Whereas my previous training has focused on acquiring a strong technical foundation in neuroimagingmethods, over time, my interests have evolved from a purely technical focus towards the application ofneuroimaging to study brain dysfunction in pediatric patient populations. K01 training and research goals willprovide me the skills and expertise needed to excel as an independent clinical imaging researcher in this area.To this end, I will obtain training in advanced state-of-the-art magnetoencephalography (MEG) analysismethods in order to study primary sensory activity in low-functioning children with autism spectrum disorder(ASD). Although neuroimaging studies, including MEG, have investigated sensory processing in ASD, thesestudies have primarily focused on higher-functioning individuals, as these patients are better able to tolerateneuroimaging exams. This leaves a significant portion of the ASD population unexamined and underserved(approximately 40% of the ASD population is low-functioning). Due to this research bias, relatively little isknown directly about brain function in low-functioning individuals with ASD, or about the degree to whichfindings in higher-functioning ASD generalize to the entire ASD population. Although focusing on low-functioning ASD, K01 training and research is generalizable, specifically applicable to the examination of otherlow-functioning patient populations such as individuals with moderate to severe intellectual disability andcerebral palsy. It is towards these underserved and understudied low-functioning patient populations that I willfocus my subsequent research.K01 work achieves significant advancements in several areas, with advancements moving me towardsindependence as a clinical imaging researcher. First, as part of my K01 research work, I will develop technicalsolutions to address primary obstacles to studying lower-functioning populations with MEG, namely the lack ofanatomical information from structural MRI and the often considerable subject motion during a MEG exam.This technical work will serve as an enabling technology, allowing the inclusion of lower-functioningparticipants in MEG imaging studies. Second, significant time is spent on training activities that will provide mewith a greater appreciation for the clinical and behavioral phenotypes exhibited in neurodevelopmentaldisorders as well as improving my understanding of the underlying neurobiology. To this end, under theguidance of Drs. Levy and Miller, I will participate in ongoing educational clinical activities already in place fortraining psychologists and other clinicians. I will spend 1 day per week in K01 Years 1 and 2 (2 days per monththereafter) performing clinical training and observing clinical and cognitive assessments at the Regional AutismCenter’s young child clinic (seeing children under 6 years) and the Center for Autism Research’s school ageclinic. These clinics see over 300 patients (~25-50% low-functioning) a year, offering ample opportunity toobserve subjects with a wide variety of behavioral phenotypes and severity levels. This is in addition toattending case assessment meetings (as part of clinical observation), bi-monthly clinical team meetings andregular individual meetings with Drs. Levy and Miller. Training in the neurobiology of developmental disordersas well as the neurobiology of primary sensory processes will be achieved via coursework and one-on-onemeetings with Dr. Contreras. Training, workshops, and coursework in the biology, presentation and clinicalcare of neurodevelopmental disorders will better enable me to anticipate and address the specific challenges inthe study of these patient groups and to formulate and address biological questions central to these pediatricpatient populations.Completion of this K01 encompasses the achievement of significant advancements in MEG acquisition andanalysis. In particular, methods for atlas-based head modeling and motion compensation, developed in Aim 1,will permit accurate source localization of evoked primary sensory activity without the requirement of an MRIand in cases of large continuous motion. These methods will enable the study of primary sensory processes inlow-functioning and non-compliant patient populations. Similarly, the real-time analysis system (Aim 3)represents a significant step forward in MEG acquisition in these patient groups, promising decreased scantime and thus decreased patient discomfort and fatigue. Technical advancements will be underpinned byadditional training in advanced MEG physics and analysis provided Drs. Roberts, Mosher, and Dammersthrough one-on-one meetings and instruction. The utility and validity of these methods will be demonstratedthrough their application to low-functioning children and adolescents with ASD and via increases in successrate (evaluable data) and data quality. Investigation of atypical sensory activity, previously only reportedin high-functioning ASD, will thus be enabled in a low-functioning ASD population, addressing thecritical and presently unevaluated question of the generalizability of sensory abnormalities in ASD. K01research will provide data in support of a future R01 which will likely focus on contrasting the sensory activity oflow-functioning individuals with ASD to non-ASD neurodevelopmental disorders (e.g., 22q11.2 deletionsyndrome, cerebral palsy) to identify the specific versus common pathways of sensory processing brainabnormalities in neurodevelopmental disorders.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
