Recruitment of extra neural resources may allow people to maintain normal cognition despite amyloid-β (Aβ) plaques. Previous fMRI studies have reported such hyperactivation, but it is unclear whether increases represent compensation or aberrant overexcitation. We found that older adults with Aβ deposition had reduced deactivations in task-negative regions, but increased activation in task-positive regions related to more detailed memory encoding. The association between higher activity and more detailed memories suggests that Aβ-related hyperactivation is compensatory.
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Jack, C.R. et al. Lancet Neurol. 12, 207–216 (2013).
Bennett, D.A. et al. Neurology 66, 1837–1844 (2006).
Morris, J.C. et al. Ann. Neurol. 67, 122–131 (2010).
Aizenstein, H.J. et al. Arch. Neurol. 65, 1509–1517 (2008).
Sperling, R.A. et al. Alzheimers Dement. 7, 280–292 (2011).
Sperling, R.A. et al. Neuron 63, 178–188 (2009).
Mormino, E.C. et al. Cereb. Cortex 22, 1813–1823 (2012).
Dickerson, B.C. et al. Ann. Neurol. 56, 27–35 (2004).
Qin, S., van Marle, H.J.F., Hermans, E.J. & Fernández, G. J. Neurosci. 31, 8920–8927 (2011).
Naghavi, H.R. & Nyberg, L. Conscious. Cogn. 14, 390–425 (2005).
Raichle, M.E. et al. Proc. Natl. Acad. Sci. USA 98, 676–682 (2001).
Walsh, D.M. et al. Nature 416, 535–539 (2002).
Palop, J.J. & Mucke, L. Nat. Neurosci. 13, 812–818 (2010).
Oh, H. & Jagust, W.J. J. Neurosci. 33, 18425–18437 (2013).
Morcom, A.M., Li, J. & Rugg, M.D. Cereb. Cortex 17, 2491–2506 (2007).
Spreng, R.N., Wojtowicz, M. & Grady, C.L. Neurosci. Biobehav. Rev. 34, 1178–1194 (2010).
Bakker, A. et al. Neuron 74, 467–474 (2012).
O'Brien, J.L. et al. Neurology 74, 1969–1976 (2010).
Cirrito, J.R. et al. Neuron 48, 913–922 (2005).
Jagust, W.J. & Mormino, E.C. Trends Cogn. Sci. 15, 520–526 (2011).
Oh, H., Habeck, C., Madison, C. & Jagust, W. Hum. Brain Mapp. 35, 297–308 (2014).
Agosta, F. et al. Proc. Natl. Acad. Sci. USA 106, 2018–2022 (2009).
Rabinovici, G.D. et al. Neurology 68, 1205–1212 (2007).
Friston, K.J., Ashburner, J.T., Kiebel, S.J., Nichols, T.E. & Penny, W.D. Statistical Parametric Mapping: The Analysis of Functional Brain Images (Academic, 2011).
Logan, J. et al. J. Cereb. Blood Flow Metab. 16, 834–840 (1996).
Price, J.C. et al. J. Cereb. Blood Flow Metab. 25, 1528–1547 (2005).
Dale, A.M., Fischl, B. & Sereno, M.I. Neuroimage 9, 179–194 (1999).
Jenkinson, M., Beckmann, C.F., Behrens, T.E.J., Woolrich, M.W. & Smith, S.M. NeuroImage 62, 782–790 (2012).
Casanova, R. et al. Neuroimage 34, 137–143 (2007).
Yang, X., Beason-Held, L., Resnick, S.M. & Landman, B.A. Neuroimage 57, 423–430 (2011).
Van Essen, D.C. Neuroimage 28, 635–662 (2005).
We thank S. Qin for task stimuli and W. Huijbers for discussion. Supported by US National Institutes of Health grant AG034570.
The authors declare no competing financial interests.
Integrated supplementary information
A scanned encoding session was followed by an approximately 15 minute delay and 2 unscanned memory tasks. a.) During the scanned fMRI encoding session, subjects studied 150 pictures of scenes. b.) In the unscanned gist task, subjects judged whether written descriptions corresponded to scenes studied during encoding. c.) In the details task, subjects determined whether 6 written details were true or false about each of the previously studied scenes.
Activity for hits versus baseline was assessed for age and PIB effects. To distinguish between relative increases and decreases from baseline, tests of age (panel a) and PIB (panel e) were masked by task positive and negative networks (defined by contrasting hits with baseline, averaged across all groups). Plots displaying mean z-scores of significant clusters accompany masked results to better visualize underlying patterns of activity in the voxelwise analysis. Error bars represent s.e.m. a.) Greater activity for remembered gist in young compared to old PIB– subjects (warm colors). b.) Task positive regions show greater activation in young than PIB– subjects (warm colors). c.) Task negative regions show reduced deactivation in young compared to PIB– subjects (cool colors). d.) Aβ effects revealed greater activity for hits in old PIB+ compared to PIB– subjects (warm colors). e.) Task positive regions indicate greater activity in old PIB+ than PIB– subjects (warm colors). f.) Task negative regions indicate reduced deactivation in old PIB+ compared to PIB– subjects (cool colors). Results are thresholded at p<0.05, cluster corrected for multiple comparisons.
Activity for hits versus misses was assessed for age and PIB effects. a.) Age effects revealed greater activity for hits compared to misses in young compared to old PIB– subjects (warm colors) in lateral posterior and inferior regions. There was greater activity for hits compared to misses in old PIB– compared to young subjects (cool colors) in prefrontal cortex and mid-line structures. b.) Aβ effects revealed greater activity for hits compared to misses in old PIB– compared to PIB+ subjects (warm colors). Results are thresholded at p<0.05, cluster corrected for multiple comparisons. The PIB effect when comparing hits versus misses appears to be inconsistent with results from the comparison of hits to baseline. It should be noted that the above results are primarily driven by group differences on miss trials, suggesting that this condition serves as an incomparable baseline by which to compare activity for hits.
The relationship between linear increases of activity across detail level and PIB Index was tested on a voxelwise basis in all older subjects controlling for age, hit rate and gray matter. Results are thresholded at p<0.05, cluster corrected for multiple comparisons. Greater parametric increases were positively related to the amount of amyloid deposition as measure by PIB Index (warm colors). The results are similar to those when subjects were dichotomized into PIB+ and PIB– groups.
To explore whether parametric increases in activity vary with the amount of amyloid deposition, linear contrast values were extracted from regions in the task positive network demonstrating significant PIB effects (clusters displayed in Fig. 2e). These values were regressed against the PIB Index of PIB+ subjects, controlling for age, hit rate and gray matter. There is a negative relationship [B=–1.89, t(11)=–2.413, p= 0.034] such that parametric increases are reduced at high levels of amyloid accumulation. Contrast values of the old PIB– group are displayed on the left for comparison purposes. It should be noted that the linear contrast values of subjects with a high PIB Index are still greater than much of the PIB– group.
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Elman, J., Oh, H., Madison, C. et al. Neural compensation in older people with brain amyloid-β deposition. Nat Neurosci 17, 1316–1318 (2014). https://doi.org/10.1038/nn.3806
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