强迫症眶额叶-小脑连接的相关分析北大核心CSCD

目的探讨小脑局部脑区与大脑局部脑区间的功能连接在强迫症发病中的作用。方法纳入2014年6月至2016年1月河南省精神病医院门诊及住院收治的首发强迫症患者55例(强迫症组),以及50例性别、年龄、民族、受教育程度与之相匹配的正常健康对照者(对照组)。所有受试者均接受全脑静息态功能磁共振(rs-fMRI)检查、采集数据。利采用rs-fMRI处理辅助软件(DPARSF V2.3)和数据分析软件(REST)处理两组数据后,采用双样本t检验对两组局部一致性(ReHo)图进行分析,得出强迫症组的异常脑区,以异常脑区为感兴趣区(ROI)行全脑功能连接分析。结果(1)与对照组相比,强迫症组左侧小脑8区(t=3.473 2)、右侧丘脑(t=4.321 7)ReHo值增高,左内侧眶部额上回(t=-4.582 6)ReHo值减低,差异均有统计学意义(P<0.05,Alphasim校正,簇集大小>40个体素);(2)功能连接分析显示左内侧眶部额上回、左侧小脑8区、右侧丘脑之间存在异常功能连接(P<0.05,Alphasim校正,簇集大小>20个体素)。结论强迫症存在左内侧眶部额上回-左侧小脑8区-右丘脑环路,左侧小脑8区可能通过此环路参与强迫症的发病。     

强迫症执行功能障碍的神经机制研究进展

执行功能障碍是强迫症的重要特征。神经影像学和基因研究表明，强迫症患者皮质 - 纹 状体 - 丘脑 - 皮质回路、顶叶、小脑等脑区的功能异常，以及 5- 羟色胺、谷氨酸系统中的基因变异，可能 是导致患者执行功能障碍的原因。但由于强迫症的异质性和执行功能的复杂性，目前关于强迫症执行 功能障碍的神经机制尚未得出一致的结论。整合强迫症执行功能障碍的神经机制和基因模式，有助于 加深对强迫症发病机制的理解；结合神经影像和遗传学研究结果确定标志物，有助于为强迫症执行功 能障碍的识别和干预提供新方向。现对强迫症执行功能障碍的脑结构、脑功能的神经机制以及基因研 究展开综述。     

弥散张量成像在情感障碍研究中的应用

情感障碍是一种常见的精神疾病,以往大量神经解剖学、脑代谢、影像学研究等结果证实:双相障碍皮层-皮层下网状系统和边缘系统调节区域(杏仁核,小脑中部)的中枢功能异常可能是情感失调的原因[1];抑郁症存在“边缘-皮层-纹状体-苍白球-丘脑”病理神经环路,其中前额皮层、海马、前     

强迫症神经影像学研究进展

强迫症是一种难治性的精神疾病,病因复杂。影像学技术在精神疾病中的应用愈加广泛, 并在探究强迫症发病机制中起到了重要的作用。有研究通过功能性磁共振成像技术（fMRI）发现强迫症 患者的前额皮质及皮质下结构存在异常功能连接。由于强迫症是一种异质性疾病,因此不同的神经环 路可能介导不同的强迫症状的产生。现从脑部发病机制的角度出发,分析近些年来强迫症功能磁共振 方面的研究进展,综述目前强迫症发病机制及其与临床症状相关性的研究成果。     

强迫症与尾状核容量减少

强迫症与尾状核容量减少【英】ＲｏｂｉｎｓｏｎＤ…ＡｒｃｈＧｅｎＰｓｙｃｈｉａｔｒｙ，１９９５，５２（５），－３９３～３９８目前有关强迫症的神经解剖结构研究认为，强迫症患者存在皮质－纹状体－丘脑通路异常。结构性脑成像技术常用于研究与该通路有关的大脑解剖...     

强迫症患者脑结构异常的多模态研究

目的探讨强迫症患者脑灰质和白质结构改变是否在同一样本中反映了相同环路的异常。方法对54例强迫症患者(强迫症组)和54名健康对照(对照组)进行3D结构磁共振成像扫描和弥散张量成像扫描。基于SPM分析软件,采用基于体素的形态学分析方法分析强迫症组全脑灰质体积与对照组的差异;基于FSL软件,采用基于纤维束示踪的空间统计学探讨强迫症组各向异性分数(fractional anisotropy,FA)与对照组的差异。结果与对照组相比,强迫症组左侧额中回、左侧前扣带和旁扣带脑回、左侧中央前回及右侧颞下回灰质体积减小(P<0.05,Alphasim校正),胼胝体体部和胼胝体膝部FA值减小(P<0.05,FWE校正)。结论强迫症患者的灰质体积和白质完整性均存在异常,且异常区域多位于皮质-纹状体-丘脑-皮质环路相关脑区,强迫症的灰、白质结构异常可能同时出现。     

Huntington舞蹈病大脑免疫病理改变及其和痴呆精神异常的关系

目的：研究Huntington舞蹈病的组织病理改变特点,观察泛素阳性营养不良性神经突起和神经细胞核内包涵体在大脑不同部位的分布规律,探讨痴呆和精神异常的病理基础,方法：先症者为－49岁的男性病人,表现为进行性痴呆、舞蹈和精神异常,于病后17年死亡。家族中连续5代人中15例出现类似临床表现,先症者死亡后进行部头解剖和组织学检查,对大脑皮层和基底节不同区域进行tau蛋白和泛素免疫比喻杂色,分析不同区域的病理改变规律。结果：脑病理改变特点为新纹状体显著萎缩,神经细胞脱失伴胶质细胞增生,泛素阳性的营养不良性神经突起和神经细胞核包涵体主要出现在大脑皮层的Ⅲ-Ⅳ层,神经细胞核内泛素阳性包涵体在大脑额叶前区皮层达22％,依次为顶叶7％、枕叶3％、颞叶1％和哲带回1％。相就细胞核出现变性改变,包涵体不含有tau蛋白。泛素阳性营养不良性神经突起在大脑额叶前区皮层最多,每低倍视野达5个以上,其次为顶叶、颞叶和扣带回的皮层,低倍视野在1－5个之间,海马和纹状体仅偶见营养不性神经突起,没有神经细胞核内包涵体,结论：大脑皮层出现泛素阳性神经细胞内包涵体和营养不良神经突起在大脑不同区域的分布存在很大的差异,由于额极也存在明显的病理改变,所以此病的智能减退属于额叶皮层－皮层下性痴呆。额叶、颞叶和扣带皮层出现神经细胞核内包涵体或营养不良性神经突起可能是精神异常的病理学基础。     

难治性癫的神经病理学特点

难治性癫(refractoryepilepsy)临床表现为长期、反复的癫发作,经过一定阶段的正规药物治疗仍无法控制,发病率占癫的30%左右,大部分难治性癫要借助于手术治疗,这就为癫的病理学研究提供了研究资料。近年来,神经内科、功能神经外科、神经影像学、神经电生理学等各个学科的发展也为癫的病理学发展提供了更多的信息。与难治性癫密切相关的神经病理学改变主要有以下2大类:一类为皮层发育不良、一类为肿瘤。本文综述国际上近期的相关文献,结合影像学和临床特点对难治性癫的神经病理学特点进行简要介绍。1皮层发育不良皮层发育不良…     

导航辅助皮层功能拓扑定位在累及功能区致痫灶手术中的初步应用

目的 应用神经导航影像融合并结合皮层电刺激功能定位技术,初步实现三维可视化皮层功能拓扑定位,辅助累及皮层功能区致痫灶的手术,提高疗效.方法 1例药物难治性癫痫患者,行双侧皮层电极埋藏覆盖中央区,术后予皮层脑电图监测,并实施皮层电刺激定位功能区.神经导航系统融合头颅MRI和CT影像,三维可视化拓扑定位皮层功能和致痫灶,第二次手术在导航辅助定位保护功能区的前提下,行致痫灶切除术,对累及功能区的病变实施皮层热灼术.结果 患者成功埋藏32导、24导及6导皮层电极各一枚覆盖中央区,皮层脑电图监测捕获临床发作4次,定位致痫灶;皮层电刺激确定功能区.神经导航影像融合建立覆盖皮层电极的三维大脑模型,还原电生理资料,实现拓扑定位.手术成功实施病灶切除,术后无发作情况,无并发症.结论 应用神经导航影像融合技术,使作为脑-机接口的脑皮层电极技术与影像学技术相结合,将皮层电极的空间位置,精确融合在基于头颅MRI建立的大脑皮层解剖模型上,还原皮层脑电图和皮层电刺激结果,实现三维可视化拓扑定位,对于累及功能区致痫灶的神经外科手术具有重要指导意义.     

抑郁症患者眶额叶皮层功能连接偏离的研究

目的 通过功能磁共振成像技术,研究抑郁症患者和健康对照组在情感处理时眶额叶皮层的功能连接偏离,为抑郁症的早期诊断和疗效评估提供影像学依据.方法 对25例重度抑郁症患者和15名健康对照组在执行面貌一致性任务时进行功能性磁共振成像.结果 和健康对照组相比重度抑郁症患者的背侧前扣带回皮层、楔前叶、小脑与眶额叶的活动连接减少;抑郁症患者的眶额叶皮层和背外侧前额叶皮层、右额叶岛盖部、左运动区之间的功能连接比健康对照组有所增加.结论 眶额叶皮层在抑郁症的病理生理学机制中发挥着关键作用.眶额叶皮层连接的失衡似乎代表加工偏离的神经机制.从神经生物学的角度来看,楔前叶和扣带回的连接解离活动与眶额叶皮层的自我架构规则的问题相关,而背外侧前额叶皮层到眶额叶的连接增加可能代表更高消极刺激的神经反应.     

Review of structural neuroimaging in patients with refractory obsessivecompulsive disorder

The notion that some special brain regions may be involved in the pathogenesis of obsessive-compulsive disorder (OCD) dates back to the beginning of the twentieth century. Structural neuroimaging studies in the past 2 decades have revealed important findings that facilitate understanding of OCD pathogenesis. Current knowledge based on functional and structural neuroimaging investigations largely emphasizes abnormalities in fronto-striatal-thalamic-cortical and orbitofronto-striato-thalamic circuits in the pathophysiology of OCD. However, these neuroimaging studies did not focus on refractory OCD. The present review mainly focused on structural neuroimaging performed in OCD, which had been ignored previously, and highlighted current evidence supporting that orbito-frontal cortex and thalamus are key brain regions, and that the hippocampus-amygdala complex is associated with refractoriness to the available treatment strategies. However, to fully reveal the neuroanatomy of refractoriness, longitudinal studies with larger samples are required.     

Brain-behavior relationships in obsessive-compulsive disorder

Advances in neuroimaging have led to a greater understanding of brain-behavior relationships in obsessive-compulsive disorder (OCD). This article provides an updated review and analysis of the structural and functional neuroimaging studies in OCD published to date and discusses how evidence from various types of neuroimaging studies has been synthesized to generate and test hypotheses regarding these relationships. We also review the basic science literature on the functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and integrate this information with neuroimaging data in OCD, to present a theoretical model of brain mediation of OCD symptoms and response to treatment. Taken together, neuroimaging studies indicate that OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to an imbalance of tone between direct and indirect striato-pallidal pathways. Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, thereby decreasing activity in the overall circuit that exists in the symptomatic state.     

Spontaneous magnetoencephalographic activity in patients with obsessive-compulsive disorder

Non-invasive functional imaging techniques have begun to delineate the underlying neurophysiological basis of obsessive-compulsive disorder (OCD). In the present study, we investigated slow (2-6 Hz) and fast (12.5-30 Hz) spontaneous magnetoencephalographic (MEG) activity in ten patients with obsessive-compulsive disorders compared to ten healthy control subjects. Fast MEG activity was significantly elevated in OCD patients. The corresponding dipole density maxima were concentrated on the left superior temporal gyrus. Although no differences were detected in the absolute dipole numbers between controls and OCD patients regarding slow MEG activity, only the latter showed a clustering of slow MEG activity over their left dorsolateral prefrontal cortex. We conclude that alterations of spontaneous MEG activity in prefrontal and temporal cortices may be linked to the pathogenesis of OCD. Therefore, we provide further functional neuroimaging evidence that the complex features of OCD have neural correlates, which may help in a future understanding of this disease.     

Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder.

Functional neuroimaging studies have advanced the understanding of the brain mediation of OCD by orbitofrontal-subcortical circuitry, but much is still unknown. Phenotypic heterogeneity could account for many of the inconsistencies among previous neuroimaging studies of OCD. Current studies are seeking to find the neurobiological basis of OCD symptom subtypes and predictors of treatment response. Future studies combining genetics and basic neuroanatomic research with neuroimaging may clarify the cause and pathophysiology of OCD. Although many lines of evidence point to dysfunction of orbitofrontal-subcortical circuitry in patients with OCD, many questions remain unanswered. Some have suggested that orbitofrontal-subcortical hyperactivity in OCD may be the result of abnormal neuroanatomic development of these structures or a failure of pruning of neuronal connections between them, as occurs in normal development, but no postmortem neuroanatomic studies of OCD exist to delineate its pathophysiology. Interventions that directly alter the indirect-direct pathway balance within frontal-subcortical circuits will allow for direct testing of the pathophysiologic hypotheses presented here. The roles of various neurochemical systems in OCD are similarly unclear. Although an abundance of indirect evidence suggests serotonergic abnormalities in patients with OCD, no direct evidence demonstrates what those abnormalities are or whether they are primary or secondary phenomena in patients with OCD. Ongoing studies of 5-HT synthesis in the brains of patients with OCD may shed light on this question.     

Perseveration and not strategic deficits underlie delayed alternation impairment in obsessive–compulsive disorder (OCD)

The claim that the prefrontal cortex, particularly its orbito-frontal part, is involved in obsessive–compulsive disorder (OCD) is based upon evidence from neuroimaging as well as behavioral studies. Studies have repeatedly suggested problems with delayed alternation learning in OCD, an executive dysfunction that presumably involves the orbito-frontal cortex. However, it is unclear whether such impairment stems from perseveration or strategic deficits as these aspects are intertwined in the original task. In the present study, 36 OCD and 16 healthy controls underwent a variant of the delayed alternation task involving three response options instead of two as in the original task. This modification enabled us to separate perseveration errors (i.e., the participant incorrectly chooses the same response option as before) from shift errors (i.e., the decision is switched to an incorrect response alternative). We found that patients with OCD committed significantly more perseveration errors following previously valid response options, whereas perseveration for previously invalid responses and shift errors did not distinguish groups. Group differences were not accounted for by comorbid depression and may be linked to the pathogenesis of OCD.     

Disgust and obsessive-compulsive disorder: an update

In this paper, we review the growing body of literature investigating the association between obsessive-compulsive disorder (OCD) and the emotion of disgust. Initially studied with regard to specific phobias, the potential role of disgust responses in contamination concerns has led researchers to investigate possible associations between disgust and OCD symptoms. The literature on disgust-sensitivity in OCD is reviewed. Studies of disgust recognition in OCD and research using neuroimaging methods are then summarized. We suggest that disgust has a moderate association with OCD symptoms, particularly those which are contamination-based or which have a religious focus. Evidence for a disgust recognition deficit in patients with OCD is lacking; however, neuroimaging findings have confirmed hypothesized associations between contamination-focused OCD and the insula cortex, which has been implicated in disgust processing. Finally, treatment implications are discussed, and suggestions are made for further research.     

New approach to obsessive-compulsive disorder: dopaminergic theories

In patients with obsessive-compulsive disorder (OCD), structural and volumetric abnormalities have been identified by up-to-date neuroimaging techniques both in the prefrontal region and in the basal ganglia (striatum, thalamus, amygdala). The dysfunction of these regions also has been proved by neuroimaging techniques. These alterations can be described as dopaminergic hyperfunction in the prefrontal cortex and serotonergic hypofunction in the basal ganglia. The dysfunction of the so-called 'cortico-striato-thalamic' loops is strongly linked to the symptoms of OCD, where the dopamine is the most dominant neurotransmitter. The ascending serotonergic projections from the raphe nuclei restrain and control the function of these loops. Thus, when serotonergic hypofunction is present, the predominantly dopaminergic loops became overactive, which has been confirmed by neuroimaging techniques and by neurocognitive tests as well. The linkage of the two predominant neurotransmitter systems affected in OCD can be the reason for the fact that SSRIs have limited success in the treatment of OCD symptoms. In recent international, multicentric studies, the treatment of SSRI non-responder subgroup of OCD patients were supplemented by antipsychotics with dopaminergic activity. Many studies have confirmed the beneficial effect of these antidopaminergic substances on the hyperactive cortico-striato-thalamic loops in OCD. The investigation of these dysfunctional loops is also connected to the genetic background of OCD, because some of the candidate gene regions of OCD are coding proteins of the dopamine synthesis (for example: COMT). In this paper, we present a detailed overview of these relationships based on recent findings of OCD research.     

Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder

CONTEXT: There is strong evidence from family and twin studies that genetic determinants play an important role in the etiology of obsessive-compulsive disorder (OCD). In the only genome scan of OCD to date that we are aware of, suggestive linkage was reported to the chromosomal region 9p24, a finding that was subsequently replicated. This region contains the gene encoding the neuronal glutamate transporter, SLC1A1. SLC1A1 represents an excellent candidate gene for OCD based on evidence from neuroimaging and animal studies that altered glutamatergic neurotransmission is implicated in the pathogenesis of this disorder. OBJECTIVE: To determine whether sequence variants in SLC1A1 are associated with transmission of the OCD trait. DESIGN: A family-based candidate gene association study. SETTING: A specialized anxiety disorders outpatient clinic. PARTICIPANTS: One hundred fifty-seven white probands with DSM-IV OCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total). INTERVENTION: Nine single nucleotide polymorphisms spanning SLC1A1 were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined included DSM-IV OCD diagnosis and highest lifetime symptom severity as measured using the Yale-Brown Obsessive-Compulsive Scale. Correction for multiple comparisons was performed using permutation tests. RESULTS: After correction for multiple comparisons, 2 variants, rs301434 (chi 2 = 12.04; P = .006) and rs301435 (chi 2 = 9.24; P = .03), located within a single haplotype block were found to be associated with transmission of OCD. Furthermore, a specific 2-marker haplotype within this block was significantly associated with OCD (chi 2 = 12.60; P = .005). This haplotype association was statistically significant in transmissions to male but not female offspring. CONCLUSIONS: Although requiring replication in larger samples, these findings provide preliminary evidence that sequence variation in SLC1A1 is associated with susceptibility to OCD, particularly in males. Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.     

An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive–compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi‐site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA''s OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA‐OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.     

Neurobiological model of obsessive–compulsive disorder: Evidence from recent neuropsychological and neuroimaging findings

Obsessive–compulsive disorder (OCD) was previously considered refractory to most types of therapeutic intervention. There is now, however, ample evidence that selective serotonin reuptake inhibitors and behavior therapy are highly effective methods for treatment of OCD. Furthermore, recent neurobiological studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. A large number of previous neuroimaging studies using positron emission tomography, single‐photon emission computed tomography or functional magnetic resonance imaging (fMRI) have identified abnormally high activities throughout the frontal cortex and subcortical structures in patients with OCD. Most studies reported excessive activation of these areas during symptom provocation. Furthermore, these hyperactivities were decreased after successful treatment using either selective serotonin reuptake inhibitors or behavioral therapy. Based on these findings, an orbitofronto‐striatal model has been postulated as an abnormal neural circuit that mediates symptomatic expression of OCD. On the other hand, previous neuropsychological studies of OCD have reported cognitive dysfunction in executive function, attention, nonverbal memory, and visuospatial skills. Moreover, recent fMRI studies have revealed a correlation between neuropsychological dysfunction and clinical symptoms in OCD by using neuropsychological tasks during fMRI. The evidence from fMRI studies suggests that broader regions, including dorsolateral prefrontal and posterior regions, might be involved in the pathophysiology of OCD. Further, we should consider that OCD is heterogeneous and might have several different neural systems related to clinical factors, such as symptom dimensions. This review outlines recent neuropsychological and neuroimaging studies of OCD. We will also describe several neurobiological models that have been developed recently. Advanced findings in these fields will update the conventional biological model of OCD.