部分多模态MRI在重度抑郁症中的研究进展

重度抑郁症是最常见的高致残性的精神疾病之一,其发病机制尚不清楚。MRI技术作为非侵入性的神经影像技术,可揭示重度抑郁症患者大脑功能状态。与健康对照者相比,重度抑郁症患者额叶、颞叶、海马、扣带回、基底节、小脑等脑区功能改变,可能提示重度抑郁症的病理生理异常。现就多模态MRI,包括弥散张量成像(DTI)、弥散峰度成像(DKI)、磁共振波谱成像(MRS)、功能MRI(fMRI)、神经突方向分散度和密度成像(NODDI)在重度抑郁症中的最新研究成果进行综述,以期对其神经生物学机制有更充分的理解。     

Differences in fMRI and MRS in a monozygotic twin pair discordant for schizophrenia (case report)

OBJECTIVE: This paper presents functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) findings in a monozygotic twin pair discordant for schizophrenia. METHOD: Functional magnetic resonance imaging was used to determine hemispheric lateralization for speech and proton MRS (1H-MRS) was employed to assess the extent of putative insult to anterior hippocampus. RESULTS: Despite concordant right handedness, subject with schizophrenia displayed bilateral activation in areas subserving speech with greater extent of the total activated area compared with the healthy twin. The affected twin displayed relative bilateral decrease in N-acetylaspartate/creatin concentration in the anterior hippocampus compared with the healthy one. CONCLUSION: This is an evidence for non-genetic impairment of cerebral lateralization in monozygotic twin with schizophrenia.     

Language lateralization in temporal lobe epilepsy using functional MRI and probabilistic tractography

Purpose: Language functional magnetic resonance imaging (fMRI) is used to noninvasively assess hemispheric language specialization as part of the presurgical work-up in temporal lobe epilepsy (TLE). White matter asymmetries on diffusion tensor imaging (DTI) may be related to language specialization as shown in controls and TLE. To refine our understanding of the effect of epilepsy on the structure–function relationships, we focused on the arcuate fasciculus (ArcF) and the inferior occipitofrontal fasciculus (IOF) and tested the relationship between DTI- and fMRI-based lateralization indices in TLE.
Methods: fMRI with three language tasks and DTI were obtained in 20 patients (12 right and 8 left TLE). The ArcF, a major language-related tract, and the IOF were segmented bilaterally using probabilistic tractography to obtain fractional anisotropy (FA) lateralization indices. These were correlated with fMRI-based lateralization indices computed in the inferior frontal gyrus (Pearson's correlation coefficient).
Results: fMRI indices were left-lateralized in 16 patients and bilateral or right-lateralized in four. In the ArcF, FA was higher on the left than on the right side, reaching significance in right but not in left TLE. We found a positive correlation between ArcF anisotropy and fMRI-based lateralization indices in right TLE (p < 0.009), but not in left TLE patients. No correlation was observed for the IOF.
Conclusions: Right TLE patients with more left-lateralized functional activations also showed a leftward-lateralized arcuate fasciculus. The decoupling between the functional and structural indices of the ArcF underlines the complexity of the language network in left TLE patients.     

fMRI及DTI技术在成人工作记忆研究的初步探索

目的：联合应用脑功能磁共振成像（BOLD—fMRI）和弥散张量成像（DTI）两种磁共振技术,探索工作记忆功能激活部位与叶间白质纤维束的关系。方法：健康志愿者16名,以步进式视觉累加试验作为刺激模式,扫描获得fMRI激活图及各向异性（FA）图。将两者叠加,选取双侧额顶叶白质兴趣区测量其部分FA值。结果：①额顶叶皮质为工作记忆功能最主要的激活区;②脑的激活像素几乎均位于FA程度低的区域（P〈0．01）;③左额顶间白质FA值较对侧高（P〈0．02）。结论：联合应用fMRI和DTI技术提示成人工作记忆功能与额顶叶白质纤维髓鞘化程度密切相关。     

Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5-18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full-scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito-parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts.     

A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states

Cerullo MA, Fleck DE, Eliassen JC, Smith MS, DelBello MP, Adler CM, Strakowski SM. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 2012: 14: 175–184. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally. Methods: fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole‐brain functional connectivity analysis was performed using the left and right amygdala as seed regions. Results: Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group. Conclusions: In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical–amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.     

Association of White Matter Integrity With Executive Function and Antidepressant Treatment Outcome in Patients With Late-Life Depression

ObjectiveWhile patients with late-life depression (LLD) often exhibit microstructural white matter alterations that can be identified with diffusion tensor imaging (DTI), there is a dearth of information concerning the links between DTI findings and specific cognitive performance, as well as between DTI measures and antidepressant treatment outcomes.DesignNeuroimaging and cognitive tests were conducted at baseline in 71 older adults participating in a larger, 8-week duration antidepressant randomized controlled trial. Correlations between DTI measures of white matter integrity evaluated with tract-based spatial statistics, baseline neurocognitive performance, and prospective antidepressant treatment outcome were evaluated.ResultsFractional anisotropy (FA), an index of white matter integrity, was significantly positively associated with better cognitive function as measured by the Initiation/Perseveration subscale of the Dementia Rating Scale in the bilateral superior longitudinal fasciculus (SLF), bilateral SLF-temporal, and right corticospinal tract (CST). An exploratory analysis limited to these tracts revealed that increased FA in the right CST, right SLF, and right SLF-temporal tracts was correlated with a greater decrease in depressive symptoms. Increased FA in the right CST predicted a greater chance of remission, while increased FA in the right CST and the right SLF predicted a greater chance of treatment response.ConclusionIn late-life depression LLD subjects, white matter integrity was positively associated with executive function in white matter tracts which act as key connecting structures underlying the cognitive control network. These tracts may play a role as a positive prognostic factor in antidepressant treatment outcome.     

Amygdala and hippocampus volumes in pediatric major depression.

BACKGROUND: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. METHODS: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. RESULTS: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. CONCLUSIONS: Smaller amygdalas are present early in the course of pediatric depression and may predispose to the development of this disorder or perhaps more generally of childhood mood disorders. Future research should examine the longitudinal course and functional correlates of amygdala volume abnormalities in childhood-onset depression, including their possible moderation by gender.     

White matter integrity alterations in post‐traumatic stress disorder

Post‐traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy‐five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma‐exposed age‐ and gender‐matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non‐trauma‐exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.     

Altered white matter integrity of forebrain in treatment-resistant depression: a diffusion tensor imaging study with tract-based spatial statistics

Background

The association between alterations of the white matter (WM) integrity in brain regions and mood dysregulation has been reported in major depressive disorder (MDD). However, there has never been a neuroimaging study in patients who have treatment-resistant depression (TRD) and are in a current treatment-resistant state. In the present study, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) method to investigate the WM integrity of different brain regions in patients who had TRD and were in a current treatment-resistant state.

Methods

Twenty-three patients with TRD and Hamilton Rating Scale total score of ≥ 18 and 19 healthy controls matched with age, gender, and education level to patients were scanned with DTI. Thirty 4 mm thick, no gap, contiguous axial slices were acquired and fractional anisotropy (FA) images were generated for each participant. An automated TBSS approach was used to analyze the data.

Results

Voxel-wise statistics revealed that patients with TRD had lower FA values in the right anterior limb of internal capsule, the body of corpus callosum, and bilateral external capsule compared to healthy subjects. Patients with TRD did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain region and patients' demographics and the severity of illness.

Conclusions

Our findings suggest the abnormalities of the WM integrity of neuronal tracts connecting cortical and subcortical nuclei and two brain hemispheres may play a key role in the pathogenesis of TRD.     

轻度创伤性脑损伤后脑组织微环境变化:多模态磁共振成像研究

目的探讨弥散张量成像(DTI)联合磁共振波谱(MRS)及磁敏感加权成像(SWI)的功能磁共振成像方法,在评估轻度创伤性脑损伤(mTBI)脑组织代谢及微结构变化的应用价值,为临床制定相应的治疗方案提供影像学参考。方法纳入21例mTBI患者和16例健康志愿者,mTBI患者在伤后4～72 h内接受T1WI、T2WI、FLAIR、DTI、MRS及SWI序列扫描,通过各序列图像及参数值评估mTBI患者伤侧脑组织和对照组内囊前肢、内囊后肢、胼胝体膝部、胼胝体压部、扣带回、半卵圆中心、额叶白质及视辐射的差异。结果两组FA值比较,仅胼胝体压部差异有统计学意义(P0.01)。mTBI组胼胝体膝部NAA/Cr值低于对照组,差异有统计学意义(P0.01)。mTBI组内囊后肢和胼胝体膝部Cho/Cr值均高于对照组,差异均有统计学意义(P0.05或0.01)。结论 FA值及NAA、Cho、Cr值能测定mTBI后脑组织水分子扩散及代谢情况,DTI联合MRS及SWI可以作为一项客观指标,定量评估mTBI患者的病情及预后。     

肌萎缩侧索硬化38例弥散张量成像及磁共振波谱表现

目的 研究肌萎缩侧索硬化(ALS)的弥散张量成像(DTI)和磁共振波谱(MRS)特点,并对ALs的病理生理机制进行初步探讨.方法 ALS患者38例,单纯下运动神经元受累疾病患者8例,混合型颈椎病5例和健康对照34名,行常规头颅MRI、DTI和1H-MRS测定.结果 21%(8/38)的ALS患者可见T2 FLAIR序列双侧锥体束走行异常高信号,强度高于皮质灰质.ALS组和健康对照组相比,中央前回(ALS组0.492±0.059,健康对照组0.552 4-0.045,F=17.150,P<0.01)、内囊后肢(分别为0.679 ±0.048、0.727±0.031,F=19.481,P<0.01)、大脑脚(左侧0.740±0.038、0.761±0.024,F=4.290;右侧0.720±0.044、0.746±0.034,F=3.264,均P<0.01)的部分各向异性(FA值)显著降低;ALS组上述部位的N-乙酰大冬氨酸/肌酸(NAA/Cr)值和健康对照组相比亦存在显著降低.AKS组各部位FA值降低百分率分别为10.9%、6.6%、2.8%～3.5%,以中央前回处最为显著;内囊前肢、枕叶处的FA值亦有不同程度降低.结论 DTI和MRS枪测不仪有助于ALS患者:运动神经元高位受累的确认和ALS的诊断和鉴别诊断,而且还可促进对ALS病理机制和病损分布的了解.     

Diffusion Tensor and Functional Magnetic Resonance Imaging of Diffuse Axonal Injury and Resulting Language Impairment

Diffuse axonal injury (DAI) is a common aftermath of brain trauma. The diagnosis of DAI is often difficult using conventional magnetic resonance imaging (MRI). We report a diffusion tensor imaging (DTI) study of a patient who sustained DAI presenting with language impairment. Fractional anisotropy (FA) and DTI tractography revealed a reduction of white matter integrity in the left frontal and medial temporal areas. White matter damage identified by DTI was correlated with the patient's language impairment as assessed by functional MRI (fMRI) and a neuropsychological exam. The findings demonstrate the utility of DTI for identifying white matter changes secondary to traumatic brain injury (TBI).     

抑郁症与正常人静息态脑功能变化对照研究

目的:利用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,研究静息状态下重性抑郁症患者经抗抑郁药治疗前后脑局部一致性变化的特点. 方法:20例重性抑郁症患者(抑郁症组),以20名在性别、年龄、受教育年限均与之相匹配的健康人作为对照(对照组),在抗抑郁治疗前和治疗10周进行静息状态fMRI扫描. 结果:与治疗前比较,抑郁症组治疗后大脑左侧黑质、左额中回(BA9,BA10)、左额内侧回(BA10)、左颞中回(BA21)、右额中回(BA11)、右额内侧回(BA25)、右额下回(BA45)及右颞上回(BA38)局部一致性减低.与对照组比较,抑郁症组治疗前双侧楔前叶(BA7)局部一致性增高,而治疗后右前扣带回腹侧(BA31)、右额下回(BA46)、右额内侧回(BAIO)及左海马旁回(BA36)局部一致性减低. 结论:静息状态下抑郁症患者存在部分脑功能异常,经抗抑郁治疗后可逆转.     

Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM

Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph‐theoretical measures ‘local clustering coefficient’ and ‘shortest path length’ derived from resting‐state functional MRI (rs‐fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave‐one‐out cross‐validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs‐fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone. Hum Brain Mapp 36:2118–2131, 2015. © 2015 Wiley Periodicals, Inc.     

抑郁症患者情绪图片反应特征及杏仁核反应模式的研究

目的 探讨抑郁症患者对情感刺激的行为学反应模式及其相关的杏仁核时程反应过程.方法 12例首次发病、未经治疗的抑郁症患者(抑郁症组)和13名健康个体(健康对照组)对观看正性、中性和负性情绪图片的愉悦度等评分;并在被动注视任务下行功能磁共振成像,采用感兴趣区分析方法,比较两组杏仁核在不同情绪图片任务组块间的血氧水平依赖(BOLD)信号时间反应特征.结果 (1)抑郁症组情绪图片愉悦度评分[正性:(6.6 ±0.2)分;中性:(4.7 ±0.1)分]低于健康对照组[分别为(7.7 ±0.2)分和(5.1 ±0.1)分],负性情绪图片评分[(3.4 ±0.3)分]高于健康对照组[(2.2 ±0.2)分;P<0.01].(2)对正性情绪图片任务,两组间右侧杏仁核存在"组×时间"交互作用(P=0.002);抑郁症组杏仁核BOLD信号变化率为(0.02±0.09)%,激活时间后移至Block 2.对负性情绪图片任务,两组间左侧杏仁核有"组×时间"交互作用(P=0.008),右侧杏仁核存在组主效应(P=0.007)和时间主效应(P=0.016),抑郁症组BOLD信号变化率低于(-0.06 ±0.14)%.结论 杏仁核是抑郁症患者丧失愉悦体验和情绪低落的神经基础之一.     

Elevated amygdala activity to negative faces in young adults with early onset major depressive disorder

Abnormalities in amygdala activity have been implicated in adolescents and older adults with major depressive disorder (MDD), but few studies have focused on young adults with early-onset MDD. In this study, we measured amygdala activity in 27 young adults with early-onset MDD and 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) with an emotional processing task. Both groups showed significant bilateral activation within the amygdala to threat-related facial expressions. In the matching face task, the activations of the left amygdala, thalamus, prefrontal and temporal cortex were significantly greater while the activation of the right prefrontal was significantly lower for the MDD group compared with the HC group. For the MDD group, there was a significant positive correlation between the activity of the amygdala and scores on the Chinese version of the Center for Epidemiologic Studies Depression Scale. Overall, our findings suggest that young adults with early-onset MDD may be characterized by abnormalities in nodes along the fronto-limbic pathways when facing threat-related facial expression.     

Neural correlates of processing emotional prosody in unipolar depression

Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five‐point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence‐specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.     

Disruption of Limbic Pathways in a Case of Profound Amnesia

We report a case of episodic amnesia in which the anatomical basis of injury was investigated by diffusion tensor imaging (DTI). Two months after an adult male suffered severe closed head injury, conventional magnetic resonance imaging (CMRI) revealed only a right superior frontal lesion. However, 14 years later, DTI revealed structural anomalies not visible on CMRI involving limbic white matter tracts, notably the fornix, which could explain the amnesia.     

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.