scholarly journals The Temporal Dedifferentiation of Global Brain Signal Fluctuations During Human Brain Aging

2021 ◽  
Author(s):  
Yifeng Wang ◽  
Yujia Ao ◽  
Chengxiao Yang ◽  
Juan Kou ◽  
Lihui Huang ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Brain Aging ◽  
Power Spectra ◽  
Head Motion ◽  
Aging Brain ◽  
Functional Magnetic Resonance ◽  
Hemodynamic Response Function ◽  
Brain Organization ◽  
Global Signal ◽  
Global Brain

Abstract The variation of brain organization as healthy aging has been discussed widely using resting-state functional magnetic resonance imaging. Previous conclusions may be misinterpreted without considering the effects of global signal (GS) on local activities and the variation of GS as age is still unknown. To fill this gap, we systematically examined the correlation between GS fluctuations and age. Correlations were evaluated between age and parameters of GS fluctuations including power at each frequency point, spectral centroids, and trends of power spectra. Data with hemodynamic response function (HRF) de-convolution and head motion parameter were further analyzed to test whether the age effect of GS fluctuations has neural origins. GS fluctuations varied as age in three ways. First, general GS power reductions were found in both time and frequency dimensions. Second, the GS power at lower frequencies transferring to higher frequencies was observed. Third, more evenly distributed power across frequencies was showed in aging brain. These trends were partly impacted by HRF de-convolution, but not by head motion. These results suggest that GS fluctuations are weaker and more evenly distributed across frequencies in elderly brain. It may indicate the temporal dedifferentiation hypothesis of brain aging from the global signal level.

scholarly journals Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-Vianney Haure-Mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Normal Aging ◽  
Aging Brain ◽  
Normal Brain ◽  
Older Individuals ◽  
Cognitively Normal

Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.

scholarly journals Resting state connectivity during total sleep deprivation: A functional magnetic resonance study

2020 ◽  
Author(s):  
Vivianne Jakobsson
Keyword(s):  
Magnetic Resonance ◽  
Sleep Deprivation ◽  
Resting State ◽  
Resting State Fmri ◽  
Head Motion ◽  
Functional Magnetic Resonance ◽  
Global Signal ◽  
Significant Difference ◽  
Before And After ◽  
Eyes Open

Introduction: Sleep deprivation is a common problem that may have serious consequences. In this study, functional magnetic resonance imaging (fMRI), a technique frequently used to study networks in the brain, was used to investigate the resting state of the sleep deprived brain, in order to discover whether this state affects the intrinsic connectivity and the global signal variability (GSV). Aims: To investigate whether GSV increases with sleep deprivation. Material and Methods: In this cross over study 18 healthy participants, age 20 – 30, underwent in randomized order resting-state fMRI for 20min before and after 24h sleep deprivation. We extracted the global signal, calculated the standard deviation per participant, and analysed it with respect to sleep depraved yes/no, head motion, eyes open/closed and self-evaluation of sleepiness using Karolinska Sleepiness Score (KSS). Results: We found that GSV was higher during sleep deprivation (0.3362 ± 0.0241, p<0.0001) without KSS data. With KSS, sleep deprivation was not significant (0.0619 ± 0.1145, p=0.5889). High KSS rating had a significant effect on GSV (0.1497 ± 0.0409, p=0.0003), as had head motion (1.7974 ± 0.1539, p<0.0001). There was no significant difference between having eyes open or closed (0.0126 ± 0.0578, p=0.8278), and no significant increase for each time period of 20s in the scanner (0.0065 ± 0.0021, p=0.0029). Conclusions: We found that the global signal variation is increased by sleep deprivation and sleepiness. More specific conclusions cannot be made from our data so far.

scholarly journals Replicating Global Brain Connectivity as an Imaging Marker for Depression – Influence of Preprocessing Strategies and Randomized Placebo-Controlled Ketamine Treatment

2019 ◽  
Author(s):  
Christoph Kraus ◽  
Anahit Mkrtchian ◽  
Bashkim Kadriu ◽  
Allison C. Nugent ◽  
Carlos A. Zarate ◽  
...  
Keyword(s):  
Antidepressant Treatment ◽  
Brain Connectivity ◽  
Physiological Parameter ◽  
Functional Magnetic Resonance ◽  
Major Depressive ◽  
Global Signal ◽  
Z Scores ◽  
Independent Replication ◽  
Global Brain ◽  
Large Clusters

AbstractMajor depressive disorder (MDD) is associated with altered global brain connectivity (GBC), as assessed via resting state functional magnetic resonance imaging (rsfMRI). Previous studies found that antidepressant treatment with ketamine normalized aberrant GBC changes in the prefrontal and cingulate cortices, warranting further investigations of GBC as a putative imaging marker. However, the results were only obtained via global signal regression (GSR). This study is an independent replication of that analysis using a separate dataset. GBC was analyzed in 28 individuals with MDD and 22 healthy controls (HCs) at baseline, post-placebo, and post-ketamine. To investigate the effects of preprocessing, three distinct pipelines were used: 1) regression of white matter (WM)/cerebrospinal fluid (CSF) signals only (BASE); 2) WM/CSF+GSR (GSR); and 3) WM/CSF+physiological parameter regression (PHYSIO). Compared to PHYSIO and BASE regression, GSR reduced Fisher Z-scores (Fz-scores) in large clusters. PHYSIO did not resemble GBC preprocessed with GSR (GBCr). Reduced GBCr was observed in individuals with MDD at baseline in the anterior and medial cingulate cortices, as well as in the prefrontal cortex. Significant results were only found with GSR. Ketamine had no effect compared to baseline or placebo in either group. These results concur with several studies that used GSR to study GBC. Altered GBCr was observed in the cingulate and prefrontal cortices, but ketamine treatment had no effect. Further investigations are warranted into disease-specific components of global fMRI signals that may drive these results and of GBCr as a potential imaging marker in MDD.

scholarly journals Altered Global Brain Signal during Physiologic, Pharmacologic, and Pathologic States of Unconsciousness in Humans and Rats

2020 ◽  
Vol 132 (6) ◽  
pp. 1392-1406 ◽  
Author(s):  
Sean Tanabe ◽  
Zirui Huang ◽  
Jun Zhang ◽  
Yali Chen ◽  
Stuart Fogel ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Signal Amplitude ◽  
Global Network ◽  
Unresponsive Wakefulness Syndrome ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Temporal Coordination ◽  
Global Signal ◽  
Global Brain

Abstract Background Consciousness is supported by integrated brain activity across widespread functionally segregated networks. The functional magnetic resonance imaging–derived global brain signal is a candidate marker for a conscious state, and thus the authors hypothesized that unconsciousness would be accompanied by a loss of global temporal coordination, with specific patterns of decoupling between local regions and global activity differentiating among various unconscious states. Methods Functional magnetic resonance imaging global signals were studied in physiologic, pharmacologic, and pathologic states of unconsciousness in human natural sleep (n = 9), propofol anesthesia (humans, n = 14; male rats, n = 12), and neuropathological patients (n = 21). The global signal amplitude as well as the correlation between global signal and signals of local voxels were quantified. The former reflects the net strength of global temporal coordination, and the latter yields global signal topography. Results A profound reduction of global signal amplitude was seen consistently across the various unconscious states: wakefulness (median [1st, 3rd quartile], 0.46 [0.21, 0.50]) versus non-rapid eye movement stage 3 of sleep (0.30 [0.24, 0.32]; P = 0.035), wakefulness (0.36 [0.31, 0.42]) versus general anesthesia (0.25 [0.21, 0.28]; P = 0.001), healthy controls (0.30 [0.27, 0.37]) versus unresponsive wakefulness syndrome (0.22 [0.15, 0.24]; P < 0.001), and low dose (0.07 [0.06, 0.08]) versus high dose of propofol (0.04 [0.03, 0.05]; P = 0.028) in rats. Furthermore, non-rapid eye movement stage 3 of sleep was characterized by a decoupling of sensory and attention networks from the global network. General anesthesia and unresponsive wakefulness syndrome were characterized by a dissociation of the majority of functional networks from the global network. This decoupling, however, was dominated by distinct neuroanatomic foci (e.g., precuneus and anterior cingulate cortices). Conclusions The global temporal coordination of various modules across the brain may distinguish the coarse-grained state of consciousness versus unconsciousness, while the relationship between the global and local signals may define the particular qualities of a particular unconscious state. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies

2020 ◽  
Vol 30 (10) ◽  
pp. 5544-5559 ◽  
Author(s):  
Jonathan D Power ◽  
Charles J Lynch ◽  
Babatunde Adeyemo ◽  
Steven E Petersen
Keyword(s):  
Resting State ◽  
Resting State Fmri ◽  
Critical Event ◽  
Head Motion ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Decay Properties ◽  
Signal Decay ◽  
Biological Variables ◽  
Related Approach

Abstract This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like “Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties”. Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability.

scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

Aging Brain, Aging Mind

1992 ◽  
Vol 267 (3) ◽  
pp. 134-142 ◽  
Author(s):  
Dennis J. Selkoe
Keyword(s):  
Brain Aging ◽  
Aging Brain

scholarly journals A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hongli Shi ◽  
Xing Ge ◽  
Xi Ma ◽  
Mingxuan Zheng ◽  
Xiaoying Cui ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Dietary Fiber ◽  
Brain Aging ◽  
Synaptic Proteins ◽  
Aging Brain ◽  
Normal Brain ◽  
Fiber Intake ◽  
Synaptic Ultrastructure

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.

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