A previous post pointed out that the available data from studies of cortical atrophy and metabolic measures do not support the idea that semantic dementia results from focal damage to the anterior temporal lobe.
Caveat: for researchers interested in differentiating the pathologies associated with the various forms of frontotemporal dementia, AD, and related diseases, the ATL pathology in SD may very well be considered to be "focal" in the sense that the bulk of the atrophy and hypometabolism, at least in early stages of the disease, is in the anterior half of the temporal lobes. So if claims about the ATL being a semantic hub (or some similar concept) are willing to include in their definition of ATL a number of different anatomical structures and cytoarchitectonic fields, including both neocortex and limbic structures (hippocampus, amygdala), with posterior involvement including roughly half of the temporal lobe ventro-laterally, then I think SD can provide reasonable support for this idea. My own interest in the link between SD and the ATL came out of claims that used SD to argue that the lateral anterior temporal lobe (i.e., those regions corresponding to "sentence-specific" activations, and "intelligible speech" activations) was the projection site for the auditory/speech ventral stream, in contrast to the position David and I have put forward which argues for the posterior temporal lobe instead (e.g., see Scott & Wise and Hickok & Poeppel in the Special Issue of Cognition that David and I edited in 2004). The fact that SD has substantial MTL involvement and has ventro-lateral involvement that appears to extend quite a ways posterior, undermines the SD argument for an anterior-only auditory ventral stream. This is the sense in which I say SD pathology is not focal.
Caveat aside, there are still some remaining problems with associating SD and ATL dysfunction that became clear in the readings from last week.
Problem #1: Atrophy/hypometabolism is not always correlated with function.
For example, SD patients have both atrophy and hypometabolism in MTL structures -- the same MTL structures implicated in episodic memory deficits in AD, Case H.M., etc. -- yet SD patients don't have significant episodic memory impairments. Nestor, et al. (2006; NeuroImage, 30:1010-20) write, "Bilateral MTL hypometabolism in SD is, however, paradoxical since this deficit ought to be associated with episodic memory impairment." p. 1013. And regarding volumetric studies they say, "...the present observation suggests that studies aiming to corrlate MRI-derived volume loss with a given neuropsychological profile are at greater risk of producing false-positive and false negative results than previously thought." p. 1017. These authors provide reasonable explanations for these paradoxes (interaction with other damaged networks, specific pathologies involved, etc.), but the point is that these gross measures of brain structure/function are not necessarily straightforward correlates of cognitive function/dysfunction.
Other examples of this same sort of problem come from comparisons of HSVE and SD, both of which have substantial ATL involvement, but with different behavioral manifestations.
Problem #2: Case G.T.
Levy et al. (2004, PNAS, 101:6710-15) report three cases of amnesia with rather extensive bilateral damage to medial temporal lobe structures, and compare findings from these three patients with published data from SD patients on the same tests. One case in particular, G.T., is particularly interesting in light of the extent of involvement of the ATL bilaterally: "The damage involves the anterior 7 cm [!] of the left temporal lobe, [and] the anterior 5 cm of the right temporal lobe..." p. 6711. The extent of the damage can be seen clearly in the structural MRIs below shown in radiological format (left=right).
This patient should behave like an SD patient, worse even, on all the standard tests. However, G.T.'s performance was well above the standard error of the group of SD patients on tests of word recognition, picture naming, naming to description, subordinate category sorting, the Pyramids and Palm Trees test, and real/non-real object judgment. This is not to say that the patient was unimpaired on these tests relative to controls (s/he was), or that G.T. didn't have SD-like trouble on some semantic tests (e.g., category fluency for living things, yes/no questions regarding semantic features), but it is quite clear that extensive bilateral ATL+MTL damage does not produce semantic dementia.
The other two amnesic patients, whose lesions did not extend so far laterally, performed very well on all these "semantic" tests, and generally better than G.T. suggesting some role for the lateral ATL in semantic abilities. But again, the question is, why are SD patients so much worse off than G.T. who had severe damage to all the "classic" SD areas? Perhaps it is the more posterior extent of the SD pathology, together with the more anterior disruption that explains the severity of the deficit.
Overall summary from this week's readings:
1. Pathology in SD is not restricted to the ATL.
2. Structural and metabolic correlates of cognitive dysfunction are not definitive, and must be interpreted with extreme caution.
3. Medial ATL involvement in SD does not appear to account for semantic deficits (see Levy et al.).
4. Antero-lateral involvement of the ATL may account for some of the semantic impairment, but certainly not all.
My tentative conclusion, then, is that the pathology has to interrupt function in more posterior ventro-lateral portions of the temporal lobe to produce the full blown deficits in SD.
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