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Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression

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World Journal of Psychiatry 2024年第2期14卷 276-286页

作者： Xin-Lin Huang Ju Gao Yong-Ming Wang Feng Zhu Jing Qin Qian-Nan Yao Xiao-Bin Zhang Hong-Yan Sun Imaging and Nuclear Medicine Jiamusi UniversityJiamusi 154000Heilongjiang ProvinceChina Department of Psychiatry The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina School of Biology&Basic Medical Sciences Medical College of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina Department of Radiology Shanghai Anting HospitalShanghai 20000China Department of Radiology The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina

BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of suicide.In studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is sparse.Some researchers even mistakenly regard the signals generated by the WM as noise points.In fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations.The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.AIM To explore potential abnormalities in WM functional signals in adolescents with MDD.METHODS This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide inventory.In addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image data.The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC groups.Independent component analysis(ICA)was also used to evaluate the WM functional signal.Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.RESULTS Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel correction).The ICA results of WM overlapped with tho

关键词： white matter Regional homogeneity The fractional amplitude of low-frequency fluctuations Independent component analysis Adolescents Major depression disorders

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Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2107-2123页

作者： Huiyang Wang Yueyang Liu Zhenkun Guo Minghui Cui Peng Pang Jingyu Yang Chunfu Wu Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Cognitive impairment caused by chronic cerebral hypoperfusion(CCH)is associated with white matter injury(WMI),possibly through the alteration of autophagy.Here,the autophagy—lysosomal pathway(ALP)dysfunction in white matter(WM)and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion(2VO).The results showed that cognitive impairment occurred by the 28th day after 2VO.Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day.By the 14th day,abnormal accumulation of autophagy substrate,lysosomal dysfunction,and the activation of mechanistic target of rapamycin(MTOR)pathway were observed in WM,paralleled with mature oligodendrocyte death.This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction.To target the ALP dysfunction,enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1(BECN1)in oligodendrocytes reduced mature oligodendrocyte death,and subsequently alleviated the WMI and cognitive impairment after CCH.These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO,which was associated with the aggravation of WMI and cognitive impairment.This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

关键词： Chronic cerebral hypoperfusion Two vessel occlusion white matter Cognitive impairment Oligodendrocyte Myelin sheath Autophagy-lysosomal pathway Mechanistic target of rapamycin

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Assessment of cheese sign and its association with vascular risk factors: Data from PUMCH dementia cohort

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中华医学杂志(英文版) 2024年第7期137卷 830-836页

作者： Huang Xinying Hou Bo Wang Jie Li Jie Shang Li Mao Chenhui Dong Liling Liu Caiyan Feng Feng Gao Jing Peng Bin Department of Neurology State Key Laboratory of Complex Severe and Rare Disease Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing 100730 China Department of Radiology Chinese Academy of Medical Sciences and Peking Union Medical College

Background: In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods: A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related white matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results: A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120,P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983,P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259,P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity.Conclusions: The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

关键词： Dementia Cerebrovascular disease Cheese sign Dense punctate lesions Basal ganglia Risk factor white matter

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Neuroprotection and neuroregeneration:roles for the white matter

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Neural Regeneration Research 2022年第11期17卷 2376-2380页

作者： Vito Antonio Baldassarro Agnese Stanzani Luciana Giardino Laura Calzà Luca Lorenzini Department of Veterinary Medical Science University of BolognaBolognaItaly Interdepartmental Center for Industrial Research in Life Sciences and Technologies University of BolognaBolognaItaly Fondazione IRET Ozzano EmiliaItaly Department of Pharmacy and Biotechnology University of BolognaBolognaItaly Montecatone Rehabilitation Institute ImolaItaly

Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system.Over the last few decades,a great deal of attention has been focused on white matter as a potential therapeutic target,mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system,a cell type able to fully repair myelin damage,and to the development of advanced imaging techniques to visualize and measure white matter lesions.The combination of these two events has greatly increased the body of research into white matter alte rations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair,thus indirectly contributing to neuroprotection.This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system.Pivot conditions are discussed,specifically multiple scle rosis as a white matter disease;spinal cord injury,the acute lesion of a central nervous system component where white matter prevails over the gray matte r,and Alzheimer's disease,where the white matter was considered an ancilla ry component until recently.We first describe oligodendrocyte precursor cell biology and developmental myelination,and its regulation by thyroid hormones,then briefly describe white matter imaging techniques,which are providing information on white matter involvement in central nervous system lesions and degenerative diseases.Finally,we discuss pathological mechanisms which interfere with myelin repair in adulthood.

关键词： Alzheimer's disease multiple sclerosis oligodendrocyte precursor cells spinal cord injury thyroid hormone traumatic brain injury white matter white matter imaging

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Diffusion tensor imaging pipeline measures of cerebral white matter integrity: An overview of recent advances and prospects

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World Journal of Clinical Cases 2022年第24期10卷 8450-8462页

作者： Amanina Ahmad Safri Che Mohd Nasril Che Mohd Nassir Ismail Nurul Iman Nur Hartini Mohd Taib Anusha Achuthan Muzaimi Mustapha Department of Neurosciences School of Medical SciencesUniversiti Sains MalaysiaHealth CampusKubang Kerian 16150KelantanMalaysia Department of Radiology School of Medical SciencesUniversiti Sains MalaysiaHealth CampusKubang Kerian 16150KelantanMalaysia School of Computer Sciences Universiti Sains Malaysia11800 USMPenangMalaysia Department of Neurosciences Hospital Universiti Sains MalaysiaKubang Kerian 16150KelantanMalaysia

Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.

关键词： Diffusion tensor imaging white matter Cerebral small vessel disease Pipeline processing Tractography

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white matter Deficits Underlying the Impaired Consciousness Level in Patients with Disorders of Consciousness

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Neuroscience Bulletin 2018年第4期34卷 668-678页

作者： Xuehai Wu Jiaying Zhang Zaixu Cui Weijun Tang Chunhong Shao Jin Hu Jianhong Zhu Yao Zhao Lu Lu Gang Chen Georg Northoff Gaolang Gong Ying Mao Yong He Neurosurgical Department Shanghai Huashan HospitalFudan University State Key Laboratory of Cognitive Neuroscience and Learning IDG/Mc Govern Institute for Brain ResearchBeijing Normal University Centre for Medical Image Computing Department of Computer Science University College London Radiological Department Shanghai Huashan Hospital Fudan University Psychiatry Department Shanghai Huashan Hospital Fudan University Huajia Hospital Shanghai Scientific and Statistical Computing Core National Institute of Mental Health National Institutes of Health Department of Health and Human Services Institute of Mental Health Research University of Ottawa

In this study, we aimed to （1） identify white matter （WM） deficits underlying the consciousness level in patients with disorders of consciousness （DOCs） using diffusion tensor imaging （DTI）, and （2） evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/ vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest （ROIs）, and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.

关键词： Disorder of consciousness white matter Diffusion tensor imaging Brain injury

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white matter abnormalities in young males with antisocial personality disorder Evidence from voxel-based morphometry-diffeomorphic anatomical registration using exponentiated lie algebra analysis

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Neural Regeneration Research 2011年第25期6卷 1965-1970页

作者： Daxing Wu Ying Zhao Jian Liao Huifang Yin Wei Wang Medical Psychological Research Institute Second Xiangya Hospital of Central South University Changsha 410011 Hunan Province China Department of Radiology Third Xiangya Hospital of Central South University Changsha 410013 Hunan Provionce China

Voxel-based morphometry-diffeomorphic anatomical registration using exponentiated lie algebra analysis was used to investigate the structural characteristics of white matter in young males with antisocial personality disorder （APD） and healthy controls without APD. The results revealed that APD subjects, relative to healthy subjects, exhibited increased white matter volume in the bilateral prefrontal lobe, right insula, precentral gyrus, bilateral superior temporal gyrus, right postcentral gyrus, right inferior parietal Iobule, right precuneus, right middle occipital lobe, right parahippocampal gyrus and bilateral cingulate, and decreased volume in the middle temporal cortex and right cerebellum. The white matter volume in the medial frontal gyrus was significantly correlated with antisocial type scores on the Personality Diagnostic Questionnaire in APD subjects. These experimental findings indicate that white matter abnormalities in several brain areas may contribute to antisocial behaviors in APD subjects.

关键词： white matter frontal lobe antisocial personality disorder voxel-based morphometry neuroimaging

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Therapeutic Effects of Myriocin in Experimental Alcohol-Related Neurobehavioral Dysfunction and Frontal Lobe white matter Biochemical Pathology

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Journal of Behavioral and Brain Science 2022年第2期12卷 23-42页

作者： Camilla Homans Emine B. Yalcin Ming Tong Gina Gallucci David Bautista Natalia Moriel Suzanne de la Monte Biotechnology Graduate Program Brown University Providence RI USA Department of Pathology and Laboratory Medicine Warren Alpert Medical School of Brown University Providence RI USA Liver Research Center Department of Medicine Rhode Island Hospital Providence RI USA Warren Alpert Medical School of Brown University Providence RI USA Brown University Providence RI USA Department of Pathology and Laboratory Medicine Rhode Island Hospital Women and Infants Hospital of Rhode Island Providence VA Medical Center Providence RI USA

Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.

关键词： Adolescence Alcohol Behavior Binge Drinking Brain Atrophy Myriocin Neurodegeneration Rat Sulfatide white matter

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Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy

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Neural Regeneration Research 2017年第4期12卷 603-609页

作者： Hong-xin Li Xing Feng Qian Wang Xuan Dong Min Yu Wen-juan Tu Department of Neonatology Children's Hospital of Soochow University Suzhou Jiangsu Province China Department of Neonatology Changzhou Children's Hospital Changzhou Jiangsu Province China School of Biomedical Engineering Shanghai Jiao Tong University Shanghai China Department of Children's Health Research Center Changzhou Children's Hospital Changzhou Jiangsu Province China Nantong University Nantong Jiangsu Province China

With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy （14 moderate cases and 8 severe cases） underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.

关键词： nerve regeneration fractional anisotropy diffusion tensor imaging apparent diffusion coefficient voxel volume neonatal behavioralneurological assessment brain injury white matter neuroimaging neural regeneration

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Chinese Medical Journal 2014年第3期127卷 532-537页

作者： Zhang Xiang Li Baoqing Shan Baoci Department of Radiology Beijing Shijingshan Hospital Beijing 100043 China Institute of High Energy Physics Chinese Academy of Sciences Shijingshan District Beijing 100049 China

Background Diffusion tensor imaging can evaluate white matter function in human brain.Fractional anisotropy is the most important parameter.This study aimed to find regional reduction of fractional anisotropy （FA） with aging in the whole brain and the changing rules of anisotropy with aging.Methods Fifty volunteers from 20 to 75 years old were divided into five consecutive age groups; a young group and four senior groups.FA values were calculated with diffusion tensor imaging （DTI） studio software.The difference of FA between the young group and the four senior groups were analyzed by analysis of voxel-level height threshold in Statistic Parametric Mapping （SPM）,and the regions with decreased FA were obtained.The FA values of these regions were then extracted using an in-house developed program,and a multiple linear regression model was built to assess the influence of age and sex on the FA values of these regions.Results Eight regions,including frontal lobe,postcentral gyrus,optic radiation,hippocampus,cerebella hemisphere,corona radiate,corpus callosum and internal capsule,were found to have decreased FA.There was a strong negative correlation between age and the FA in the frontal lobe,postcentral gyrus,optic radiation,hippocampus,and cerebella hemisphere,while a weaker negative correlation in the corona radiate,corpus callosum,and internal capsule was found.The FA reduction in the frontal lobe,postcentral gyrus,optic radiation,hippocampus and cerebella hemisphere were found earlier than in the corona radiate,corpus callosum and internal capsule.There was no correlation between sex and FA in these regions.Conclusions The FA in the subcortical white matter area reduces earlier than that in deep white matter.The areas with decreased FA continuously enlarge with aqing.The FAs in these regions have a strong negative correlation with age.

关键词： fractional anisotropy statistical parametric mapping age-related degradation white matter diffusion tensor imaging

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