San Francisco CA USA"},{"name":"University of California, Berkeley \u2010 University of California, San Francisco Graduate Program in Bioengineering  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew K.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Weill Institute of Neurosciences University of California, San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Oganian","sequence":"additional","affiliation":[{"name":"Center for Integrative Neuroscience University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"D'Esopo","sequence":"additional","affiliation":[{"name":"Department of Neurology Weill Institute of Neurosciences, University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Krish","sequence":"additional","affiliation":[{"name":"Department of Neurology Weill Institute of Neurosciences, University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Kopald","sequence":"additional","affiliation":[{"name":"Department of Neurology Weill Institute of Neurosciences, University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina B.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Neurology Weill Institute of Neurosciences, University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Weill Institute of 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