Post-mortem measures of Abeta amyloid deposition correlate only weakly with cognitive dysfunction antemortem. We tested the hypothesis that functional reorganization forms a critical intermediary step between Abeta amyloid-associated brain injury and clinical disease expression. Fifteen patients with early-stage probable Alzheimer's disease (AD) and 16 cognitively intact controls participated in this combined functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) study. The fMRI design had two factors: task (associative-semantic versus visuoperceptual judgement) and input-modality (written words versus pictures). We measured Abeta amyloid by means of Pittsburgh Compound B (11C-PIB). In the posterior third of the left superior temporal sulcus (STS), the fMRI response during the associative-semantic compared with the visuoperceptual task was lower in AD than in controls, in particular for words. Response amplitude correlated inversely with PIB uptake in this region. Contralaterally, the functional pattern differed substantially: the fMRI response in the right posterior STS during the associative-semantic versus the visuoperceptual task was higher in AD than in controls. Accuracy on the Boston Naming test correlated positively with the degree to which AD patients were able to recruit the right STS (r = 0.84, P(corrected) = 0.014). PIB uptake did not correlate with naming accuracy. Functional reorganization of the language system in response to Abeta amyloid-related brain injury exists in early-stage AD and determines the degree of anomia more than Abeta amyloid load per se does.
Neurobiological theories of knowledge processing are biased toward the language-dominant (usually the left) hemisphere. Does the right hemisphere critically contribute to knowledge processing? J.A. is a left-hemisphere language-dominant individual who suffered a lesion confined to the right mid- and anterior fusiform gyrus. Although her language abilities are intact, she showed a partial loss of knowledge of the visual attributes of biological and nonbiological entities. This was observed regardless of the task performed: object discrimination, oral feature generation, forced-choice naming-to-definition or free-hand drawing. Functional-associative and nonvisual sensory attributes were spared. The same region that was lesioned in J.A. was activated in a functional magnetic resonance imaging study in 27 volunteers who retrieved semantic associations between concepts, but only if the concepts were represented as pictures and not as words. Therefore, right fusiform gyrus critically contributes to the conscious recollection of visual attributes of familiar entities.
The issue of the relationship between language and gesture processing and the partial overlap of their neural representations is of fundamental importance to neurology, psychology, and social sciences. Patients suffering from primary progressive aphasia, a clinical syndrome characterized by comparatively isolated language deficits, may provide direct evidence for anatomical and functional association between specific language deficits and gesture discrimination deficits. A consecutive series of 16 patients with primary progressive aphasia and 16 matched control subjects participated. Our nonverbal gesture discrimination task consisted of 19 trials. In each trial, participants observed three video clips showing the same gesture performed correctly in one clip and incorrectly in the other two. Subjects had to indicate which of the three versions was correct. Language and gesture production were evaluated by means of conventional tasks. All participants underwent high-resolution structural and diffusion tensor magnetic resonance imaging. Ten of the primary progressive aphasia patients showed a significant deficit on the nonverbal gesture discrimination task. A factor analysis revealed that this deficit clustered with gesture imitation, word and pseudoword repetition, and writing-to-dictation. Individual scores on this cluster correlated with volume in the left anterior inferior parietal cortex extending into the posterior superior temporal gyrus. Probabilistic tractography indicated this region comprised the cortical relay station of the indirect pathway connecting the inferior frontal gyrus and the superior temporal cortex. Thus, the left perisylvian temporoparietal area may underpin verbal imitative behavior, gesture imitation, and gesture discrimination indicative of a partly shared neural substrate for language and gesture resonance.
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