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.     

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study

Aims

We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms.

Methods

Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up.

Results

The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder.

Conclusion

Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.     

Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex White Matter Alterations in Late-Life Depression

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

目的 使用弥散张量成像探讨首次发病未用药老年抑郁症患者的脑白质完整性.方法 15例首次发病未用药的老年抑郁症患者和15例正常对照组接受脑弥散张量成像扫描,用基于体素的分析方法对脑内所有体素的各向异性分数(FA)逐一进行组间比较.结果 与正常对照组相比,首次发病未用药老年抑郁症患者左侧前扣带(丛集体积=106体素,t=3.21)、右侧前扣带(丛集体积=60体素,t=2.71)、右侧膝下扣带(丛集体积=63体素,t=3.37)、左侧脑干(丛集体积=62体素,t=3.25)白质FA值显著降低(检验水准为未校正的单侧P＜0.01,体素集阈值＞50体素).结论 老年抑郁症发病早期存在双侧前扣带及右侧膝下扣带白质完整性下降,经由该脑区的神经通路损害可能与老年抑郁症的病理机制有关.     

Cocaine addiction: Diffusion tensor imaging study of the inferior frontal and anterior cingulate white matter

Inferior frontal and anterior cingulate white matter integrity in 32 cocaine-dependent subjects was compared with that in 33 age-matched healthy control subjects. Diffusion tensor imaging data were acquired with a 1.5-T magnetic resonance imaging system. Cocaine-dependent subjects presented significantly lower fractional anisotropy values in inferior frontal white matter at the anterior–posterior commissure plane and higher anterior cingulate white matter values than control subjects. White matter integrity was also associated with impulsivity and motivation to change (Readiness to Change Questionnaire). These findings support the hypothesis that cocaine dependence involves a disruption of orbitofrontal connectivity and suggest that the anterior cingulate brain area might play a role in the motivation to change.     

Cerebral blood flow velocity in untreated panic disorder patients: a transcranial Doppler ultrasonography study.

BACKGROUND: The aim of this study was to compare resting cerebral blood flow velocity values of unmedicated patients in the acute phase of panic disorder with resting values of healthy control subjects. METHODS: Nineteen unmedicated panic disorder patients were assessed for degree of anxiety using the Hamilton Anxiety Scale. The patients and 20 healthy age-matched control subjects were then insonated at rest using transcranial Doppler ultrasonography (TCD). For TCD, the anterior, the middle, and the posterior cerebral arteries were insonated bilaterally in all patients. RESULTS: Compared with healthy age-matched control subjects, acute unmedicated panic disorder patients showed a significant increase in cerebral blood flow velocity, bilaterally in the middle and the anterior cerebral artery, and unilaterally in the left posterior cerebral artery. Cerebral blood flow velocity in the right middle cerebral artery correlated positively to the item "Fear" on the Hamilton Anxiety Scale, whereas pulsatility index in the posterior cerebral artery bilaterally and in the left middle cerebral artery correlated negatively to the item "Mood." CONCLUSIONS: Transcranial Doppler ultrasonography agrees well with validated psychometric methods. If follow-up studies confirm our findings, TCD could allow an objective assessment of the mental state of panic disorder patients and reliably discriminate panic disorder patients from normal control subjects.     

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.     

Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder

CONTEXT Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD. OBJECTIVES To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas. DESIGN Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging. SETTING University magnetic resonance imaging facility. PARTICIPANTS Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education. MAIN OUTCOME MEASURES The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data. RESULTS Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion. CONCLUSIONS Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.     

Differences in resting corticolimbic functional connectivity in bipolar I euthymia

Objective: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. Methods: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low‐frequency fluctuations in blood oxygen level‐dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed‐to‐voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. Results: The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). Conclusions: Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait‐related and clinically important imaging biomarker.     

The structure of the corpus callosum in obsessive compulsive disorder

Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.     

White matter abnormalities in first-episode, treatment-naive young adults with major depressive disorder

OBJECTIVE: The aim of this study was to explore the microstructural integrity of whole-brain white matter by diffusion tensor imaging in first-episode, treatment-naive young adults with major depressive disorder. METHOD: Diffusion tensor imaging scans were obtained from 14 first-episode, treatment-naive young adult patients with major depressive disorder and 14 healthy comparison subjects. A voxel-based method was used to analyze the scans. RESULTS: The patient group exhibited significantly lower fractional anisotropy values than healthy comparison subjects in the white matter of the right middle frontal gyrus, the left lateral occipitotemporal gyrus, and the subgyral and angular gyri of the right parietal lobe. There were no regions of significantly higher fractional anisotropy values in patients compared with healthy comparison subjects. CONCLUSIONS: These findings suggest that abnormalities of brain white matter may be present early in the course of major depressive disorder. They also support the idea that white matter lesions may disrupt the neural circuits involved in mood regulation and thus contribute to the neuropathology of major depressive disorder.     

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.     

Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia

Schizophrenia and Attention-Deficit/Hyperactivity Disorder (ADHD) are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n = 15) or ADHD (n = 14) and healthy controls (n = 26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers.     

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.     

Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression

The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.     

药物过度使用性头痛患者脑白质结构的变化

目的利用磁共振弥散张量成像技术研究药物过度使用性头痛患者脑白质结构的变化。方法药物过度使用性头痛患者(病例组)及年龄、性别相匹配的同期健康体检者(对照组)各80例,收集一般临床资料,进行颅脑磁共振弥散张量成像(diffusion tensor imaging,DTI)检查,测取部分各向异性(fractional anisotropy,FA)值、表观弥散系数(apparent diffusion coefficient,ADC)值,并结合临床特点进行相关性分析。结果 (1)病例组眶额皮质、前后扣带回皮质、胼胝体压部、右侧内囊前肢FA值较对照组明显降低,差异有统计学意义(P0.05);(2)病例组右侧眶额皮质、左侧额下回皮质及前扣带回皮质ADC值较对照组明显升高,差异有统计学意义(P0.05);(3)病例组双侧眶额部皮质以及右侧内囊后肢FA值与患者头痛病程及发作频率呈负相关;左侧内囊后肢FA值与头痛频率呈负相关;(4)病例组左侧眶额皮质ADC值与患者头痛病程及发作频率呈正相关;右侧眶额皮质以及前扣带回皮质ADC值与患者头痛发作频率呈正相关;后扣带回皮质ADC值与患者头痛病程呈正相关。结论药物过度使用性头痛患者双侧额叶皮质及扣带回皮质存在白质微观结构异常变化,FA值与患者头痛病程及发作频率呈负相关,ADC值则呈正相关。     

Alterations of white matter integrity related to motor activity in schizophrenia

Altered structural connectivity is a key finding in schizophrenia, but the meaning of white matter alterations for behavior is rarely studied. In healthy subjects, motor activity correlated with white matter integrity in motor tracts. To explore the relation of motor activity and fractional anisotropy (FA) in schizophrenia, we investigated 19 schizophrenia patients and 24 healthy control subjects using Diffusion Tensor Imaging (DTI) and actigraphy on the same day. Schizophrenia patients had lower activity levels (AL). In both groups linear relations of AL and FA were detected in several brain regions. Schizophrenia patients had lower FA values in prefrontal and left temporal clusters. Furthermore, using a general linear model, we found linear negative associations of FA and AL underneath the right supplemental motor area (SMA), the right precentral gyrus and posterior cingulum in patients. This effect within the SMA was not seen in controls. This association in schizophrenia patients may contribute to the well known dysfunctions of motor control. Thus, structural disconnectivity could lead to disturbed motor behavior in schizophrenia.     

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.     

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.