Stern Y, Habeck C, Moeller J, et al. Brain networks associated with cognitive reserve in healthy young and old adults

Department of Psychology, Columbia University, New York, New York, United States
Cerebral Cortex (Impact Factor: 8.67). 05/2005; 15(4):394-402. DOI: 10.1093/cercor/bhh142
Source: PubMed


In order to understand the brain networks that mediate cognitive reserve, we explored the relationship between subjects' network expression during the performance of a memory test and an index of cognitive reserve. Using H2(15)O positron emission tomography, we imaged 17 healthy older subjects and 20 young adults while they performed a serial recognition memory task for nonsense shapes under two conditions: low demand, with a unique shape presented in each study trial; and titrated demand, with a study list size adjusted so that each subject recognized shapes at 75% accuracy. A factor score that summarized years of education, and scores on the NART and the WAIS-R Vocabulary subtest was used as an index of cognitive reserve. The scaled subprofile model was used to identify a set of functionally connected regions (or topography) that changed in expression across the two task conditions and was differentially expressed by the young and elderly subjects. The regions most active in this topography consisted of right hippocampus, posterior insula, thalamus, and right and left operculum; we found concomitant deactivation in right lingual gyrus, inferior parietal lobe and association cortex, left posterior cingulate, and right and left calcarine cortex. Young subjects with higher cognitive reserve showed increased expression of the topography across the two task conditions. Because this topography, which is responsive to increased task demands, was differentially expressed as a function of reserve level, it may represent a neural manifestation of innate or acquired reserve. In contrast, older subjects with higher cognitive reserve showed decreased expression of the topography across tasks. This suggests some functional reorganization of the network used by the young subjects. Thus, for the old subjects this topography may represent an altered, compensatory network that is used to maintain function in the face of age-related physiological changes.

Download full-text


Available from: Harold A Sackeim
  • Source
    • "This simple individual differences approach can only detect compensation where its beneficial effects on performance outweigh those of any deleterious change that triggers it ( " successful " compensation;Zarahn et al., 2007) or if the deleterious change does not vary. However , there has been recognition in theory for some time that " partial " compensatory responses to neural insult that do not completely offset impairment may be much more common (e.g.,de Chastelaine, Wang, Minton, Muftuler, & Rugg, 2011;Duverne et al., 2009;Duarte et al., 2008;Zarahn et al., 2007;Persson et al., 2006;Daselaar & Cabeza, 2005;Stern et al., 2005;Buckner, 2004;Bäckman & Dixon, 1992). Partial compensation may be critical in supporting function but is unlikely to be most apparent in better performers and may be more prominent in poorer performers. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The "illusory truth" effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency.
    Full-text · Article · Jan 2016 · Journal of Cognitive Neuroscience
    • "Finally, a key benefit of using a rat model in studies of cognition is that dysfunction can be more readily detected as rats have fewer available mechanisms for neural compensation. Conceptually, cognitive reserve results from underlying neural mechanisms including neural reserve, the resilience of pre-existing cognitive networks, and neural compensation, which allows the use of compensatory neural resources (Stern et al. 2005). BDNF, which we found to be reduced at the transcript level in Alzheimer rats, enhances neural reserve in humans by increasing efficiency in cognitive networks underlying executive control (van Praag et al. 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In Alzheimer disease (AD), the accumulation of amyloid beta (Aβ) begins decades before cognitive symptoms and progresses from intraneuronal material to extracellular plaques. To date, however, the precise mechanism by which the early buildup of Aβ peptides leads to cognitive dysfunction remains unknown. Here, we investigate the impact of the early Aβ accumulation on temporal and frontal lobe dysfunction. We compared the performance of McGill-R-Thy1-APP transgenic AD rats with wild-type littermate controls on a visual discrimination task using a touchscreen operant platform. Subsequently, we conducted studies to establish the biochemical and molecular basis for the behavioral alterations. It was found that the presence of intraneuronal Aβ caused a severe associative learning deficit in the AD rats. This coincided with reduced nuclear translocation and genomic occupancy of the CREB co-activator, CRTC1, and decreased production of synaptic plasticity-associated transcripts Arc, c-fos, Egr1, and Bdnf. Thus, blockade of CRTC1-dependent gene expression in the early, preplaque phase of AD-like pathology provides a molecular basis for the cognitive deficits that figure so prominently in early AD.
    No preview · Article · Jan 2016 · Cerebral Cortex
  • Source
    • "During tasks with executive control demands, enhanced bilateral pFC engagement in older adults has been associated with better performance (Daselaar et al., 2015; Stern et al., 2005; Cabeza et al., 2004; Reuter-Lorenz et al., 2000), and this pattern of supplementary recruitment appears to be a function of task demand, occurring at lower, but not higher levels of executive control challenge (Cappell, Gmeindl, & Reuter-Lorenz, 2010; Mattay et al., 2006; Reuter- Lorenz & Lustig, 2005). An alternate account of age-related functional brain changes suggests that overrecruitment is maladaptive, reflecting a loss of functional specialization within the brain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Reduced executive control is a hallmark of neurocognitive aging. Poor modulation of lateral pFC activity in the context of increasing task challenge in old adults and a "failure to deactivate" the default network during cognitive control tasks have been observed. Whether these two patterns represent discrete mechanisms of neurocognitive aging or interact into older adulthood remains unknown. We examined whether altered pFC and default network dynamics co-occur during goal-directed planning over increasing levels of difficulty during performance on the Tower of London task. We used fMRI to investigate task- and age-related changes in brain activation and functional connectivity across four levels of task challenge. Frontoparietal executive control regions were activated and default network regions were suppressed during planning relative to counting performance in both groups. Older adults, unlike young, failed to modulate brain activity in executive control and default regions as planning demands increased. Critically, functional connectivity analyses revealed bilateral dorsolateral pFC coupling in young adults and dorsolateral pFC to default coupling in older adults with increased planning complexity. We propose a default-executive coupling hypothesis of aging. First, this hypothesis suggests that failure to modulate control and default network activity in response to increasing task challenge are linked in older adulthood. Second, functional brain changes involve greater coupling of lateral pFC and the default network as cognitive control demands increase in older adults. We speculate that these changes reflect an adaptive shift in cognition as older adults come to rely more upon stored representations to support goal-directed task performance.
    Full-text · Article · Sep 2015 · Journal of Cognitive Neuroscience
Show more