Psychiatry Research: Neuroimaging最新文献_第4页

The interplay of genetic and environmental factors on the morphology of the limbic cortex and hippocampal subfields: Insights from an MRI twin study 遗传和环境因素对边缘皮层和海马亚区形态的相互作用：核磁共振成像双胞胎研究的启示

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-10-05 DOI: 10.1016/j.pscychresns.2024.111909

Arsalan Vessal , Amirreza Alijanpourotaghsara , David Strelnikov , Aliz Persely , Marton Piroska , Amirmasoud Alijanpour , Zsofia Jokkel , Laszlo Szalontai , Bianka Forgo , Lajos Rudolf Kozak , Adam Bekesy-Szabo , Pal Maurovich-Horvat , David Laszlo Tarnoki , Adam Domonkos Tarnoki

Introduction

The limbic system and the hippocampus are complex brain structures with key roles in memory, emotions, sexual stimulation and learning, with subregion abnormalities associated with a range of disorders and psychopathologies. Our study aimed to explore the heritability of specific subfield structures within the limbic system and hippocampus first in a Caucasian twin sample with volBrain pipeline.

Materials and Methods

59 healthy adult Caucasian twin pairs from the Hungarian Twin Registry without any history of previous neurodegenerative or cerebrovascular diseases underwent brain MRI on a 3.0 T scanner (43 monozygotic, MZ and 16 dizygotic, DZ pairs, with a median age of 50±+27 years). The volBrain automated volumetry pipeline was used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Based on age- and sex-adjusted MZ and DZ intra-pair correlations, the univariate ACE model was applied to calculate additive genetic, shared and unshared environmental influences.

Results

Adjusting for age and sex, moderate to strong heritability (A: 59.7 to 73.1 %) was found for most limbic cortex volumes, except for the volumes of entorhinal area and posterior cingulate gyrus where common environmental contribution was detected (C: 56.6 % and 65.0 %, respectively). A substantial heritability (A: 67.0 to 79.4 %) was estimated for the overall hippocampus and most subfield volumes, except for the CA2-CA3 region which was determinated by common environmental factors (C: 45.7 %). Unique environmental variance was a minor to moderate contributor across all variables (E: 20.6 to 54.3 %).

Conclusions

Albeit most limbic cortex, overall hippocampus and most subfield volumes are under substantial genetic influence in healthy adult twins, the volumes of entorhinal area, posterior cingulate gyrus and the CA2-CA3 region of the hippocampus are influenced common environmental factors. The findings underline the importance of unique environmental factors which may play a role in the prevention of disorders related to limbic cortex and hippocampus.

导言边缘系统和海马是复杂的大脑结构，在记忆、情绪、性刺激和学习中起着关键作用，亚区异常与一系列疾病和精神病理学有关。我们的研究旨在利用 volBrain 管线首先在高加索双胞胎样本中探讨边缘系统和海马特定亚区结构的遗传性。材料与方法59 对来自匈牙利双胞胎登记处的健康成年高加索双胞胎，既往无任何神经退行性疾病或脑血管疾病史，在 3.0 T 扫描仪上接受了脑核磁共振成像（43 对单卵双生（MZ）和 16 对双卵双生（DZ），中位年龄为 50±+27 岁）。volBrain自动体积测量管道用于从三维T1加权图像中计算皮层下和一般脑体积。根据年龄和性别调整的 MZ 和 DZ 配对内相关性，应用单变量 ACE 模型计算加性遗传、共有和非共有环境影响因素。结果调整年龄和性别后，发现大多数边缘皮层体积的遗传率为中度至高度遗传率（A：59.7% 至 73.1%），但内侧区和扣带回后部体积除外，这两个部位的体积检测到共有环境影响因素（C：分别为 56.6% 和 65.0%）。除 CA2-CA3 区由共同环境因素决定外（C：45.7%），其他海马区和大多数子区体积的遗传率都很高（A：67.0%-79.4%）。结论尽管在健康的成年双胞胎中，大多数边缘皮层、整个海马体和大多数子野的体积都受到遗传因素的很大影响，但内侧区、扣带回后部和海马体 CA2-CA3 区的体积则受到共同环境因素的影响。这些发现强调了独特环境因素的重要性，它们可能在预防与边缘皮层和海马有关的疾病方面发挥作用。

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引用次数: 0

MRI-based deep learning for differentiating between bipolar and major depressive disorders 基于磁共振成像的深度学习用于区分双相情感障碍和重度抑郁症。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-25 DOI: 10.1016/j.pscychresns.2024.111907

Ruipeng Li , Yueqi Huang , Yanbin Wang , Chen Song , Xiaobo Lai

Mood disorders, particularly bipolar disorder (BD) and major depressive disorder (MDD), manifest changes in brain structure that can be detected using structural magnetic resonance imaging (MRI). Although structural MRI is a promising diagnostic tool, prevailing diagnostic criteria for BD and MDD are predominantly subjective, sometimes leading to misdiagnosis. This challenge is compounded by a limited understanding of the underlying causes of these disorders. In response, we present SE-ResNet, a Residual Network (ResNet)-based framework designed to discriminate between BD, MDD, and healthy controls (HC) using structural MRI data. Our approach extends the traditional Squeeze-and-Excitation (SE) layer by incorporating a dedicated branch for spatial attention map generation, equipped with soft-pooling, a 7 × 7 convolution, and a sigmoid function, intended to detect complex spatial patterns. The fusion of channel and spatial attention maps through element-wise addition aims to enhance the model's ability to discriminate features. Unlike conventional methods that use max-pooling for downsampling, our methodology employs soft-pooling, which aims to preserve a richer representation of input features and reduce data loss. When evaluated on a proprietary dataset comprising 303 subjects, the SE-ResNet achieved an accuracy of 85.8 %, a recall of 85.7 %, a precision of 85.9 %, and an F1 score of 85.8 %. These performance metrics suggest that the SE-ResNet framework has potential as a tool for detecting psychiatric disorders using structural MRI data.

情绪障碍，尤其是双相情感障碍（BD）和重度抑郁障碍（MDD），表现为大脑结构的变化，可通过结构性磁共振成像（MRI）检测到。虽然结构磁共振成像是一种很有前途的诊断工具，但目前对双相情感障碍和重度抑郁障碍的诊断标准主要是主观性的，有时会导致误诊。由于对这些疾病的根本原因了解有限，这一难题变得更加复杂。为此，我们提出了 SE-ResNet，这是一种基于残差网络（ResNet）的框架，旨在利用结构磁共振成像数据区分 BD、MDD 和健康对照（HC）。我们的方法扩展了传统的 "挤压-激发"（SE）层，加入了一个用于生成空间注意力图的专用分支，该分支配备了软池化、7 × 7 卷积和sigmoid函数，旨在检测复杂的空间模式。通过元素相加的方式融合通道和空间注意力图，旨在增强模型对特征的辨别能力。与使用最大池法进行下采样的传统方法不同，我们的方法采用了软池法，旨在保留输入特征的更丰富表征并减少数据丢失。在由 303 名受试者组成的专有数据集上进行评估时，SE-ResNet 的准确率为 85.8%，召回率为 85.7%，精确率为 85.9%，F1 分数为 85.8%。这些性能指标表明，SE-ResNet 框架具有利用结构性 MRI 数据检测精神疾病的潜力。

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引用次数: 0

(Interfering) Cortical mechanisms of standing balance and cognition in old-age depression: A functional near-infrared spectroscopy (fNIRS) study (老年抑郁症患者站立平衡和认知的皮层机制：功能性近红外光谱（fNIRS）研究。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-24 DOI: 10.1016/j.pscychresns.2024.111905

Pia Thönnessen , L.Cornelius Bollheimer , Michael Luehrs , Ute Habel , Bettina Sorger , Charlotte Huppertz

Major depressive disorder in old age can cause changes in the cerebral cortex that might lead to postural imbalance and thus increase fall risk. We aim to examine cortical activation during standing balance in depressed older patients compared to healthy controls and to determine how an additional cognitive task affects this activation. Eleven older patients (age ≥65 years) diagnosed with major depressive disorder and sixteen age-matched healthy controls participated in the study. Functional near-infrared spectroscopy (fNIRS) was used to assess cortical activation of the prefrontal (PFC) and motor (MC) cortex during standing balance with eyes closed under single and dual task (counting backwards). The present study generally revealed tendencies in the MC – and partly the PFC too – for more activation whilst balancing compared to baseline. Also, in the MC, patients tended to show more cortical activation compared to controls and dual task tended to elicit more activation. The results suggest that depressed older patients, to compensate for their illness, may require increased cortical activation to perform motor and cognitive tasks than healthy controls. The absence of PFC activation in the main analyses may be related to the small participant number and possibly to too simple task conditions.

老年重度抑郁症会导致大脑皮层发生变化，从而可能导致姿势失衡，进而增加跌倒风险。与健康对照组相比，我们旨在研究老年抑郁症患者在站立平衡时大脑皮层的激活情况，并确定额外的认知任务会如何影响这种激活。11 名被诊断为重度抑郁症的老年患者（年龄≥65 岁）和 16 名年龄匹配的健康对照组参加了研究。研究人员使用功能性近红外光谱（fNIRS）评估了闭眼站立平衡时在单一任务和双重任务（倒数）下前额叶（PFC）和运动（MC）皮层的激活情况。本研究普遍发现，与基线相比，MC（部分也包括前额叶）在平衡时的激活程度更高。此外，与对照组相比，在 MC 部分，患者倾向于表现出更多的皮质激活，而双重任务则倾向于引起更多的激活。这些结果表明，与健康对照组相比，老年抑郁症患者可能需要更多的大脑皮层激活来完成运动和认知任务，以补偿他们的疾病。在主要分析中没有发现前脑皮层激活可能与参与人数较少有关，也可能与任务条件过于简单有关。

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引用次数: 0

Longitudinal changes in neural responses to fearful faces in adolescents with anorexia nervosa – A fMRI study 神经性厌食症青少年对恐惧面孔的神经反应的纵向变化 - 一项 fMRI 研究。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-24 DOI: 10.1016/j.pscychresns.2024.111904

Lukas Stanetzky , Arne Hartz , Kimberly Buettgen , Brigitte Dahmen , Beate Herpertz-Dahlmann , Kerstin Konrad , Jochen Seitz

Objective

Although proven neuronal changes are correlated with anorexia nervosa (AN), where these changes occur and how they change during the course of this disease are often unclear; this is especially true regarding emotion processing, e.g., of anxiety, despite a growing body of literature on its importance for the pathophysiology and clinical course of patients with AN.

Methods

Twenty-two female adolescent patients with AN were scanned during acute starvation and after short-term weight recovery and were compared to 27 healthy controls. A well-established face-matching paradigm involving individuals with different emotions was used during fMRI.

Results

Patients with AN selectively showed significantly increasing neural activation in the somatomotor cortex when viewing fearful faces following short-term weight recovery. No differences were found compared to healthy controls or for neutral, angry or surprised faces. Neural activation in response to fearful faces during acute starvation was associated with lower BMI-SDS and greater illness burden.

Conclusion

Higher somatomotor activity could represent anxiety-induced preparations for motor reactions (e.g., fight or flight) that are more pronounced in more affected patients. These results align with recent models of AN that increasingly incorporate anxiety into the pathophysiological and prognostic model of AN and help elucidate its underlying neurological mechanisms.

目的：尽管神经元变化已被证实与神经性厌食症（AN）有关，但这些变化发生在何处以及在病程中如何变化往往并不清楚；情绪处理（如焦虑）方面的情况尤其如此，尽管越来越多的文献指出了情绪处理对神经性厌食症患者的病理生理学和临床病程的重要性：在急性饥饿期和短期体重恢复后对 22 名女性青少年 AN 患者进行了扫描，并与 27 名健康对照者进行了比较。在进行fMRI扫描时，采用了一种成熟的人脸匹配范式，涉及不同情绪的个体：结果：短期体重恢复后，当观察恐惧面孔时，选择性自闭症患者躯体运动皮层的神经激活明显增加。与健康对照组相比，或与中性、愤怒或惊讶面孔相比，均未发现差异。在急性饥饿期间，神经激活对恐惧面孔的反应与较低的 BMI-SDS 和较重的疾病负担有关：较高的躯体运动活动可能代表焦虑引起的运动反应准备（如战斗或逃跑），这在受影响较大的患者中更为明显。这些结果与最近的AN模型一致，这些模型越来越多地将焦虑纳入AN的病理生理学和预后模型中，并有助于阐明其潜在的神经机制。

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引用次数: 0

Altered resting-state and dynamic functional connectivity of hypothalamic in first-episode depression: A functional magnetic resonance imaging study 首发抑郁症患者下丘脑静息态和动态功能连接的改变：功能磁共振成像研究

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-23 DOI: 10.1016/j.pscychresns.2024.111906

Xue Xiao , Jifei Sun , Jing Tian , Xu Sun , Chunhong Yang , Ying Hao , Yanan Zhao , Xue Yu , Mingshan Li , Shaoyuan Li , Jiliang Fang , Xiaobing Hou

The hypothalamus is an important component of the hypothalamic-pituitary-adrenal axis and an important brain region of the limbic system. Twenty-four first depressive episode(FDE) patients and 25 healthy controls were recruited for this study. The hypothalamus was used as a seed to observe the characteristics of resting state and dynamic functional connectivity (FC) changes in FDE patients, and further observed the correlation between the different brain regions and clinical symptoms. The results found that compared with the HC group, the FDE group showed sFC was increased of the left hypothalamus with right superior parietal gyrus and right middle temporal gyrus, and dFC was increased of the left hypothalamus with left inferior occipital gyrus. And sFC was increased of the right hypothalamus with right orbital part of inferior frontal gyrus, right supplementary motor area, and right middle temporal gyrus, and the dFC was also increased of right hypothalamus with right superior parietal gyrus and left middle temporal gyrus. In addition,there was a negative correlation between dFC values of the right hypothalamus with the right superior parietal gyrus and clinical symptoms in the FDE group. This study provides new insights into understanding the altered neuropathological mechanisms of the hypothalamic circuit in FDE.

下丘脑是下丘脑-垂体-肾上腺轴的重要组成部分，也是边缘系统的重要脑区。本研究招募了24名首次抑郁发作（FDE）患者和25名健康对照者。以下丘脑为种子，观察FDE患者静息态和动态功能连接（FC）的变化特征，并进一步观察不同脑区与临床症状的相关性。结果发现，与HC组相比，FDE组左下丘脑与右顶叶上回和右颞中回的sFC增加，左下丘脑与左枕下回的dFC增加。而右侧下丘脑与右侧额叶下回眶部、右侧辅助运动区和右侧颞中回的sFC增加，右侧下丘脑与右侧顶上回和左侧颞中回的dFC也增加。此外，右下丘脑与右顶叶上回的dFC值与FDE组的临床症状呈负相关。这项研究为了解 FDE 下丘脑回路的神经病理机制改变提供了新的见解。

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引用次数: 0

Quantitative assessment of brain structural abnormalities in children with autism spectrum disorder based on artificial intelligence automatic brain segmentation technology and machine learning methods 基于人工智能自动脑部分割技术和机器学习方法的自闭症谱系障碍儿童脑部结构异常定量评估。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-16 DOI: 10.1016/j.pscychresns.2024.111901

Xiaowen Xu , Yang Li , Ning Ding , Yukun Zang , Shanshan Sun , Gaoyu Shen , Xiufeng Song

Rationale and objectives

To explore the characteristics of brain structure in Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to diagnose children with ASD using machine learning (ML) methods in combination with structural magnetic resonance imaging (sMRI) features.

Methods

A total of 60 ASD children and 48 age- and sex-matched typically developing (TD) children were prospectively enrolled from January 2023 to April 2024. All subjects were scanned using 3D-T1 sequences. Automated brain segmentation techniques were utilized to obtain the standardized volume of each brain structure (the ratio of the absolute volume of brain structure to the whole brain volume). The standardized volumes of each brain structure in the two groups were statistically compared, and the volume data of brain areas with significant differences were combined with ML methods to diagnose and predict ASD patients.

Results

Compared with the TD group, the volumes of the right lateral orbitofrontal cortex, right medial orbitofrontal cortex, right pars opercularis, right pars triangularis, left hippocampus, bilateral parahippocampal gyrus, left fusiform gyrus, right superior temporal gyrus, bilateral insula, bilateral inferior parietal cortex, right precuneus cortex, bilateral putamen, left pallidum, and right thalamus were significantly increased in the ASD group (P< 0.05). Among six ML algorithms, support vector machine (SVM) and adaboost (AB) had better performance in differentiating subjects with ASD from those TD children, with their average area under curve (AUC) reaching 0.91 and 0.92, respectively.

Conclusion

Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in children with autism spectrum disorder and typically developing children. Children with ASD show abnormalities in multiple brain structures, and when paired with sMRI features, ML algorithms perform well in the diagnosis of ASD.

理论依据和研究目的利用人工智能脑结构自动分割技术探讨中国自闭症谱系障碍（ASD）儿童的脑结构特征，并利用机器学习（ML）方法结合结构磁共振成像（sMRI）特征诊断ASD儿童：方法：2023 年 1 月至 2024 年 4 月期间，共招募了 60 名 ASD 儿童和 48 名年龄和性别匹配的典型发育（TD）儿童。所有受试者均使用 3D-T1 序列进行扫描。利用自动脑分割技术获得每个脑结构的标准化体积（脑结构绝对体积与整个脑体积之比）。对两组脑结构的标准化体积进行统计比较，并将差异显著的脑区体积数据与ML方法相结合，对ASD患者进行诊断和预测：左侧纺锤形回、右侧颞上回、双侧岛叶、双侧顶叶下皮层、右侧楔前皮层、双侧丘脑、左侧苍白球和右侧丘脑在 ASD 组显著增加（P< 0.05).在六种ML算法中，支持向量机（SVM）和adaboost（AB）在区分ASD受试者和TD儿童方面表现较好，其平均曲线下面积（AUC）分别达到0.91和0.92：基于人工智能的大脑自动分割技术可以快速、直接地测量和显示自闭症谱系障碍儿童和发育正常儿童的大脑结构体积。自闭症谱系障碍儿童表现出多种脑结构异常，如果与sMRI特征相配合，ML算法在诊断自闭症谱系障碍方面表现良好。

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引用次数: 0

Personalized fMRI tasks for grief severity in bereaved individuals: Emotional counting Stroop and grief elicitation protocols 针对丧亲者悲伤严重程度的个性化 fMRI 任务：情绪计数 Stroop 和悲伤激发协议

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-12 DOI: 10.1016/j.pscychresns.2024.111902

Jonathan Singer , Joseph S. Goveas , Lauren Elliott , Harshit Parmar , O'Connor Mary-Frances

Approximately 7–10% of people experiencing bereavement following a death develop prolonged grief disorder, a psychiatric disorder included in the DSM-5-TR. Prolonged grief disorder encompasses core symptoms of intense yearning/longing for and preoccupation with thoughts or memories of the deceased person experienced to a clinically significant degree for at least the last month, other key associated symptoms (e.g., avoidance, emotional pain), and the death must have occurred at least one year prior to diagnosis. Extant research has shown a relationship between activation in the reward pathway (e.g., nucleus accumbens) and grief severity. To date, functional MRI studies have primarily utilized the Emotional Counting Stroop task (ecStroop) and the Grief Elicitation task to explore these relationships. However, these prior studies are not without limitations, including small sample sizes and absence of a unified task protocol, hindering meaningful comparisons between studies. This protocol paper describes the ecStroop task and the Grief Elicitation task, which will be vital for facilitating multisite studies and enabling comparisons across studies. This will aid to advance the field by identifying neurophysiological measures that may, in the future, serve as potential biomarkers of prolonged grief disorder.

大约有 7-10% 的人在经历死亡后的丧亲之痛后会患上《DSM-5-TR》中所列的一种精神疾病--长期悲伤障碍。长期悲伤障碍的核心症状包括：对逝者强烈的渴望/渴求，以及对逝者的思念或回忆，这种思念或回忆至少在过去一个月内达到了临床上的显著程度，还包括其他主要的相关症状（如逃避、情感痛苦），而且死亡必须发生在诊断前至少一年。现有研究表明，奖赏通路（如伏隔核）的激活与悲伤严重程度之间存在关系。迄今为止，功能磁共振成像研究主要利用情绪计数史卓普任务（ecStroop）和悲伤激发任务来探讨这些关系。然而，这些先前的研究并非没有局限性，包括样本量小和缺乏统一的任务协议，从而阻碍了研究之间进行有意义的比较。本协议文件介绍了 ecStroop 任务和 "悲伤激发 "任务，这对于促进多地点研究和进行跨研究比较至关重要。这将有助于通过确定将来可能作为长期悲伤障碍潜在生物标志物的神经生理学措施来推动该领域的发展。

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引用次数: 0

Assessment of RNFL and macular changes in the eye related to multiple substance use using OCT 使用 OCT 评估与使用多种药物有关的眼睛 RNFL 和黄斑变化

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-07 DOI: 10.1016/j.pscychresns.2024.111889

Şüheda Kaya , Mehmet Kaan Kaya

Substance use is a chronic and recurrent public healthcare concern increasing in the world, causing negative outcomes. Two or more substance use is common among people who have substance use disorders and who receive treatment. For this reason, the present study aimed to measure Retinal Nerve Fiber Layer (RNFL), Mean Macular Thickness (MMT), Central Macular Thickness (CMT) in patients who have Multiple substance use disorder (MSUD) using Optical Coherence Tomography (OCT), considering that it will contribute to the literature. Among the inpatients who were rehabilitated in Elazig Mental Hospital Alcohol and Substance Addiction Treatment Center, 75 people who were diagnosed with MSUD according to DSM-5 and met the criteria, and 51 control groups were included in the study. RNFL, MMT and CMT measurements of both eyes of all participants were made by using the OCT. Total RNFL measurement were significantly thicker than the control group (p < 0.001). MMT and CMT of the eyes of the patient were thinner than the control group (p = 0.009, p < 0.001). The findings provide important contributions to the literature data and in light of these findings, it can be recommended to consider visual findings and possible neurodegeneration when evaluating patients in the addiction group and planning their treatment.

药物使用是全球日益严重的慢性和经常性公共医疗保健问题，会造成不良后果。在患有药物使用障碍并接受治疗的人群中，使用两种或两种以上药物的情况很常见。因此，本研究旨在使用光学相干断层扫描技术（OCT）测量多重药物使用障碍（MSUD）患者的视网膜神经纤维层（RNFL）、平均黄斑厚度（MMT）和黄斑中心厚度（CMT），以期为相关文献做出贡献。在埃拉泽格精神病院酒精和药物成瘾治疗中心的住院康复患者中，有 75 名根据 DSM-5 诊断为 MSUD 且符合标准的患者和 51 名对照组患者参与了研究。研究人员使用 OCT 测量了所有参与者双眼的 RNFL、MMT 和 CMT。总的 RNFL 测量值明显比对照组厚（p < 0.001）。患者双眼的 MMT 和 CMT 比对照组薄（p = 0.009，p < 0.001）。这些发现为文献数据做出了重要贡献，鉴于这些发现，可以建议在评估成瘾组患者和计划治疗时考虑视觉结果和可能的神经变性。

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引用次数: 0

Neuroimaging-based drug discovery for amyloid clearance therapy in Alzheimer's disease using validated causation analysis 基于神经成像的阿尔茨海默病淀粉样蛋白清除疗法药物研发，采用验证因果关系分析法

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-05 DOI: 10.1016/j.pscychresns.2024.111890

Anindita Bhattacharjee , Pratik Purohit , Prasun K. Roy

Aging-induced hepatic dysfunction can impair cholesterol metabolism, reducing the availability of cholic acid (CA, bile-acid) in brain. CA is reported to have neuroprotective characteristics in preclinical investigations of Alzheimer's disease (AD). Our aim is to probe the causal-connectivity between the players: amyloid, cholic acid and cerebral-blood-flow, and thereby explore therapeutic applicability in AD. From AD neuroimaging initiative biospecimen platform, we evaluated serum cholic-acid (182 healthy/136 AD individuals). We also assessed 50 healthy/50 Alzheimer's subjects containing MRI-ASL scanning (cerebral blood-flow, CBF) and PET-AV45 scanning (amyloid-load). We performed computational causal connectivity to determine the cause-effect relationship among the parameters. Serum cholic acid in AD subjects substantially decreased to half of controls. Causal-connectivity revealed two novel causative pathways: (i) Decreasing serum CA markedly increased amyloid-load; (ii) Increasing amyloid-load distinctly decreased CBF. We substantiated these two causation pathways respectively with collateral available preclinical observations: (a) increased cholic acid reduces amyloid formation by diminishing gamma-secretase; (b) this decreased amyloid induces capillary-flow enhancement by relaxing vascular pericytes. Indeed, cholic acid can increase amyloid-clearance factor. Neuroimaging-based causal connectivity analysis showed that repositioned pharmacological modulation by cholate derivatives may have appreciable potential as novel window for therapeutic approach to AD. Indicative clinical validation is furnished from available therapeutic trial leads.

衰老引起的肝功能障碍会损害胆固醇代谢，降低大脑中胆酸（CA，胆汁酸）的可用性。据报道，在阿尔茨海默病（AD）的临床前研究中，CA 具有神经保护特性。我们的目的是探究淀粉样蛋白、胆酸和脑血流这三者之间的因果联系，从而探索对阿尔茨海默病的治疗可行性。我们从 AD 神经影像计划生物样本平台评估了血清胆酸（182 名健康人/136 名 AD 患者）。我们还评估了 50 名健康受试者和 50 名阿尔茨海默氏症受试者，包括 MRI-ASL 扫描（脑血流，CBF）和 PET-AV45 扫描（淀粉样蛋白负荷）。我们进行了计算因果连接，以确定参数之间的因果关系。AD受试者的血清胆酸大幅下降，仅为对照组的一半。因果连通性揭示了两条新的因果途径：(i) 血清胆酸的减少明显增加了淀粉样蛋白负荷；(ii) 淀粉样蛋白负荷的增加明显降低了CBF。我们通过临床前的旁证观察分别证实了这两条致病途径：（a）增加胆酸可通过减少γ-分泌酶来减少淀粉样蛋白的形成；（b）淀粉样蛋白的减少可通过松弛血管周细胞来诱导毛细血管流量的增加。事实上，胆酸可增加淀粉样蛋白清除因子。基于神经影像学的因果连通性分析表明，胆酸衍生物重新定位的药理调节可能具有巨大的潜力，可作为治疗注意力缺失症的新窗口。现有的治疗试验线索提供了指示性临床验证。

{"title":"Neuroimaging-based drug discovery for amyloid clearance therapy in Alzheimer's disease using validated causation analysis","authors":"Anindita Bhattacharjee , Pratik Purohit , Prasun K. Roy","doi":"10.1016/j.pscychresns.2024.111890","DOIUrl":"10.1016/j.pscychresns.2024.111890","url":null,"abstract":"<div><div>Aging-induced hepatic dysfunction can impair cholesterol metabolism, reducing the availability of cholic acid (CA, bile-acid) in brain. CA is reported to have neuroprotective characteristics in preclinical investigations of Alzheimer's disease (AD). Our aim is to probe the causal-connectivity between the players: amyloid, cholic acid and cerebral-blood-flow, and thereby explore therapeutic applicability in AD. From AD neuroimaging initiative biospecimen platform, we evaluated serum cholic-acid (182 healthy/136 AD individuals). We also assessed 50 healthy/50 Alzheimer's subjects containing MRI-ASL scanning (cerebral blood-flow, CBF) and PET-AV45 scanning (amyloid-load). We performed computational causal connectivity to determine the cause-effect relationship among the parameters. Serum cholic acid in AD subjects substantially decreased to half of controls. Causal-connectivity revealed two novel causative pathways: (i) Decreasing serum CA markedly increased amyloid-load; (ii) Increasing amyloid-load distinctly decreased CBF. We substantiated these two causation pathways respectively with collateral available preclinical observations: (a) increased cholic acid reduces amyloid formation by diminishing gamma-secretase; (b) this decreased amyloid induces capillary-flow enhancement by relaxing vascular pericytes. Indeed, cholic acid can increase amyloid-clearance factor. Neuroimaging-based causal connectivity analysis showed that repositioned pharmacological modulation by cholate derivatives may have appreciable potential as novel window for therapeutic approach to AD. Indicative clinical validation is furnished from available therapeutic trial leads.</div></div>","PeriodicalId":20776,"journal":{"name":"Psychiatry Research: Neuroimaging","volume":"345 ","pages":"Article 111890"},"PeriodicalIF":2.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of neural networks involved in transdiagnostic emotion dysregulation from a pilot randomized controlled trial of a neurostimulation-enhanced behavioral intervention 神经刺激强化行为干预试点随机对照试验对跨诊断情绪失调神经网络的特征描述

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging

Pub Date : 2024-09-05 DOI: 10.1016/j.pscychresns.2024.111891

Andrada D. Neacsiu , Nimesha Gerlus , John L. Graner , Lysianne Beynel , Moria J. Smoski , Kevin S. LaBar

Background

Emotional dysregulation is a serious and impairing mental health problem. We examined functional activity and connectivity of neural networks involved in emotional dysregulation at baseline and following a pilot neurostimulation-enhanced cognitive restructuring intervention in a transdiagnostic clinical adult sample.

Methods

Neuroimaging data were analyzed from adults who scored 89 or higher on the Difficulties with Emotion Regulation (DERS) scale and had at least one DSM-5 diagnosis. These participants were part of a pilot randomized, double-blind, placebo-controlled trial combining a single therapeutic session of cognitive restructuring with active or sham transcranial magnetic stimulation over the dorsolateral prefrontal cortex. During the study, participants engaged in an emotional regulation task using personalized autobiographical stressors while undergoing functional magnetic resonance imaging (fMRI) before and after the pilot intervention. The fMRI task required participants to either experience the emotions associated with the memories or apply cognitive restructuring strategies to reduce their distress.

Results

Whole-brain fMRI results during regulation at baseline revealed increased activation in the dorsal frontoparietal network but decreased activation in the supplementary motor area, cingulate cortex, insula, and ventrolateral prefrontal cortex (vlPFC). Emotion dysregulation was associated with greater vmPFC and amygdala activation and functional connectivity between these regions. The strength of functional connectivity between the dlPFC and other frontal regions was also a marker of emotional dysregulation. Preliminary findings from a subset of participants who completed the follow-up fMRI scan showed that active neurostimulation improved behavioral indices of emotion regulation more than sham stimulation. A whole-brain generalized psychophysiological interaction analysis indicated that active neurostimulation selectively increased occipital cortex connectivity with both the insula and the dlPFC. Region-of-interest functional connectivity analyses showed that active neurostimulation selectively increased dlPFC connectivity with the insula and orbitofrontal cortex (OFC).

Conclusion

Insufficient neural specificity during the emotion regulation process and over-involvement of frontal regions may be a marker of emotional dysregulation across disorders. OFC, vlPFC, insula activity, and connectivity are associated with improved emotion regulation in transdiagnostic adults. In this pilot study, active neurostimulation led to neural changes in the emotion regulation network after a single session; however, the intervention findings are preliminary, given the small sample size. These functional network properties can inform future neuroscience-driven interventions and larger-scale studies.

背景情绪失调是一种严重影响心理健康的问题。我们研究了跨诊断临床成人样本在基线和神经刺激增强认知重组干预试验后参与情绪失调的神经网络的功能活动和连通性。方法我们分析了在情绪调节困难（DERS）量表中得分 89 分或以上并至少有一项 DSM-5 诊断的成人的神经影像数据。这些参与者参加了一项试验性随机、双盲、安慰剂对照试验，该试验将认知重组的单次治疗与对背外侧前额叶皮层的主动或假性经颅磁刺激相结合。研究期间，参与者利用个性化的自传体压力源参与情绪调节任务，同时在试点干预前后接受功能磁共振成像（fMRI）检查。结果基线调节期间的全脑 fMRI 结果显示，背侧额顶叶网络的激活增加，但辅助运动区、扣带回皮层、脑岛和腹外侧前额叶皮层（vlPFC）的激活减少。情绪失调与更高的前额叶皮质和杏仁核激活以及这些区域之间的功能连接有关。dlPFC与其他额叶区域之间的功能连接强度也是情绪失调的一个标志。完成后续 fMRI 扫描的部分参与者的初步研究结果表明，主动神经刺激比假刺激更能改善情绪调节的行为指数。全脑广义心理生理学交互分析表明，主动神经刺激选择性地增加了枕叶皮层与脑岛和大脑前交叉区域的连接。结论情绪调节过程中的神经特异性不足以及额叶区域的过度参与可能是各种情绪失调的标志。OFC、vlPFC、脑岛的活动和连接与跨诊断成人情绪调节能力的改善有关。在这项试验性研究中，主动神经刺激在单次治疗后导致了情绪调节网络的神经变化；然而，由于样本量较小，干预结果还只是初步的。这些功能网络特性可为未来神经科学驱动的干预和更大规模的研究提供参考。

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引用次数: 0