Distinctive alterations of the cingulum bundle during aging and Alzheimer's disease

Brain imaging studies have revealed frontal disruption during aging and parieto-temporal disruption during Alzheimer's disease (AD). The present study aims at developing a specific method based on precise anatomical landmarks for assessing the integrity all along the course of the cingulum bundle, so as to determine if it presents the classical aging and AD dissociation. Five regions of interest (ROIs) were placed on fractional anisotropy (FA) maps all along the cingulum in 15 young (Gyoung), 15 70-year-old (Gold), and 15 AD subjects (Galz). An age-related decrease of FA occurred in the anterior part of the bundle. Moreover, a specific alteration of the supero-posterior region of the cingulum during AD was observed since mean FA values as well as mean number of fibers were significantly decreased in Galz compared to Gold and Gyoung. This multiple ROIs placement allows for revealing distinctive alterations of the cingulum bundle during aging and AD, which could constitute the anatomical basis for the distinctive functional disconnection recently described in the literature using functional connectivity at rest.     

Effects of aging and calorie restriction on white matter in rhesus macaques

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging.     

Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.     

纤维跟踪技术在模拟显示人脑联络纤维中的应用

目的：应用弥散张量（DTI）纤维跟踪技术来模拟显示脑的联络纤维，探讨结果与经典解剖学知识的一致性。方法：对1个志愿者行单次激发回波平面弥散张量成像，利用纤维跟踪技术来模拟显示其联络纤维，并观察与经典解剖学知识的一致性。结果：通过选择恰当的感兴趣区，各向异性阈值、角度阈值、步长和体素内采样数目等参数，利用弥散张量纤维跟踪技术可模拟显示扣带、上枕额束、下枕额束、钩束、下纵束等联络纤维。结论：利用弥散张量纤维跟踪技术可模拟显示人脑联络纤维，且与经典解剖学有高度一致性，是在活体中研究人脑联络纤维的一种新方法。     

Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study

Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.     

Testing the white matter retrogenesis hypothesis of cognitive aging

The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging.     

Clinical correlations of microstructural changes in progressive supranuclear palsy

In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both “intrinsic” and “extrinsic” frontal lobe dysfunction, likely related to cerebellar disconnection.     

Developmental dyscalculia: a dysconnection syndrome?

Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.     

Structural correlates of cognitive domains in normal aging with diffusion tensor imaging

The involvement of brain structures in specific cognitive functions is not straightforward. In order to characterize the brain micro-structural correlates of cognitive domains, 52 healthy subjects, age 25–82 years, completed a computerized neuropsychological battery and were scanned using magnetic resonance diffusion tensor imaging. Factor analysis of 44 different cognitive scores was performed, isolating three cognitive domains—executive function, information processing speed and memory. Partial correlation was conducted between DTI parameters and each of the three cognitive domains controlling for age and motor function. Regions showing significant correlations with cognitive domains are domain-specific and are consistent with previous knowledge. While executive function was correlated with diffusion tensor imaging (DTI) parameters in frontal white matter and in the superior longitudinal fasciculus, information processing speed was correlated with DTI parameters in the cingulum, corona radiata, inferior longitudinal fasciculus, parietal white matter and in the thalamus. Memory performance was correlated with DTI measures in temporal and frontal gray matter and white matter regions, including the cingulate cortex and the parahippocampus. Thus, inter-subject variability in cognitive performance and tissue morphology, as expressed by diffusion tensor magnetic resonance imaging, can be used to relate tissue microstructure with cognitive performance and to provide information to corroborate other functional localization techniques.     

Influence of citalopram and environmental temperature on exercise-induced changes in BDNF

Differences and similarities in microstructural white matter alterations between bipolar I and bipolar II disorder were investigated. Twelve patients with bipolar I disorder, 12 patients with bipolar II disorder and 22 healthy controls underwent diffusion tensor imaging. Fractional anisotropy (FA) and mean apparent diffusion coefficient (ADC) maps were compared between groups using voxel-based whole brain analyses. Both bipolar I and II groups had a FA decrease in the corpus callosum, cingulate and right prefrontal regions, and a ADC increase in the medial frontal, anterior cingulate, insular and temporal regions, compared to controls. The bipolar I group had a FA decrease in the right temporal white matter and a ADC increase in the frontal, temporal, parietal and thalamic regions, compared to the bipolar II group. The results suggest disrupted integrity of commissural fibers and white matter in the anterior paralimbic structures in bipolar disorder. Relative sparing of the dorsal system and long association fibers may differentiate bipolar II from I disorder.     

Right lateralized white matter abnormalities in first-episode,drug-naive paranoid schizophrenia

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.     

精神分裂症白质损害与发病年龄的弥散张量成像研究

目的:应用弥散张量成像(DTI)比较精神分裂症患者脑白质与正常人群间的差异,并探究各向异性比值(FA)的改变与发病年龄之间的相关性。方法:纳入27例精神分裂症患者和29名性别、年龄及受教育程度相匹配的健康对照。两组研究对象均接受头颅磁共振检测。患者组按照发病年龄分为早发组(发病年龄18岁)和成年发病组(发病年龄≥18岁)。采用基于体素的分析方法,分别比较患者组和对照组、早发组和成年发病组之间FA值的差异,并在控制性别、病程和药物剂量影响的前提下,分析FA值与患者发病年龄的相关性。结果:与健康对照比较,患者组在右侧上纵束、右侧放射冠上部的FA值降低;患者组中早发组和成年发病组间FA值的差异无显著性。患者组FA值与发病年龄呈正相关的脑区包括右侧放射冠前部(r=0.70,P0.01)、右侧胼胝体膝部(r=0.65,P0.01);未发现呈负相关的脑区。结论:本研究提示精神分裂症患者右侧脑区上纵束及放射冠部位存在白质损害,发病年龄愈早,右侧放射冠及胼胝体膝部白质纤维的受损愈重。这对精神分裂症病理生理改变及脑结构异常的进一步研究具有提示作用。     

Diffusion tensor imaging and Tract-Based Spatial Statistics in Alzheimer's disease and mild cognitive impairment

We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.     

Neural tracts injuries in patients with hypoxic ischemic brain injury: Diffusion tensor imaging study

Many studies have reported on vulnerable areas of the brain in hypoxic ischemic brain injury (HI-BI). However, little is known about the involvement of neural tracts following HI-BI. We investigated neural tract injuries in adult patients with HI-BI, using diffusion tensor tractography (DTT). Twelve consecutive patients with HI-BI and 12 control subjects were recruited for this study. We classified the patients into two subgroups according to the preservation of alertness: subgroup A-5 patients who had intact alertness and subgroup B-7 patients who had impaired alertness. DTI-Studio software was used for evaluation of seven neural tracts: corticospinal, cingulum, fornix, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and optic radiation. We measured the DTT parameters (fractional anisotropy, apparent diffusion coefficient and voxel number) of each neural tract. In the individual analysis, all 12 patients showed injuries in all 24 neural tracts in terms of both DTT parameters and integrity, except for the corticospinal tract (75.0% injury). In the group analysis, the patient group showed neural injuries in all 24 neural tracts. In comparison of subgroups A and B, subgroup B showed more severe injuries: subgroup B showed a higher rate of disruption (39.8%) than subgroup A (12.9%) on individual DTTs and subgroup B had more severe injuries in both the cingulum and superior longitudinal fasciculus. In conclusion, we found that extensive injuries in the neural tracts were accompanied by HI-BI. Patients with impaired alertness appeared to show more severe injuries of neural tracts.     

Frontal white matter integrity in adults with Down syndrome with and without dementia

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS.     

The extreme capsule in humans and rethinking of the language circuitry

Experimental and imaging studies in monkeys have outlined various long association fiber pathways within the fronto-temporo-parietal region. In the present study, the trajectory of the extreme capsule (EmC) fibers has been delineated in five human subjects using DT-MRI tractography. The EmC seems to be a long association fiber pathway, which courses between the inferior frontal region and the superior temporal gyrus extending into the inferior parietal lobule. Comparison of EmC fibers with the adjacent association fiber pathway, the middle longitudinal fascicle (MdLF), in the same subjects reveals that EmC is located in a medial and rostral position relative to MdLF flanking in part the medial wall of the insula. The EmC can also be differentiated from other neighboring fiber pathways such as the external capsule, uncinate fascicle, arcuate fascicle, superior longitudinal fascicles II and III, and the inferior longitudinal fascicle. Given the location of EmC within the language zone, specifically Broca’s area in the frontal lobe, and Wernicke’s area in the temporal lobe and inferior parietal lobule, it is suggested that the extreme capsule could have a role in language function. Human research statement: The experiments undertaken in this paper were performed with the understanding and written informed consent of each subject.     

Microstructural changes and atrophy in brain white matter tracts with aging

Diffusion tensor (DT) magnetic resonance imaging (MRI) tractography was used to investigate microstructural and volumetric abnormalities of the major brain white matter (WM) tracts with aging in 84 healthy subjects. Linear relationships were found between age and mean diffusivity (MD) increase and fractional anisotropy (FA) decrease in all WM tracts, except the right cingulum and bilateral uncinate, where a linear correlation with age was found for FA only. Quadratic model fitted better MD and FA values of several tracts, including the corpus callosum, limbic pathways, and bilateral association, and corticospinal tracts. Age-related MD and FA abnormalities were associated with radial diffusivity increase in all WM tracts, while axial diffusivity changes were characterized by a considerable variation from a tract to another. A linear negative relationship with age was found for the volumes of the left cingulum and fornix, while the quadratic model fitted better age-related volume loss of corpus callosum and right inferior fronto-occipital fasciculus. Diffusion tensor magnetic resonance imaging may shed light into the complex pathological substrates of WM changes with aging.     

Anatomy and White Matter Connections of the Superior Frontal Gyrus

The superior frontal gyrus (SFG) is an important region implicated in a variety of tasks including motor movement, working memory, resting-state, and cognitive control. A detailed understanding of the subcortical white matter of the SFG could improve postoperative morbidity related to surgery around this gyrus. Through DSI-based fiber tractography validated by gross anatomical dissection, we characterized the fiber tracts of the SFG based on their relationships to other well-known neuroanatomic structures. Diffusion imaging from the Human Connectome Project from 10 healthy adult subjects was used for fiber tractography. We evaluated the SFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to delineate the location of major tracts integrated within the SFG. We identified four major SFG connections: the frontal aslant tract connecting to the inferior frontal gyrus; the inferior fronto-occipital fasciculus connecting to the cuneus, lingual gyrus, and superior parietal lobule; the cingulum connecting to the precuneus and parahippocampal gyrus/uncus; and a callosal fiber bundle connecting the SFG bilaterally. The functional networks of the SFG involve a complex series of white matter tracts integrated within the gyrus, including the FAT, IFOF, cingulum, and callosal fibers. Postsurgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study. Clin. Anat. 33:823–832, 2020. © 2019 Wiley Periodicals, Inc.     

Subcortical anatomy of the lateral association fascicles of the brain: A review

Precise knowledge of the connectivities of the different white matter bundles is of great value for neuroscience research. Our knowledge of subcortical anatomy has improved exponentially during recent decades owing to the development of magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI tractography has led to important progress in understanding white matter anatomy, the precise trajectory and cortical connections of the subcortical bundles remain poorly determined. The recent literature was extensively reviewed in order to analyze the trajectories and cortical terminations of the lateral association fibers of the brain.The anatomy of the following tracts is reviewed: superior longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, uncinate fasciculus, frontal aslant tract, and vertical occipital fasciculus. The functional role of a tract can be inferred from its topography within the brain. Knowing the functional roles of the cortical areas connected by a certain bundle, it is possible to develop new insights into the putative functional properties of such connections. Clin. Anat. 563–569, 2014. © 2014 Wiley Periodicals, Inc.     

Voxel-based assessment of gray and white matter volumes in Alzheimer's disease

Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimer's disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future.