Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer's disease. A study of cortical attention sites in man

This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer's disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer's disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer's disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of attention as hypothesized by Mesulam stating that the parietal cortex is polymodal, receiving input from the primary cortices of all sensory modalities. Thus, the parietal attention site is not only involved in visual spatial selective attention as claimed by some research groups. My data also indicate that the parietal attention site is organized in a 'homunculus-like' fashion, similar to the cortical connections in the Macaque monkey. In the Alzheimer patients, the primary sensory stimulations elicited an altered pattern with activation of medial frontal structures in additional to the expected activations of the primary sensory cortices. During sustained attention the patients had a tendency to activate the same attention sites as the healthy elderly, but in addition significant deactivations were noted in the left and right medial and left superior frontal gyri (Brodmann Area 10), and the right posterior cingulate gyrus (Brodmann Area 23/31). During divided attention the activation pattern in the patients was very different from that of the healthy elderly. The right medial frontal gyrus (Broadmann Area 32) was activated but not the right-sided parietal or the frontal attention sites. Deactivations were seen in the right cuneus and putamen. The different activation patterns elicited by sustained and divided attention in the Alzheimer patients provide evidence of differential deficits in two attention sbutypes in Alzheimer's disease, as reported in neuropsychological studies. The resting rCBF deficits and the altered cortical activation patterns during attention in the Alzheimer patients indicate that Alzheimer's disease is the result of a specific pathophysiological process with distinct and localized lesions indicating that the disease is not a diffuse and global brain disease. The results further support the disconnection hypothesis of Alzheimer's disease wich consider the disorder as a neocortical isolationsyndrome created by a disease process that spreads along functionally connected corticocortical pathways. (au)