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The connectionist triangle model of reading aloud proposes that semantic activation of phonology is particularly important for correct pronunciation of low-frequency exception words. Our consideration of this issue (Woollams, Lambon Ralph, Plaut, & Patterson, 2007) reported computational simulations demonstrating that reduction and disruption of this semantic activation resulted in the marked deficit in low-frequency exception word reading that is characteristic of surface dyslexia. We then presented 100 observations of reading aloud from 51 patients with semantic dementia (SD) demonstrating a universal decline into surface dyslexia, a phenomenon we termed "SD-squared." Coltheart, Tree, and Saunders have more recently provided a simulation of the SD-squared data within the dual route cascaded (DRC) model, achieved by varying the amount of damage to components of the lexical and nonlexical pathways. Although they suggested that these simulations provide a closer fit to the SD patients' reading data than our own, we demonstrate here that this is not the case. Moreover, we argue that the connectionist triangle model account has substantially greater explanatory and predictive power than the DRC account.

Semantic dementia (SD) is a condition in which atrophy to the anterior temporal lobes (ATL) produces a selective deterioration of conceptual knowledge. As this atrophy is always bilateral but usually asymmetrical, differences in performance of the two SD subgroups-with left > right (L > R) versus right > left (R > L) atrophy-constitute a major source of evidence regarding the roles of the left and right sides of this region. We explored this issue using large scale case-series methodology, with a pool of 216 observations of neuropsychological data from 72 patients with SD. Anomia was significantly more severe in the L > R subgroup, even when cases from the two subgroups were matched on severity of comprehension deficits. For subgroups matched on the degree of anomia, we show that asymmetry of atrophy also affected both the nature of the naming errors produced, and the degree of a semantic category effect (living things vs artefacts). A comparison across tasks varying in their loading on verbal and visual processing revealed a greater deficit in object naming for L > R cases and in a picture-based semantic association test for R > L cases; this held true whether severity across subgroups was controlled using pairwise matching or statistically via principal components analysis. Importantly, the size of our sample allowed us to demonstrate considerable individual variation within each of the L > R and R > L subgroups, with consequent overlap between them. Our results paint a clear picture of how asymmetry of atrophy affects cognitive performance in SD, and we discuss the results in terms of two mechanisms that could contribute to these differences: variation in the information involved in semantic representations in the left and right ATL, and preferential connectivity between each ATL and other more modality specific intra-hemispheric regions.

The extent to which meaning is involved in reading aloud has proven an area of longstanding debate, and current computational models differ on this dimension. The connectionist triangle model proposes that normal individuals rely on semantic information for correct reading of words with atypical spelling-sound relationships, but to varying degrees. This proposed individual difference would account for the varying stage of decline at which patients with semantic dementia first show the reading impairment known as surface dyslexia. Recent neuroimaging data has provided validation of this view, showing that individual differences in degree of semantic reliance during exception word reading predict the amount of activation in left anterior temporal regions associated with semantic processing. This study aimed to establish the cognitive correlates of individual differences in semantic reliance during exception word reading. Experiment 1 used a subgrouping approach with 32 participants and found larger imageability and semantic priming effects specifically for exception word reading amongst high relative to low semantic reliance readers. High semantic reliance readers also tended to read nonwords more slowly than low semantic reliance readers. A second experiment used a regression approach with 129 readers and confirmed the relationship of degree of semantic reliance both to imageability effects in exception word reading and speed of nonword reading. Further, while the performance of the higher semantic readers revealed no significant association with semantic processing tasks, there was a negative relationship with rhyme processing tasks. We therefore speculate that differences in phonological abilities may be responsible for varying degrees of semantic reliance in reading aloud. This proposal accords with the results of functional imaging showing that higher semantic reliance during exception word reading corresponds to lower activation in left pre-central gyrus, an area associated with direct spelling sound mapping and phonological processing. Our results therefore establish the nature of systematic individual differences in degree of semantic involvement amongst normal readers, and suggest directions for future neuroimaging and computational modeling research to uncover their origins.

In this commentary, though acknowledging that a case-series approach in neuropsychology is not always possible, we set out a series of considerations that in our view make this approach generally superior to single-case study. We argue that case-series designs are crucial for theory-testing, assessment of computational models, evaluation of inter-patient variation (including selection criteria, patient homogeneity/heterogeneity, premorbid individual differences, etc.) and to establish solid foundations for the interpretation of behavioural dissociations and associations. We conclude by suggesting that, alongside other neuroscience techniques, case-series cognitive neuropsychology provides a crucial contribution to the future of clinical and cognitive neuroscience.