Steven E. Petersen - US grants

My long term objective is to understand the neural mechanisms underlying attention. Considerable progress has been made in the study of attention in cognitive psychological studies, single unit recordings from animals, and human and animal lesion-behavior studies. Position emission tomographic (PET) studies of local cerebral blood flow (CBF) change in the brains of normal humans will be used to address remaining questions about the identification and contribution of specific brain areas activated during the performance of tasks related to different aspects of attention. The proposed research will focus on three aspects of selective attention: 1) activation of areas related to the direction of visual spatial attention, and the relation of spatial attention to visual orienting in the form of saccadic (rapid), and smooth pursuit eye movements; 2) to identify areas that are related to attentional effects on pattern recognition through a comparison of the areas activated by the search for targets in arrays of elements that require little effort (or can take place preattentively), with areas activated when target detection in similar arrays requires exhaustive search; 3) to study the conditions necessary to activate a region (or regions) along the anterior midline that have been shown to be activated during the performance of many different tasks, and in particular to test the hypothesis that the activation of this region is concurrent with focal attention. While the main purpose of these experiments is to further our basic understanding of mechanisms underlying attention, there are clinical implications as well. There is diagnostic significance in the ability to more clearly define structure-function relationships in the brain, and the ability to determine the anatomical location, within an individual, of areas related to important functions can allow for the avoidance of these areas during neurosurgical procedures.

My long term objective is to understand the neural mechanisms underlying attention. Considerable progress has been made in the study of attention in cognitive psychological studies, single unit recordings from animals, and human and animal lesion-behavior studies. Position emission tomographic (PET) studies of local cerebral blood flow (CBF) change in the brains of normal humans will be used to address remaining questions about the identification and contribution of specific brain areas activated during the performance of tasks related to different aspects of attention. The proposed research will focus on three aspects of selective attention: 1) activation of areas related to the direction of visual spatial attention, and the relation of spatial attention to visual orienting in the form of saccadic (rapid), and smooth pursuit eye movements; 2) to identify areas that are related to attentional effects on pattern recognition through a comparison of the areas activated by the search for targets in arrays of elements that require little effort (or can take place preattentively), with areas activated when target detection in similar arrays requires exhaustive search; 3) to study the conditions necessary to activate a region (or regions) along the anterior midline that have been shown to be activated during the performance of many different tasks, and in particular to test the hypothesis that the activation of this region is concurrent with focal attention. While the main purpose of these experiments is to further our basic understanding of mechanisms underlying attention, there are clinical implications as well. There is diagnostic significance in the ability to more clearly define structure-function relationships in the brain, and the ability to determine the anatomical location, within an individual, of areas related to important functions can allow for the avoidance of these areas during neurosurgical procedures.

My long term objective is to understand the neural mechanisms underlying attention. Considerable progress has been made in the study of attention in cognitive psychological studies, single unit recordings from animals, and human and animal lesion-behavior studies. Position emission tomographic (PET) studies of local cerebral blood flow (CBF) change in the brains of normal humans will be used to address remaining questions about the identification and contribution of specific brain areas activated during the performance of tasks related to different aspects of attention. The proposed research will focus on three aspects of selective attention: 1) activation of areas related to the direction of visual spatial attention, and the relation of spatial attention to visual orienting in the form of saccadic (rapid), and smooth pursuit eye movements; 2) to identify areas that are related to attentional effects on pattern recognition through a comparison of the areas activated by the search for targets in arrays of elements that require little effort (or can take place preattentively), with areas activated when target detection in similar arrays requires exhaustive search; 3) to study the conditions necessary to activate a region (or regions) along the anterior midline that have been shown to be activated during the performance of many different tasks, and in particular to test the hypothesis that the activation of this region is concurrent with focal attention. While the main purpose of these experiments is to further our basic understanding of mechanisms underlying attention, there are clinical implications as well. There is diagnostic significance in the ability to more clearly define structure-function relationships in the brain, and the ability to determine the anatomical location, within an individual, of areas related to important functions can allow for the avoidance of these areas during neurosurgical procedures.

My long term objective is to understand the neural mechanisms underlying attention. Considerable progress has been made in the study of attention in cognitive psychological studies, single unit recordings from animals, and human and animal lesion-behavior studies. Position emission tomographic (PET) studies of local cerebral blood flow (CBF) change in the brains of normal humans will be used to address remaining questions about the identification and contribution of specific brain areas activated during the performance of tasks related to different aspects of attention. The proposed research will focus on three aspects of selective attention: 1) activation of areas related to the direction of visual spatial attention, and the relation of spatial attention to visual orienting in the form of saccadic (rapid), and smooth pursuit eye movements; 2) to identify areas that are related to attentional effects on pattern recognition through a comparison of the areas activated by the search for targets in arrays of elements that require little effort (or can take place preattentively), with areas activated when target detection in similar arrays requires exhaustive search; 3) to study the conditions necessary to activate a region (or regions) along the anterior midline that have been shown to be activated during the performance of many different tasks, and in particular to test the hypothesis that the activation of this region is concurrent with focal attention. While the main purpose of these experiments is to further our basic understanding of mechanisms underlying attention, there are clinical implications as well. There is diagnostic significance in the ability to more clearly define structure-function relationships in the brain, and the ability to determine the anatomical location, within an individual, of areas related to important functions can allow for the avoidance of these areas during neurosurgical procedures.

The major goal of the proposed research is to employ modern functional neuroimaging in normal subjects to characterize brain areas related to specific aspects of explicit memory and skill learning. This proposal focuses on three specific areas of research including: 1) experiments designed to identify brain regions used during various encoding and retrieval tasks. Models of explicit (or declarative) memory often include processes related to selection of information to be stored, encoding of that information, information storage, and information retrieval. An extension of previous work on the functional anatomy of retrieval processes and a beginning exploration of brain regions related to encoding processes are proposed. 2. experiments designed to determine what task demands modulate blood flow in medial temporal lobe regions particularly in the hippocampus. Because damage to the medial temporal lobe, particularly the hippocampus and adjacent structures, produces specific deficits in explicit (or declarative) memory, much attention has been focused on the hippocampal contribution to memory. Experiments are proposed to explore the contribution the hippocampal regions might make to memory, focusing on ideas related to specific aspects of encoding. 3. experiments designed to explore the functional anatomy of skill learning. Skill learning appears to be intact in amnesic individuals. Skill learning also shows several properties that may be implemented by different neural systems. For example, evidence gathered from this and other laboratories supports the hypothesis that different brain regions are used in the performance of very similar tasks in skilled and unskilled versions. Experiments are proposed to assess the generality of these effects. Further experiments are proposed to explore other properties of skill learning, including passage through multiple stages of skill acquisition, chunking of simple skills Into more complex units, and hierarchical encoding of high-level motor programs. While this proposal focuses on memory and learning in normal subjects, the knowledge gained from such studies should be relevant across a wide range of health issues. Memory impairment is one of the most tragic consequences of degenerative illnesses, such as Alzheimer's disease and other dementias, as well as being a frequent complaint even in normal aging. An understanding of the normal human biology of memory can not help but to deepen our understanding of these health problems and lead to better approaches to their solution.

My long term objective is to understand the neural mechanisms underlying attention. Considerable progress has been made in the study of attention in cognitive psychological studies, single unit recordings from animals, and human and animal lesion-behavior studies. Position emission tomographic (PET) studies of local cerebral blood flow (CBF) change in the brains of normal humans will be used to address remaining questions about the identification and contribution of specific brain areas activated during the performance of tasks related to different aspects of attention. The proposed research will focus on three aspects of selective attention: 1) activation of areas related to the direction of visual spatial attention, and the relation of spatial attention to visual orienting in the form of saccadic (rapid), and smooth pursuit eye movements; 2) to identify areas that are related to attentional effects on pattern recognition through a comparison of the areas activated by the search for targets in arrays of elements that require little effort (or can take place preattentively), with areas activated when target detection in similar arrays requires exhaustive search; 3) to study the conditions necessary to activate a region (or regions) along the anterior midline that have been shown to be activated during the performance of many different tasks, and in particular to test the hypothesis that the activation of this region is concurrent with focal attention. While the main purpose of these experiments is to further our basic understanding of mechanisms underlying attention, there are clinical implications as well. There is diagnostic significance in the ability to more clearly define structure-function relationships in the brain, and the ability to determine the anatomical location, within an individual, of areas related to important functions can allow for the avoidance of these areas during neurosurgical procedures.

The major goal of the proposed research is to employ modern functional neuroimaging in normal subjects to characterize brain areas related to specific aspects of language processing. This current proposal narrows the focus from language as a whole to experiments at the level of single words in three areas: 1) experiments designed to identify brain regions involved in rule- based vs. associative memory based language processes. Many recent cognitive psychological studies have focused upon the distinction between language processes which produce transformations using rule-based mechanisms, and those which are based upon stored associations. Many studies, including some of our own work, suggest these different types of processes involve distinct sets of brain regions. Experiments are proposed which address the generality of this dissociation and the extent to which the use of the different types of processes can be experimentally manipulated. 2) experiments designed to explore brain regions to phonological processes. Both lesion-behavior and functional imaging studies have suggested specific correlations between specific brain regions and different phonological processes (including acoustic, articulatory, and word-sound processes). There are currently some intriguing overlaps between studies, as well as some interesting dissociations. The proposed studies will allow us to further explore the nature of the processes involved in different phonological tasks, and to address the different roles played by temporal and frontal regions. 3) to explore specific areas related to semantic processes. Several studies have suggested both left middle temporal and frontal regions may be activated by tasks which include some form of semantic (word meaning) analysis. The proposed experiments build upon previous studies by examining the effect of factors such as the modality of input, the type of semantic information subjects are required to analyze, and how that information is accessed on the activation of brain regions. While this proposal focuses on language processes in normal subjects, the knowledge gained from such studies should be relevant across a wide range of health issues. For example, language impairment is one of the most tragic consequences of stroke, and imaging studies as these may provide information relevant to understanding behavioral deficits. Likewise, a deeper understanding of normal function should provide more targeted rehabilitative strategies in the future. In the broadest sense, studies of normal language function, using all avenues available to us, including functional neuroimaging, should lead to a deeper understanding of the related problems, and to better approaches to their solution.

This award permits the Psychology Department at Washington University to purchase instrumentation to store and analyze functional magnetic resonance imaging and positron emission typography data. Currently cognitive scientists in the department conduct cognitive research using fMRI and PET machines located at the Washington University Medical School campus and they must analyze the resultant data there. This makes convenient and continuous access difficult both for senior researchers and students. The instrumentation provided will allow transmission of this information to the Psychology Department where it can be analyzed. The system includes: a server computer which will receive the large data structures and store the images for distribution to other work stations; an SGI Work Station that takes advantage of programs that have been developed to provide 2-dimensional surface reconstructrions of the human cortex; three work-stations; an eithernet hub; a color printing device; a half-time technician who will be responsible for the initial development and maintenance of the system. Two projects currently under way will make immediate use of the system. Both address the neural underpinnings of cognitive components of behavior. The first - PET Activation Studies of Words - addresses those areas of the brain which are actively engaged in processing distinct aspects of words and the neural underpinnings of the attentional control systems that coordinate such processes. The second project - Imaging Studies of Learning and Memory - addresses those brain areas which are involved in the distinct aspects of encoding and retrieval of information from episodic, semantic and procedural memory systems. This equipment will also be used for training graduate students and postdoctoral fellows in the area of cognitive neuroscience.

Many children who have had strokes in the perinatal period develop normal or near-normal linguistic abilities. Consequently, these children should serve as an excellent model system for studying developmental plasticity using functional MRI (fMRI). This exploratory project is designed to develop a substrate for an extensive and long-term fMRI-based investigation of children with perinatal stroke. The following specific aims are proposed: Aim 1: To explore the feasibility and validity of using current fMRI methodologies in normal children. Methods for the characterization of brain activity have been developed over several years for use in normal and abnormal adult populations. Whereas some of these methods might be straightforwardly applied to children, others are less obviously generalizable. Studies in Aim1 will assess and develop methodologies for fMRI studies in normal children and children with perinatal stroke. Aim 2: To begin studies, in normal children, of behavioral profiles and associated brain activation patterns using previously characterized language tasks. Tasks and fMRI protocols, similar to those previously employed in adult studies of the processing of single words, will be tested and modified. Initially, children ages 7-10 will be studied. These experiments will also be extended to a small group of children ages 3-6 to identify problems specifically associated with studying this younger age group. Aim 3: To explore the feasibility of using language tasks developed in Aim 2 for the study o f the relationship of perinatal lesion to behavioral profiles and patterns of brain activation. Studies successfully implemented in Aim 2 will then be performed on children ages 7-10 who, despite enduring a focal unilateral stroke in the perinatal period, do not manifest significant cognitive or linguistic sequelae. Aim 4: To begin development of new sets of tasks that address aspects of language more broadly. The tasks that have been used in many functional neuroimaging experiments, including ours, have tended to focus on the phonology and semantics of single words. Preliminary studies of single words. Preliminary studies of syntactic processes, including grammatical morphology and syntactic comprehension, will be initiated in normal adults and normal children.

DESCRIPTION (provided by applicant): A major issue in cognitive neuroscience is how specific neural pathways are organized for task performance. The major hypothesis of this proposal is that task-level control is implemented, in part, by activity sustained across task trials, and can be studied using fMRI. This hypothesis is addressed through 3 Specific Aims. Specific Aim 1: To refine paradigm designs and analysis methods for separating sustained and transient fMRI signals. The main hypothesis is that the mixed block/event related paradigm can be optimized for the accurate and sensitive identification of sustained "control" signals from transient "trial-related" fMRI signals. Specific Aim 2: To characterize the functional attributes of different regions exhibiting sustained activity across trials. Three general hypotheses will be tested: 1) Some regions will exhibit sustained activity across a wide range of tasks, implicating them in general control functions; 2) In spite of this commonality, manipulation of separable aspects of control (e.g., input or response selection) will differentially affect specific subsets of these regions; 3) Some regions will show sustained activity related to specific task domains, implicating them as sources of domain specific control, or as sites at which control signals affect ongoing trial-related processing. Specific Aim 3: To use properties of sustained signals to address issues specific to memory retrieval. Several episodic retrieval studies have shown activation of right frontal regions, and it has been proposed that this activity may be related to "retrieval mode". Two related hypotheses are tested: 1) Right frontal sustained activity will be found across conditions that demand "re-collective effort" or "re-collective mode"; 2) The right frontal sustained activity will not be specific to "recollection", but will also be present when complex retrieval constraints are placed at "intermediate levels" between recollection and familiarity. As a group, these studies should improve our understanding of task control processes in the brain. Several psychiatric and neurological diseases (e.g., Tourette's syndrome, frontal lobe strokes) have been related to deficits of control; a deeper understanding of the neural mechanisms related to control processes may allow more specific diagnostic, prognostic, or rehabilitative approaches to these difficulties than currently exist.

DESCRIPTION (provided by applicant): A major issue in cognitive neuroscience is how specific neural pathways are organized for task performance. The major hypothesis of this proposal is that task-level control is implemented, in part, by activity sustained across task trials, and can be studied using fMRI. This hypothesis is addressed through 3 Specific Aims. Specific Aim 1: To refine paradigm designs and analysis methods for separating sustained and transient fMRI signals. The main hypothesis is that the mixed block/event related paradigm can be optimized for the accurate and sensitive identification of sustained "control" signals from transient "trial-related" fMRI signals. Specific Aim 2: To characterize the functional attributes of different regions exhibiting sustained activity across trials. Three general hypotheses will be tested: 1) Some regions will exhibit sustained activity across a wide range of tasks, implicating them in general control functions; 2) In spite of this commonality, manipulation of separable aspects of control (e.g., input or response selection) will differentially affect specific subsets of these regions; 3) Some regions will show sustained activity related to specific task domains, implicating them as sources of domain specific control, or as sites at which control signals affect ongoing trial-related processing. Specific Aim 3: To use properties of sustained signals to address issues specific to memory retrieval. Several episodic retrieval studies have shown activation of right frontal regions, and it has been proposed that this activity may be related to "retrieval mode". Two related hypotheses are tested: 1) Right frontal sustained activity will be found across conditions that demand "re-collective effort" or "re-collective mode"; 2) The right frontal sustained activity will not be specific to "recollection", but will also be present when complex retrieval constraints are placed at "intermediate levels" between recollection and familiarity. As a group, these studies should improve our understanding of task control processes in the brain. Several psychiatric and neurological diseases (e.g., Tourette's syndrome, frontal lobe strokes) have been related to deficits of control; a deeper understanding of the neural mechanisms related to control processes may allow more specific diagnostic, prognostic, or rehabilitative approaches to these difficulties than currently exist.

This Integrative Graduate Education and Research Training (IGERT) award supports the establishment of an interdisciplinary graduate training program in Cognitive, Computational, and Systems Neuroscience at Washington University in Saint Louis. Understanding how the brain works under normal circumstances and how it fails are among the most important problems in science. The purpose of this program is to train a new generation of systems-level neuroscientists who will combine experimental and computational approaches from the fields of psychology, neurobiology, and engineering to study brain function in unique ways. Students will participate in a five-course core curriculum that provides a broad base of knowledge in each of the core disciplines, and culminates in a pair of highly integrative and interactive courses that emphasize critical thinking and analysis skills, as well as practical skills for developing interdisciplinary research projects. This program also includes workshops aimed at developing the personal and professional skills that students need to become successful independent investigators and educators, as well as outreach programs aimed at communicating the goals and promise of integrative neuroscience to the general public. This training program will be tightly coupled to a new research focus involving neuro-imaging in nonhuman primates. By building upon existing strengths at Washington University, this research and training initiative will provide critical new insights into how the non-invasive measurements of brain function that are available in humans (e.g. from functional MRI) are related to the underlying activity patterns in neuronal circuits of the brain. IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries.

DESCRIPTION (provided by applicant): The cerebral cortex is anatomically organized at many physical scales. This organization extends from the level of a neuron and its connections, collections of neurons into columns, collections of columns into functional areas or maps, and collections of areas into systems or networks. Current functional magnetic resonance imaging (fMRI) techniques in humans focuses above the level of cells and columns, most often at the scale of functional areas and systems. Except in rare circumstances, e.g. topographically-organized sensory regions, it is difficult to determine areal boundaries in the human brain using fMRI. The ability to non- invasively delineate functional areas in greater extents of cortex would allow both within-subject definition of separate areas of cortex, and allow for more appropriate comparison of areas across subjects, enhancing the precision of many types of both functional and structural studies, including those investigating special populations such as infants/children and patients. Preliminary measures of resting correlated activity, so-called resting state functional connectivity (fcMRI), show strong localized differences in correlation strength across expanses of cortex. This observation provides hope that, in similar fashion to connectional anatomy in non-human primates, fcMRI measures could aid in the definition of functional area boundaries in the human brain. Aim 1: To develop methods to define functional area boundaries using resting state fcMRI. We will utilize the relatively new metric of resting state fcMRI to define boundaries between putative functional areas based on abrupt changes in the correlation profiles of adjacent points in fcMRI data. Various image processing strategies (e.g., edge detection and image segmentation algorithms) will be used to produce maps of fcMRI-derived boundaries that circumscribe putative functional areas in the cortex. Aim 2: To validate methods using multiple converging tests. After putative fcMRI boundary maps are constructed, their reliability and validity will be tested using several converging approaches: 1) repeated within-subject examinations to test the reliability of fcMRI-derived boundaries;2) comparison of functionally-defined (fMRI) boundaries in topographically organized visual cortical regions with fcMRI-defined borders;3) Comparison of reliable functional activations (e.g. eye- movement and error-related activity) with fcMRI-defined regions to determine whether functional activations respect fcMRI-derived boundaries;4) examination of multiple subjects to test the generalizability of these maps. PUBLIC HEALTH RELEVANCE This grant proposes a series of methods development and validations for using a specific imaging measure, resting-state functional connectivity magnetic resonance imaging, to parcellate the cortex of the brain into individual functional regions in individual subjects. Successful developments would allow researchers to move beyond current macrostructural, stereotactic and combined methods to provide more accurate locations of functional areas. This would advance neuroimaging studies generally, but particularly in situations where individual or group variability would be high, such as development studies, and studies of neuropsychiatric and neurological disease including schizophrenia, depression, movement disorders, and stroke.

DESCRIPTION (provided by applicant): Project Summary The fields of biology, psychology, and biomedical engineering have generated exciting new advances in the study of neural systems underlying behavior. Individually, these disciplines have individually provided novel insights into brain function and provide opportunities for improved understanding of disorders of the nervous system, healthy and disordered development, and communication. However, the rapid advancement of scientific progress has been limited by the boundaries surrounding the disciplines. Moreover, neuroscientists that are firmly grounded in an array of approaches used by biologists, psychologists, and engineers will best advance new research technologies such as non-invasive functional imaging and neural prosthetics. A training model that is thoroughly interdisciplinary is needed. At Washington University, we have developed such a model: The Cognitive, Computational, and Systems Neuroscience (CCSN) Pathway produces rigorously trained independent investigators that will lead a new generation of scientists who study the brain in truly integrated interdisciplinary investigations. CCSN serves students from the PhD programs in Biomedical Engineering, Psychology, and Neuroscience. The core of CCSN is a two-year curriculum that emphasizes interdisciplinarity, collaboration, and project-based instruction. In the first year, students take courses that bring them up to speed on the core concepts and methods in Cognitive Psychology, Biological Neural Computation, and Neural Systems. In the second year, students participate in two unique courses that have been specially designed as the capstone to the CCSN pathway Advanced CCSN and Project Building in CCSN. Advanced CCSN consists of a series of interdisciplinary case studies in cutting-edge brain science topics. Each topic is presented as a module by a faculty team drawn from the three home programs. Modules include team-based projects and peer review as well as primary source readings and classroom lectures and discussions. Project Building in CCSN is a fully student-driven course. In collaboration with the faculty leader, each student designs an independent interdisciplinary research project. The faculty leader helps them to assemble an interdisciplinary faculty advising team, to whom they present their project multiple times throughout the semester. Faculty advising is complemented by peer advising including written peer review, culminating in a research grant-style project proposal. Surrounding the core CCSN curriculum is a rich penumbra of activities. These are designed to provide intellectual training and to build a cohort of scientists with the identification and social skills necessary to conduct research in interdisciplinary teams. Formal coursework is provided in Mathematics and Statistics of Experimental Neuroscience, and by an intensive mini- course preceding Advanced CCSN. Immersive Encounters with distinguished visiting scientists provide high-intensity exposure to cutting-edge research. In collaboration with the Saint Louis Science Center, CCSN trains students to communicate with the public and helps them build programs and presentations to teach children and adults about the brain and mind. In its initial phases, CCSN has produced cohorts of young brain scientists on the fast track to new discoveries. Evaluations from students, faculty, and an outside advisory team indicate the pathway is on track for continued growth. PUBLIC HEALTH RELEVANCE: Project)Narrative) Cutting edge research in brain science is increasingly interdisciplinary, and traditional discipline-based graduate training programs strain to accommodate this development. The Cognitive, Computational &Systems Neuroscience pathway at Washington University represents a unique new model for training 21st century brain scientists. Such training will produce a generation of scientists effectively equipped to produce breakthroughs in neurological disease, mental illness, and neural engineering.

Developmental Neuroimaging Core Project Summary The goals of the Developmental Neuroimaging Core (DNC) are: to provide a flexible concierge approach to facilitating investigation, from consultation and assistance with study design, to full acquisition and interpretation of human imaging data, to training investigative teams to progressive levels of mastery that will allow them to continue and extend their own IDD research agendas. The DNC will provide state-of-the art neuroimaging services to maximize the quality and impact of IDD research by Center investigators, to optimize the application of imaging as a translational tool for innovation in prediction and intervention in developmental disabilities, and to provide a range of consultative and analytic services that will help new and early stage investigators to incorporate imaging research into their research efforts. The DNC is designed to provide capacity to ascertain neural signatures of developmental disability as a critical facet of the comprehensive characterization of patients and pathogenic mechanisms. Moreover, as rapid advances in imaging technology occur, the DNC will continue to make the latest innovations in neuroimaging accessible to the large and growing investigator community at WUSTL studying IDD. This Core advances IDD research through focused expertise in neuroimaging technology: mock scanning; specialized approaches to data acquisition in un- sedated infants and children with IDD; data analyses predicated upon established brain-behavior relationships in developing children; complete data analyses for early through to experienced investigators; an informatics platform with serial measurement and mapping of developmental trajectories. The Specific Aims are: 1) To provide high-quality comprehensive consultation for study design, including sample selection, subject preparation, technological methods for addressing specific scientific questions, statistical power considerations relevant to sample size and composition, data analytic approaches, brain-behavioral, brain-gene, and brain- environment data linkage, the interpretation of acquired neuroimaging data, and, via the Informatics Unit, its archival storage with other key study variables; 2) To conduct highly cost-efficient data acquisition for IDDRC investigators collecting neuroimaging data in IDD research efforts. This assistance will specify acquisition parameters for each study, implement appropriate subject preparation protocols (e.g. un-sedated infants), optimize image quality for the intended target structures and circuits, and provide all necessary technical support for conducting the scanning procedures, titrated to the need-for-assistance of each respective investigator; 3) To provide data processing and analytic services that optimize the hypothesis-driven analysis, exploration, as well as accurate interpretation of neuroimaging data in IDD research at WUSTL, recognizing that analysis of imaging data?and its integration with genomic, phenomic, and environmental data, can be complex and highly dependent upon the particular imaging modality employed.