scholarly journals Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests

2021 ◽  
Author(s):  
Zack Hall ◽  
Billy Chien ◽  
Yi Zhao ◽  
Shannon L. Risacher ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
White Matter ◽  
Interaction Analysis ◽  
Memory Function ◽  
Structural Connectivity ◽  
Neurocognitive Performance ◽  
Association Patterns ◽  
Neurocognitive Tests ◽  
White Matter Connectivity ◽  
Network Metrics

AbstractTau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity.

scholarly journals Tau Deposition and Structural Connectivity Demonstrate Differential Association Patterns with Neurocognitive Tests

2021 ◽  
Author(s):  
Zack Hall ◽  
Billy Chien ◽  
Yi Zhao ◽  
Shannon L. Risacher ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
White Matter ◽  
Interaction Analysis ◽  
Memory Function ◽  
Structural Connectivity ◽  
Neurocognitive Performance ◽  
Association Patterns ◽  
Neurocognitive Tests ◽  
White Matter Connectivity ◽  
Network Metrics

Abstract Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity

scholarly journals The convergence and divergence of episodic and semantic functions across lateral parietal cortex

2020 ◽  
Author(s):  
Gina F. Humphreys ◽  
JeYoung Jung ◽  
Matthew A. Lambon Ralph
Keyword(s):  
White Matter ◽  
Semantic Memory ◽  
Parietal Cortex ◽  
Memory Retrieval ◽  
Task Difficulty ◽  
Structural Connectivity ◽  
Angular Gyrus ◽  
Episodic Retrieval ◽  
Semantic Retrieval ◽  
White Matter Connectivity

AbstractSeveral decades of neuropsychological and neuroimaging research have highlighted the importance of lateral parietal cortex (LPC) across a myriad of cognitive domains. Yet, despite the prominence of this region the underlying function of LPC remains unclear. Two domains that have placed particular emphasis on LPC involvement are semantic memory and episodic memory retrieval. From each domain, sophisticated models have been proposed as to the underlying function, as well as the more domain-general that LPC is engaged by any form of internally-directed cognition (episodic and semantic retrieval both being examples if this process). Here we directly address these alternatives using a combination of fMRI and DTI white-matter connectivity data. The results show that ventral LPC (angular gyrus) was positively engaged during episodic retrieval but disengaged during semantic memory retrieval. In addition, the level of activity negatively varied with task difficulty in the semantic task whereas episodic activation was independent of difficulty. In contrast, dorsal LPC (intraparietal sulcus) showed domain general activation that was positively correlated with task difficulty. In terms of structural connectivity, a dorsal-ventral and anterior-posterior gradient of connectivity was found to different processing networks (e.g., mid-angular gyrus (AG) connected with episodic retrieval). We propose a unifying model in which LPC as a whole might share a common underlying function (e.g., multimodal buffering) and variations across subregions arise due to differences in the underlying white matter connectivity.

scholarly journals Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder

2019 ◽  
Vol 45 (6) ◽  
pp. 1367-1378 ◽  
Author(s):  
Ellen Ji ◽  
Pamela Guevara ◽  
Miguel Guevara ◽  
Antoine Grigis ◽  
Nicole Labra ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Language Processing ◽  
Structural Connectivity ◽  
Anterior Cingulate ◽  
Precentral Gyrus ◽  
Psychiatric Illnesses ◽  
And Function ◽  
Post Hoc

Abstract Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

scholarly journals Effects of Alzheimer’s and Vascular Pathologies on Structural Connectivity in Early- and Late-Onset Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Wha Jin Lee ◽  
Cindy W. Yoon ◽  
Sung-Woo Kim ◽  
Hye Jin Jeong ◽  
Seongho Seo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Hyperintensities ◽  
Late Onset ◽  
Structural Connectivity ◽  
Resonance Imaging ◽  
White Matter Connectivity

Early- and late-onset Alzheimer’s disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.

scholarly journals Bundle-Specific Axon Diameter Index as a New Contrast to Differentiate White Matter Tracts

2021 ◽  
Vol 15 ◽  
Author(s):  
Muhamed Barakovic ◽  
Gabriel Girard ◽  
Simona Schiavi ◽  
David Romascano ◽  
Maxime Descoteaux ◽  
...  
Keyword(s):  
White Matter ◽  
Internal Capsule ◽  
Mean Value ◽  
Axon Diameter ◽  
Posterior Limb ◽  
Weighted Magnetic Resonance Imaging ◽  
The Central Nervous System ◽  
Index Value ◽  
White Matter Connectivity

In the central nervous system of primates, several pathways are characterized by different spectra of axon diameters. In vivo methods, based on diffusion-weighted magnetic resonance imaging, can provide axon diameter index estimates non-invasively. However, such methods report voxel-wise estimates, which vary from voxel-to-voxel for the same white matter bundle due to partial volume contributions from other pathways having different microstructure properties. Here, we propose a novel microstructure-informed tractography approach, COMMITAxSize, to resolve axon diameter index estimates at the streamline level, thus making the estimates invariant along trajectories. Compared to previously proposed voxel-wise methods, our formulation allows the estimation of a distinct axon diameter index value for each streamline, directly, furnishing a complementary measure to the existing calculation of the mean value along the bundle. We demonstrate the favourable performance of our approach comparing our estimates with existing histologically-derived measurements performed in the corpus callosum and the posterior limb of the internal capsule. Overall, our method provides a more robust estimation of the axon diameter index of pathways by jointly estimating the microstructure properties of the tissue and the macroscopic organisation of the white matter connectivity.

scholarly journals Effects of Acupuncture on Cancer-Related Cognitive Impairment in Chinese Gynecological Cancer Patients: A Pilot Cohort Study

2018 ◽  
Vol 17 (3) ◽  
pp. 737-746 ◽  
Author(s):  
Yingchun Zeng ◽  
Andy S. K. Cheng ◽  
Ting Song ◽  
Xiujie Sheng ◽  
Shaojing Wang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cognitive Impairment ◽  
White Matter ◽  
Pilot Study ◽  
Cancer Patients ◽  
Gynecological Cancer ◽  
Structural Connectivity ◽  
Control Group ◽  
Healthy Controls ◽  
Neurocognitive Tests

Background: Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. Methods: This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. Results: This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA ( N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture’s ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. Conclusion: This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment.

Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss

2001 ◽  
Vol 19 (2) ◽  
pp. 472-479 ◽  
Author(s):  
Raymond K. Mulhern ◽  
Shawna L. Palmer ◽  
Wilburn E. Reddick ◽  
John O. Glass ◽  
Larry E. Kun ◽  
...  
Keyword(s):  
White Matter ◽  
Sustained Attention ◽  
Verbal Memory ◽  
Young Age ◽  
Factual Knowledge ◽  
Test Results ◽  
Neurocognitive Deficits ◽  
Neurocognitive Performance ◽  
Neurocognitive Tests ◽  
Neurocognitive Test

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.

scholarly journals Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition

2016 ◽  
Vol 22 (2) ◽  
pp. 191-204 ◽  
Author(s):  
Martina Ly ◽  
Nagesh Adluru ◽  
Daniel J. Destiche ◽  
Sharon Y. Lu ◽  
Jennifer M. Oh ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Negative Impact ◽  
Interaction Analysis ◽  
Memory Performance ◽  
Structural Connectivity ◽  
Middle Frontal Gyrus ◽  
Age Related ◽  
White Matter Microstructure ◽  
Psychophysiological Interaction

AbstractObjectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain–at least in part–connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191–204)

scholarly journals Breastfeeding Duration Is Associated with Regional, but Not Global, Differences in White Matter Tracts

2019 ◽  
Vol 10 (1) ◽  
pp. 19
Author(s):  
Christopher E. Bauer ◽  
James W. Lewis ◽  
Julie Brefczynski-Lewis ◽  
Chris Frum ◽  
Margeaux M. Schade ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Positive Association ◽  
Breastfeeding Duration ◽  
Neurocognitive Performance ◽  
Superior Longitudinal Fasciculus ◽  
Significant Positive Association ◽  
White Matter Tracts ◽  
White Matter Connectivity

Extended breastfeeding through infancy confers benefits on neurocognitive performance and intelligence tests, though few have examined the biological basis of these effects. To investigate correlations with breastfeeding, we examined the major white matter tracts in 4–8 year-old children using diffusion tensor imaging and volumetric measurements of the corpus callosum. We found a significant correlation between the duration of infant breastfeeding and fractional anisotropy scores in left-lateralized white matter tracts, including the left superior longitudinal fasciculus and left angular bundle, which is indicative of greater intrahemispheric connectivity. However, in contrast to expectations from earlier studies, no correlations were observed with corpus callosum size, and thus no correlations were observed when using such measures of global interhemispheric white matter connectivity development. These findings suggest a complex but significant positive association between breastfeeding duration and white matter connectivity, including in pathways known to be functionally relevant for reading and language development.

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