Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease

Abstract

Objective-Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. Methods-Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. Results-Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic diYculty compared with patients with Alzheimer's disease with relatively preserved semantic processing. Conclusion-These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing. (J Neurol Neurosurg Psychiatry 1997;63:152-158)

Neural substrates of phonological and lexicosemantic representations in Alzheimer's disease

“…Interaction analyses revealed that a network including the left temporoparietal and inferior frontal regions was significantly less recruited in AD patients than in the control group, when comparing word to WL2 nonword conditions. This result is in keeping with previous neuroimaging findings showing a correlation between semantic deficits in AD patients and impairment of left temporoparietal areas, as measured by structural MRI or resting brain metabolism [Desgranges et al, 1998;Grossman et al, 1997Grossman et al, , 1998]. As suggested by Grossmann et al [2003], impaired activity in the left temporoparietal and frontal regions in AD patients could reflect impaired integration of lexicosemantic information, regardless of the domain of knowledge or the nature of the task.…”

The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization

“…focal lesions, semantic dementia, Coughlan and Warrington, 1978;Grossi et al, 1988;Hodges et al, 1992) and activation studies during semantic tasks (for review, see Buckner and Tulving, 1995). Our findings also agree with earlier related work in demented patients (Foster et al, 1983;McGeer et al, 1990;Perani et al, 1993;Slansky et al, 1995; see also the recent report by Grossman et al, 1997). Finally, our observations of a preferential involvement of the left temporoparietal cortex in semantic fluency and the left prefrontal cortex in formal fluency concurs with the principles of these tasks, as well as with the PET activation study of Mummery et al (1996) in healthy subjects.…”

“…the tests used were not targeted in a prospective manner on particular memory systems, while the possible confounding effect of age (Duara et al, 1984;Eustache et al, 1995) was rarely considered. Recent studies (Collette et al, 1997;Grossman et al, 1997) aimed at identifying the cerebral regions underlying memory deficits, but they were each limited to one system only (short-term and semantic memory, respectively). Only Perani et al (1993) studied several memory systems with reference to an organizational model of memory (Squire and Zola-Morgan, 1991) and found significant associations between memory scores and CMRGlc values in various regions of interest by means of multivariate analysis.…”

Multiple systems of category learning

“…This distribution of disease results in difficulty in retrieving information from familiar categories ("semantic memory") in 30% to 50% of AD patients (Grossman et al, 1996). Several imaging studies with AD patients have shown correlations between difficulty in semantic-mmory retrieval and functional cortical defects in dorsolateral prefrontal and posterolateral temporal-parietal cortices (Grossman et al, 1997;Desgranges et al, 1998). Thus there is abundant evidence that AD patients have difficulties in using familiar categories.…”