The Ventral and Inferolateral Aspects of the Anterior Temporal Lobe Are Crucial in Semantic Memory: Evidence from a Novel Direct Comparison of Distortion-Corrected fMRI, rTMS, and Semantic Dementia

Richard J. Binney 2 3 Karl V. Embleton 1 2 3 Elizabeth Jefferies 0 2 Geoffrey J. M. Parker 1 2 Matthew A. Lambon Ralph 2 3 0 Department of Psychology, University of York , York YO10 5DD , UK 1 Imaging Sciences Research Group, Research School of Cancer and Imaging Sciences, School of Medicine, University of Manchester , Manchester, M13 9PT , UK 2 The Author 2010. Published by Oxford University Press. All rights reserved. For permissions , please 3 Neuroscience and Aphasia Research Unit, School of Psychological Sciences, University of Manchester , Manchester, M13 9PL , UK Although there is an emerging consensus that the anterior temporal lobes (ATLs) are involved in semantic memory, it is currently unclear which specific parts of this region are implicated in semantic representation. Answers to this question are difficult to glean from the existing literature for 3 reasons: 1) lesions of relevant patient groups tend to encompass the whole ATL region; 2) while local effects of repetitive transcranial magnetic stimulation (rTMS) are spatially more specific, only the lateral aspects of the ATL are available to stimulation; and 3) until recently, functional magnetic resonance imaging (fMRI) studies were hindered by technical limitations such as signal distortion and dropout due to magnetic inhomogeneities and also, in some cases, by methodological factors, including a restricted field of view and the choice of baseline contrast for subtraction analysis. By utilizing the same semantic task across semantic dementia, rTMS, and distortion-corrected fMRI in normal participants, we directly compared the results across the 3 methods for the first time. The findings were highly convergent and indicated that crucial regions within the ATL for semantic representation include the anterior inferior temporal gyrus, anterior fusiform gyrus, and the anterior superior temporal sulcus. Introduction Semantic cognition refers to a collection of higher cortical functions that permit us to encode and use the meaning of words and objects in order to generate flexible and sophisticated verbal and nonverbal behavior (Rogers and McClelland 2004; Jefferies and Lambon Ralph 2006). Although it was an issue of considerable debate (e.g., Martin 2007), there is now a growing consensus that the (bilateral) anterior temporal lobe (ATL) plays an important role in semantic memory (Patterson et al. 2007; Lambon Ralph and Patterson 2008; Simmons and Martin 2009). The longest standing and richest evidence stems from patients with semantic dementia (SD), who exhibit a progressive yet highly selective impairment of semantic memory whilst other aspects of perception and cognition function are largely unaffected (Hodges et al. 1992). Semantic performance is impaired in receptive and expressive tasks across all modalities, including spoken and written words, pictures, environmental sounds, smell, touch, and taste (Lambon Ralph et al. 1999, 2001; Bozeat et al. 2000, 2002, 2003; Coccia et al. 2004; Luzzi et al. 2007; Piwnica-Worms et al. forthcoming). This striking behavioral profile is coupled with relatively circumscribed atrophy and hypometabolism of the bilateral ATLs. The pairing of a selective pan-modal semantic impairment with ATL atrophy has led to the suggestion that this region (bilaterally) is critical in the formation of amodal conceptual representations (Rogers et al. 2004; Patterson et al. 2007; Lambon Ralph and Patterson 2008; Lambon Ralph et al. forthcoming). Some forms of neuroimaging also implicate a role for the ATL in semantic processing (Binder et al. 2009; Visser et al. forthcoming)including positron emission tomography (PET) (Vandenberghe et al. 1996; Scott et al. 2000; Crinion et al. 2003; Rogers et al. 2006; Spitsyna et al. 2006) and magnetoencephalography (MEG) (e.g., Marinkovic et al. 2003). Furthermore, repetitive transcranial magnetic stimulation (rTMS) to the lateral ATL selectively slows performance in receptive (synonym judgment) and expressive (picture-naming) semantic tasks but has no effect on nonsemantic (number-based) tests matched for overall difficulty (Pobric et al. 2007). This pattern holds whether left or right temporal poles are stimulated (Lambon Ralph et al. 2009). Convergent evidence from functional neuroimaging and transcranial magnetic stimulation (TMS) is important for 2 reasons. First, because SD is underpinned by a neurodegenerative disease, there is a possibility that subthreshold damage or dysfunction due to spreading pathology contributes to the patients semantic impairment (Hickok and Poeppel 2004; Martin 2007). The second motivation for convergent evidence, especially from functional magnetic resonance imaging (fMRI) in neurologically intact participants, concerns our ability to answer a new set of research questions that have arisen from the recent inclusion of the ATL in models of semantic cognition: 1) Which specific regions within the ATL contribute to semantic memory and 2) what role or type of information do they add (Lambon Ralph and Patterson 2008; Simmons and Martin 2009; Lambon Ralph et al. forthcoming)? The first of these new research questions is the target of the present study. At present, even the simple definition of what constitutes the ATL is somewhat unclear. Many authors, including ourselves, have used the term ATL to simply refer to those regions primarily affected in SD (e.g., Patterson et al. 2007). This lacks specificity, given that, on the basis of relevant volumetric and metabolic studies (Mummery et al. 2000; Galton et al. 2001; Nestor et al. 2006), SD implicates a rather broad region incorporating a large proportion of the rostral half of the temporal lobe (see Fig. 1e). Moreover, it might be inferred from the theories and computational models predicated on SD studies (e.g., Rogers et al. 2004; Patterson et al. 2007) that the ATL is a functionally homogenous structure. It has yet to become apparent, however, whether the semantic function ascribed to it really requires this entire area. Neuroanatomically speaking, the prospect of this ATL region existing as a single unified functional entity seems unlikely. In considering the area typically affected in SD, it is possible to identify at least 8 cytoarchitecturally distinguishable albeit graded subregions (Brodmann 1909). In fact, it has been shown more recently that, in the temporopolar cortex alone, there is a minimum of 7 distinct subareas (Ding et al. 2009). Nonhuman primate studies also suggest that these subareas display differential patterns of connectivity to other cortical and subcortical regions (Mora n et al. 1987; Gloor 1997). The primary goal of this study was, therefore, to determine which of these subregions are the most important for performing a semantic task and thus increase the anatomical specificity of hypotheses regarding anterior temporal involvement in conceptual processing. The use of fMRI will be critical to achieving this goal, not only due to its superio (...truncated)