Clinical/Scientific Notes K. Lidzba, PhD M. Staudt, MD, PhD F. Zieske, MSc E. Schwilling, MA H. Ackermann, MD, PhD PRESTROKE/POSTSTROKE fMRI IN APHASIA: PERILESIONAL HEMODYNAMIC ACTIVATION AND LANGUAGE RECOVERY fMRI points to a contribution of left-hemisphere (LH) perilesional tissue and right-hemisphere (RH) homologues of the perisylvian “language zones” to aphasia recovery.1 Since, however, “language representation” may vary across individuals, both in terms of gyral topography and lateralization,2 the interpretation of poststroke fMRI data obtained in aphasic patients may face difficulties, e.g., in terms of a differentiation between hemodynamic responses of residual eloquent cortex and perilesional reorganization of tissue adjacent to perisylvian “language areas.” We had the extraordinary opportunity to compare fMRI data obtained during the same speech task prior to and after LH ischemic infarction— providing further insights into the development of perilesional hemodynamic responses. To our knowledge, this is the first prestroke/poststroke follow-up study in aphasia. Methods. Clinical history. At 33 years of age, the patient had participated as a healthy control subject in a language fMRI study (pre).3 Six years later, he experienced sudden right-sided hemiplegia and Broca aphasia. MRI revealed a large ischemic infarction within the territory of the left middle cerebral artery (figure, A). One year after stroke, the patient was re-examined (post), using the same design and measurement protocol (fMRI, neuropsychology). At post, the patient still had right-sided hemiparesis, but speech/language functions had almost entirely recovered, apart from slight apraxia of speech, occasional phonemic paraphasias, and word-finding difficulties, as documented by a certified clinical linguist (E.S.). Evaluation. Neuropsychological tests. HAWIE-R (German Wechsler Adult Intelligence Scale), Block Tapping Test (BTT),4 and semantic (VF-S) and phonemic (VF-P) verbal fluency were administered. Z transformation of test scores (reference frames: normative data [HAWIE-R] or data from 32 controls [18 –34 years]) was performed. (f)MRI. Anatomical and EPI datasets (pre/post: repetition time 8/3 s; acquisition time 4.87/3 s; voxel size 2 ⫻ 2 ⫻ 5/3 ⫻ 3 ⫻ 3 mm3; 27/36 slices) were acquired with 1.5-T Siemens scanners. Word-chain task. The patient silently generated continuous series of words, with each word starting with the final letter of the previous word. The task was delivered in 4 alternating activation and rest epochs (pre/post: 6/10 scans per epoch). Data analysis (SPM8). Realigned functional images were coregistered to the post fluid-attenuated inversion recovery (FLAIR) image in native space, smoothed (9 mm full width at half maximum), and subjected to firstlevel statistical analysis. To achieve comparable statistical power, pre sparse sampling was approximated by selecting only odd-numbered scans of the post dataset (qualitative visual inspection of T-maps, p ⬍ 0.005, false discovery rate). Approval of the local ethics review board and written informed consent of the patient had been obtained prior to pre and post investigations. Results. The frontal component of the activated LH network during silent word-chain generation displays nearly identical pre and post localizations, centered around posterior parts of the middle frontal gyrus, adjacent to the precentral convolution (figure, B and C). Concerning LH inferior-parietal cortex, pre hemodynamic responses were bound predominantly to an area later destroyed by ischemic infarction, but included also a smaller cluster inferior and posterior to the main activation site. At post investigation, the caudal-perisylvian response was centered around this second—now perilesional—focus of activity (figure, B and C). No significant RH hemodynamic activation emerged at either session. The figure, D, depicts pre/post comparison of the tests on verbal cognition. Nonverbal performance differed only in the subtests “Digit-Symbol-Coding” and “Object Assembly.” Discussion. Given the substantial improvement of the subject’s initial “motor aphasia,” the post frontal “activation spot” might be assumed to reflect perilesional reorganization, localized dorsal to Broca area. However, comparison with the intact prestroke language network reveals a, by and large, invariant frontal fMRI pattern across sessions, the pre and post activation peaks located only a few millimeters apart. A different distribution of pre and post hemodynamic responses emerged in the posterior perisylvian cortex: the activation focus had shifted from the Neurology 78 January 24, 2012 289 Figure Pre/post fMRI and neuropsychological data (A) Ischemic lesion at post follow-up investigation (axial fluid-attenuated inversion recovery [FLAIR] image). (B) Convergent frontal and divergent inferior-parietal activation (arrows) during word-chain task vs rest at pre (green) and post (red). (C) Three main activation peaks within individual space. (D) Z-transformed pre (green) and post (red) verbal test scores. Asterisks: pre/post difference ⬎1 SD. initial—now damaged—main activation site into perilesional tissue, which had displayed only a weak pre response. Given the neuropsychological follow-up data, obviously, these reorganizational processes did not allow for a full functional recovery of speech-based cognitive capacities. Nevertheless, 290 Neurology 78 January 24, 2012 significant recruitment of RH homologues could not be observed. First, these observations are in line with the notion of only a minor contribution of RH homologues of the LH “language zones” to later stages of aphasia recovery.1 Second, these findings provide evidence for a re-recruitment of original language ar- eas during the course of their full functional restoration.5 Finally, the obtained data corroborate a “systemic view” on brain plasticity in that single components of the “language network” may not be “transferred” in isolation to the opposite hemisphere. Data from patients with congenital LH stroke support this hypothesis: frontal RH language reorganization entails a shift of parietal and even cerebellar parts of the language network to the opposite side.6 Ministry of Science and the Arts, Baden Württemberg. Dr. Staudt serves as Executive Editor for Neuropediatrics. F. Zieske reports no disclosures. E. Schwilling has received research support from the German Research Foundation (Collaborative Research Center 833). Dr. Ackermann serves on the editorial board of Brain and Language. From the Departments of Pediatric Neurology (K.L., M.S., F.Z.) and Experimental Pediatric Neuroimaging (K.L.), University Children’s Hospital Tübingen, Tübingen; SFB 833 (K.L., E.S.) and Department of General Neurology, Hertie Institute for Clinical Brain Research (H.A.), University Tübingen, Tübingen; and Clinic for Neuropediatrics and Neurorehabilitation (M.S.), Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany. 1. Author contributions: Dr. Lidzba: study conceptualization (neuropsychology), collection and interpretation of neuropsychological data, analysis of fMRI data, drafting of the manuscript. E. Schwilling: study conceptualization (linguistics), collection and interpretation of linguistic data, revision of the manuscript. F. Zieske: collection and interpretation of neuropsychological and (f)MRI data, revision of the manuscript. Dr. Staudt: study conceptualization, collection and interpretation of neuropsychological and (f)MRI data, revision of the manuscript. Dr. Ackermann: interpretation of neuropsychological, linguistic, and (f)MRI data, revision of the manuscript. 3. Study funding: Part of the data were acquired in a DFG-funded project (SFB 550; C4); K.L. is supported by European Social Fund/ Ministry of Science, Research and the Arts Baden-Württemberg. 6. Disclosure: Dr. Lidzba has received research support from the European Social Fund, the German Research Foundation, and the Correspondence & reprint requests to Dr. Lidzba: Karen.lidzba@ med.uni-tuebingen.de Received July 11, 2011. Accepted in final form September 23, 2011. Copyright © 2012 by AAN Enterprises, Inc. 2. 4. 5. Saur D, Lange R, Baumgaertner A, et al. Dynamics of language reorganization after stroke. Brain 2006;129: 1371–1384. Seghier ML, Lazeyras F, Pegna AJ, et al. Variability of fMRI activation during a phonological and semantic language task in healthy subjects. Hum Brain Mapp 2004;23: 140 –155. Staudt M, Grodd W, Niemann G, Wildgruber D, Erb M, Krägeloh-Mann I. Early left periventricular brain lesions induce right hemispheric organization of speech. Neurology 2001;57:122–125. Schelling D. Block Tapping Test. Frankfurt: Swets Test Services; 1997. Fridriksson S. Preservation and modulation of specific left hemisphere regions is vital for treated recovery from anomia in stroke. J Neurosci 2010;30:11558 –11564. Lidzba K, Wilke M, Staudt M, Krägeloh-Mann I, Grodd W. Reorganization of the cerebro-cerebellar network of language production in patients with congenital left-hemispheric brain lesions. Brain Lang 2008;106: 204 –210. Neurologists Needed to Volunteer in Haiti The AAN is working with Operation Blessing International (OBI) to promote opportunities for neurologists to aid the victims of the January 2010 earthquake in Haiti. For one to two weeks, physician volunteers will care for patients with a variety of needs, and offer neurologic care when necessary. To learn more about the work of OBI and this unique volunteer program, visit www.ob.org/haitiprojects/volunteer.asp. Save These Dates for AAN CME Opportunities! Mark these dates on your calendar for exciting continuing education opportunities, where you can catch up on the latest neurology information. AAN Annual Meeting ● April 21–28, 2012, New Orleans, Louisiana, Morial Convention Center Neurology 78 January 24, 2012 291 Prestroke/poststroke fMRI in aphasia: Perilesional hemodynamic activation and language recovery K. Lidzba, M. Staudt, F. Zieske, et al. Neurology 2012;78;289-291 Published Online before print January 11, 2012 DOI 10.1212/WNL.0b013e318243679a This information is current as of January 11, 2012 Updated Information & Services including high resolution figures, can be found at: http://www.neurology.org/content/78/4/289.full.html Supplementary Material Supplementary material can be found at: http://www.neurology.org/content/suppl/2013/01/03/WNL.0b013e3182 43679a.DC1.html References This article cites 5 articles, 3 of which you can access for free at: http://www.neurology.org/content/78/4/289.full.html##ref-list-1 Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): All Cerebrovascular disease/Stroke http://www.neurology.org//cgi/collection/all_cerebrovascular_disease_ stroke Aphasia http://www.neurology.org//cgi/collection/aphasia fMRI http://www.neurology.org//cgi/collection/fmri Plasticity http://www.neurology.org//cgi/collection/plasticity Permissions & Licensing Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions Reprints Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus Neurology ® is the official journal of the American Academy of Neurology. 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