scholarly journals Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

2019 ◽  
Author(s):  
Shauna M. Stark ◽  
Amy Frithsen ◽  
Craig E.L. Stark

AbstractAging causes hippocampal circuit alterations that differentially affect hippocampal subfields and are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and PHC and PRC. This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior shift in older adults between hippocampus and PHC was predictive of lure discrimination performance on the MST, suggesting that this shift may reflect a compensation mechanism that preserves memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related A-P shift in hippocampal connectivity may also contribute significantly to memory decline in older adults.

2021 ◽  
Author(s):  
Seyma Bayrak ◽  
Reinder Vos de Wael ◽  
H. Lina Schaare ◽  
Benoit Caldairou ◽  
Andrea Bernasconi ◽  
...  

The hippocampal formation is an uniquely infolded anatomical structure in the medial temporal lobe and it is involved in a broad range of cognitive and emotional processes. It consists of anatomically and functionally different subfields, including the subiculum (SUB), cornu ammonis areas (CA), and the dentate gyrus (DG). However, despite ample research on learning and plasticity of the hippocampal formation, heritability of its structural and functional organization is not fully known. To answer this question, we extracted microstructurally sensitive neuroimaging (i.e., T1w/T2w ratios) and resting-state functional connectivity information along hippocampal subfield surfaces from a sample of healthy twins and unrelated individuals of the Human Connectome Project Dataset. Our findings robustly demonstrate that functional connectivity and local microstructure of hippocampal subfields are highly heritable. Second, we found marked covariation and genetic correlation between the microstructure of the hippocampal subfields and the isocortex, indicating shared genetic factors influencing the microstructure of the hippocampus and isocortex. In both structural and functional measures, we observed a dissociation of cortical projections across subfields. In sum, our study shows that the functional and structural organization of the hippocampal formation is heritable and has a genetic relation to divergent macroscale functional networks within the isocortex.


2020 ◽  
Vol 11 ◽  
Author(s):  
Natasha Y. Fourquet ◽  
Tara K. Patterson ◽  
Changrui Li ◽  
Alan D. Castel ◽  
Barbara J. Knowlton

Previous work has shown that memory performance in older adults is affected by activation of a stereotype of age-related memory decline. In the present experiment, we examined whether stereotype threat would affect metamemory in older adults; that is, whether under stereotype threat they make poorer judgments about what they could remember. We tested older adults (MAge = 66.18 years) on a task in which participants viewed words paired with point values and “bet” on whether they could later recall each word. If they bet on and recalled a word, they gained those points, but if they bet on and failed to recall a word, they lost those points. Thus, this task required participants to monitor how much they could remember and prioritize high value items. Participants performed this task over six lists of items either under stereotype threat about age-related memory decline or not under stereotype threat. Participants from both groups performed similarly on initial lists, but on later lists, participants under stereotype threat showed impaired performance as indicated by a lower average point score and a lower average gamma coefficient. The results suggest that a modest effect of stereotype threat on recall combined with a modest effect on metacognitive judgments to result in a performance deficit. This pattern of results may reflect an effect of stereotype threat on executive control reducing the ability to strategically use memory.


2021 ◽  
pp. 1-17
Author(s):  
Junyeon Won ◽  
Daniel D. Callow ◽  
Gabriel S. Pena ◽  
Leslie S. Jordan ◽  
Naomi A. Arnold-Nedimala ◽  
...  

Background: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction. Objective: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance). Methods: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression. Results: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants. Conclusion: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.


2018 ◽  
Vol 115 (40) ◽  
pp. 10160-10165 ◽  
Author(s):  
Anna Rieckmann ◽  
Keith A. Johnson ◽  
Reisa A. Sperling ◽  
Randy L. Buckner ◽  
Trey Hedden

Age-related changes in striatal function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65–86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2–7 years). Analyses showed that cortical–caudate functional connectivity was less differentiated in older compared with younger adults (n= 63, age 18–32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less “decoupling” of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical–caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.


2016 ◽  
Vol 28 (6) ◽  
pp. 792-802 ◽  
Author(s):  
Bengi Baran ◽  
Janna Mantua ◽  
Rebecca M. C. Spencer

Consolidation of declarative memories has been associated with slow wave sleep in young adults. Previous work suggests that, in spite of changes in sleep, sleep-dependent consolidation of declarative memories may be preserved with aging, although reduced relative to young adults. Previous work on young adults shows that, with consolidation, retrieval of declarative memories gradually becomes independent of the hippocampus. To investigate whether memories are similarly reorganized over sleep at the neural level, we compared functional brain activation associated with word pair recall following a nap and equivalent wake in young and older adults. SWS during the nap predicted better subsequent memory recall and was negatively associated with retrieval-related hippocampal activation in young adults. In contrast, in older adults there was no relationship between sleep and memory performance or with retrieval-related hippocampal activation. Furthermore, compared with young adults, postnap memory retrieval in older adults required strong functional connectivity of the hippocampus with the PFC, whereas there were no differences between young and older adults in the functional connectivity of the hippocampus following wakefulness. These results suggest that, although neural reorganization takes place over sleep in older adults, the shift is unique from that seen in young adults, perhaps reflecting memories at an earlier stage of stabilization.


2019 ◽  
Vol 3 (1) ◽  
pp. 173-194 ◽  
Author(s):  
Simon W. Davis ◽  
Amanda Szymanski ◽  
Homa Boms ◽  
Thomas Fink ◽  
Roberto Cabeza

Understanding the precise relation between functional connectivity and structural (white matter) connectivity and how these relationships account for cognitive changes in older adults are major challenges for neuroscience. We investigate these issues using an approach in which structural equation modeling (SEM) is employed to integrate functional and structural connectivity data from younger and older adults ( n = 62), analyzed with a common framework based on regions connected by canonical tract groups (CTGs). CTGs (e.g., uncinate fasciculus) serve as a common currency between functional and structural connectivity matrices, and ensure equivalent sparsity in connectome information. We used this approach to investigate the neural mechanisms supporting memory for items and memory for associations, and how they are affected by healthy aging. We found that different structural and functional CTGs made independent contributions to source and item memory performance, suggesting that both forms of connectivity underlie age-related differences in specific forms of memory. Furthermore, the relationship between functional and structural connectivity was best explained by a general relationship between latent constructs—a relationship absent in any specific CTG group. These results provide insights into the relationship between structural and functional connectivity patterns, and elucidate their relative contribution to age-related differences in source memory performance.


2014 ◽  
Vol 28 (3) ◽  
pp. 148-161 ◽  
Author(s):  
David Friedman ◽  
Ray Johnson

A cardinal feature of aging is a decline in episodic memory (EM). Nevertheless, there is evidence that some older adults may be able to “compensate” for failures in recollection-based processing by recruiting brain regions and cognitive processes not normally recruited by the young. We review the evidence suggesting that age-related declines in EM performance and recollection-related brain activity (left-parietal EM effect; LPEM) are due to altered processing at encoding. We describe results from our laboratory on differences in encoding- and retrieval-related activity between young and older adults. We then show that, relative to the young, in older adults brain activity at encoding is reduced over a brain region believed to be crucial for successful semantic elaboration in a 400–1,400-ms interval (left inferior prefrontal cortex, LIPFC; Johnson, Nessler, & Friedman, 2013 ; Nessler, Friedman, Johnson, & Bersick, 2007 ; Nessler, Johnson, Bersick, & Friedman, 2006 ). This reduced brain activity is associated with diminished subsequent recognition-memory performance and the LPEM at retrieval. We provide evidence for this premise by demonstrating that disrupting encoding-related processes during this 400–1,400-ms interval in young adults affords causal support for the hypothesis that the reduction over LIPFC during encoding produces the hallmarks of an age-related EM deficit: normal semantic retrieval at encoding, reduced subsequent episodic recognition accuracy, free recall, and the LPEM. Finally, we show that the reduced LPEM in young adults is associated with “additional” brain activity over similar brain areas as those activated when older adults show deficient retrieval. Hence, rather than supporting the compensation hypothesis, these data are more consistent with the scaffolding hypothesis, in which the recruitment of additional cognitive processes is an adaptive response across the life span in the face of momentary increases in task demand due to poorly-encoded episodic memories.


2020 ◽  
Author(s):  
Francesca Farina ◽  
Marc Patrick Bennett ◽  
James William Griffith ◽  
Bert Lenaert

Evidence concerning the impact of fear of memory decline on health-related outcomes is limited. To determine the relationship between fear-avoidance of memory decline, quality of life and subjective memory in older adults using a novel scale to measure fear of memory decline. Sixty-seven older adults (59-81 years) completed a 23-item self-report questionnaire designed to capture experiential, cognitive and behavioral components of fear of memory decline, known as the fear and avoidance of memory decline (FAM) scale. Memory performance was assessed using the Wechsler Memory Scale (WMS-IV) and the Memory Failures Scale (MFS). General anxiety was assessed using the Depression, Anxiety and Stress Scales (DASS) and the Geriatric Anxiety Inventory (GAI). Quality of life was assessed using the Older Person’s Quality of Life scale (OPQOL-35). The FAM scale demonstrated good reliability and validity. Three latent factors were observed including: (1) fear-avoidance, (2) problematic beliefs and (3) resilience. After adjusting for age, education, memory performance and general anxiety, higher fear-avoidance predicted lower quality of life (p=.021) and increased memory failures (p=.022). Increased fear of memory decline predicts lower quality of life and subjective memory failures in healthy older adults. Based on these findings, we propose a preliminary fear-avoidance model that explains the development and maintenance of dementia-related functional disability in terms of psychological processes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Tang Chang ◽  
Stephanie K. Langella ◽  
Yichuan Tang ◽  
Sahar Ahmad ◽  
Han Zhang ◽  
...  

AbstractThe hippocampus is critical for learning and memory and may be separated into anatomically-defined hippocampal subfields (aHPSFs). Hippocampal functional networks, particularly during resting state, are generally analyzed using aHPSFs as seed regions, with the underlying assumption that the function within a subfield is homogeneous, yet heterogeneous between subfields. However, several prior studies have observed similar resting-state functional connectivity (FC) profiles between aHPSFs. Alternatively, data-driven approaches investigate hippocampal functional organization without a priori assumptions. However, insufficient spatial resolution may result in a number of caveats concerning the reliability of the results. Hence, we developed a functional Magnetic Resonance Imaging (fMRI) sequence on a 7 T MR scanner achieving 0.94 mm isotropic resolution with a TR of 2 s and brain-wide coverage to (1) investigate the functional organization within hippocampus at rest, and (2) compare the brain-wide FC associated with fine-grained aHPSFs and functionally-defined hippocampal subfields (fHPSFs). This study showed that fHPSFs were arranged along the longitudinal axis that were not comparable to the lamellar structures of aHPSFs. For brain-wide FC, the fHPSFs rather than aHPSFs revealed that a number of fHPSFs connected specifically with some of the functional networks. Different functional networks also showed preferential connections with different portions of hippocampal subfields.


2021 ◽  
pp. 1-13
Author(s):  
Alexandra L. Clark ◽  
Alexandra J. Weigand ◽  
Kelsey R. Thomas ◽  
Seraphina K. Solders ◽  
Lisa Delano-Wood ◽  
...  

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s <  0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.


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