Functional connectivity substrates of social and non-social deficits in ASD

自闭症谱系障碍（ASD）社会和非社会缺陷的功能连接基础

• 批准号: 9291492
• 负责人: Tal Kenet
• 金额: $ 55.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9291492
• 关键词: Address; Age; Auditory Perception; Autistic Disorder; Behavior; Behavioral; Biological; Biological Markers; Brain Diseases; Child; Coupling; Data; Development; Diagnosis; Disease; Early Diagnosis; Evaluation; Executive Dysfunction; Exhibits; Frequencies; Functional disorder; Future; Goals; Individual; Link; Measures; Modeling; Nature; Participant; Phase; Phenotype; Research; Resolution; Severities; Stimulus; Symptoms; Testing; Traction; analytical tool; auditory processing; autism spectrum disorder; base; executive function; face perception; graph theory; improved; innovation; neurophysiology; novel; novel strategies; public health relevance; relating to nervous system; restrictive repetitive behavior; social; social communication; spatiotemporal; speech processing; temporal measurement; tool; treatment response

DESCRIPTION (provided by applicant): Over the past decade, the hypothesis that autism spectrum disorder (ASD) is a disorder of reduced long-range and increased local functional connectivity has been gaining traction. To date, however, there is no evidence of increased local functional connectivity in ASD. If, furthermore, ASD is indeed a disorder of functional connectivity, then similar abnormalities ought to manifest in both the social communication (core/defining) and the non-social communication (non-core/non-defining) domains of deficits. Whether this is the case, however, has never been systematically tested in one group of participants. The objectives of the current proposal are to determine the nature of local and long-range functional connectivity abnormalities in ASD, the relationship between them, whether they are manifested similarly in both the core social and non-core non-social domains of ASD deficits, and their correlations with behavioral and structural measures. Our central hypotheses are that ASD is in fact a disorder of connectivity, and that reduced long-range and reduced, not increased, local functional connectivity are distributed, cortex-wide features of ASD, manifested in all domains of deficits. We further hypothesize that local and long-range functional connectivity are reduced proportionally to one another in ASD. These hypotheses will be tested by investigating local and long-range functional connectivity in the social communication (Aim 1) and non-social (Aim 2) domains of deficits of ASD, and their correlation with the ASD phenotype (Aim 3). The proposed studies will take advantage of MEG's high spatial and temporal resolutions to examine functional connectivity in 45 ASD children, ages 8-12, and 45 matched typically developing children, as they perform tasks that tap into core social communication (face perception and speech processing) and non-core (executive control and auditory processing) domains of ASD deficits. The proposed research is conceptually innovative because our hypothesis challenges the prevailing notion that local functional connectivity is increased in ASD, and further proposes a direct correlation between the reductions in local and long-range functional connectivity. Furthermore, it addresses multiple domains of deficits simultaneously in the same participants. The proposed research is analytically innovative because it uses novel analytical tools to study phase-amplitude cross-frequency coupling (a measure of local functional connectivity) non-invasively in cortical space. The proposed research is significant because (a) it will examine the nature of both local and long-range functional connectivity abnormalities in multiple domains of deficits simultaneously, (b) it will determine whether local and long-range functional connectivity abnormalities are directly correlated in ASD, (c) it will provide a novel approach for non-invasively measuring local functional connectivity in cortical space, (d) it will set the stage for developing novel functiona-connectivity based neurophysiological biomarkers for ASD, which have potential applications for treatment and early diagnosis.

DESCRIPTION (provided by applicant): Over the past decade, the hypothesis that autism spectrum disorder (ASD) is a disorder of reduced long-range and increased local functional connectivity has been gaining traction. To date, however, there is no evidence of increased local functional connectivity in ASD. If, furthermore, ASD is indeed a disorder of functional connectivity, then similar abnormalities ought to manifest in both the social communication (core/defining) and the non-social communication (non-core/non-defining) domains of deficits. Whether this is the case, however, has never been systematically tested in one group of participants. The objectives of the current proposal are to determine the nature of local and long-range functional connectivity abnormalities in ASD, the relationship between them, whether they are manifested similarly in both the core social and non-core non-social domains of ASD deficits, and their correlations with behavioral and structural measures. Our central hypotheses are that ASD is in fact a disorder of connectivity, and that reduced long-range and reduced, not increased, local functional connectivity are distributed, cortex-wide features of ASD, manifested in all domains of deficits. We further hypothesize that local and long-range functional connectivity are reduced proportionally to one another in ASD. These hypotheses will be tested by investigating local and long-range functional connectivity in the social communication (Aim 1) and non-social (Aim 2) domains of deficits of ASD, and their correlation with the ASD phenotype (Aim 3). The proposed studies will take advantage of MEG's high spatial and temporal resolutions to examine functional connectivity in 45 ASD children, ages 8-12, and 45 matched typically developing children, as they perform tasks that tap into core social communication (face perception and speech processing) and non-core (executive control and auditory processing) domains of ASD deficits. The proposed research is conceptually innovative because our hypothesis challenges the prevailing notion that local functional connectivity is increased in ASD, and further proposes a direct correlation between the reductions in local and long-range functional connectivity. Furthermore, it addresses multiple domains of deficits simultaneously in the same participants. The proposed research is analytically innovative because it uses novel analytical tools to study phase-amplitude cross-frequency coupling (a measure of local functional connectivity) non-invasively in cortical space. The proposed research is significant because (a) it will examine the nature of both local and long-range functional connectivity abnormalities in multiple domains of deficits simultaneously, (b) it will determine whether local and long-range functional connectivity abnormalities are directly correlated in ASD, (c) it will provide a novel approach for non-invasively measuring local functional connectivity in cortical space, (d) it will set the stage for developing novel functiona-connectivity based neurophysiological biomarkers for ASD, which have potential applications for treatment and early diagnosis.

项目成果

Normal Evoked Response to Rapid Sequences of Tactile Pulses in Autism Spectrum Disorders.

• DOI: 10.3389/fnhum.2016.00433
• 发表时间: 2016
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Ganesan S;Khan S;Garel KA;Hämäläinen MS;Kenet T
• 通讯作者: Kenet T

Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder.

• DOI: 10.3389/fnins.2016.00255
• 发表时间: 2016
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Khan S;Hashmi JA;Mamashli F;Bharadwaj HM;Ganesan S;Michmizos KP;Kitzbichler MG;Zetino M;Garel KL;Hämäläinen MS;Kenet T
• 通讯作者: Kenet T