A longitudinal study of brain development in children with autism

自闭症儿童大脑发育的纵向研究

• 批准号: 10584837
• 负责人: James Christopher EDGAR
• 金额: $ 81.57万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584837
• 关键词: 8 year old; Adolescent; Adult; Age; Alpha Rhythm; Anxiety; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory area; Brain; Brain Diseases; Brain imaging; Child; Child Development; Childhood; Clinic; Clinical; Clinical Research; Clinical Treatment; Clinical assessments; Communication; Development; Developmental Process; Diagnosis; Disease; Electroencephalography; Foundations; Future; Gene Expression Regulation; Goals; Hearing problem; Intention; Interneurons; Intervention; Language; Left; Location; Longitudinal Studies; Magnetoencephalography; Maps; Measures; Methods; Pattern; Preventive; Process; Pyramidal Cells; Reporting; Research; Rest; Sampling; Scalp structure; Sensory; Series; Source; Specificity; Structure; Symptoms; Time; Translating; Work; aging brain; autism spectrum disorder; autistic children; base; brain abnormalities; clinically significant; cognitive ability; cognitive process; comorbidity; density; design; diagnostic biomarker; early adolescence; early childhood; infancy; neural circuit; process repeatability; rate of change; relating to nervous system; response

Project Summary/Abstract Although differences in auditory encoding and resting-state (RS) neural activity are often reported in children with typical development (TD) versus autism spectrum disorder (ASD), the pattern of findings across studies is inconsistent. The PI has sought to understand the above via studying the maturation of these processes, this work supported by his current R01 (locally referred to as the ‘Brains Change’ study). A consistent finding has been a pattern of brain development that indicates overly rapid followed by too slow brain maturation in ASD. The continuation R01 will demonstrate that this pattern of brain maturation in ASD continues through at least early adolescence as a basis for developing disease-stage-specific assessment and treatment methods. In addition to continuing to map the maturation of RS neural activity, two auditory cortex neural processes that emerge during late childhood are targeted. First is the auditory M100 response, with findings from the current R01 already suggesting that M100, reflecting higher-order auditory encoding, emerges too early in ASD. Second, a new 40 Hz auditory steady-state response exam will assess the emergence and development of cortical inhibitory interneuron and pyramidal cell excitation and inhibition processes. Maturation findings, expected to demonstrate early accelerated then later flat development in ASD, will show a process that repeats itself across childhood and thus leads to a patterned derailment of emerging neural processes in ASD that extends far beyond infancy and early childhood. Tied to the above are two additional goals. First, given group differences in brain maturation rates, studies that average findings across a large age range will miss effects, and cross-sectional comparisons will be complicated. The PI’s research identifies age-specific brain markers in order to provide a basis for developing disease-stage-specific assessment and treatment targets. Second, and building upon the PIs adult studies, analysis of simultaneously collected MEG and EEG is expected to demonstrate the advantage of obtaining regionally specific measures when assessing group differences as well as enable identification of EEG-only assessment methods that are routinely feasible in the clinic. Our intention is that Brains Change findings will change the way ASD research is conducted via demonstrations that the pattern of group differences changes across time (even across a 3-year period), and via identifying very specific brain abnormalities in ASD with respect to age, brain location, and brain process. The current project assesses brain function, structure, and clinical measures in children 6 to 8 years old, and then 18 and 36 months later. For the renewal R01, each child will be followed another 3 years (3 brain imaging exams with 18 months between exams). Allowing attrition of the current sample across time, the Time 3 sample (N = 35/group) will be increased by 65+/group to start the continuation with 100 ASD and 100 TD.

Project Summary/Abstract Although differences in auditory encoding and resting-state (RS) neural activity are often reported in children with typical development (TD) versus autism spectrum disorder (ASD), the pattern of findings across studies is inconsistent. The PI has sought to understand the above via studying the maturation of these processes, this work supported by his current R01 (locally referred to as the ‘Brains Change’ study). A consistent finding has been a pattern of brain development that indicates overly rapid followed by too slow brain maturation in ASD. The continuation R01 will demonstrate that this pattern of brain maturation in ASD continues through at least early adolescence as a basis for developing disease-stage-specific assessment and treatment methods. In addition to continuing to map the maturation of RS neural activity, two auditory cortex neural processes that emerge during late childhood are targeted. First is the auditory M100 response, with findings from the current R01 already suggesting that M100, reflecting higher-order auditory encoding, emerges too early in ASD. Second, a new 40 Hz auditory steady-state response exam will assess the emergence and development of cortical inhibitory interneuron and pyramidal cell excitation and inhibition processes. Maturation findings, expected to demonstrate early accelerated then later flat development in ASD, will show a process that repeats itself across childhood and thus leads to a patterned derailment of emerging neural processes in ASD that extends far beyond infancy and early childhood. Tied to the above are two additional goals. First, given group differences in brain maturation rates, studies that average findings across a large age range will miss effects, and cross-sectional comparisons will be complicated. The PI’s research identifies age-specific brain markers in order to provide a basis for developing disease-stage-specific assessment and treatment targets. Second, and building upon the PIs adult studies, analysis of simultaneously collected MEG and EEG is expected to demonstrate the advantage of obtaining regionally specific measures when assessing group differences as well as enable identification of EEG-only assessment methods that are routinely feasible in the clinic. Our intention is that Brains Change findings will change the way ASD research is conducted via demonstrations that the pattern of group differences changes across time (even across a 3-year period), and via identifying very specific brain abnormalities in ASD with respect to age, brain location, and brain process. The current project assesses brain function, structure, and clinical measures in children 6 to 8 years old, and then 18 and 36 months later. For the renewal R01, each child will be followed another 3 years (3 brain imaging exams with 18 months between exams). Allowing attrition of the current sample across time, the Time 3 sample (N = 35/group) will be increased by 65+/group to start the continuation with 100 ASD and 100 TD.