Functional activation studies of word processing in the recovery from aphasia Roland Zahn a,b, * , Michael Schwarz a , Walter Huber c a Department of Neurology, and Neurolinguistics Section, University of Technology, RWTH Aachen, Germany b Department of Psychiatry and Psychotherapy, University of Freiburg, Germany c Neurolinguistics Section, University of Technology, RWTH Aachen, Germany Abstract Some reviews on theories of recovery in aphasia put an emphasis on neural network models based on empirical data from evoked- potentials in aphasia as an approach to mapping recovery of cognitive function to neural structure. We will focus here on what we call an ‘‘anatomical’’ approach to look at recovery in aphasia. ‘‘Anatomical’’ theories of recovery stated by classical aphasiologists have con- tributed to the understanding of language representations in the human brain. But many aspects of these theories can only be investi- gated by using modern techniques of lesion analysis, psychometric assessment and functional imaging. Whereas structure–function relations have been primarily established by looking for the association of deficit symptoms with certain lesions, functional activation methods offer a means to study more directly the functional anatomy of recovered or retained functions in neuropsychological patients. To falsify or build up anatomical theories of recovery we will propose a stepwise approach of inference. The methodological pitfalls of this approach will be discussed by focussing on anatomical hypotheses of semantic word comprehension and its impairment and recovery in aphasia. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Aphasia; Recovery; Functional magnetic resonance imaging; Positron emission tomography; Magnetic resonance imaging; Language 1. Theories of recovery in aphasia 1.1. Introducing the ‘‘anatomical’’ approach Theories of recovery in aphasia have been reviewed by Code (2001), who tried to integrate theories of recovery at the behavioural, cognitive and neural level using a mul- tileveled framework. Whereas Code puts his emphasis on neural network models including empirical data from evoked-potentials in aphasia (Pulvermu ¨ ller, 1999) as an approach to mapping recovery of cognitive function to neural structure, we will focus here on what we call an ‘‘anatomical’’ approach to look at recovery in aphasia. ‘‘Anatomical’’ theories of recovery stated by classical apha- siologists (for example Broca, 1865; Lichtheim, 1885; Goldstein, 1917; Von Kleist, 1922) have contributed to the understanding of language representations in the human brain. But many aspects of these theories can only be investigated by using modern techniques of lesion anal- ysis, psychometric assessment and functional imaging. Whereas structure–function relations have been primarily established by looking for the association of deficit symp- toms with certain lesions, functional activation methods offer a means to study more directly the functional anat- omy of recovered or retained functions in neuropsycholog- ical patients (for a review of theories of deficit and compensation in aphasia see Springer et al., 2000). To fal- sify or build up anatomical theories of recovery one could propose a stepwise approach of inference: 0928-4257/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2006.03.013 * Corresponding author. NIH/NINDS Cognitive Neuroscience Section, Building 10, 5C206, 10 Centre Drive, MSC 1440, Bethesda, MD 20892- 1440, USA. Tel.: +1 301 402 6392; fax: +1 301 480 2909. E-mail address: zahnr@ninds.nih.gov (R. Zahn). www.elsevier.com/locate/jphysparis Journal of Physiology - Paris 99 (2006) 370–385