Identifying Brain-Based Biomarkers for ASD & their Biological Subtypes

识别 ASD 的脑生物标志物

• 批准号: 7937889
• 负责人: BRADLEY S PETERSON
• 金额: $ 122.49万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937889
• 关键词: Adult; Affect; Age; Amygdaloid structure; Anterior; Arousal; Attention; Autistic Disorder; Award; Base of the Brain; Behavior; Behavioral; Biological; Biological Markers; Biological Neural Networks; Brain; Brain Diseases; Brain region; Cell Nucleus; Cereals; Chemical Shift Imaging; Child; Childhood; Classification; Clinical; Communication; Comorbidity; Complex; Control Groups; Data; Data Analyses; Deformity; Detection; Development; Devices; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Early Diagnosis; Emotional; Emotions; Enrollment; Esthesia; Eye; Face; Fiber; Functional Magnetic Resonance Imaging; Fusiform gyrus; Genes; Gilles de la Tourette syndrome; Goals; Gold; Handedness; Heterogeneity; Hippocampus (Brain); Hyperactive behavior; Image; Impaired cognition; Impairment; Individual; Intellectual functioning disability; Intelligence; Intelligence quotient; Interview; Judgment; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measures; Medial; Mediator of activation protein; Medical; Memory; Methods; Mind; Modality; Morphology; Neuroanatomy; Neurobiology; Neurons; Neuropsychological Tests; Participant; Pattern; Performance; Persons; Prefrontal Cortex; Prevention strategy; Process; Public Health; Publishing; Race; Research; Resolution; Scanning; Schedule; Severities; Shapes; Socioeconomic Status; Statistical Models; Stimulus; Structure of superior temporal sulcus; Surface; Symptoms; System; Techniques; Testing; Thick; Time; Visuospatial; autism spectrum disorder; base; brain volume; density; disorder subtype; executive function; flexibility; gaze; gray matter; image processing; imaging modality; improved; instrument; mirror neuron system; neuropsychiatry; procedural memory; programs; public health relevance; relating to nervous system; sample fixation; sex; social; white matter

DESCRIPTION (provided by applicant): The ultimate goal of this research program is to identify brain biomarkers of Autism Spectrum Disorders (ASDs) and biologically-based ASD subtypes using multimodal Magnetic Resonance Imaging (MRI). Previous research into the neurobiology of ASD provides evidence for anatomical and functional disturbances across multiple neural systems that correlate with ASD symptom severity. Our research program builds on these findings by showing how disturbances in different neural systems in ASD correspond to unique profiles of behavioral and cognitive impairment. Thus far, 38 children and adults with ASD and 39 healthy controls, group-matched by age, sex, race, intelligence quotient (IQ), socio-economic status, and handedness, have been enrolled (targeted enrollment 100 ASD and 100 control subjects). Phenotypic profiling includes gold standard clinical instruments to assess the severity of impairment in the core behavioral domains of ASD along with measures of intelligence, procedural and declarative memory, visuospatial processing, and executive functioning. Participants undergo high-resolution anatomical MRI, functional MRI (fMRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) in a 3 Tesla scanner. Anatomical measures include fine-grained measures of local volumes of the cortical surface, the underlying white matter, and subcortical gray matter nuclei. DTI provides information about the orientation and integrity of white matter fiber tracts. Multiplanar Chemical Shift Imaging (MPCSI) provides extremely high quality measures of metabolites, including measures of neuronal density, in small contiguous voxels throughout the brain. Brain activation during a task of emotional face recognition is measured using fMRI in conjunction with eye-tracking. We analyze these diverse forms of data within a single imaging space using advanced image acquisition, image processing, and statistical modeling. These methods enable the precise detection of inter-individual and inter-group variability at each voxel, within and across modalities, permitting a deeper understanding of the relationships between local volumes, functional activity, metabolite concentrations, and connectivity. We hypothesize that neurobiological ASD subtypes will emerge based on differential patterns of disturbances in distinct neural systems that have been shown to be altered in ASD, such as amygdala-hippocampal, frontostriatal, and the mirror neuron systems, among others. We have previously defined neuroanatomical signatures for Tourette Syndrome1, 2, Attention-Deficit/Hyperactivity Disorder3, 4, familial depression5, adult schizophrenia6, and prematurely born children.7 We have also developed methods that enable the classification of neuropsychiatric disorders and their subtypes based on detailed measures of neuroanatomy. Using these techniques, our research program will define brain biomarkers for ASD, biologically-based ASD subtypes, and the neural bases for the phenotypic heterogeneity of these complex disorders. PUBLIC HEALTH RELEVANCE: Autism Spectrum Disorders (ASDs), affecting an estimated 1 in 150 individuals, are complex disorders of brain development that cause lifelong impairments in social ability, communication and behavioral flexibility with high rates of intellectual disability and medical comorbidities. The identification of brain-based biomarkers in individuals with ASD will illuminate the neural bases of this heterogeneous disorder and identify biological subtypes of ASD thereby yielding enormous benefits in the search for vulnerability genes for ASDs. Our proposed research plan will advance public health by enabling strategies for prevention, early detection, and personalized treatment of ASDs.

描述（由申请人提供）：该研究计划的最终目标是使用多模式磁共振成像（MRI）鉴定自闭症谱系障碍（ASD）和基于生物学的ASD亚型的脑生物标志物。先前对ASD神经生物学的研究为与ASD症状严重程度相关的多个神经系统的解剖和功能障碍提供了证据。我们的研究计划以这些发现为基础，通过显示ASD中不同神经系统中的干扰如何对应行为和认知障碍的独特概况。到目前为止，已经招募了38名患有ASD的儿童和成年人和39个健康对照，由年龄，性别，种族，智能商（IQ），社会经济状况和惯用性匹配（目标注册100 ASD和100个控制受试者）。表型分析包括黄金标准临床工具，以评估ASD核心行为领域的损害严重程度，以及智能，程序和声明性记忆，视觉空间处理以及执行功能的衡量标准。参与者在3个Tesla扫描仪中进行高分辨率解剖学MRI，功能性MRI（fMRI），扩散张量成像（DTI）和磁共振光谱（MRS）。解剖学措施包括对皮质表面的局部体积的细粒度测量，潜在的白质和皮层灰质核。 DTI提供了有关白质纤维区域的方向和完整性的信息。多平台化学位移成像（MPCSI）提供了整个大脑中小连续体素的代谢物的极高质量测量，包括神经元密度的度量。通过fMRI结合眼睛跟踪，在情感面部识别任务期间的大脑激活测量。我们使用高级图像采集，图像处理和统计建模分析了单个成像空间中这些不同形式的数据。这些方法能够精确检测每个体素的个人间和组间变异性，内部和跨模态，从而可以更深入地了解局部体积，功能活性，代谢物浓度和连接性之间的关系。我们假设神经生物学ASD亚型将基于已显示在ASD中已改变的不同神经系统中的干扰模式而出现，例如杏仁核 - 甲状腺膜片，额叶和镜像神经元系统等。我们以前已经定义了Tourette综合征1、2，注意力缺陷/多动障碍的神经解剖学特征3、4，家族性抑郁症5，成人精神分裂症6和过早出生的儿童。使用这些技术，我们的研究计划将定义ASD，基于生物学的ASD亚型的脑生物标志物，以及这些复杂疾病的表型异质性的神经碱基。 公共卫生相关性：影响大约150个人的自闭症谱系障碍（ASDS）是大脑发育的复杂疾病，这会导致社会能力，沟通和行为灵活性的终生障碍，并具有高智力残疾和医疗合并症的速度。 ASD患者中基于大脑的生物标志物的鉴定将阐明这种异质性疾病的神经碱基，并鉴定ASD的生物亚型，从而在寻找ASD的脆弱性基因时产生巨大的好处。我们提出的研究计划将通过实现预防，早期检测和对ASD的个性化治疗的策略来提高公共卫生。

项目成果

Using tissue microstructure and multimodal MRI to parse the phenotypic heterogeneity and cellular basis of autism spectrum disorder.

• DOI: 10.1111/jcpp.13531
• 发表时间: 2022-08
• 期刊: JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
• 影响因子: 7.6
• 作者: Peterson, Bradley S.;Liu, Jiaqi;Dantec, Louis;Newman, Courtney;Sawardekar, Siddhant;Goh, Suzanne;Bansal, Ravi
• 通讯作者: Bansal, Ravi

Geometry-derived statistical significance: A probabilistic framework for detecting true positive findings in MRI data.

• DOI: 10.1002/brb3.2865
• 发表时间: 2023-04
• 期刊: BRAIN AND BEHAVIOR
• 影响因子: 3.1
• 作者: Bansal, Ravi;Peterson, Bradley S.
• 通讯作者: Peterson, Bradley S.

Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging.

• DOI: 10.1001/jamapsychiatry.2014.179
• 发表时间: 2014-06
• 期刊: JAMA PSYCHIATRY
• 影响因子: 25.8
• 作者: Goh, Suzanne;Dong, Zhengchao;Zhang, Yudong;DiMauro, Salvatore;Peterson, Bradley S.
• 通讯作者: Peterson, Bradley S.