Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease.

Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 age-matched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life- and waiting-time statistics of oscillation bursts. We found that Alzheimer's patients had a strongly reduced incidence of alpha-band oscillation bursts with long life- or waiting-times (< 1 s) over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1-25 seconds). Interestingly, the life- and waiting-times of theta oscillations over medial prefrontal regions were greatly increased. Whereas both temporo-parietal alpha and medial prefrontal theta oscillations are associated with retrieval and retention of information, metabolic and structural deficits in early-stage AD are observed primarily in temporo-parietal areas, suggesting that the enhanced oscillations in medial prefrontal cortex reflect a compensatory mechanism. Together, our results suggest that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.

Resting-state oscillatory brain dynamics in Alzheimer disease.

Altered oscillatory brain activity in Alzheimer disease (AD) may reflect underlying neuropathological changes, and its characterization might lead to new diagnostic possibilities. The present study using quantitative magnetoencephalography was set up to examine power spectrum changes in AD patients, and their diagnostic strength. Whole-head 151-channel magnetoencephalography was recorded during an eyes-closed resting state. Magnetoencephalography channels were grouped in 10 cortical regions, and both global and regional relative power was analyzed for the commonly used frequency bands. Eighteen AD patients [mean age 72.1 years +/- 5.6 (SD); 7 women; mean Mini Mental State Examination score 19.2, range: 13-25] and 18 healthy controls [mean age 69.1 +/- 6.8 (SD), 11 women; mean Mini Mental State Examination score 29, range: 27-30] were recruited, controls being mainly spouses of patients. Relative power analysis showed significant differences in most frequency bands, particularly in the temporo-parietal regions, with some relation to Mini Mental State Examination scores. Greatest diagnostic accuracy was found in the beta band, especially in the right occipital area (sensitivity 94%, specificity 78%). Quantitative relative power analysis of magnetoencephalography recordings is able to show widespread abnormalities in oscillatory brain dynamics in AD patients. By analyzing distinct cortical regions, this study provides a more detailed topographical view of abnormal brain activity in AD.

Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat.

In the present study we aimed to determine the topographical and laminar characteristics of cingulate projections to the parahippocampal region and hippocampal formation in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextranamine. The results show that all areas of the cingulate cortex project extensively to the parahippocampal region but not to the hippocampal formation. Rostral cingulate areas (infralimbic-, prelimbic cortices, rostral 1/3 of the dorsal anterior cingulate cortex) primarily project to the perirhinal and lateral entorhinal cortices. Projections from the remaining cingulate areas preferentially target the postrhinal and medial entorhinal cortices as well as the presubiculum and parasubiculum. At a more detailed level the projections show differences in topographical specificities according to their site of origin within the cingulate cortex suggesting the functional contribution of cingulate areas may differ at an individual level. This organization of the cingulate-parahippocampal projections relates to the overall organization of postulated parallel parahippocampal-hippocampal processing streams mediated through the lateral and medial entorhinal cortex respectively. The mid-rostrocaudal part of the dorsal anterior cingulate cortex appears to be connected to both networks as well as to rostral and caudal parts of the cingulate cortex. This region may therefore responsible for integrating information across these specific networks.

Atrophy rates of the cingulate gyrus and hippocampus in AD and FTLD.

This study explores the diagnostic utility of atrophy rates of the cingulate gyrus, its subdivisions and the hippocampus in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Regions were manually outlined on MR images of a group of pathologically or genetically confirmed patients with AD (n=19), FTLD (n=8) and age-matched controls (n=11). Mean (S.D.) atrophy rates (%year(-1)) in the cingulate in controls, AD and FTLD were -0.3 (1.2), 5.9 (3.5), and 8.6 (4.1), respectively. Hippocampal atrophy rates in controls, AD and FTLD were -0.1 (0.8), 3.4 (2.2), and 5.2 (5.4), respectively. Atrophy rates were significantly higher in the cingulate and hippocampi in AD and FTLD compared with controls (p<0.01). There was evidence of a difference in trends of atrophy in the cingulate (more anterior in FTLD and more posterior in AD) between the disease groups (p=0.03). Cingulate atrophy rates discriminated perfectly between FTLD and controls. Significantly better discrimination between AD and controls was obtained by hippocampal rather than cingulate rates. In conclusion, cingulate atrophy is as significant a feature of AD and FTLD as hippocampal atrophy.

Differential regional atrophy of the cingulate gyrus in Alzheimer disease: a volumetric MRI study.

Magnetic resonance imaging-based volumetric measurements provide a useful technique for quantifying in vivo regional cerebral atrophy in Alzheimer disease (AD). Histopathological studies have shown the cingulate cortex, a cytoarchitectonically heterogeneous region, to be severely affected in AD. In this study, we developed and validated a manual segmentation protocol, based on macroscopic characteristics such as gyri and sulci patterns, in order to assess volumetric changes in 4 cingulate regions of interest. Cingulate cortical volumes of 10 familial AD patients were compared with 10 age- and sex-matched controls. Inter- and intrarater reliability coefficients were high for all cingulate regions (91.9-99.4%). All 4 cingulate regions were significantly smaller (P < 0.05) in AD cases compared with controls: rostral anterior cingulate gyrus (22.5% smaller), caudal anterior cingulate gyrus (20.7% smaller), posterior cingulate gyrus (44.1% smaller), and retrosplenial cortex (21.5% smaller). The atrophy in the posterior cingulate region was significantly greater than that in other cingulate regions (P < 0.001), suggesting a higher vulnerability for this region in familial AD. Considering the functional and connectional differences of these 4 cingulate regions, detection and monitoring of their atrophy may provide insights into the natural history of AD and may help in the search for diagnostic markers for early AD.