Prefrontalcortex rTMS enhances action naming in progressive non-fluent aphasia M. Cotelli a , R. Manenti a , A. Alberici b , M. Brambilla a , M. Cosseddu b , O. Zanetti a , A. Miozzo b , A. Padovani b , C. Miniussi a,c and B. Borroni b a IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia; b Centre for Aging Brain and Neurodegenerative Disorders, Neurology unit, University of Brescia, Brescia; and c Department of Biomedical Sciences and Biotechnologies, National Neuroscience Institute, University of Brescia, Brescia, Italy Keywords: language, non-invasive brain stimu- lation, Progressive non- fluent aphasia, semantic dementia, transcranial magnetic stimulation Received 9 August 2011 Accepted 9 February 2012. Background and purpose: Progressive non-fluent aphasia (PNFA) is a neurodegen- erative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral pre-frontal cortex (DLPFC) im- proves action naming in healthy subjects and in subjects with AlzheimerÕs disease. Purpose: To investigate whether the modulation of DLPFC circuits by rTMS mod- ifies naming performance in patients with PNFA. Methods: Ten patients with a diagnosis of PNFA were enrolled. High-frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. Results: A repeated-measure analysis of variance with stimulus site (sham, left and right rTMS) showed significant effects. Action-naming performances during stimula- tion of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. Conclusions: Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required. Introduction Humans are highly dependent on language in their day- to-day functioning. As a result, language disorders are associated with substantial disability [1]. Progressive non-fluent aphasia (PNFA) is a neuro- degenerative condition that presents in the presenium and belongs to the primary progressive aphasia spec- trum that includes semantic dementia (SD) and log- openic progressive aphasia [2]. PNFA is characterized by a progressive effortful, non-fluent speech with grammatical errors and omissions [1,3] and naming impairment, with greater difficulty in naming actions than in naming objects [4]. Speech worsens gradually, and patients eventually become mute. The anatomical localization of PNFA is represented by focal anterior peri-Sylvian atrophy that involves the inferior, opercular and insular portions of the left frontal lobe and the left dorsolateral pre-frontal cortex (DLPFC) [2,5]. Progressive non-fluent aphasia is considered an or- phan disorder because no evidence-based treatments are currently available to improve language perfor- mances or delay disease progression. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) is effective in modulating the excitability of the DLPFC circuits and in facilitating naming [6–10]. In particular online, high- frequency repetitive transcranial magnetic stimulation (rTMS) administered at appropriate time intervals reduces vocal reaction times (vRTs) for picture naming in healthy individuals [7,11] and improves the number of correct responses in patients with AlzheimerÕs disease [8,9]. Although the neuropsychological mechanisms responsible for rTMS-induced facilitation are still Correspondence: M. Cotelli, IRCCS Centro San Giovanni di Dio, Fatebenefratelli Via Pilastroni, 425125 Brescia, Italy (tel.: +0039 0303501593; fax: 0039-0303533513; e-mail: mcotelli@fatebe- nefratelli.it). Ó 2012 The Author(s) European Journal of Neurology Ó 2012 EFNS 1 European Journal of Neurology 2012 doi:10.1111/j.1468-1331.2012.03699.x