Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants

Abstract

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks.repetitive transcranial magnetic stimulation ͉ semantic cognition ͉ temporal pole S emantic memory encompasses the meaning of all types of verbal and nonverbal stimuli including words, pictures, objects, and faces. In addition to underpinning comprehension, it also allows us to express knowledge in a wide variety of domains, both verbal (e.g., naming and verbal definitions) and nonverbal (e.g., drawing and object use). As such, it is integral to our everyday lives, and impairments of semantic memory are extremely debilitating. Key questions for neuroscience research, therefore, are which parts of the brain support semantic memory, and how do they function?Various neurological disorders cause impairments of semantic processing; however, the purest syndrome is semantic dementia (SD; the temporal lobe variant of frontotemporal dementia) (1). This neurodegenerative disease results in relatively focal atrophy and hypometabolism of the anterior temporal lobes (ATL) bilaterally (2, 3). SD is characterized by progressive impairment of verbal and nonverbal semantic tasks, with anomia as the first presenting symptom (4-6). Strikingly, other aspects of language and cognition remain largely intact. SD patients have increasing difficulty distinguishing concepts from their semantic neighbors, reflecting an increasing loss of ''semantic acuity'' (6, 7). As such, the patients have greater difficulty activating specific semantic information (e.g., ''zebras have stripes'') than more general properties (e.g., ''zebras are animals'') (6, 8). Likewise, their naming difficulties are graded by specificity (higher naming accuracy for basic-level concepts such as dog than specific ones, e.g., springer spaniel) (9) with errors reflecting more general semantic knowledge (e.g., dog 3 ''animal'').Careful and extensive assessment of SD patients indicates that bilateral anterior temporal lobe regions support the formation of amodal semantic representations. Accordingly, SD patients exhibit poor comprehension of items presented in every modality, including spoken and written words, pictures, environmental sounds, smells, and touch (4, 10, 11). The marked semantic deficit is also apparent in production task...

Establishing task- and modality-dependent dissociations between the semantic and default mode networks

“…The overlap was particularly clear for regions within the ATL. These data are consistent with a convergence of results from neuropsychology, TMS, functional neuroimaging, and intracranial recordings, which points to these ATL regions underpinning a transmodal semantic representational hub (7,8,16,20,37). This outcome is highly consistent with the "semantic hypothesis" for the DMN.…”

“…For instance, semantic processing typically engages a fronto-temporoparietal network (3); however, the role of certain regions within the network is currently under debate. A wealth of converging evidence from neuropsychology, transcranial magnetic stimulation (TMS), PET, and distortion-corrected fMRI suggests that regions within the ATL are crucial in transmodal semantic representation (16)(17)(18)(19)(20). However, it is currently unclear as to whether the AG serves a similar function.…”

Distinct loci of lexical and semantic access deficits in aphasia: Evidence from voxel-based lesion-symptom mapping and diffusion tensor imaging

“…This is consistent with the anterior MTG BOLD activation found in healthy subjects for tasks tapping associative semantic relationship judgments (Vandenberghe, Price, Wise, Josephs, & Frackowiak, 1996) and for the comprehension of sentences ending in semantically anomalous nouns (e.g., I ordered a ham and cheese scissors) as compared to those ending in semantically appropriate nouns (e.g., when you go to bed turn off the living room lights; McCarthy, Nobre, Bentin, & Spencer, 1995). Because semantic relationships -especially those incongruous with a given sentence -elicit activation in the anterior MTG, this suggests that this region processes fine-grained semantic information as accessed from a given word form (e.g., Nobre & McCarthy, 1995;Rogers et al, 2006) and lines up with a number of studies demonstrating the role of anterior portions of the temporal lobe in processing semantic information (e.g., Binney et al, 2010;Pobric, Jefferies, Lambon Ralph, 2007Rogers et al, 2006). Together, the picture that emerges illustrates that damage to the posterior MTG creates noisy access to lexical representations while damage to the anterior MTG produces noisy access to semantic representations, resulting in increased competition from M A N U S C R I P T…”

Triangulation of the neurocomputational architecture underpinning reading aloud

“…We took coordinates on the border of the anterior fusiform and inferior temporal gyri (MNI coordinates −36, −15, −30) from an fMRI study in which participants made synonym judgments to written words (29). In parallel, transcranial magnetic stimulation has been used to probe the functions of the lateral ATL (68,69). To investigate this area, we selected coordinates in the anterior middle temporal gyrus (MNI coordinates −53, 4, −32) that were the stimulation target in the aforementioned studies.…”