Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder

Recent functional connectivity magnetic resonance imaging and diffusion tensor imaging (DTI) studies have suggested atypical functional connectivity and reduced integrity of long-distance white matter fibers in autism spectrum disorder (ASD). However, evidence for short-distance white matter fibers is still limited, despite some speculation of potential sparing of local connectivity in ASD. Short-distance U-fibers are an important component of neural networks and are thought to play a crucial role in cognitive function. In the present study, we applied tract-based spatial statistics to derive short- and long-distance white matter tracts in frontal, parietal, and temporal lobes in both hemispheres. DTI data were acquired from 26 children with ASD and 24 typically developing (TD) children. A mean fractional anisotropy (FA) image was created and thinned to represent centers of all common tracts. Evidence of compromised short-distance tracts for the ASD group was found in frontal lobe (reduced FA, increased mean diffusivity [MD] and radial diffusivity) as well as in temporal and parietal lobes (increased MD and radial diffusivity). Significant positive correlations between age and FA and negative correlations between age and MD and radial diffusivity were also found for short-distance tracts in each lobe in the TD, but not the ASD group. These results suggest white matter compromise in short-distance tracts in ASD. Absence of typical age-related correlations with DTI indices may reflect altered maturation of short-distance tracts in ASD. Our results are inconsistent with a notion of selective sparing of short-distance connectivity in ASD.     

Treatment outcome of posttraumatic stress disorder: A white matter tract analysis

Despite the development of empirically supported treatments for posttraumatic stress disorder (PTSD), many individuals remain symptomatic following therapy or dropout prematurely. Neuroimaging studies examining PTSD treatment outcome may offer valuable insights into possible mechanisms that may impact treatment efficacy. To date, few studies of PTSD have used neuroimaging to examine symptom change following completed treatment, and most have focused on gray matter. Studies of white matter are equally important, as changes in white matter integrity (WMI) are connected to a host of detrimental outcomes. The current study examined symptom change of 21 women with PTSD as a result of interpersonal violence who received baseline diffusion tensor imaging (DTI) scans and completed 12 weeks of Cognitive Processing Therapy (CPT). After controlling for baseline PTSD severity, fractional anisotropy (FA) in the left internal capsule, posterior limb of the internal capsule, left cingulate gyrus, superior longitudinal fasciculus, and splenium of the corpus callosum was predicted by PTSD symptom change. Results contribute to understanding neural changes within therapy and may assist in predicting individual treatment response. Namely, by identifying areas potentially impacted by PTSD treatment, future studies may be able to connect the function of these white matter areas to better predict patient PTSD treatment outcome.     

Altered white matter connectivity in never‐medicated patients with schizophrenia

Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication‐naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract‐based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group‐related differences as disease‐related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. Hum Brain Mapp 34:2353–2365, 2013. © 2012 Wiley Periodicals, Inc.     

基于弥散张量成像技术的双相障碍患者脑白质纤维束异常分析

目的探讨抑郁期双相障碍患者脑白质纤维束的变化。方法选取42例未用药双相障碍抑郁期患者(患者组)和年龄、性别及右利手与之相匹配的59名对照者(对照组)进行DTI检查,根据约翰霍普金斯大学人类白质纤维束图谱,将大脑白质组织分割为20条公认存在的粗大纤维束,应用PANDA软件计算每个被试者每条白质纤维束的4项平均弥散属性,采用非参数置换检验比较2组在20条白质纤维束上弥散指标的差异,将差异有统计学意义的脑白质纤维束弥散指标与临床指标进行Pearson相关分析。结果患者组左侧钩束各向异性分数(fractional anisotropy,FA)值低于对照组(0.40±0.01与0.41±0.01,P=0.001);胼胝体辐射线额部FA值低于对照组(0.36±0.02与0.38±0.02,P<0.001);左侧钩束径向弥散率(radial diffusivity,RD)值高于对照组(6.57×10^-4±2.41×10^-5与6.40×10^-4±2.42×10^-5,P=0.0017)。Pearson相关分析显示,2组弥散指标差异有统计学意义的白质纤维束与临床指标之间均无相关性。结论抑郁期双相障碍患者钩束及胼胝体辐射线额部存在脑白质完整性破坏。     

Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: A diffusion tensor imaging study

BackgroundClinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning.Methods49 adult BD patients ((M ± SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M ± SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity – MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A).ResultsBD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities.ConclusionsThe reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination.     

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.     

Alterations of white matter connectivity in first episode schizophrenia

Cerebral disconnectivity due to white matter alterations in patients with chronic schizophrenia assessed by diffusion tensor imaging has been reported previously. The aim of this preliminary study is to investigate whether cerebral disconnectivity can be detected as early as the first episode of schizophrenia. Intervoxel coherence values were compared by voxel-based t test in 12 patients with first episode schizophrenia and 12 age- and gender-matched control groups. We detected 14 circumscribed significant clusters (P < 0.02), 3 of them with higher, and 11 of them with lower IC values for patients with schizophrenia than for healthy control groups. We interpret these white matter alterations in different regions to be disconnected fiber tracts already present early in schizophrenic disease progression.     

Altered cortical gyrification patterns in panic disorder: Deficits and potential compensation

Abnormal gyrification patterns may reflect aberrant cortical connectivity during an early period of brain maturation. We here investigated anatomical distribution of cortical gyrification deficits underlying panic disorder and the relationships of these potential neurodevelopmental markers with panic symptom severity. High-resolution three-dimensional T1-weighted structural images were obtained from 23 patients with panic disorder and 33 matched healthy individuals. Local gyrification indices were measured in each genetically-based parcellated cortical subregion and regional gyrification patterns were compared between groups. Cortical areas in which gyrification patterns were associated with panic symptom severity were also determined. Significant reductions in cortical gyrification were observed in panic patients compared with healthy individuals, which were mainly distributed in the lateral brain extending from the fronto-parietal to the temporal areas. In contrast, hyper-gyrification in the posteromedial cortical regions which exert interconnecting roles in the default mode network, was associated with less severe panic symptoms. Post-hoc analysis for the inter-regional covariance of local gyrification indices revealed that interconnections of the posteromedial cortical regions with other cortical areas which belong to the default mode network were reduced in panic patients with severe symptoms relative to either less severe patients or healthy individuals. Our findings suggest not only substantial perturbation in cortical gyrification patterns in panic disorder but also potential contribution of integrated cortical folding pattern of the default mode network to alleviated panic severity.     

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。     

Altered white matter integrity in primary restless legs syndrome patients: diffusion tensor imaging study

Abstract

Objectives:

A prior diffusion tensor imaging (DTI) of restless legs syndrome (RLS) subjects found alterations in brain white matter (WM). The aim of this study was to explore the possible mechanism of altered integrity of brain WM in RLS patients.

Methods:

The DTI measurement was performed in 22 subjects with RLS and 22 age-matched control subjects. Using a voxel-based analysis, fractional anisotropy (FA) and axial and radial diffusivities (AD and RD) were compared between RLS and control subjects with a two-sample t-test, and correlation analysis was performed in RLS subjects.

Results:

RLS subjects demonstrated decreased FA in the genu of the corpus callosum and frontal WM adjacent to the inferior frontal gyrus compared with the control subjects. For areas of decreased FA, both the AD and RD were higher than that in the control subjects.

Discussion:

Our findings suggest that loss of axonal density and myelin may account for WM changes seen in a prior study of RLS subjects.     

惊恐障碍患者血清脂质水平的初步研究

采用酶法测定在性别、年龄上相匹配的３０例惊恐障碍患者、３０例抑郁症患者及３０例正常对照者的血清脂质水平。结果显示：惊恐障碍患者的血清胆固醇（Ｔｃｈ）水平明显高于抑郁症患者和正常对照者，稳定内科疾病与高血清Ｔｃｈ水平无关；在抑郁症组中，焦虑障碍史与高血清Ｔｃｈ水平明显有关。提示惊恐障碍患者的高血清Ｔｃｈ水平，可能涉及去甲肾上腺素或５羟色胺活性增高假说机制。     

Anterior cingulate cortex volume reduction in patients with panic disorder

Aim:  Recent neuroimaging studies have suggested that the anterior cingulate cortex (ACC) has an important role in the pathology of panic disorder. Despite numerous functional neuroimaging studies that have elucidated the strong relationship between functional abnormalities of the ACC and panic disorder and its symptoms and response to emotional tasks associated with panic disorder, there has been no study showing volumetric changes of the ACC or its subregions.
Methods:  To clarify the structural abnormalities of ACC and its subregions, the combination of region of interest (ROI) and optimized voxel-based morphometry (VBM) methods were performed on 26 patients with panic disorder, and 26 age and sex-matched healthy subjects. In the ROI study, ACC was divided into four subregions: dorsal, rostral, subcallosal and subgenual ACC.
Results:  The results of the manually traced ROI volume comparison showed significant volume reduction in the right dorsal ACC. VBM also showed a volume reduction in the right dorsal as well as a part of the rostral ACC as a compound mass.
Conclusions:  Both manual ROI tracing and optimized VBM suggest a subregion-specific pattern of ACC volume deficit in panic disorder. In addition to functional abnormalities, these results suggest that structural abnormalities of the ACC contribute to the pathophysiology of panic disorder.     

Tract-specific white matter structural disruption in patients with bipolar disorder

Benedetti F, Absinta M, Rocca MA, Radaelli D, Poletti S, Bernasconi A, Dallaspezia S, Pagani E, Falini A, Copetti M, Colombo C, Comi G, Smeraldi E, Filippi M. Tract‐specific white matter structural disruption in patients with bipolar disorder. Bipolar Disord 2011: 13: 414–424. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: A growing body of evidence suggests that, independent of localized brain lesions, mood disorders can be associated with dysfunction of brain networks involved in the modulation of emotional and cognitive behavior. We used diffusion tensor (DT) tractography to quantify the presence and extent of structural injury to the connections between the amygdala and other brain regions, which included the subgenual, the supragenual and posterior cingulate, the parahippocampal, the orbitofrontal and dorsolateral prefrontal cortices, as well as the insula. Methods: Using a 3.0 Tesla scanner, conventional and DT magnetic resonance imaging sequences of the brain were acquired from 15 adult patients with major depressive disorder (MDD), 15 with bipolar disorder (BD), and 21 age‐matched healthy controls. Using FSL software, diffusivity changes of the white matter (WM) fiber bundles belonging to the emotional network were measured. Results: Compared to controls and MDD patients, BD patients had significantly decreased average fractional anisotropy, increased average mean diffusivity, and increased average axial and radial diffusivity values in the majority of the WM fiber bundles connecting structures of the anterior limbic network (p‐values ranging from 0.002 to 0.040). Medication load did not influence the results with the exception of lithium, which was associated with normal diffusivity values in tracts connecting the amygdala with the subgenual cingulate cortex. Conclusions: We detected specific WM abnormalities, suggestive of disrupted integrity of fiber bundles in the brains of patients with BD. These abnormalities might contribute to understanding both mood dysregulation and cognitive disturbances in BD, and might provide an objective marker to monitor treatment efficacy in this condition.     

惊恐障碍患者血清脂质水平的初步研究

探讨惊恐障碍患者的血脂水平及明确高胆固醇 (Tch)水平是否仅伴发于惊恐障碍或与其他精神障碍有关。　　方法　采用酶法测定在性别、年龄上相匹配的 3 0例惊恐障碍患者、3 0例抑郁症患者及 3 0例正常对照者的血清脂质水平。　　结果　惊恐障碍男患者的血清Tch水平明显高于抑郁症患者和正常对照者 ,稳定内科疾病与高血清Tch水平无关 ;在抑郁症组中 ,焦虑障碍史者的血清Tch水平显著增高。　　结论　提示惊恐障碍男患者的血清高Tch水平 ,可能涉及去甲肾上腺素或 5-羟色胺活性增高假说机制     

Pre-treatment peripheral biomarkers associated with treatment response in panic symptoms in patients with major depressive disorder and panic disorder: A 12-week follow-up study

ObjectivePeripheral biomarkers have been studied to predict treatment response of panic symptoms. We hypothesized that depressive disorder (MDD) vs. panic disorder (PD) would exhibit different peripheral biomarkers, and their correlation with severity of panic attacks (PA) would also differ.MethodsForty-one MDD patients, 52 PD patients, and 59 healthy controls were followed for 12 weeks. We measured peripheral biomarkers along with the Panic Disorder Severity Scale (PDSS) at each visit—pre-treatment, 2, 4, 8, and 12 weeks on a regular schedule. Peripheral biomarkers including serum cytokines, plasma and serum brain-derived neurotrophic factor (BDNF), leptin, adiponectin, and C-reactive protein (CRP) were quantified using enzyme-linked immunosorbent assay (ELISA).ResultsPatients with MDD and PD demonstrated significantly higher levels of pre-treatment IL-6 compared to controls, but no differences were seen in plasma and serum BDNF, leptin, adiponectin, and CRP. Pre-treatment leptin showed a significant clinical correlation with reduction of panic symptoms in MDD patients at visit 5 (p = 0.011), whereas pre-treatment IL-6 showed a negative correlation with panic symptom reduction in PD patients (p = 0.022). An improvement in three panic-related items was observed to be positively correlated with pre-treatment leptin in MDD patients: distress during PA, anticipatory anxiety, and occupational interference.ConclusionHigher pre-treatment leptin was associated with better response to treatment regarding panic symptoms in patients with MDD, while higher IL-6 was associated with worse response regarding panic symptoms in PD patients. Different predictive peripheral biomarkers observed in MDD and PD suggest the need for establishing individualized predictive biomarkers, even in cases of similar symptoms observed in different disorders.     

Evaluation of subcortical white matter and deep white matter tracts in malformations of cortical development

AIMS: Abnormal cortical development will lead to abnormal axons in white matter. The purpose was to investigate (1) the microstructural changes in subcortical white matter adjacent to malformations of cortical development (MCD) and (2) the deep white matter tracts using diffusion tensor imaging (DTI). METHODS: Thirteen children with a variety of MCD were recruited. The fractional anisotropy (FA), trace, and eigenvalues (lambdamajor, lambdamedium, lambdaminor) of subcortical white matter of MCD were compared with contralateral normal side. The deep white matter tracts were graded based on the size, color hues and displacement of the tracts as visualized on color vector maps and tractography; grade 1 was normal tract size and color hue, grade 2 was reduced tract size but preserved color hue and grade 3 was loss of color hue or failure of tracking on tractography. RESULTS: The subcortical white matter adjacent to abnormal cortex demonstrated reduced FA (p < 0.05) and tendency to increase trace (p = 0.06). There was a significant elevation in lambdamedium and lambdaminor (p < 0.05), but no significant change in lambdamajor (p > 0.05). Twelve cases demonstrated alteration in white matter tracts. Seven cases of focal cortical dysplasia and two cases of transmantle MCD demonstrated grade 3 pattern of white matter tract. CONCLUSION: Reduced FA is a sensitive but nonspecific marker of alteration in microstructure of white matter. The elevated lambdamedium and lambdaminor may reflect a dominant effect of abnormal myelin. Alteration in white matter tracts was observed in most cases of MCD.     

Audiovestibular functioning in patients with panic disorder

OBJECTIVE: The objective of this study was to investigate audiovestibular function in patients with panic disorder and healthy subjects by using vestibular and audiologic tests. METHODS: Thirty-four panic disorder patients and 20 healthy control subjects were assessed by using clinical otoneurological examination, pure tone audiometry, tympanometry, and electronystagmography (ENG). All patients were evaluated with the Panic and Agoraphobia Scale (PAS), the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the State-Trait Anxiety Inventory (STAI). RESULTS: On vestibular testing, abnormal responses were more prevalent in panic disorder patients compared to healthy controls. The presence of agoraphobia in panic disorder patients did not make a significant difference on vestibular test results. The only variable that may be a predictor of vestibular abnormalities in panic disorder patients was found to be dizziness between attacks. CONCLUSION: The results show that dizziness between panic attacks may warrant audiovestibular testing among other medical investigations.     

Magnetoencephalography and diffusion tensor imaging in gelastic seizures secondary to a cingulate gyrus lesion

Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.