scholarly journals The functional brain favours segregated modular connectivity at old age unless targeted by neurodegeneration

2018 ◽  
Author(s):  
Luis R Peraza ◽  
John T O’Brien ◽  
Andrew Blamire ◽  
Marcus Kaiser ◽  
John-Paul Taylor

AbstractBrain’s modular connectivity gives this organ resilience and adaptability. The ageing process alters the human brain, leading to modifications to its organised modularity and these changes are further accentuated by neurodegeneration, leading to disorganisation. To understand this further, we analysed modular variability—heterogeneity of modules—and modular dissociation—detachment from segregated connectivity—in two ageing cohorts and a mixed cohort of neurodegenerative diseases. Our results revealed that the brain follows a universal pattern of modular variability that matches highly active and metacognitive brain regions: the association cortices. We also proved that in ageing the brain moves towards a modular segregated structure despite presenting with increased modular heterogeneity—modules in older adults are not only segregated but their shape and size are more variable than in young adults. In the presence of neurodegeneration, the brain maintains its segregated connectivity globally but not locally; the modular brain shows patterns of differentiated pathology.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xue Chen ◽  
Joe Necus ◽  
Luis R. Peraza ◽  
Ramtin Mehraram ◽  
Yanjiang Wang ◽  
...  

AbstractBrain’s modular connectivity gives this organ resilience and adaptability. The ageing process alters the organised modularity of the brain and these changes are further accentuated by neurodegeneration, leading to disorganisation. To understand this further, we analysed modular variability—heterogeneity of modules—and modular dissociation—detachment from segregated connectivity—in two ageing cohorts and a mixed cohort of neurodegenerative diseases. Our results revealed that the brain follows a universal pattern of high modular variability in metacognitive brain regions: the association cortices. The brain in ageing moves towards a segregated modular structure despite presenting with increased modular heterogeneity—modules in older adults are not only segregated, but their shape and size are more variable than in young adults. In the presence of neurodegeneration, the brain maintains its segregated connectivity globally but not locally, and this is particularly visible in dementia with Lewy bodies and Parkinson’s disease dementia; overall, the modular brain shows patterns of differentiated pathology.


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.


2021 ◽  
Vol 11 (1) ◽  
pp. 118
Author(s):  
Blake R. Neyland ◽  
Christina E. Hugenschmidt ◽  
Robert G. Lyday ◽  
Jonathan H. Burdette ◽  
Laura D. Baker ◽  
...  

Elucidating the neural correlates of mobility is critical given the increasing population of older adults and age-associated mobility disability. In the current study, we applied graph theory to cross-sectional data to characterize functional brain networks generated from functional magnetic resonance imaging data both at rest and during a motor imagery (MI) task. Our MI task is derived from the Mobility Assessment Tool–short form (MAT-sf), which predicts performance on a 400 m walk, and the Short Physical Performance Battery (SPPB). Participants (n = 157) were from the Brain Networks and Mobility (B-NET) Study (mean age = 76.1 ± 4.3; % female = 55.4; % African American = 8.3; mean years of education = 15.7 ± 2.5). We used community structure analyses to partition functional brain networks into communities, or subnetworks, of highly interconnected regions. Global brain network community structure decreased during the MI task when compared to the resting state. We also examined the community structure of the default mode network (DMN), sensorimotor network (SMN), and the dorsal attention network (DAN) across the study population. The DMN and SMN exhibited a task-driven decline in consistency across the group when comparing the MI task to the resting state. The DAN, however, displayed an increase in consistency during the MI task. To our knowledge, this is the first study to use graph theory and network community structure to characterize the effects of a MI task, such as the MAT-sf, on overall brain network organization in older adults.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xueyan Fu ◽  
Will Patterson ◽  
Gregory Dolnikowski ◽  
Bess Dawson-Hughes ◽  
Martha Morris ◽  
...  

Abstract Objectives Very little is known about the forms of vitamin D and vitamin K in the human brain. The objective of this study is to evaluate concentrations of vitamin D and vitamin K forms in human brain and their correlations across four human brain regions. Methods Vitamin D [D3, 25(OH)D and 1,25(OH)2D] and vitamin K [phylloquinone and menaquinone-4 (MK4)] concentrations were measured by LC/MS/MS and HPLC, respectively, in four brain regions from post-mortem samples obtained from participants in the Rush Memory and Aging Project (n = 130, mean age 82 yrs, 81% female). The brain regions analyzed were the mid-frontal cortex (MF) and mid-temporal cortex (MT) [two regions important for memory in Alzheimer's Disease (AD)], the cerebellum (CR, a region not affected by AD), and the anterior watershed white matter (AWS, a region associated with vascular disease). The correlations among the vitamin forms across brain regions were calculated using Spearman rank order correlation coefficients. Significance was set at P < 0.001. Results The average concentrations of vitamin D3, 25(OH)D and MK4 were 604 pg/g, 535 pg/g, and 3.4 pmol/g, respectively. 25(OH)D and MK4 were detected in >95% of the brain samples. Nearly 92% of 1,25(OH)2D and 80% of phylloquinone samples had concentrations below the limit of assay detection (LOD) 1,25(OH)2D = 20 ng/g, phylloquinone = 0.1 pmol/g). Vitamin D3 and 25(OH)D concentrations were positively correlated across all four regions (all Spearman r ≥ 0.78, P < 0.0001). The 1,25(OH)2D was significantly correlated between the MF and CR regions only (Spearman r = 0.30, P < 0.001, all other P ≥ 0.002). MK4 and PK were positively correlated across the four regions studied (MK4 all Spearman r ≥ 0.78, phylloquinone r ≥ 0.49, all P < 0.001). Conclusions To the best of our knowledge, this study is the first evaluation of the concentrations of vitamin D and vitamin K forms in multiple regions of the human brain. Overall, the vitamin D and vitamin K forms were each positively correlated across the four brain regions studied. Future studies are needed to clarify the roles of these nutrients in AD and dementia. Funding Sources National Institute of Aging.


2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.


2020 ◽  
Vol 36 (3) ◽  
pp. 156-162
Author(s):  
Rebecca L. Krupenevich ◽  
Ross H. Miller

The causes of age-related differences in lower-extremity joint moments and powers are unknown. The purpose of this study was to determine the effects of highly physically active older adults walking with (1) a step length similar to young adults and (2) an upright trunk posture, on hip and ankle joint kinetics. The authors hypothesized that, compared with their self-selected walking mechanics, older adults would exhibit decreased hip kinetics and increased ankle kinetics when prescribed a young adult step length, and would exhibit decreased hip extension moments when maintaining an upright trunk posture during walking. A total of 12 active older adults (67 [5] y) and 13 active young adults (21 [3] y) walked at 1.3 m/s. The older adults also walked at 1.3 m/s with step lengths prescribed from height-matched young adults and, in a separate condition, walked with an upright trunk. The older adults did not display larger ankle kinetics or smaller hip kinetics in either condition compared to walking with a self-selected step length. These findings indicate that step length and trunk position do not primarily contribute to age-related differences in kinetics in highly active older adults and should serve as a starting point for investigating alternative explanations.


2020 ◽  
Vol 10 (1) ◽  
pp. 31 ◽  
Author(s):  
Smart Ikechukwu Mbagwu ◽  
Luis Filgueira

Cerebral microvascular endothelial cells (CMVECs) line the vascular system of the brain and are the chief cells in the formation and function of the blood brain barrier (BBB). These cells are heterogeneous along the cerebral vasculature and any dysfunctional state in these cells can result in a local loss of function of the BBB in any region of the brain. There is currently no report on the distribution and variation of the CMVECs in different brain regions in humans. This study investigated microcirculation in the adult human brain by the characterization of the expression pattern of brain endothelial cell markers in different brain regions. Five different brain regions consisting of the visual cortex, the hippocampus, the precentral gyrus, the postcentral gyrus, and the rhinal cortex obtained from three normal adult human brain specimens were studied and analyzed for the expression of the endothelial cell markers: cluster of differentiation 31 (CD31) and von-Willebrand-Factor (vWF) through immunohistochemistry. We observed differences in the expression pattern of CD31 and vWF between the gray matter and the white matter in the brain regions. Furthermore, there were also regional variations in the pattern of expression of the endothelial cell biomarkers. Thus, this suggests differences in the nature of vascularization in various regions of the human brain. These observations also suggest the existence of variation in structure and function of different brain regions, which could reflect in the pathophysiological outcomes in a diseased state.


2020 ◽  
Author(s):  
Adrien Folville ◽  
Jon Simons ◽  
Arnaud D'Argembeau ◽  
Christine Bastin

It has been frequently described that older adults subjectively report the vividness of their memories as being as high, or even higher, than young adults, despite poorer objective memory performance and/or lower activity in the associated brain regions. Here, we review studies that examined age-related changes in the cognitive and neural basis of the subjective experience of remembering. Together, these studies reveal that older adults assign subjective memory ratings that are as high or higher than young adults but rely on retrieved memory details to a lesser extent. We discuss potential mechanisms underlying this observation. Overestimation of subjective ratings may stem from metamemory changes, psycho-social factors or methodological issues. As for poorer calibration of the ratings, this may be explained by the fact that older adults rely on/weight other types of information (conceptual knowledge, personal memories, and socioemotional or gist aspects of the memory trace) to a greater extent than young adults when judging the subjective vividness of their memories. We further highlight that a desirable avenue for future research would be to investigate how subjective ratings follow the richness of the corresponding mental representations in other cognitive operations than episodic memory and in other populations than healthy older adults. Finally, we recommend that future studies explore the bases of the subjective sense of remembering across the lifespan while considering recent accounts focusing both on individual and collective/shared aspects of recollection.


2019 ◽  
Author(s):  
Verena R. Sommer ◽  
Yana Fandakova ◽  
Thomas H. Grandy ◽  
Yee Lee Shing ◽  
Markus Werkle-Bergner ◽  
...  

AbstractAge-related memory decline is associated with changes in neural functioning but little is known about how aging affects the quality of information representation in the brain. Whereas a long-standing hypothesis of the aging literature links cognitive impairments to less distinct neural representations in old age, memory studies have shown that high similarity between activity patterns benefits memory performance for the respective stimuli. Here, we addressed this apparent conflict by investigating between-item representational similarity in 50 younger (19–27 years old) and 63 older (63–75 years old) human adults (male and female) who studied scene-word associations using a mnemonic imagery strategy while electroencephalography was recorded. We compared the similarity of spatiotemporal frequency patterns elicited during encoding of items with different subsequent memory fate. Compared to younger adults, older adults’ memory representations were more similar to each other but items that elicited the most similar activity patterns early in the encoding trial were those that were best remembered by older adults. In contrast, young adults’ memory performance benefited from decreased similarity between earlier and later periods in the encoding trials, which might reflect their better success in forming unique memorable mental images of the joint picture–word pair. Our results advance the understanding of the representational properties that give rise to memory quality as well as how these properties change in the course of aging.Significance statementDeclining memory abilities are one of the most evident limitations for humans when growing older. Despite recent advances of our understanding of how the brain represents and stores information in distributed activation patterns, little is known about how the quality of information representation changes during aging and thus affects memory performance. We investigated how the similarity between neural representations relates to subsequent memory quality in younger and older adults. We present novel evidence that the interaction of pattern similarity and memory performance differs between age groups: Older adults benefited from increased similarity during early encoding whereas young adults benefited from decreased similarity between early and later encoding. These results provide insights into the nature of memory and age-related memory deficits.


2021 ◽  
Author(s):  
Sara N Gallant ◽  
Briana L Kennedy ◽  
Shelby L Bachman ◽  
Ringo Huang ◽  
Tae-Ho Lee ◽  
...  

During a challenge or emotional experience, increases in arousal help us focus on the most salient or relevant details and ignore distracting stimuli. The noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate this adaptive attentional selectivity. However, age-related changes in the noradrenergic system and attention networks in the brain may reduce the efficiency of arousal to modulate selective processing in older adults. In the current neuroimaging study, we examined age differences in how arousal affects bottom-up attention to category-selective stimuli differing in perceptual salience. We found a dissociation in how arousal modulates selective processing in the young and older brain. In young adults, emotionally arousing sounds enhanced selective incidental memory and brain activity in the extrastriate body area for salient versus non-salient images of bodies. Older adults showed no such advantage in selective processing under arousal. These age differences could not be attributed to changes in the arousal response or less neural distinctiveness in old age. Rather, our results suggest that, relative to young adults, older adults become less effective at focusing on salient over non-salient details during increases in emotional arousal.


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