scholarly journals White matter microstructure predicts focal and broad functional brain dedifferentiation in normal aging

2019 ◽  
Author(s):  
Jenny R. Rieck ◽  
Karen M. Rodrigue ◽  
Denise C. Park ◽  
Kristen M. Kennedy

AbstractVentral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed “dedifferentiation”. The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20-89, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as functional magnetic resonance imaging to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure-function relationship became weaker with age and was no longer significant after age 70. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.

2020 ◽  
Vol 32 (8) ◽  
pp. 1536-1549
Author(s):  
Jenny R. Rieck ◽  
Karen M. Rodrigue ◽  
Denise C. Park ◽  
Kristen M. Kennedy

Ventral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed “dedifferentiation.” The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20–89 years, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as fMRI to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure–function relationship became weaker with age and was no longer significant after the age of 70 years. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.


2016 ◽  
Vol 113 (17) ◽  
pp. 4853-4858 ◽  
Author(s):  
Robin L. Carhart-Harris ◽  
Suresh Muthukumaraswamy ◽  
Leor Roseman ◽  
Mendel Kaelen ◽  
Wouter Droog ◽  
...  

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.


2011 ◽  
Vol 23 (12) ◽  
pp. 4094-4105 ◽  
Author(s):  
Chien-Te Wu ◽  
Melissa E. Libertus ◽  
Karen L. Meyerhoff ◽  
Marty G. Woldorff

Several major cognitive neuroscience models have posited that focal spatial attention is required to integrate different features of an object to form a coherent perception of it within a complex visual scene. Although many behavioral studies have supported this view, some have suggested that complex perceptual discrimination can be performed even with substantially reduced focal spatial attention, calling into question the complexity of object representation that can be achieved without focused spatial attention. In the present study, we took a cognitive neuroscience approach to this problem by recording cognition-related brain activity both to help resolve the questions about the role of focal spatial attention in object categorization processes and to investigate the underlying neural mechanisms, focusing particularly on the temporal cascade of these attentional and perceptual processes in visual cortex. More specifically, we recorded electrical brain activity in humans engaged in a specially designed cued visual search paradigm to probe the object-related visual processing before and during the transition from distributed to focal spatial attention. The onset times of the color popout cueing information, indicating where within an object array the subject was to shift attention, was parametrically varied relative to the presentation of the array (i.e., either occurring simultaneously or being delayed by 50 or 100 msec). The electrophysiological results demonstrate that some levels of object-specific representation can be formed in parallel for multiple items across the visual field under spatially distributed attention, before focal spatial attention is allocated to any of them. The object discrimination process appears to be subsequently amplified as soon as focal spatial attention is directed to a specific location and object. This set of novel neurophysiological findings thus provides important new insights on fundamental issues that have been long-debated in cognitive neuroscience concerning both object-related processing and the role of attention.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lars Michels ◽  
Philipp Stämpfli ◽  
Njoud Aldusary ◽  
Marco Piccirelli ◽  
Patrick Freund ◽  
...  

Background: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant binocular flickering or pixilation of the whole visual field. The underlying neurophysiological and structural alterations remain elusive.Methods: In this study, we included patients (final n = 14, five dropouts; five females, mean age: 32 years) with visual snow syndrome (VSS) and age- and sex-matched controls (final n = 20, 6 dropouts, 13 females, mean age: 28.2 years). We applied diffusion tensor imaging to examine possible white matter (WM) alterations in patients with VSS.Results: The patient group demonstrated higher (p-corrected < 0.05, adjusted for age and sex) fractional anisotropy (FA) and lower mean diffusivity (MD) and radial diffusivity (RD) compared to controls. These changes were seen in the prefrontal WM (including the inferior fronto-occipital fascicle), temporal and occipital WM, superior and middle longitudinal fascicle, and sagittal stratum. When additionally corrected for migraine or tinnitus—dominant comorbidities in VSS—similar group differences were seen for FA and RD, but less pronounced.Conclusions: Our results indicate that patients with VSS present WM alterations in parts of the visual cortex and outside the visual cortex. As parts of the inferior fronto-occipital fascicle and sagittal stratum are associated with visual processing and visual conceptualisation, our results suggest that the WM alterations in these regions may indicate atypical visual processing in patients with VSS. Yet, the frequent presence of migraine and other comorbidities such as tinnitus in VSS makes it difficult to attribute WM disruptions solely to VSS.


2013 ◽  
Vol 25 (2) ◽  
pp. 188-202 ◽  
Author(s):  
Viola S. Störmer ◽  
Shu-Chen Li ◽  
Hauke R. Heekeren ◽  
Ulman Lindenberger

Declines in selective attention are one of the sources contributing to age-related impairments in a broad range of cognitive functions. Most previous research on mechanisms underlying older adults' selection deficits has studied the deployment of visual attention to static objects and features. Here we investigate neural correlates of age-related differences in spatial attention to multiple objects as they move. We used a multiple object tracking task, in which younger and older adults were asked to keep track of moving target objects that moved randomly in the visual field among irrelevant distractor objects. By recording the brain's electrophysiological responses during the tracking period, we were able to delineate neural processing for targets and distractors at early stages of visual processing (∼100–300 msec). Older adults showed less selective attentional modulation in the early phase of the visual P1 component (100–125 msec) than younger adults, indicating that early selection is compromised in old age. However, with a 25-msec delay relative to younger adults, older adults showed distinct processing of targets (125–150 msec), that is, a delayed yet intact attentional modulation. The magnitude of this delayed attentional modulation was related to tracking performance in older adults. The amplitude of the N1 component (175–210 msec) was smaller in older adults than in younger adults, and the target amplification effect of this component was also smaller in older relative to younger adults. Overall, these results indicate that normal aging affects the efficiency and timing of early visual processing during multiple object tracking.


2021 ◽  
Vol 12 ◽  
Author(s):  
Katelyn V. Batterman ◽  
Payton E. Cabrera ◽  
Tara L. Moore ◽  
Douglas L. Rosene

Normal aging is characterized by declines in processing speed, learning, memory, and executive function even in the absence of neurodegenerative diseases such as Alzheimer's Disease (AD). In normal aging monkeys and humans, neuronal loss does not account for cognitive impairment. Instead, loss of white matter volume and an accumulation of myelin sheath pathology begins in middle age and is associated with cognitive decline. It is unknown what causes this myelin pathology, but it likely involves increased neuroinflammation in white matter and failures in oligodendrocyte function (maturation and repair). In frontal white matter tracts vulnerable to myelin damage, microglia become chronically reactive and secrete harmful pro-inflammatory cytokines. Despite being in a phagocytic state, these microglia are ineffective at phagocytosing accruing myelin debris, which directly inhibits myelin sheath repair. Here, we asked whether reported age-related increases in pro-inflammatory markers were accompanied by an adaptive immune response involving T cells. We quantified T cells with immunohistochemistry in the brains of 34 cognitively characterized monkeys and found an age-related increase in perivascular T cells that surround CNS vasculature. We found a surprising age-related increase in T cells that infiltrate the white matter parenchyma. In the cingulum bundle the percentage of these parenchymal T cells increased with age relative to those in the perivascular space. In contrast, infiltrating T cells were rarely found in surrounding gray matter regions. We assessed whether T cell infiltration correlated with fibrinogen extravasation from the vasculature as a measure of BBB leakiness and found no correlation, suggesting that T cell infiltration is not a result of passive extravasation. Importantly, the density of T cells in the cingulum bundle correlated with microglial reactivity and with cognitive impairment. This is the first demonstration that T cell infiltration of white matter is associated with cognitive decline in the normal aging monkey.


2020 ◽  
Vol 40 (12) ◽  
pp. 2475-2490 ◽  
Author(s):  
Ben Schager ◽  
Craig E Brown

Vessel loss in the aging brain is commonly reported, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we imaged and quantified vessel length, tortuosity and width in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical grey matter regions, while some regions (visual cortex, amygdala, thalamus) showed no decline with aging. Regions supplied by the anterior cerebral artery were more vulnerable to loss than those supplied by middle or posterior cerebral arteries. Vessel width and tortuosity generally increased with age but neither reliably predicted regional vessel loss. Since capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning, we hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. These findings indicate that age-related vessel loss is region specific and can be explained, at least partially, by regional susceptibilities to capillary plugging.


2012 ◽  
Vol 507 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Ming-Chung Ho ◽  
Chia-Yi Chou ◽  
Chin-Fei Huang ◽  
Yu-Te Lin ◽  
Ching-Sen Shih ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 766-766
Author(s):  
Qu Tian ◽  
Luigi Ferrucci

Abstract The functional consequences of the aging brain include several aspects of physical and cognitive decline that ultimately cause loss of mobility and dementia. Although in certain individuals, the cognitive and physical correlates of the aging brain occur in parallel, others show decline in one of these functional parameters. Underlying mechanism of this complex process that lead to different manifestations is not well understood. Proposed mechanisms include brain structural changes, tau pathology, specific white matter degeneration, metabolic derangement mostly including lipids metabolism and others. This symposium aims to address the complexity of the aging brain by showcasing studies that span the continuum from normal aging to dementia using data from the Baltimore Longitudinal Study of Aging (BLSA). The wealth of neuroimaging and phenotype data from the BLSA provides the unique opportunity to investigate neural substrates and predictors of aging phenotype, and mechanisms of age-related neurodegeneration and pathology, such as dementia, and loss of mobility. First, we identify multimodal neuroimaging predictors of important aging phenotypes of gait decline (Sargent/Tian) and memory decline (Bilgel). Second, using advanced quantitative MRI technology, we investigate underlying mechanisms of age-related white matter degeneration through potential oligodendrocyte metabolism (Bouhrara). Third, we demonstrate unique cognitive and neuroimaging profiles of dual memory and gait decline (Tian) and neural substrates for bile acids, the primary cholesterol breakdown products (Varma) in relation to dementia. We seek to generate discussions of mechanisms of the aging brain that connect the age-related phenotypes, such as decline of mobility and cognition, to the development of dementia.


2021 ◽  
Vol 13 ◽  
Author(s):  
Hsin-Yu Lin ◽  
Chu-Chung Huang ◽  
Kun-Hsien Chou ◽  
Albert C. Yang ◽  
Chun-Yi Zac Lo ◽  
...  

The cerebral cortex is a highly convoluted structure with distinct morphologic features, namely the gyri and sulci, which are associated with the functional segregation or integration in the human brain. During the lifespan, the brain atrophy that is accompanied by cognitive decline is a well-accepted aging phenotype. However, the detailed patterns of cortical folding change during aging, especially the changing age-dependencies of gyri and sulci, which is essential to brain functioning, remain unclear. In this study, we investigated the morphology of the gyral and sulcal regions from pial and white matter surfaces using MR imaging data of 417 healthy participants across adulthood to old age (21–92 years). To elucidate the age-related changes in the cortical pattern, we fitted cortical thickness and intrinsic curvature of gyri and sulci using the quadratic model to evaluate their age-dependencies during normal aging. Our findings show that comparing to gyri, the sulcal thinning is the most prominent pattern during the aging process, and the gyrification of pial and white matter surfaces were also affected differently, which implies the vulnerability of functional segregation during aging. Taken together, we propose a morphological model of aging that may provide a framework for understanding the mechanisms underlying gray matter degeneration.


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