Lucina Q. Uddin - US grants

DESCRIPTION (provided by applicant): The long-term objective of this Career Development Award to Promote Diversity in Neuroscience Research is to develop the candidate's skills in applying novel brain network approaches to the study of neurodevelopmental disorders, and in conducting clinical assessments, so that she can become an independent investigator in the fields of neuroimaging and autism research. Specifically, the candidate will develop expertise in using diffusion tensor imaging (DTI) data in conjunction with recently developed multivariate pattern classification and effective connectivity analyses of functional magnetic resonance imaging (fMRI) data to examine structural and intrinsic functional brain connectivity underlying atypical behavior and cognition in children with autism spectrum disorders (ASD). To this end, the candidate will be mentored and trained by experts in the fields of neuroimaging, engineering, clinical psychology, neurology and psychiatry. The candidate will also gain critical experience in clinical assessments necessary for successfully working with children with ASD. In addition, the candidate will undertake formal coursework and attend seminars in functional neuroimaging, clinical psychology, and computer programming to achieve this goal. The research project proposed by the candidate will enable the acquisition of the skills required to become a successful independent investigator in the field of developmental cognitive neuroscience. ASD is a complex neurodevelopmental disorder of largely unknown etiology, characterized by social communicative impairments, restricted interests, and repetitive and stereotyped behaviors. The main goal of the proposed research is to examine aberrant structural and functional brain connectivity underlying atypical cognition and behavior in children with ASD. The candidate proposes to probe large-scale brain networks using DTI and fMRI to examine possible aberrant cortical connectivity and compromises in dynamic interactions between networks in children with ASD. She will specifically test a novel systems-level hypothesis she has put forth, synthesizing recent advances in brain network connectivity with converging evidence from neuroimaging studies in autism. The hypothesis is that hypoactivity of the anterior insula during processing of social stimuli results in reduced salience detection in individuals with ASD, which impairs dynamic switching between other large-scale brain networks important for cognition. Additionally, she will explore methods to establish brain-based biomarkers to distinguish children with ASD from typically developing children using a combination of brain connectivity measures and cognitive and behavioral measures. Completion of this research project and training plan will enable Dr. Uddin to gain proficiency relevant to her goal of becoming an independent investigator in the fields of autism and neuroimaging research, and will also facilitate the principled development of biomarkers of brain network dysfunction in ASD. This Career Development Award is consistent with the NIH goals to promote diversity in neuroscience research. ) PUBLIC HEALTH RELEVANCE: Autism spectrum disorders (ASD) affect 1:150 individuals, and the incidence continues to rise steadily, making the disorder an urgent public health concern. ASD results in lifelong difficulties for afflicted individuals and their families, and there is no known cure. Recently developed analytic tools have enabled the study of brain connectivity in vivo, revealing important principles of brain organization in individuals with ASD. Characterization of the integrity and functional roles of brain networks, as well as interactions between them, will help us to understand the underlying brain differences in individuals with ASD and eventually lead to the development of more effective treatments and therapies. )

DESCRIPTION (provided by applicant): The long-term objective of this Career Development Award to Promote Diversity in Neuroscience Research is to develop the candidate's skills in applying novel brain network approaches to the study of neurodevelopmental disorders, and in conducting clinical assessments, so that she can become an independent investigator in the fields of neuroimaging and autism research. Specifically, the candidate will develop expertise in using diffusion tensor imaging (DTI) data in conjunction with recently developed multivariate pattern classification and effective connectivity analyses of functional magnetic resonance imaging (fMRI) data to examine structural and intrinsic functional brain connectivity underlying atypical behavior and cognition in children with autism spectrum disorders (ASD). To this end, the candidate will be mentored and trained by experts in the fields of neuroimaging, engineering, clinical psychology, neurology and psychiatry. The candidate will also gain critical experience in clinical assessments necessary for successfully working with children with ASD. In addition, the candidate will undertake formal coursework and attend seminars in functional neuroimaging, clinical psychology, and computer programming to achieve this goal. The research project proposed by the candidate will enable the acquisition of the skills required to become a successful independent investigator in the field of developmental cognitive neuroscience. ASD is a complex neurodevelopmental disorder of largely unknown etiology, characterized by social communicative impairments, restricted interests, and repetitive and stereotyped behaviors. The main goal of the proposed research is to examine aberrant structural and functional brain connectivity underlying atypical cognition and behavior in children with ASD. The candidate proposes to probe large-scale brain networks using DTI and fMRI to examine possible aberrant cortical connectivity and compromises in dynamic interactions between networks in children with ASD. She will specifically test a novel systems-level hypothesis she has put forth, synthesizing recent advances in brain network connectivity with converging evidence from neuroimaging studies in autism. The hypothesis is that hypoactivity of the anterior insula during processing of social stimuli results in reduced salience detection in individuals with ASD, which impairs dynamic switching between other large-scale brain networks important for cognition. Additionally, she will explore methods to establish brain-based biomarkers to distinguish children with ASD from typically developing children using a combination of brain connectivity measures and cognitive and behavioral measures. Completion of this research project and training plan will enable Dr. Uddin to gain proficiency relevant to her goal of becoming an independent investigator in the fields of autism and neuroimaging research, and will also facilitate the principled development of biomarkers of brain network dysfunction in ASD. This Career Development Award is consistent with the NIH goals to promote diversity in neuroscience research. ) PUBLIC HEALTH RELEVANCE: Autism spectrum disorders (ASD) affect 1:150 individuals, and the incidence continues to rise steadily, making the disorder an urgent public health concern. ASD results in lifelong difficulties for afflicted individuals and their families, and there is no known cure. Recently developed analytic tools have enabled the study of brain connectivity in vivo, revealing important principles of brain organization in individuals with ASD. Characterization of the integrity and functional roles of brain networks, as well as interactions between them, will help us to understand the underlying brain differences in individuals with ASD and eventually lead to the development of more effective treatments and therapies. )

? DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a complex neurodevelopment disorder of largely unknown etiology affecting 1 in 68 children. While much progress has been made towards understanding the neurobiology of social and communication deficits associated with the disorder, very little is known regarding the neurobiological basis of restricted and repetitive behaviors central to the ASD diagnosis. The goal of the current project is to understand the relationship between cognitive flexibility and brain function during evoked (task) and intrinsic (resting) states in youth with and without ASD. Cognitive flexibility, the capacity to switch between mental processes, is often impaired in children with ASD in ways that can severely impact transitions during day-to- day activities of life. Cognitive inflexibilitymay underlie the emergence of restricted and repetitive behaviors in ASD. Understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat tis under-studied yet pervasive symptom. The PI has recently published preliminary evidence of reduced dynamic range of connectivity patterns, or neural inflexibility, in children with ASD. The proposed research will go beyond these preliminary findings and explicitly test whether one aspect of restricted and repetitive behaviors --cognitive inflexibility-- is linked with a corresponding neural inflexibility in ASD. A novel approach to assessing brain function and dysfunction is the quantification of dynamic functional connectivity, or time-varying patterns of functional coupling between brain regions. The goals of the study are to address three aims: 1) to understand the neural bases of cognitive flexibility in children with ASD and TD children during evoked brain states, 2) to understand the neural bases of cognitive flexibility in children with ASD and TD children during intrinsic brain states, and 3) to investigate relationships between activation patterns during evoked brain states, dynamic functional connectivity patterns during intrinsic brain states, and behavioral measures of flexibility in ASD. To address these aims, the project will implement traditional task- based functional MRI, dynamic functional connectivity analyses of resting-state fMRI, and integration of task and resting state fMRI with behavioral measures of cognitive flexibility. This program of research responds to the Interagency Autism Coordinating Committee's strategic plan to understand the neural circuitry that is affected in ASD. As behavioral inflexibility is an important cause of difficulties in carin for autistic individuals, these findings will potentially have a major impact on quality of life for children with ASD and their caregivers.