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 cingulum bundle development in autism: A probabilistic tractography study

There is now considerable evidence that white matter abnormalities play a role in the neurobiology of autism. Little research has been directed, however, at understanding (a) typical white matter development in autism and how this relates to neurocognitive impairments observed in the disorder. In this study we used probabilistic tractography to identify the cingulum bundle in 21 adolescents and young adults with Autism Spectrum Disorder (ASD), and 21 age- and sex-matched healthy volunteers. We investigated group differences in the relationships between age and fractional anisotropy, a putative measure of white matter integrity, within the cingulum bundle. Moreover, in a preliminary investigation, we examined the relationship between cingulum fractional anisotropy and executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). The ASD participants demonstrated significantly lower fractional anisotropy within the cingulum bundle compared to the typically developing volunteers. There was a significant group-by-age interaction such that the ASD group did not show the typical age-associated increases in fractional anisotropy observed among healthy individuals. Moreover, lower fractional anisotropy within the cingulum bundle was associated with worse BRIEF behavioral regulation index scores in the ASD group. The current findings implicate a dysregulation in cingulum bundle white matter development occurring in late adolescence and early adulthood in ASD, and suggest that greater disturbances in this trajectory are associated with executive dysfunction in ASD.     

Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics

Chan W‐Y, Yang G‐L, Chia M‐Y, Woon P‐S, Lee J, Keefe R, Sitoh Y‐Y, Nowinski WL, Sim K. Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics.
Bipolar Disord 2010: 12: 383–389. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first‐episode mania and hypothesized that first‐episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum). Methods: Diffusion tensor images were acquired from 16 patients with remitted first‐episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract‐Based Spatial Statistics. Results: Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum. Conclusion: Our findings highlighted that white matter abnormalities were present by the time of remission of first‐episode mania. The widespread occurrence of these white matter abnormalities both in first‐episode mania and chronic bipolar disorder suggested that disruption of white matter cortical‐subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.     

Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls

Background

Neuregulin1 (NRG1) influences the development of white matter connectivity and is implicated in genetic susceptibility to schizophrenia. The cingulum bundle is a white matter structure implicated in schizophrenia. Its anterior component is especially implicated, as it provides reciprocal connections between brain regions with prominent involvement in the disorder. Abnormalities in the structural integrity of the anterior cingulum in patients with schizophrenia have been reported previously. The present study investigated the potential contribution of NRG1 variation to anterior cingulum abnormalities in participants with schizophrenia.

Methods

We studied 31 men with schizophrenia and 36 healthy men using diffusion tensor imaging to investigate the association between fractional anisotropy in the anterior cingulum and a single-nucleotide polymorphism (SNP8NRG221533: rs35753505) of NRG1.

Results

Consistent with previous reports, fractional anisotropy was significantly reduced in the anterior cingulum in the schizophrenia group. Moreover, the results revealed a significant group (schizophrenia, control) by genotype (C/C, T carriers, including CT and TT) interaction between genetic variation in NRG1 and diagnosis of schizophrenia, such that the patients with the T allele for SNP8NRG221533 had significantly decreased anterior cingulum fractional anisotropy compared with patients homozygous for the C allele and healthy controls who were T carriers.

Limitations

Limitations of our study included the small sample size of the TT subgroup and our use of only fractional anisotropy as an index of myelin integrity. In addition, the use of diffusion tensor imaging acquisition methods limited our ability to study other brain regions that may be involved in schizophrenia.

Conclusion

Our results suggest that NRG1 variation may play a role in the pathophysiology of anterior cingulum abnormalities in patients with schizophrenia.     

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.     

White matter abnormalities observed in bipolar disorder: a diffusion tensor imaging study

OBJECTIVES: An increased incidence in white matter abnormalities is among the most frequently reported brain change in patients with bipolar disorder. The objective of the present study was to examine white matter tract integrity, using diffusion tensor imaging (DTI), in bipolar patients and healthy comparison subjects. METHODS: Eleven DSM-IV bipolar I patients and 10 healthy age- and sex-matched controls were studied. DTI data were acquired on a 1.5 Tesla scanner. Fractional anisotropy (FA) and diffusivity (trace) were determined from axial images using region of interest (ROI) analyses. The ROIs were manually placed in the midline and forward projecting arms of the genu (anterior) and the midline of the splenium (posterior) of the corpus callosum. RESULTS: Bipolar patients had significantly higher FA in the midline of the genu compared with healthy controls. Regional white matter differences were also observed, with significantly lower FA in the genu than forward projecting regions in both groups and lower FA in the genu than the splenium in controls. CONCLUSIONS: Diffusion tensor imaging revealed significant microstructural differences in the genu, as measured by elevated FA in bipolar patients compared with healthy controls. These preliminary findings further support the hypothesis that anomalous frontal brain mechanisms may be associated with bipolar disorder.     

Asymmetrically altered integrity of cingulum bundle in posttraumatic stress disorder

Previously, our group reported the altered white matter tract integrity of the left anterior cingulate in posttraumatic stress disorder (PTSD) in whole-brain exploration. Current study intended to explore whether the alteration was more prominent in any specific regions of the cingulum bundle. Diffusion tensor images of 21 PTSD subjects and 21 healthy comparison subjects were acquired. Eight isocubic regions of interest (ROIs), i.e. bilateral rostral, subgenual, dorsal, and upper cingulum bundle, were selected. Fractional anisotropy values in each ROI, which indicate the white matter tract integrity, were measured and compared between groups. Relative to comparison subjects, PTSD subjects had significantly smaller fractional anisotropy values in the left side of rostral, subgenual and dorsal cingulum bundle (26.7, 25.0, 22.2% decrease, respectively), but not in the right side ROIs. We report an asymmetrical alteration of the cingulum bundle in PTSD.     

Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study

OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions that bipolar disorder is characterized by subtle white matter changes. The chronic nature of the study population, however, has limited interpretation of these findings. In this study the authors utilized diffusion tensor imaging to study white matter tracts of adolescents in their first episode of mania to address whether abnormalities are present in early bipolar disorder. METHOD: Eleven medication-naive adolescents in their first episode of mania and 17 healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy and trace apparent diffusion coefficients of prefrontal and posterior regions of interest were compared between groups. RESULTS: Bipolar adolescents showed significantly decreased fractional anisotropy only in superior-frontal white matter tracts. Trace apparent diffusion coefficients did not significantly differ in any regions examined. CONCLUSIONS: These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.     

Microstructural white matter changes in euthymic bipolar patients: a whole-brain diffusion tensor imaging study

Objectives:  Brain structures of a distributed ventral-limbic and dorsal brain network have been associated with altered mood states and emotion regulation in affective disorders. So far, diffusion tensor imaging studies in bipolar patients have focused on frontal/prefrontal brain regions and found alterations in white matter integrity in manic, depressed, and euthymic bipolar patients, observed as changes in fractional anisotropy and mean diffusivity. To extend previous findings, we investigated whole-brain modifications in white matter integrity in euthymic bipolar patients with minimal manic and depressive symptoms.
Methods:  Twenty-two patients with a DSM-IV-TR diagnosis of bipolar I and II disorder in remission, with no lifetime or present comorbidities of substance abuse, and 21 sex- and age-matched healthy controls underwent diffusion tensor imaging with diffusion gradients applied along 41 directions. Fractional anisotropy and mean diffusivity group differences were explored using two voxel-based, whole-brain analyses that differ in their normalization approaches.
Results:  Fractional anisotropy was significantly increased in bipolar patients relative to healthy controls in medial frontal, precentral, inferior parietal, and occipital white matter. No group differences in mean diffusivity were found.
Conclusions:  The result of increased fractional anisotropy in euthymic bipolar patients in the present study suggests increased directional coherence of white matter fibers in bipolar patients during remission.     

Whiter matter abnormalities in medication-naive subjects with a single short-duration episode of major depressive disorder

Convergent studies have implicated white matter abnormalities in the pathophysiology of major depressive disorder (MDD). In this study, diffusion tensor imaging (DTI) was used to examine white matter abnormalities in 23 single-episode, medication-naive MDD participants versus 21 healthy control participants. Voxel-based analysis was used to investigate whole brain white matter abnormalities in the MDD group. Fractional anisotropy was significantly lower and apparent diffusion coefficient was significantly higher in the right superior longitudinal fasciculus (SLF) within the frontal lobe, right middle frontal and left parietal white matter in the MDD group compared with the healthy group.     

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.     

Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study

OBJECTIVES: Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder. METHODS: Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups. RESULTS: The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC. CONCLUSIONS: Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.     

创伤后应激障碍患者扣带束及胼胝体纤维束FA值的初步研究

目的探讨创伤后应激障碍患者(PTSD)是否存在连合纤维束胼胝体及联络纤维扣带纤维束的超微结构异常。方法1.5T的MR成像仪下对12例PTSD患者及12名正常对照进行磁共振弥散张量成像(DTI),测量受试者胼胝体膝部、体部、压部、及双侧扣带水平部、后部等感兴趣区内主要白质纤维束的各向异性分数(FA)值,并进行组间比较。结果患者组双侧(左侧、右侧)扣带束水平部、胼胝体压部的FA值较对照组明显降低,差异均有统计学意义(t分别为3.26、-4.13、2.84,P均小于0.05)。结论PTSD患者的边缘系统纤维束可能存在结构异常。     

基于扩散张量成像的双相障碍Ⅰ型患者全脑白质完整性研究

目的比较双相情感障碍(BD)Ⅰ型患者和健康对照组脑白质部分各向异性分数(FA),探索BD-Ⅰ型患者的脑白质完整性。方法 2012年1月-2014年7月于中南大学湘雅二医院纳入符合《精神障碍诊断与统计手册(第4版)》(DSM-Ⅳ)诊断标准的BD-Ⅰ型患者22例为患者组,同期在中南大学湘雅二医院周边社区招募性别、年龄及受教育年限与患者组匹配的24名健康者为对照组。采用3.0T磁共振成像系统采集所有被试的脑白质结构相数据,使用FSL、SPM完成FA参数图计算、空间标准化、高斯平滑,采用两独立样本t检验分析患者组与对照组FA值差异有统计学意义的脑区。结果与对照组相比,患者组FA值增高的脑区为右侧小脑后叶(P0.01),降低的脑区包括颞上回、小脑前叶、左侧岛叶和左侧尾状核(P均0.01)。结论 BD-Ⅰ型患者白质完整性受损,边缘系统、颞叶和小脑白质完整性受损可能与BD-Ⅰ型的病理生理学机制有关。     

Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum （splenium and genu） as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.     

A diffusion tensor imaging study of fasciculi in schizophrenia

OBJECTIVE: Cognitive models propose that the symptoms and psychological impairments associated with schizophrenia arise as a consequence of impaired communication between brain regions, especially the prefrontal cortex and the temporal and parietal lobes. Functional imaging and electrophysiological data have provided evidence of functional dysconnectivity, but it is unclear whether this reflects an underlying problem with anatomical connectivity. This study used diffusion tensor imaging to examine the integrity of the major white matter fasciculi, which connects the frontal and temporal-parietal cortices, and the corpus callosum in patients with schizophrenia. METHOD: A 1.5-T magnetic resonance scanner was used to acquire diffusion tensor images giving whole brain coverage at an isotropic 2.5-mm voxel size. Fractional anisotropy was measured in 33 patients with schizophrenia and 40 healthy comparison subjects with an automated voxel-based method of analysis. RESULTS: There was reduced fractional anisotropy in patients with schizophrenia in regions corresponding to the superior longitudinal fasciculi bilaterally and in the genu of the corpus callosum. However, within the patient group, the propensity to experience auditory hallucinations was associated with relatively increased fractional anisotropy in superior longitudinal fasciculi and in the anterior cingulum. CONCLUSIONS: Schizophrenia is associated with altered white matter integrity in the tracts connecting the frontal cortex with the temporal and parietal cortices and with the contralateral frontal and temporal lobes. The severity of these changes may vary with the pattern of symptoms associated with the disorder.     

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.     

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 abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.     

A comparative diffusion tensor imaging study of corpus callosum subregion integrity in bipolar disorder and schizophrenia

Structural magnetic resonance imaging (MRI) studies have provided evidence for corpus callosum (CC) white matter abnormalities in bipolar disorder (BD) and schizophrenia (SZ). These findings include alterations in shape, volume, white matter intensity and structural integrity compared to healthy control populations. Although CC alterations are implicated in both SZ and BD, no study of which we are aware has investigated callosal subregion differences between these two patient populations. We used diffusion tensor imaging (DTI) to assess CC integrity in patients with BD (n=16), SZ (n=19) and healthy controls (HC) (n=24). Fractional anisotropy (FA) of CC subregions was measured using region of interest (ROI) analysis and compared in the three groups. Significant group differences of FA values were revealed in five CC subregions, including the anterior genu, middle genu, posterior genu, posterior body and anterior splenium. FA values of the same subregions were significantly reduced in patients with SZ compared with HC. FA values were also significantly reduced in patients with BD compared to the HC group in the same subregions, excepting the middle genu. No significant difference was found between patient groups in any region. Most of the alterations in CC subregions were present in both the BD and SZ groups. These results imply an overlap in potential pathology, possibly relating to risk factors common to both disorders. The one region that differed between patient groups, the middle genu area, may serve as an illness marker and is perhaps involved in the different cognitive impairments observed in BD and SZ.