Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.     

White matter integrity and math performance in pediatric multiple sclerosis: a diffusion tensor imaging study

Multiple sclerosis is associated with reduced white matter integrity and deficits in key cognitive processes important for arithmetic. This study examined the relationship between white matter microstructure and academic ability in 31 youths with multiple sclerosis (aged 11-19 years) and 34 demographically matched controls. Using diffusion tensor imaging, fractional anisotropy was calculated in corpus callosum and in lateralized hemispheric lobes. Difficulties with written arithmetic ability were observed in 26% of patients. Arithmetic ability correlated with fractional anisotropy values across all segments of the corpus callosum and in right frontal and parietal regions, controlling for age (r values >0.5, P<0.005). Findings highlight the functional impact of compromised white matter microstructure across diffuse regions of the brain on mathematical ability.     

White matter integrity of the whole brain is disrupted in first-episode schizophrenia

Diffusion tensor imaging studies in schizophrenia have demonstrated lower diffusion anisotropy within white matter that provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode schizophrenia by using diffusion tensor imaging. Twenty-one schizophrenic patients and healthy controls underwent diffusion tensor imaging scans that analyzed by using a rigorous voxel-based approach. We found that fractional anisotropy in white matter of the patients was lower than that in controls at the cerebral peduncle, frontal regions, inferior temporal gyrus, medial parietal lobes, hippocampal gyrus, insula, right anterior cingulum bundle and right corona radiata. These results suggested that white matter integrity of the whole brain was disrupted in early illness onset of schizophrenia.     

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.     

Diffusion tensor imaging in schizophrenia.

BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. RESULTS: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.     

MRI study of white matter diffusion anisotropy in schizophrenia

Diffusion tensor imaging (DTI) can provide information about brain white matter integrity. The results of DTI studies in schizophrenia are somewhat variable and could benefit from standardized image processing methods. Fourteen patients with schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent variable, fractional anisotropy, was lower for patients in the corpus callosum, left superior temporal gyrus, parahippocampal gyri, middle temporal gyri, inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual region. Regions showing reduced white matter fractional anisotropy are known to be abnormal in schizophrenia. The voxelwise method used in the current study can provide the basis for hypothesis-driven research.     

Microstructural white matter abnormalities and remission of geriatric depression

OBJECTIVE: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. METHOD: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. RESULTS: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. CONCLUSIONS: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.     

皮质下缺血性血管性认知损害扩散张量成像研究

目的通过扩散张量成像(DTI)探讨皮质下缺血性血管性认知损害患者白质微结构变化及其与认知功能之间的相关性。方法采集49例皮质下缺血性脑血管病患者[轻度血管性痴呆(VaD)10例、非痴呆型血管性认知损害(VCIND)20例、认知功能正常19例]DTI数据并观察皮质下白质微结构改变,分析VaD组患者DTI参数与认知功能间的相关性。结果与对照组相比,VaD组内侧前额叶、前扣带回、胼胝体干、双侧顶叶、右侧颞叶、双侧眶额叶,以及VCIND组右侧额下回、右侧海马、双侧楔前叶FA值减低(均P=0.000);与VCIND组比较,VaD组内侧前额叶、前扣带回、胼胝体、双侧顶叶、右侧颞叶FA值减低(P=0.000)。与对照组相比,VaD组内侧前额叶、胼胝体、双侧顶叶、双侧颞叶、前扣带回,以及VCIND组双侧楔前叶、右侧海马MD值升高(均P=0.000);与VCIND组相比,VaD组右侧内侧前额叶、前扣带回、胼胝体干、双侧顶叶、双侧颞叶MD值升高(均P=0.000)。VaD组内侧前额叶FA值与数字连线测验A时呈显著负相关(r=-0.782,P=0.007),双侧额下回MD值与数字连线试验A时程呈显著正相关(r=0.877,P=0.001)。结论 DTI对皮质下缺血性认知损害患者白质微结构改变更敏感,能够反映患者认知功能早期异常改变;内侧前额叶白质微结构的改变是影响患者执行能力的重要因素。     

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。     

阿尔茨海默病与轻度认知障碍弥散张量成像研究

目的:应用磁共振弥散张量成像技术(DTI)研究阿尔茨海默病(AD)与轻度认知障碍患者(MCI)脑白质损伤情况。方法:对21例AD患者、15例MCI患者和20名健康志愿者进行脑部DTI扫描后,测量双脑区感兴趣区的各向异性分数值(FA)且进行比较。结果:AD患者额叶、顶叶、颞叶和胼胝体的FA值与MCI组和对照组均存在显著性差异,MCI患者仅颞叶和胼胝体的FA值与对照组均存在显著性差异。结论:AD患者与MCI患者存在脑白质结构的差异,DTI技术能够在一定程度上提供MCI的早期诊断指标。     

White matter microstructural abnormalities in late-life depression

OBJECTIVE: To evaluate the location and the degree of white matter damage in late-life depression using diffusion tensor imaging (DTI). METHODS: Thirty-one patients with late-life depression and 15 healthy volunteers matched for age, gender and years of education received conventional MRI (magnetic resonance imaging) and MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter were measured respectively in frontal and temporal regions and the corpus callosum. RESULTS: FA values were significantly decreased in the frontal (superior and middle frontal gyrus), and temporal (right parahippocampal gyrus) regions of elderly patients with depression compared with healthy controls. CONCLUSION: Microstructural changes in the frontal (superior and middle frontal gyrus) and temporal (right parahippocampal gyrus) areas are associated with late-life depression.     

White matter structure in autism: preliminary evidence from diffusion tensor imaging.

BACKGROUND: Individuals with autism have severe difficulties in social communication and relationships. Prior studies have suggested that abnormal connections between brain regions important for social cognition may contribute to the social deficits seen in autism. METHODS: In this study, we used diffusion tensor imaging to investigate white matter structure in seven male children and adolescents with autism and nine age-, gender-, and IQ-matched control subjects. RESULTS: Reduced fractional anisotropy (FA) values were observed in white matter adjacent to the ventromedial prefrontal cortices and in the anterior cingulate gyri as well as in the temporoparietal junctions. Additional clusters of reduced FA values were seen adjacent to the superior temporal sulcus bilaterally, in the temporal lobes approaching the amygdala bilaterally, in occipitotemporal tracts, and in the corpus callosum. CONCLUSIONS: Disruption of white matter tracts between regions implicated in social functioning may contribute to impaired social cognition in autism.     

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD

Background: Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI. Method: A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms "DTI" or "diffusion tensor;" "whole brain" or "voxel-based;" and "depress*." Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region. Results: We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum. Limitations: The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences. Conclusion: Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This isstrong evidence for the involvement of these neural circuits in the pathology of MDD.     

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.     

White matter integrity predicts delay discounting behavior in 9- to 23-year-olds: a diffusion tensor imaging study

Healthy participants (n = 79), ages 9-23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.     

轻中型颅脑损伤后认知功能障碍的DTI研究

目的应用弥散张量成像(diffusion tensor imaging,DTI)技术探讨轻中型颅脑损伤病人不同部位脑白质微结构改变与其认知功能障碍的相关性。方法分析127例轻中型颅脑损伤病人的临床资料,伤后10 d采用蒙特利尔认知评估量表(Mo CA)评定有无认知功能障碍,并常规行头颅MRI检查,采集DTI数据,测量两侧额叶、颞叶内侧、顶叶,胼胝体膝部和压部,中脑部位的感兴趣区各向异性分数(FA值)、表观弥散系数(ADC值),并与Mo CA评估结果进行相关性分析。结果以Mo CA量表为标准评定,无认知功能障碍41例(32.28%,无认知障碍组),存在认知功能障碍86例(67.72%,认知障碍组),主要表现为视空间与执行功能、注意力和计算力、语言、抽象能力、延迟记忆的障碍。与无认知障碍的病人相比,认知障碍的病人两侧额叶、颞叶内侧、胼胝体膝部FA值降低,ADC值增加,差异具有统计学意义(P0.01)。结论轻中型颅脑损伤病人早期存在显著认知功能障碍,以视空间与执行功能、注意力和计算力、语言、抽象能力、延迟记忆障碍为主。颅脑损伤后早期认知功能障碍与病人额叶、颞叶、胼胝体白质受损密切相关。     

Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study

OBJECTIVE: Velocardiofacial syndrome, caused by a deletion on chromosome 22q11.2, is often accompanied by cognitive, behavioral, and psychiatric impairments. Specifically, velocardiofacial syndrome has been proposed as a disease model for a genetically mediated subtype of schizophrenia. Velocardiofacial syndrome is also known to affect brain structure. The most prominent structural findings in velocardiofacial syndrome are reduced white matter volumes. However, the structure of white matter and extent of specific regional involvement in this syndrome have never been investigated. The current study used diffusion tensor imaging to investigate white matter structure in children and young adults with velocardiofacial syndrome. METHOD: Nineteen participants with velocardiofacial syndrome and 19 age- and gender-matched comparison subjects underwent diffusion-weighted magnetic resonance imaging scans. Whole brain voxel-by-voxel analyses were conducted to investigate white matter fractional anisotropy differences between the groups. RESULTS: Relative to the comparison group, the velocardiofacial syndrome group had reduced white matter anisotropy in the frontal, parietal, and temporal regions as well as in tracts connecting the frontal and temporal lobes. CONCLUSIONS: This study demonstrates that alterations of white matter tract structure occur in velocardiofacial syndrome. Reduced white matter anisotropy was observed in individuals with velocardiofacial syndrome in areas previously implicated in the neurocognitive phenotype of velocardiofacial syndrome. The finding of aberrant parietal white matter tracts as well as aberrant frontotemporal connectivity in velocardiofacial syndrome and in previous schizophrenia studies may be associated with increased vulnerability for development of psychotic symptoms.     

The microstructural integrity of the corpus callosum and associated impulsivity in alcohol dependence: a tractography-based segmentation study using diffusion spectrum imaging

Previous post-mortem and structural magnetic resonance imaging (MRI) studies in patients with alcohol dependence have demonstrated abnormalities of brain white matter. The present study investigated the microstructural integrity in the corpus callosum and the associations of this integrity with neurobehavioral assessments. Twenty-five male cases fulfilling the DSM-IV diagnosis of alcohol dependence and 15 male control subjects were scanned using a 3T MRI system. Callosal fiber tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into seven functionally distinct segments. The microstructural integrity was quantified in terms of generalized fractional anisotropy (GFA). Compared with normal subjects, men with alcohol dependence showed lower GFA values on all segments of the corpus callosum. The segment interconnecting the bilateral orbitofrontal cortices was the most affected. The score on the Barratt Impulsivity Scale showed an inverse relationship with GFA on the callosal fiber tracts connecting the bilateral orbitofrontal cortices. Furthermore, the duration of regular use was negatively associated with GFA on the callosal fiber tracts connecting the bilateral temporal and parietal cortices. Our findings suggest that a high self-rated impulsivity level was associated with low anisotropy in white matter of corpus callosum sectors extending to the orbitofrontal cortex.     

Diffusion tensor anisotropy in adolescents and adults

We acquired diffusion tensor images on 33 normal adults aged 22-64 and 15 adolescents aged 14-21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.     

Maturation of white matter is associated with the development of cognitive functions during childhood

In the human brain, myelination of axons continues until early adulthood and is thought to be important for the development of cognitive functions during childhood. We used diffusion tensor MR imaging and calculated fractional anisotropy, an indicator of myelination and axonal thickness, in children aged between 8 and 18 years. Development of working memory capacity was positively correlated with fractional anisotropy in two regions in the left frontal lobe, including a region between the superior frontal and parietal cortices. Reading ability, on the other hand, was only correlated with fractional anisotropy in the left temporal lobe, in the same white matter region where adults with reading disability are known to have lower fractional anisotropy. Both the temporal and the frontal regions were also correlated with age. These results show that maturation of white matter is an important part of brain maturation during childhood, and that maturation of relatively restricted regions of white matter is correlated with development of specific cognitive functions.