Frontal white matter anisotropy and symptom severity of late-life depression: a magnetic resonance diffusion tensor imaging study

OBJECTIVES: To investigate the disruption of neural circuits in the frontal lobes and limbic structures in late-life depressed patients compared with healthy controls, and to examine the correlation between the degree of microstructural abnormalities of white matter and clinical symptom severity in late-life depression. METHODS: Thirteen patients with late-life depression and matched control subjects underwent diffusion tensor imaging. Fractional anisotropy (FA), an index of the integrity of white matter tracts, was determined in the white matter of frontal, temporal, and occipital brain regions and the corpus callosum. RESULTS: A significant reduction was found in white matter FA values of widespread regions of the frontal and temporal lobes of depressed patients. Also, there was some evidence suggesting that white matter FA values of the inferior frontal brain region are inversely related to severity of depression. CONCLUSIONS: These results suggest the possible loss of integrity within frontal and temporal white matter fibre tracts and implicate the orbitofrontal circuit in symptom severity in late-life depression.     

28例脑淀粉样血管病白质损害的临床特征

目的明确脑淀粉样血管病(CAA)患者白质损害的影像学特征,以及与其他脑小血管病(CSVD)标志物的相关性。方法回顾性分析2014年12月至2016年12月收集的28例很可能的CAA患者(CAA组)和56例合并CSVD危险因素的健康老年人(非CAA组)在临床信息,影像学标志物和白质损害之间的差异;白质损害分别从脑网络连接改变和定量白质高信号(WMH)体积的严重程度和分布特征(后-前部梯度)进行评估,以弥散张量成像中各向异性分数(FA)作为测量脑网络连接参数。分析CAA患者白质损害与脑微出血灶(CMBs)、血管周间隙(PVS)、CSVD积分等影像标志物的相关性。结果白质损害方面,与非CAA组比较,CAA组的全脑WMH体积(P0.001)和后-前部梯度(P=0.004)增加,FA后部均值(P=0.037)和后-前部梯度(P=0.004)降低。相关性分析表明:CAA组的全脑FA均值与WMH体积无相关性(P=0.151),而两组的后-前部梯度线性相关(P=0.029);全脑FA均值与脑叶CMBs数目(P=0.036)、CSVD积分(P=0.049)存在相关性,但这一相关性未在WMH体积中发现。结论脑网络连接下降、WMH体积增加是CAA白质损害的重要影像学标志物,具有后部分布为主的显著特征。脑网络连接下降可在一定程度上反映CAA的病理改变和疾病严重程度。     

White matter integrity and cortical metabolic associations in aging and dementia

BackgroundStudies show that white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigated how regional white matter integrity (measured as fractional anisotropy [FA]) relates to brain metabolism, to unravel the complex relationship between white matter changes and brain metabolism.ObjectiveTo elucidate the relationship between white matter integrity and gray matter metabolism using diffusion tensor imaging and fluorodeoxyglucose-positron emission tomography in a cohort of 16 subjects ranging from normal to demented (age, >55 years).MethodsMean FA values from white matter regions underlying the medial prefrontal, inferior-lateral prefrontal, parietal association, and posterior temporal areas and the corpus callosum were regressed with glucose metabolism (by positron emission tomography), using statistical parametric mapping (P < 0.005; voxel cluster, >100). Regional cerebral glucose metabolism was the primary outcome measure. According to our hypothesis, those hypometabolic cortical regions affected by Alzheimer's disease would correlate with a lower FA of associated tracks.ResultsOur data show inter-regional positive correlations between FA and gray matter metabolism for the prefrontal cortex, temporal, and parietal regions. Our results suggest that left prefrontal FA is associated with left temporal and parietal metabolism. Further, left posterior temporal FA correlated with left prefrontal metabolism. Finally, bilateral parietal FA correlated with bilateral temporal metabolism.ConclusionsThese regions are associated with cognitive processes affected in Alzheimer's disease and cerebrovascular disease, suggesting a link with white matter degeneration and gray matter hypometabolism. Therefore, cortical function and white matter degeneration are related in aging and dementia.     

Regional White Matter Anisotropy and Reading Ability in Patients Treated for Pediatric Embryonal Tumors

Children treated with cranial irradiation for brain tumors have reduced white matter volume and deficits in reading ability. This study prospectively examined the relationship between reading and white matter integrity within this patient group. Patients (n = 54) were treated with post-surgical radiation followed by 4 cycles of high-dose chemotherapy with stem cell support. At 12 months post-diagnosis, all patients completed a neuropsychology evaluation and a diffusion tensor imaging (DTI) exam. White matter integrity was determined through measures of fractional anisotropy (FA). Significant group differences in FA were found between above average readers and below average readers within the left and right posterior limb of the internal capsule, and right knee of the internal capsule with a trend within the left temporaloccipital region. The integrity of the white matter in these regions may affect communication among visual, auditory, and language cortical areas that are engaged during reading.     

White matter integrity correlates with residual consciousness in patients with severe brain injury

Previous studies have suggested that white matter disruption plays an important role in disorders of consciousness (DOC) after severe brain injury. Nevertheless, the integrity of white matter architecture supporting consciousness and its relations with clinical severity in patients with DOC remain to be established. In this study, diffusion tensor imaging (DTI) data was collected from 14 DOC patients and 15 healthy control subjects. We combined tract-based spatial statistics (TBSS) with region of interest (ROI) analysis to examine differences of DTI metrics on white matter skeletons between DOC patients and healthy controls, and the association between white matter integrity and patients’ residual consciousness assessed by Coma Recovery Scale-Revised (CRS-R). We found that: (1) patients with DOC had widespread white matter integrity disruptions, especially in the fornix; (2) the alteration of white matter microstructure was mainly attributed to the increase in radial diffusivity, possibly reflecting demyelination; (3) the behavioral CRS-R assessment score was positively correlated with white matter integrity in the fornix, uncinate fasciculus, pontine crossing tract, and posterior limb of internal capsule. Our results suggest that despite the widespread abnormalities of white matter following severe brain injury, the impairment of consciousness is likely to result from disruptions of key pathways that link brain regions in distributed networks.     

White matter integrity in kleptomania: a pilot study

This study's goal was to examine microstructural organization of frontal white matter in kleptomania. Ten females with DSM-IV kleptomania and 10 female controls underwent diffusion tensor imaging. Inferior frontal white matter was the a priori region of interest. Trace and fractional anisotropy (FA) were also calculated for frontal and posterior cortical regions in both subject groups. Kleptomania subjects had significantly higher mean frontal Trace, and significantly lower mean frontal FA than control subjects. Group differences remained significant when right and left frontal Trace and FA were analyzed. Groups did not differ significantly in posterior Trace or FA. Kleptomania may be associated with decreased white matter microstructural integrity in inferior frontal brain regions.     

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.     

Frontal white matter integrity is related to psychomotor retardation in major depression

Altered frontal white matter integrity has been reported in major depression. Still, the behavioral correlates of these alterations are not established. In healthy subjects, motor activity correlated with white matter integrity in the motor system. To explore the relation of white matter integrity and motor activity in major depressive disorder, we investigated 21 medicated patients with major depressive disorder and 21 matched controls using diffusion tensor imaging and wrist actigraphy at the same day. Patients had lower activity levels (AL) compared with controls. Fractional anisotropy (FA) differed between groups in frontal white matter regions and the posterior cingulum. AL was linearly associated with white matter integrity in two clusters within the motor system. Controls had an exclusive positive association of FA and AL in white matter underneath the right dorsal premotor cortex. Only patients had a positive association within the posterior cingulum. Furthermore, patients had negative associations of FA and AL underneath the left primary motor cortex and within the left parahippocampal gyrus white matter. These differences in the associations between structure and behavior may contribute to well-known impaired motor planning or gait disturbances in major depressive disorder. Therefore, signs of psychomotor slowing in major depressive disorder may be linked to changes of the white matter integrity of the motor system.     

Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study

Diffusion tensor imaging (DTI) can non-invasively examine the molecular diffusion of water in vivo and directly reflects the anatomical integrity of neural fibers in white matter. Fractional anisotropy (FA) can be calculated from DTI data, and utilized to evaluate white matter integrity. DTI was performed on 30 patients with schizophrenia and 19 healthy controls, and their FA values were subsequently measured in multiple brain regions. Statistical analyses revealed that FA values were decreased in the anterior cingulum of schizophrenia subjects. There were no significant differences between patients and controls in any other regions. This study supports the hypothesis that schizophrenia is associated with abnormal white matter integrity of the anterior cingulum.     

Global Association Between Cortical Thinning and White Matter Integrity Reduction in Schizophrenia

Previous neuroimaging studies have revealed that both gray matter (GM) and white matter (WM) are altered in several morphological aspects in schizophrenia patients. Although several studies reported associations between GM and WM alterations in restricted regions, the existence of a global association between GM and WM pathologies is unknown. Considering the wide distribution of GM morphological changes and the profound genetic background of WM abnormalities, it would be natural to postulate a global association between pathologies of GM and WM in schizophrenia. In this investigation, we studied 35 schizophrenia patients and 35 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) and investigated the association between GM thickness and WM fractional anisotropy (FA) as a proxy of pathology in each tissue. To investigate cortical thickness, surface-based analysis was used. The mean cortical thickness for the whole brain was computed for each hemisphere, and group comparisons were performed. For DTI data, mean FA for the whole brain was calculated, and group comparisons were performed. Subsequently, the correlation between mean cortical thickness and mean FA was investigated. Results showed that the mean cortical thickness was significantly thinner, and the mean FA was significantly lower in schizophrenia patients. Only in the patient group the mean cortical thickness and mean FA showed significant positive correlations in both hemispheres. This correlation remained significant even after controlling for demographic and clinical variables. Thus, our results indicate that the GM and WM pathologies of schizophrenia are intertwined at the global level.Key words: schizophrenia, white matter integrity, diffusion tensor imaging, cortical thickness, surface-based approach     

Cardiorespiratory fitness and white matter integrity in Alzheimer’s disease

The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain’s white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer’s disease (AD) population. We recruited older adults in the early stages of AD (n?=?37; CDR?=?0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO₂peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A?×?D]) were also correlated with VO₂peak. The tract-of-interest approach showed that higher VO₂peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p?=?0.035, r?=?0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO₂peak measures (p?<?0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.     

Age‐related differences in multiple measures of white matter integrity: A diffusion tensor imaging study of healthy aging

Diffusion tensor imaging (DTI) measures diffusion of molecular water, which can be used to calculate indices of white matter integrity. Early DTI studies of aging primarily focused on two global measures of integrity; the average rate (mean diffusivity, MD) and orientation coherence (fractional anisotropy, FA) of diffusion. More recent studies have added measures of water movement parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction, which are thought to reflect the neural bases of age differences in diffusion (i.e., axonal shrinkage and demyelination, respectively). In this study, patterns of age differences in white matter integrity were assessed by comparing younger and healthy older adults on multiple measures of integrity (FA, AD, and RD). Results revealed two commonly reported patterns (Radial Increase Only and Radial/Axial Increase), and one relatively novel pattern (Radial Increase/Axial Decrease) that varied by brain region and may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In addition, larger age differences in FA in frontal white matter were consistent with the anterior–posterior gradient of age differences in white matter integrity. Together, these findings complement other recent studies in providing information about patterns of diffusivity that are characteristic of healthy aging. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.     

未经治疗的抑郁症首次发病患者脑弥散张量成像的研究

目的 通过对未经治疗的抑郁症首次发病(以下简称首发)患者进行弥散张最成像(DTI)检查,探讨抑郁症患者脑门质的完整性及其与病程和抑郁严重程度的相关性.方法 对17名首发末服药抑郁症患者(以下简称患者组)和17名年龄、性别和文化程度相匹配的健康对照(以下简称对照组)进行全脑DTI扫描.以基于体素的分析比较两组受试者脑白质的分数各向异性(FA)的差异.提取差异有统计学意义的脑区的FA绝对值,将其与汉密尔顿抑郁量表(17项,HAMD)总分和患者病程进行相关分析.结果 患者组的双侧额中回、左侧扣带回和颞下回白质的FA值显著低于对照组(P＜0.01,cluster＞100).右侧额中回的FA值与病程呈显著负相关(r=-0.732,P=0.001).未发现各脑区的FA值与HAMD总分存在相关.结论脑白质完整性异常可能是抑郁症的生物学特征之一,抑郁症病程对脑白质的完整性有明显影响.     

Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: a voxel-based diffusion tensor imaging study

Although not consistently replicated, diffusion tensor imaging (DTI) studies in schizophrenia have revealed lower fractional anisotropy (FA) in various white matter regions, a finding consistent with the disruption of white matter integrity. In this study, we used voxel-based DTI to investigate possible whole-brain differences in the white matter FA values between 58 schizophrenia patients and 58 healthy controls. We also explored the association between FA values and clinical symptoms in schizophrenia. Compared with the controls, the schizophrenia patients showed significant FA reductions in bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, and genu of right internal capsule. Furthermore, in the patient group, the FA value of the anterior part of the corpus callosum was negatively correlated with the avolition score on the Scale for the Assessment of Negative Symptoms. These findings suggest widespread disruption of white matter integrity in schizophrenia, which could partly explain the severity of negative symptomatology.     

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D‐HFE Polymorphism Carriers

BACKGROUND AND PURPOSE

The H63D‐HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity.

METHODS

Fifteen subjects heterozygous for the HFE‐H63D SNP and 25 controls with wild‐type HFE had diffusion‐weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D‐HFE SNP and myelin integrity.

RESULTS

A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D‐HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi.

CONCLUSIONS

The MRI data presented here demonstrate that H63D‐HFE polymorphism carriers have diffusivity changes in white matter compared to wild‐type subjects. The reduced integrity white matter tracts in H63D‐HFE carriers are hypothesized to be related to increased susceptibility of these late‐myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.     

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.     

Diffusion tensor imaging of cocaine-treated rodents

Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared with non-drug-using controls. It is not known whether the differences in fractional anisotropy (FA) seen on DTI in white matter regions of cocaine-dependent humans result from a pre-existing predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed an 18% FA decrease in the splenium of the corpus callosum (CC) in cocaine-treated animals relative to saline controls. On histology, significant increase in neurofilament expression (125%) and decrease in myelin basic protein (40%) were observed in the same region in cocaine-treated animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration.     

Frontal white matter integrity in borderline personality disorder with self-injurious behavior

Self-injurious behavior in borderline personality disorder is a frequent cause of morbidity and mortality, but neurobiological studies examining this behavior are few. Nine women with borderline personality disorder self-injurious behavior and seven comparison subjects underwent diffusion tensor imaging (DTI). Trace and fractional anisotropy (FA) were calculated for frontal and posterior regions. Borderline personality disorder-self-injurious behavior subjects also underwent a battery of neuropsychological tests that emphasized executive functions. They had significantly higher trace and lower FA in inferior frontal but not posterior regions. Correlational analyses between DTI and cognitive variables showed a pattern of results that was contrary to expectations with posterior white matter integrity correlating with isolated measures of executive function and anterior white matter integrity correlating with a component of verbal memory test performance. Women with borderline personality disorder-self-injurious behavior exhibit decreased white matter microstructural integrity in inferior frontal brain regions that may include components of orbito-frontal circuitry.     

An investigation of the relationship between cortical connectivity and schizotypy in the general population

Recent neuroimaging investigations have identified a relationship between psychotic symptoms in schizophrenia and abnormal brain connectivity. On the basis of the continuum model of psychosis, it was hypothesized that schizotypal traits in healthy control participants would be associated with relatively impaired frontotemporal white matter health as assessed using diffusion tensor imaging. Twenty-one participants (12 women and 9 men aged 18 to 58 years) completed the Schizotypal Personality Questionnaire (SPQ) and underwent diffusion-weighted magnetic resonance imaging scanning as part of a larger study. White matter integrity for the major association fibre tracts was assessed using standard measures of diffusivity, specifically fractional anisotropy (FA) and axial and radial diffusivity. A series of negative binomial regressions yielded significant relationships between reduced FA in seven white matter tracts and increased scores on the SPQ cognitive-perceptual factor. These findings are consistent with research relating brain connectivity to the positive symptoms of schizophrenia, suggesting that the neurobiological bases of schizotypal personality in healthy controls may be analogous to the neurobiological bases of schizophrenia spectrum disorders.