Repeating through the insula: evidence from two consecutive strokes Antonio Carota a , Jean-Marie Annoni a and Paola Marangolo b a Department of Neurology, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland and b Neuropsychology Research Center, IRCCS Fondazione Santa Lucia, Rome, Italy Correspondence to Dr Paola Marangolo, Centro Ricerche di Neuropsicologia, IRCCS Fondazione Santa Lucia, Via Ardeatina 306 00179 Rome, Italy Tel: + 390651501597; fax: + 390651501366; e-mail: p.marangolo@hsantalucia.it Received 27 March 2007; accepted17 May 2007 Mixed transcortical aphasia is a very rare syndrome characterized by intact repetition, despite severe impairment in all other lan- guage modalities. In some cases, however, preservation of repeti- tion is accompanied by intact reading. We report the case of a left-handed man who, after a subcortical stroke in the left hemi- sphere, showed the typical features of mixed transcortical aphasia with spared repetition and reading. After 10 days, a second stroke, involving the anterior insula and adjacent white matter bundles, markedly deteriorated repetition while his reading abilities recovered. By comparing features of repetition and reading before and after the second stroke, we provide evidence for the existence of a modular organization of language abilities, pointing to the primary role of the insula and surrounding white matter in phonological processing. NeuroReport 18:1367^1370  c 2007 Lippincott Williams & Wilkins. Keywords: arcuate fasciculus, insula, phonology, reading, repetition, transcortical aphasia Introduction Since Broca first reported an anatomoclinical correlation in the patient ‘Tan’ [1], several single case studies have highlighted the existence of double dissociations between different linguistic modalities. These dissociations gave rise to the well-known classification of the aphasia syndromes [2]. Mixed transcortical aphasia (MTA) is a rare syndrome, with less than 0.5% incidence in acute stroke [3], which is characterized by a marked dissociation between reduced speech, severe comprehension deficit, naming difficulties and intact or relatively spared repetition [4]. Another distinctive linguistic feature often reported with MTA is the unimpaired ability to read aloud despite a severe written comprehension deficit. This pattern of aphasic deficits distinguishes MTA from other transcortical aphasias in which comprehension (in motor transcortical aphasia) or fluent speech production (in sensorial transcortical aphasia) are maintained, although repetition is almost intact. Recently, the modern cognitive approach has considered the existence of these dissociations as evidence of a modular organization of language. Therefore, patients with MTA who show intact repetition and reading abilities, despite severe comprehension impairment, provide a unique opportunity to investigate how distinct functional neural modules process different language abilities. The existence of distinct and somehow independent language modules is hypothe- sized by the ‘triple route’ cognitive model [5] (Fig. 1), which describes the existence of a lexical-semantic pathway (first route) and two alternative routes for single word and nonword repetition and reading. The second route involves simple acoustic-to-phonological (for repetition) and graphemic-to-phonological (for reading) translation processes that allow repeating and reading pronounceable nonwords and new words, which do not yet have a stored phonological representation. The third route proposes a direct link between the auditory (or graphemic) input lexicon and the phonological output lexicon. With this route, therefore, pronunciation is achieved lexically, without the activation of meaning, explaining how some aphasic patients can read orthographically irregular words (whose representations are stored in the lexicon) without comprehending them and how they can repeat and read words better than nonwords [6,7]. Over the last two decades, developments in the area of functional neuroimaging have allowed deeper investigation of the neurological correlates of linguistic functions. However, most of these studies were performed on healthy participants [8–10], and there are very few reports of linguistic abilities and neuroanatomical correlations in aphasic patients in whom a second consecutive stroke induced selective changes of the initial aphasic symptom [11–13]. Here we report the performance of a 76-year-old French participant (G.P.) in various linguistic tasks. The patient was submitted to language assessment on two different occa- sions: immediately after a first subcortical stroke, when he showed the classical MTA features, and 10 days later, immediately after a second stroke in the anterior insula and surrounding white matter, when his repetition was mark- edly deteriorated and his reading improved. By analyzing the double dissociation between repetition and reading BRAIN IMAGING NEUROREPORT 0959-4965  c Lippincott Williams & Wilkins Vol18 No 13 27 August 2007 1367 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.