Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia.

OBJECTIVE: Down's syndrome is characterized by the genetically programmed accumulation of substantial Alzheimer's disease neuropathology after age 40 and the development of early dementia years later, providing a unique human model to investigate the preclinical phases of Alzheimer's disease. Older nondemented adults with Down's syndrome show normal rates of regional cerebral glucose metabolism at rest before the onset of dementia, indicating that their neurons maintain function at rest. The authors hypothesized that an audiovisual stimulation paradigm, acting as a stress test, would reveal abnormalities in cerebral glucose metabolism before dementia in the neocortical parietal and temporal areas most vulnerable to Alzheimer's disease. METHOD: Regional cerebral glucose metabolism was assessed by means of positron emission tomography (PET) with [18F]fluorodeoxyglucose in eight younger (mean age = 35 years, SD = 2) and eight older (mean age = 50, SD = 7) healthy, nondemented adults with trisomy 21 Down's syndrome. PET scans were performed at rest and during audiovisual stimulation in the same scanning session. Levels of general intellectual functioning and compliance were similar in the two groups. RESULTS: At rest the two groups showed no difference in glucose metabolism in any cerebral region. In contrast, during audiovisual stimulation the older subjects with Down's syndrome had significantly lower glucose metabolic rates in the parietal and temporal cortical areas. CONCLUSIONS: Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. These results indicate that a stress test paradigm can detect metabolic abnormalities in the preclinical stages of Alzheimer's disease despite normal cerebral metabolism at rest.

Cortical regions involved in visual texture perception: a fMRI study.

To determine visual areas of the human brain involved in elementary form processing, functional magnetic resonance imaging (fMRI) was used to measure regional responses to two types of achromatic textures. Healthy young adults were presented with 'random' textures which lacked spatial organization of the black and white pixels that make up the image, and 'correlated' textures in which the pixels were ordered to produce extended contours and rectangular blocks at multiple spatial scales. Relative to a fixation condition, random texture stimulation resulted in increased signal intensity primarily in the striate cortex, with slight involvement of the cuneus and middle occipital, lingual and fusiform gyri. Correlated texture stimulation also resulted in activation of these areas, yet the regional extent of this activation was significantly greater than that produced by random textures. Unlike random stimulation, correlated stimulation additionally resulted in middle temporal activation. Direct comparison of the two stimulation conditions revealed significant differences most consistently in the anterior fusiform gyrus, but also in striate, middle occipital, lingual and posterior temporal regions in subjects with robust activation patterns. While both random and correlated stimulation produced activation in similar areas of the occipital lobe, the increase in regional activation during the correlated condition suggests increased recruitment of neuronal populations occurs in response to textures containing visually salient features. This increased recruitment occurs within striate, extrastriate and temporal regions of the brain, also suggesting the presence of receptive field mechanisms in the ventral visual pathway that are sensitive to features produced by higher-order spatial correlations.

Striate cortex in humans demonstrates the relationship between activation and variations in visual form.

Electrophysiologic and functional imaging studies have shown that the visual cortex produces differential responses to the presence or absence of structure within visual textures. To further define and characterize regions involved in the analysis of form, functional magnetic resonance imaging (fMRI) was used to detect changes in activation during the viewing of four levels of isodipole textures. The texture levels systematically differed in the density of visual features such as extended contours and blocks of solid color present within the images. A linear relationship between activation level and density of structure was observed in the striate cortex of human subjects. This finding suggests that a special subpopulation of striate cortical neurons participates in the ability to extract and process structural continuity within visual stimuli.

PET reveals occipitotemporal pathway activation during elementary form perception in humans.

To define brain regions involved in feature extraction or elementary form perception, regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in subjects viewing two classes of achromatic textures. Textures composed of local features (e.g. extended contours and rectangular blocks) produced activation or increased rCBF along the occipitotemporal pathway relative to textures with the same mean luminance, contrast, and spatial-frequency content but lacking organized form elements or local features. Significant activation was observed in striate, extrastriate, lingual, and fusiform cortices as well as the hippocampus and brain stem. On a scan-by-scan basis, increases in rCBF shifted from the occipitotemporal visual cortices to medial temporal (hippocampus) and frontal lobes with increased exposure to only those textures containing local features. These results suggest that local feature extraction occurs throughout the occipitotemporal (ventral) pathway during extended exposure to visually salient stimuli, and may indicate the presence of similar receptive-field mechanisms in both occipital and temporal visual areas of the human brain.