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Huijbers W, Mormino EC, Wigman SE, Ward AM, Vannini P, McLaren DG, Becker JA, Schultz AP, Hedden T, Johnson KA, Sperling RA. Amyloid deposition is linked to aberrant entorhinal activity among cognitively normal older adults. J Neurosci. 2014 Apr 9;34(15):5200-10. PubMed.
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Cyceron
The authors made an elegant study in which they assessed the profile of activations and deactivations in young adults and cognitively normal elderly, and then performed additional analyses from two regions of interest (ROI): one preferentially located in the hippocampus and showing activation in both groups, and the other located mainly in the entorhinal cortex and showing deactivation (i.e., lower activity during the task than during the reference—cross fixation). They showed that age educed both hippocampal activation and entorhinal deactivation, and that amyloid deposition was associated with less deactivation in the entorhinal cortex.
This study is interesting in that it emphasizes the complex relationships among amyloid deposition and brain activity and connectivity, hence reviving the debate on whether Aβ causes abnormal activity or whether aberrant activity promotes amyloid deposition. Longitudinal studies would probably help answer this question. The fact that this Aβ-related activity change was unrelated to memory performance further complicates the picture and our understanding of the effects of amyloid deposition and Aβ-related brain changes on cognition and clinical outcome.
An intriguing finding is the different networks highlighted in assessing the functional connectivity of each ROI, with the default mode network (DMN) highlighted with the entorhinal ROI, while the hippocampal ROI revealed a more restricted network, including posterior ventro-medial areas. Whether the hippocampus is or is not part of the DMN may also in part reflect the antero-posterior location of the ROIs (when using seed-based connectivity analyses) because important intrinsic connectivity differences have been highlighted over the antero-posterior axis of the medial temporal lobe (see, for instance, La Joie et al., 2014; and Ranganath and Ritchey, 2012). Similarly, the inclusion of the hippocampus in the deactivation network may depend on the task, and is less likely to occur when using episodic memory tasks. This is another interesting question to explore: How much are the results, and especially the effect of amyloid deposition on the age-related decrease of entorhinal cortex deactivation, related to the nature of the activation task used to measure deactivation?
References:
La Joie R, Landeau B, Perrotin A, Bejanin A, Egret S, Pélerin A, Mézenge F, Belliard S, de La Sayette V, Eustache F, Desgranges B, Chételat G. Intrinsic connectivity identifies the hippocampus as a main crossroad between Alzheimer's and semantic dementia-targeted networks. Neuron. 2014 Mar 19;81(6):1417-28. PubMed.
Ranganath C, Ritchey M. Two cortical systems for memory-guided behaviour. Nat Rev Neurosci. 2012 Oct;13(10):713-26. PubMed.
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