Reduced precuneus deactivation during object naming in Dementia

Posterior midline areas have been associated with the default mode network of the human brain, as they typically exhibit a decrease from high baseline activity during task-related, goal-directed behavior (1). Metabolic alterations of these areas (2, 3) as well as cortical thinning (4) in dementia patients have been demonstrated previously. We used fMRI to test whether task-related activation or de-activation was different in dementia patients compared to healthy elderly controls during an overt picture naming task. The event-related paradigm comprised presentation of single Snodgrass-like pictures which had to be named as fast and correct as possible. Responses were recorded with MR-compatible audio equipment. We included 16 patients (mean age: 67 years, SD=11) with clinically diagnosed frontotemporal dementia (FTD; N=8), dementia of Alzheimer's type (DAT; N=4), or mild cognitive impairment (MCI; N=4). Fourteen healthy elderly volunteers served as a control group (mean age: 61 years, SD=7). Functional and structural MR data were acquired at 3T, data were analyzed with SPM5. We modeled picture onset as the critical event and determined associated activation/de-activation patterns in each subject. Only correct trials were included in order to take performance variability into account. Using an ANCOVA with age and naming latency as co-variates, we tested for the effect of group (healthy controls vs. patients) on the second level (p<0.001, k=5 contiguous voxels).

Task-related activation across groups was found primarily in bilateral occipital, central, superior temporal, and superior parietal cortex. Stronger activation in controls compared to patients was not observed at any site. We found a predominant group difference in the precuneus (MNI-coordinates -9–60 30), with the controls showing task-related de-activation in this area, which was absent in patients. Effect sizes in the precuneus voxel that exhibited the maximum difference between controls and patients did not differ between FTD and other patients (MCI or AD). Effect sizes at this site were not significantly correlated with naming latencies. Our results are in line with recent neuroimaging literature demonstrating altered metabolism and activity in the posterior midline areas in dementia and MCI patients (2, 5, 6). Notably, in our study this effect was present across patient subgroups. A deficient down-regulation of this brain region's activity during goal-directed behavior – when resources should be allocated to task-related areas – might reflect impaired cognitive performance in dementia and MCI patients.

References:

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[2] R. Zahn et al., Psychiatry Res 140, 115 (2005).

[3] A. Drzezga et al., Neuroimage 39, 619 (2008).

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[5] S. A. Rombouts, F. Barkhof, R. Goekoop, C. J. Stam, P. Scheltens, Hum Brain Mapp 26, 231 (2005).

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