Reading disorders in primary progressive aphasia: A behavioral and neuroimaging study

Abstract

Previous neuropsychological studies on acquired dyslexia revealed a double dissociation in reading impairments. Patients with phonological dyslexia have selective difficulty in reading pseudo-words, while those with surface dyslexia misread exception words. This double dissociation in reading abilities has often been reported in brain-damaged patients, but it has not been consistently shown in patients with neurodegenerative diseases.

In this study, we investigated reading impairments and their anatomical correlates in various neurodegenerative diseases. First, we performed a behavioral analysis to characterize the reading of different word types in primary progressive aphasia (PPA). Then, we conducted a voxel-based morphometry neuroimaging study to map the brain areas in which gray matter volume correlated with the accurate reading of exception and pseudo-words.

The results showed a differential pattern of exception and pseudo-word reading abilities in different clinical variants of PPA. Patients with semantic dementia, a disorder characterized by selective loss of semantic memory, revealed a pattern of surface dyslexia, while patients with logopenic/phonological progressive aphasia, defined by phonological loop deficits, showed phonological dyslexia. Neuroimaging results showed that exception word reading accuracy correlated with gray matter volume in the left anterior temporal structures, including the temporal pole, the anterior superior and middle temporal and fusiform gyri, while pseudo-word reading accuracy correlated with left temporoparietal regions, including the posterior superior and middle temporal and fusiform gyri, and the inferior parietal lobule.

These results suggest that exception and pseudo-word reading not only rely upon different language mechanisms selectively damaged in PPA, but also that these processes are sustained by separate brain structures.

Introduction

Neuropsychological studies on brain-damaged patients with acquired dyslexia have revealed a double dissociation in reading of different word types. Patients with phonological dyslexia show a discrepancy between reading regular words (e.g., words with regular spelling-to-sound correspondence, such as ‘apple’) and pseudo-words (e.g., pronounceable letter string with no semantic representation, such as ‘voot’ and ‘yull’), with relatively preserved reading of exception words (e.g., words with atypical spelling to sound correspondence, such as ‘yacht’ and ‘colonel’). On the other hand, patients with surface dyslexia show a discrepancy in their reading of regular and exception words, with relatively preserved reading of pseudo-words.

Different computational models have tried to account for this neuropsychological dissociation by postulating the existence of at least two means by which reading aloud can occur. The dual route cascaded (DRC) model (Coltheart, 2006; Coltheart, Curtis, Atkins, & Haller, 1993; Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001) postulates the existence of two distinct reading-specific pathways that work independently from other language and cognitive systems: (1) the non-lexical route relies on a system of grapheme-to-phoneme conversion rules and it is employed in the reading of pseudo-words; (2) the direct lexical route retrieves a word's sound representation from the phonological lexicon by first accessing its whole orthographic representation. This route is believed to be employed in the reading of regular and exception words. According to this model, the reading deficits characteristic of phonological and surface dyslexia would be caused by the disruption of the non-lexical and lexical route respectively, and they would be isolated from other language and cognitive impairments.

A second theory, the connectionist triangle model (Plaut, McClelland, Seidenberg, & Patterson, 1996; Seidenberg & McClelland, 1989; Woollams, Lambon Ralph, Plaut, & Patterson, 2007) proposes that the reading of words is determined by the modulation of connections between orthography, phonology and the semantic system. The strength of connections is determined by both the proficiency of the reader and word features, such as word type and frequency. Within this framework, two serially working pathways contribute to the reading of different word types: (1) the direct pathway from orthography to phonology (O → P) is more involved in regular and pseudo-word reading; (2) the indirect pathway from orthography to phonology mediated via the semantic system (O → S → P) is more involved in less frequent and exception word reading. According to this model, a pattern of phonological dyslexia would be associated with a defective phonological system, while a pattern of surface dyslexia would arise in the case of a defective semantic system.

The hypothesis of an association between semantic memory impairments and surface dyslexia is supported by evidence in patients with semantic dementia (SD), a variant of primary progressive aphasia (PPA) characterized by progressive loss of semantic memory and anterior temporal lobe degeneration (Chan et al., 2001, Galton et al., 2001, Gorno-Tempini et al., 2004, Mummery et al., 2000, Rosen et al., 2002). In fact, patients with SD not only present with surface dyslexia (Caine, Breen, & Patterson, 2009; Hodges, Patterson, Oxbury, & Funnell, 1992; Hodges et al., 1999, Neary et al., 1998, Woollams et al., 2007), but there is also a strong association between the severity of the reading deficit and the extent of the semantic loss (Graham, Patterson, & Hodges, 2000; Jefferies, Lambon Ralph, Jones, Bateman, & Patterson, 2004; Patterson & Hodges, 1992; Woollams et al., 2007). A pattern of surface dyslexia has also been reported in Alzheimer's disease, but only in patients manifesting semantic deficits (Patterson, Graham, & Hodges, 1994; Strain, Patterson, Graham, & Hodges, 1998).

On the other hand, the presence of a pattern of phonological dyslexia has not been described in other neurodegenerative syndromes characterized by language deficits. This absence in the literature of a double dissociation in reading disorders could be partly due to the lack of studies investigating reading abilities in other clinical variants of PPA, besides SD. To our knowledge, no studies specifically investigated reading abilities in patients with progressive nonfluent aphasia (PNFA), which is characterized by apraxia of speech, agrammatism and inferior frontal and insular atrophy (Gorno-Tempini et al., 2004, Grossman et al., 1996; Hodges & Patterson, 1996). We also know of no such studies in patients with logopenic/phonological progressive aphasia (LPA), another variant of PPA, in which patients present with phonological loop deficits and atrophy in left temporoparietal structures (Gorno-Tempini et al., 2004, Gorno-Tempini et al., 2008).

From an anatomical point of view, previous functional imaging studies have attempted to identify brain areas differentially involved in exception and pseudo-word reading. A pattern of activation consistent among studies has been found for reading of pseudo-words compared to exception words, but the pattern associated with the reverse comparison is less defined (for a discussion, see Mechelli et al., 2005). In general, the data suggest that the inferior parietal regions and the posterior inferior frontal gyrus (IFG) are more involved in pseudo-word reading (Jobard, Crivello, & Tzourio-Mazoyer, 2003; Mechelli et al., 2005; Mechelli, Gorno-Tempini, & Price, 2003; Wilson et al., 2009), while the anterior portion of the IFG is involved in exception word reading (Mechelli et al., 2003, Mechelli et al., 2005). Moreover, a differential involvement of the left fusiform gyrus has been reported in the reading of different word types, with the anterior portion underpinning the reading of exception words, while the posterior portion is involved with the reading of pseudo-words (Brunswick, McCrory, Price, Frith, & Frith, 1999; Mechelli et al., 2003, Mechelli et al., 2005, Price et al., 2003).

In order to better define the nature of reading impairments and to determine their anatomical correlates, we studied patterns of reading deficits and associated anatomical changes in patients with various neurodegenerative diseases. First, we performed a behavioral study to characterize the profile of reading impairments for different word types (regular/exception/pseudo-words) in patients with different clinical variants of PPA. A voxel-based morphometry (VBM) neuroimaging study was then conducted on a subset of participants in order to map the neurological correlates of exception and pseudo-word reading disorders.