Aberrant frontostriatal connectivity in Alzheimer's disease with positive palmomental reflex.

BACKGROUND AND PURPOSE: Primitive reflexes may reoccur in various neurodegenerative diseases. However, little is known about their structural and functional correlates in the human brain. Notably, the neural mechanisms underlying a positive palmomental reflex (PMR) are poorly understood. As recent studies link Alzheimer's disease (AD)-related primitive reflexes to a dysfunction of the corticostriatal motor circuit (CMC), we conducted the present study to investigate functional and structural correlates of a positive PMR. We hypothesized an involvement of frontostriatal structures and an impairment of the CMC. METHODS: Using whole-brain resting-state functional connectivity (FC), hypothesis and FC result-based probabilistic tractography, and voxel-based morphometry analyses, we compared two groups of AD patients with either positive (n = 12) or negative PMR (n = 12). RESULTS: No significant differences in grey matter volume or structural connectivity (SC) could be observed between the PMR-positive and PMR-negative groups. In contrast, the PMR-positive group showed a decreased seed-to-voxel FC between the bilateral supplementary motor area and parts of the right-hemispherical caudate nucleus and thalamus and a decreased region of interest (ROI)-to-ROI FC between the left putamen and the left superior frontal gyrus. CONCLUSION: Data suggest that dysfunction of the CMC reflected by decreased FC underlies a positive PMR in patients with AD. The lack of significant grey matter or SC differences might reflect that changes in FC appear before changes in SC in the structures of the CMC and brain atrophy.

Test-retest variability of resting-state networks in healthy aging and prodromal Alzheimer's disease.

In recent years, changes in resting-state networks (RSN), identified by functional magnetic resonance imaging (fMRI), have gained increasing attention as potential biomarkers and trackers of neurological disorders such as Alzheimer's disease (AD). Intersession reliability of RSN is fundamental to this approach. In this study, we investigated the test-retest reliability of three memory related RSN (i.e., the default mode, salience, and executive control network) in 15 young, 15 healthy seniors (HS), and 15 subjects affected by mild cognitive impairment (MCI) with positive biomarkers suggestive of incipient AD (6 females each). FMRI was conducted on three separate occasions. Independent Component Analysis decomposed the resting-state data into RSNs. Comparisons of variation in functional connectivity between groups were made applying different thresholds in an explorative approach. Intersession test-retest reliability was evaluated by intraclass correlation coefficient (ICC) comparisons. To assess the effect of gray matter volume loss, motion, cerebrospinal fluid based biomarkers and the time gap between sessions on intersession variation, the former four were correlated separately with the latter. Data showed that i) young subjects ICCs (relative to HS/MCI-subjects) had higher intersession reliability, ii) stringent statistical thresholds need to be applied to prevent false-positives, iii) both HS and MCI-subjects (relative to young) showed significantly more clusters of intersession variation in all three RSN, iv) while intersession variation was highly correlated with head motion, it was also correlated with biomarkers (especially phospho-tau), the time gap between sessions and local GMV. Results indicate that time gaps between sessions should be kept constant and that head motion must be taken into account when using RSN to assess aging and neurodegeneration. In patients with prodromal AD, re-test reliability may be increased by accouting for overall disease burden by including biomarkers of neuronal injury (especially phospho-tau) in statistical analyses. Local atrophy however, does not seem to play a major role in regards to reliability, but should be used as covariate depending on the research question.