White matter pathways associated with working memory in normal aging

Introduction

Previous studies by our group have found that white matter integrity as determined by Diffusion Tensor Imaging (DTI) is associated with working memory decline. It has been proposed that subtle white matter integrity loss may lead to the disruption of working memory in particular because it relies on the dynamic and reiterative activity of cortico-cortical pathways.

Methods

DTI and working memory measurement were acquired for 99 adults from our GENIE study of healthy middle aged and elderly individuals. Voxel-based statistics were used to identify clusters of voxels in mean diffusivity images specifically associated with variations in working memory performance. Tractography then identified the cortico-cortical white matter pathways passing through these clusters, between the temporal, parietal and frontal cortices.

Results

Significant clusters were identified which were associated with working memory in the white matter of the temporal and frontal lobes, the cingulate gyrus, and in the thalamus. The tracts that passed through these clusters included the superior parietal lobule pathway, the medial temporo-frontal pathway, the uncinate fasciculus, the fronto-parietal fasciculus, and the cingulum.

Conclusions

Significant clusters were identified in the white matter that were associated with working memory performance. Tractography performed through these clusters identified white matter fiber tracts which pass between grey matter regions known to be activated by working memory tasks and also mirror working memory pathways suggested by previous functional connectivity imaging.     

Quantification of age- and gender-related changes in diffusion tensor imaging indices in deep grey matter of the normal human brain

This study aimed to demonstrate age-related and gender-related changes in diffusion tensor imaging (DTI) indices of deep grey matter (GM) nuclei of the normal human brain. DTI was performed on 142 subjects (age: 10-52 years). Regions of interest were placed on the caudate nucleus (CN), putamen, globus pallidus, frontal white matter (WM), occipital WM, anterior and posterior limb of internal capsule, genu of the corpus callosum and splenium in all participants. The quadratic regression model was used to describe age-related and gender-related changes in DTI indices for GM and WM. We observed increased fractional anisotropy (FA) values with age up to adulthood in GM, and a rise up to the third decade of life followed by a decrease in FA for WM. We observed higher FA values in males compared to females in CN and all WM regions. Decreased mean diffusivity with age was observed in GM and WM irrespective of gender. This normative data may be valuable in the diagnosis of neurodegenerative diseases.     

多发性硬化患者MRI扩散张量成像脑白质束示踪的三维仿真定量研究

目的 研究多发性硬化(MS)患者脑白质束示踪的三维仿真影像表现,评价其定量结果与残疾状态扩展评分(EDSS)的相关性. 方法 对28例MS患者(MS组)和28名健康自愿者(对照组)通过MRI扩散张量成像扫描进行脑白质束示踪,测量示踪纤维数和示踪纤维密度,并应用配对t检验比较两组间差异;对MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值和FA值进行方差分析,使用线性回归模型计算MS组脑白质束示踪的定量结果与EDSS评分的相关性. 结果 在MS组脑白质束示踪三维仿真图像中可直接观察到脑白质束的受损和减少.MS组的示踪纤维数(2220±100)和示踪纤维密度(0.75±0.04)明显低予对照组(2750±70、0.93±0.02),差异有统计学意义(P＜0.05).MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值依次下降,分别为(1.23 ±0.13)× 10-3 mm2/s、(0.76±0.09)× 10-3 mm2/s、(0.63 ±0.10)×10-3 mm2/s; FA值依次升高,分别为0.24±0.04、0.42±0.07、0.48±0.06,差异均有统计学意义(P＜0.05).MS组示踪纤维数和示踪纤维密度都与EDSS评分呈负相关关系(r=-0.782,P=0.000;r=-0.771,P=0.000). 结论 通过MRI扩散张量成像扫描进行脑白质束示踪可以发现MS患者脑白质束的受损情况,其较常规MRI能提供更多的空间信息.     

精神分裂症患者全脑白质纤维弥散张量成像的初步研究

目的运用能够提示白质纤维(white matter,WM)完整性的弥散张量成像(diffusion tensor imaging,DTI)技术,探讨精神分裂症患者全脑白质纤维是否受到损害。方法对21例精神分裂症患者(患者组)和21名健康人(对照组)进行全脑DTI扫描,用SPM2(Statistical Parametric Maps,SPM)软件对图像进行处理,采用以像素为基础的分析方法(voxel-based analysis,VBA)对两组的分数各向异性(fractional anisotropy,FA)值进行组间比较。结果患者组下列脑区的FA值显著低于对照组(P<0·001):左侧额眶区和右侧额中回的白质、双侧颞下回白质、双侧顶叶内侧白质、右侧前扣带、双侧海马、双侧大脑脚、双侧岛叶、右侧放射冠和右侧小脑上脚。结论精神分裂症多个部位脑白质纤维的完整性受到破坏。     

The effects of puberty on white matter development in boys

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone.     

Verbal working memory performance correlates with regional white matter structures in the frontoparietal regions

Working memory is the limited capacity storage system involved in the maintenance and manipulation of information over short periods of time. Previous imaging studies have suggested that the frontoparietal regions are activated during working memory tasks; a putative association between the structure of the frontoparietal regions and working memory performance has been suggested based on the analysis of individuals with varying pathologies. This study aimed to identify correlations between white matter and individual differences in verbal working memory performance in normal young subjects. We performed voxel-based morphometry (VBM) analyses using T1-weighted structural images as well as voxel-based analyses of fractional anisotropy (FA) using diffusion tensor imaging. Using the letter span task, we measured verbal working memory performance in normal young adult men and women (mean age, 21.7 years, SD = 1.44; 42 men and 13 women). We observed positive correlations between working memory performance and regional white matter volume (rWMV) in the frontoparietal regions. In addition, FA was found to be positively correlated with verbal working memory performance in a white matter region adjacent to the right precuneus. These regions are consistently recruited by working memory. Our findings suggest that, among normal young subjects, verbal working memory performance is associated with various regions that are recruited during working memory tasks, and this association is not limited to specific parts of the working memory network.     

Direct evidence of the relationship between brain metastatic adenocarcinoma and white matter fibers: A fiber dissection and diffusion tensor imaging tractography study

It is commonly known that brain metastases usually have clear boundaries in magnetic resonance imaging. However, little is known regarding the trajectory of white matter fibers around the tumors, especially using the fiber dissection technique. Here, we focused on the anatomical interaction between white matter fibers and the tumor, using the fiber dissection in a postmortem brain with metastatic tumor and compared the findings with those of diffusion tensor imaging (DTI) tractography. One postmortem human brain hemisphere with metastatic adenocarcinoma in the Broca’s area was dissected using fiber dissection following the Klingler’s method. In order to compare the in vitro and in vivo results, additional brains from 15 patients with metastatic adenocarcinomas, the volumes of which were comparable to that of the adenocarcinoma in the brain used for fiber dissection, were analyzed using DTI tractographic reconstruction. Morphological findings of white matter bundles running around the tumor were compared between the two techniques. In the fiber dissection technique, the superior longitudinal fascicle, arcuate fascicle, and frontal aslant tract could be dissected, and the white matter bundles were curved and retracted to avoid the tumor. In all the cases analyzed, white matter fibers or streamlines surrounding the tumor avoided the lesion. Using the fiber dissection technique, this is the first direct evidence to elucidate the anatomy of white matter fibers affected by a metastatic brain. This suggests that brain metastatic adenocarcinoma is an intra-axial neoplasm with extra-axial white matter structures.     

Regional differences in cerebral asymmetries of human cortical white matter

The form of the structural asymmetries across the cerebral hemispheres, that support well-established functional asymmetries, are not well understood. Although, many previous studies have investigated structural differences in areas associated with strong functional asymmetries, such as language processes, regions of the brain with less well established functional laterality have received less attention. The current study aims to address this by exploring global white matter asymmetries of the healthy human brain using diffusion tensor imaging (DTI) and tractography. DTI was conducted on twenty-nine healthy right-handed males, and pathways from the four major lobes were reconstructed using probabilistic tractography. Mean FA, parallel and perpendicular diffusion values were calculated and compared across hemispheres for each pathway generated. Significant asymmetries in the parietal (rightward asymmetry) and occipital (leftward asymmetry) pathways were found in FA measures. However, asymmetric patterns in parallel and/or perpendicular diffusion were observed in all four lobes, even in pathways with symmetrical FA. For instance, significant rightward asymmetry in parallel diffusion was found in the parietal and frontal lobes, whereas significant leftward asymmetry was found in the temporal and occipital lobes. We suggest that these different patterns of diffusion asymmetry reflect differences in microanatomy that support the known patterns of differential functional asymmetry. The different directions of anatomical asymmetry support the notion that there may be a number of different lateralising influences operating in the brain.     

Aging,cognition, and the brain: effects of age-related variation in white matter integrity on neuropsychological function

Alterations in brain structure are viewed as neurobiological indicators which are closely tied to cognitive changes in healthy human aging. The current study used diffusion tensor imaging (DTI) tractography to investigate the relationship between age, brain variation in white matter (WM) integrity, and cognitive function. Sixteen younger adults (aged 20–28 years) and 18 healthy older adults (aged 60–75 years) underwent DTI scanning and a standardized battery of neuropsychological measures. Behaviorally, older adults exhibited poorer performance on multiple cognitive measures compared to younger adults. At the neural level, the effects of aging on theWM integrity were evident within interhemispheric (the anterior portion of corpus callosum) and transverse (the right uncinate fasciculus) fibers of the frontal regions, and the cingulum-angular fibers. Our correlation results showed that age-related WM differentially influenced cognitive function, with increased fractional anisotropy values in both the anterior corpus callosum and the right cingulum/angular fibers positively correlated with performance on the visuospatial task in older adults. Moreover, mediation analysis further revealed that the WM tract integrity of the frontal interhemspheric fibers was a significant mediator of age–visuospatial performance relation in older adults, but not in younger adults. These findings support the vulnerability of the frontal WM fibers to normal aging and push forward our understanding of cognitive aging by providing a more integrative view of the neural basis of linkages among aging, cognition, and brain.     

Drawing connections between white matter and numerical and mathematical cognition: A literature review

In this review we examine white matter tracts that may support numerical and mathematical abilities and whether abnormalities in these pathways are associated with deficits in numerical and mathematical abilities. Diffusion tensor imaging (DTI) yields indices of white matter integrity and can provide information about the axonal organization of the brain. A growing body of research is using DTI to investigate how individual differences in brain microstructures relate to different numerical and mathematical abilities. Several tracts have been associated with numerical and mathematical abilities such as the superior longitudinal fasciculus, the posterior segment of the corpus callosum, inferior longitudinal fasciculus, corona radiata, and the corticospinal tract. Impairments in mathematics tend to be associated with atypical white matter structures within similar regions, especially in inferior parietal and temporal tracts. This systematic review summarizes and critically examines the current literature on white matter correlates of numerical and mathematical abilities, and provides directions for future research.     

White matter: beyond focal disconnection

The complex phenomenology of white matter dementia and many neuropsychiatric disorders implies that they originate from involvement of distributed neural networks, and white matter neuropathology is increasingly implicated in the pathogenesis of these network disconnection syndromes. White matter disorders produce functional asynchrony of interdependent cerebral regions subserving normal cognitive and emotional functions. Accumulating evidence suggests that white matter dementia primarily reflects disturbed frontal systems connectivity, whereas disruption of frontal and temporal lobe systems is implicated in the pathogenesis of neuropsychiatric disorders. Continued study of normal and abnormal white matter promises to help resolve challenging problems in behavioral neurology and neuropsychiatry.     

The relationship between episodic long-term memory and white matter integrity in normal aging

It has been proposed that episodic long-term memory (LTM) declines in normal aging and may be affected by disruption of white matter networks. This was explored in 104 healthy adults aged 50-90 years in the GENIE study; white matter integrity was assessed using diffusion tensor imaging (DTI) in large regions of interest, with additional measures of white matter hyperintensities (WMH), normalized brain and hippocampal volumes. LTM was compared with executive function, working memory and information processing speed. LTM correlated significantly with DTI, WMH and whole brain volume, but not with hippocampal volume. Using linear regression, only DTI measures explained the variance (approximately 19%) in LTM; mediational analyses explored the extent to which other cognitive functions mediate the association between DTI changes and memory. The results suggest that reduced LTM performance in normal aging is related to reduced integrity of a distributed network dependent on white matter pathways supporting episodic memory.     

Altered white matter integrity in primary restless legs syndrome patients: diffusion tensor imaging study

Abstract

Objectives:

A prior diffusion tensor imaging (DTI) of restless legs syndrome (RLS) subjects found alterations in brain white matter (WM). The aim of this study was to explore the possible mechanism of altered integrity of brain WM in RLS patients.

Methods:

The DTI measurement was performed in 22 subjects with RLS and 22 age-matched control subjects. Using a voxel-based analysis, fractional anisotropy (FA) and axial and radial diffusivities (AD and RD) were compared between RLS and control subjects with a two-sample t-test, and correlation analysis was performed in RLS subjects.

Results:

RLS subjects demonstrated decreased FA in the genu of the corpus callosum and frontal WM adjacent to the inferior frontal gyrus compared with the control subjects. For areas of decreased FA, both the AD and RD were higher than that in the control subjects.

Discussion:

Our findings suggest that loss of axonal density and myelin may account for WM changes seen in a prior study of RLS subjects.     

A systematic review of diffusion weighted MRI studies of white matter microstructure in adolescent substance users

Recent studies using diffusion weighted magnetic resonance imaging (DW-MRI) have provided evidence of abnormal white matter microstructure in adults with substance use disorders (SUDs). While there is a growing body of research using DW-MRI to examine the impact of heavy substance use during adolescence, this literature has not been systematically reviewed. Online databases were searched for DW-MRI studies of adolescent substance users, and 10 studies fulfilled the inclusion and exclusion criteria. We identified consistent evidence for abnormal white matter microstructure in neocortical association pathways as well as in projection and thalamic pathways. Dose-dependent relationships between DW-MRI measures and patterns of substance use were also observed. The consistency of these findings with DW-MRI research in adults suggests that white matter microstructure is impacted in the early stages of heavy substance use. However, given the largely cross-sectional nature of the available data, important questions remain regarding the extent to which white matter abnormalities are a consequence of adolescent exposure to alcohol and other drugs of abuse or reflect pre-existing differences that increase risk for SUDs.     

Cognitive impairment in progressive supranuclear palsy-Richardson’s syndrome is related to white matter damage

IntroductionBeside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs.MethodsWe enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level.ResultsPSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from −0.80 to 0.74).ConclusionsPSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs.     

高功能孤独症患儿全脑白质纤维的弥散张量成像研究

目的 分析高功能孤独症患儿的全脑白质纤维的完整性.方法 对18例高功能孤独症患儿(病例组)以及10名年龄、性别、智商与病例组相匹配的健康儿童(对照组)进行全脑弥散张量成像(DTI)测量;应用基于体素的分析方法,比较两组全脑各向异性分数(FA)的差异.使用Spearman相关分析,分析病例组各感兴趣区FA值与儿章期孤独症评定表(CARS)总分及各项目之间的关系.结果 与对照组相比,病例组右侧额下回、左侧额中回及右侧颞下回邻近白质的FA值低(分别为0.67±0.10、0.57±0.09、0.50 ±0.12),左顶上小叶邻近白质的FA值高(0.55±0.15;P<0.001).病例组左额中回邻近白质的FA值与CARS中的与非生命物体的关系的得分呈负相关(r=-0.63,P=0.005).结论 高功能孤独症患儿多个部位的脑白质纤维的完整性受到破坏.     

Investigating the association between sleep quality and diffusion-derived structural integrity of white matter in early adolescence

IntroductionPoor sleep quality has been linked to reduced neural connectivity through decreased white matter (WM) structural integrity. WM tract development has been shown to continue throughout adolescence with studies reporting positive correlations between diffusion-derived estimates of structural integrity and reduced sleep quality in adult samples. Few studies have investigated this relationship exclusively within a sample of young adolescents.MethodsN = 51 participants aged 12 years (M = 151.5 months, SD = 4 months) completed a self-report questionnaire which included the Pittsburgh Sleep Quality Index (PSQI) and underwent Diffusion Tensor Imaging (DTI) as part of their baseline assessment in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Fractional anisotropy (FA) were extracted using Tract-Based Spatial Statistics (TBSS) to investigate associations between sleep quality and WM integrity across the brain.ResultsSignificant correlations were found between the posterior limb of the internal capsule and the PSQI total sleep quality and sleep latency scores. There was also a significant difference in sleep duration between male and female participants.ConclusionThese findings provide an important insight of the impact that sleep may have on early adolescent WM development. Ongoing longitudinal assessment of sleep on WM development across adolescence is likely to provide further important information about how WM maturation relates to variations in sleep quality as circadian rhythm changes occur during middle and late adolescence.     

Association between white matter microstructure,executive functions,and processing speed in older adults: The impact of vascular health

Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate–severe hypertensive BP range (43–87 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.