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However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the \u201clesion\u201d (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion\u2010symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion\u2010symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion\u2010symptom mapping at the acute stage of stroke addresses a different sort of question about brain\u2013behavior relationships than lesion\u2010symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. <jats:italic>Hum Brain Mapp 38:2990\u20133000, 2017<\/jats:italic>. \u00a9 <jats:bold>2017 Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.23567","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T05:06:50Z","timestamp":1489986410000},"page":"2990-3000","source":"Crossref","is-referenced-by-count":45,"title":["Important considerations in lesion\u2010symptom mapping: Illustrations from studies of word comprehension"],"prefix":"10.1002","volume":"38","author":[{"given":"Hinna","family":"Shahid","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland 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