Julie A. Fiez - US grants

This research advances the mapping of human brain function and the development of computational models of brain structures involved in human cognition. Brain imaging, utilizing functional magnetic resonance imaging (fMRI), allows task and process related tracking of brain activity. Cognitive modeling allows the prediction of human behavior in complex intellectual tasks. This project will bring together researchers who represent distinct and successful cognitive modeling architectures with researchers who are at the forefront of fMRI imaging, in an effort to relate cognitive function to human cortical dynamics.

A set of complex tasks will be identified which involve various aspects of learning, problem solving, and language, and for which models exist in one or more architectures. Brain imaging studies will be conducted with people performing all of these tasks. The complex tasks will include: rule learning, strategy learning, memory retrieval, problem solving, and language processing. To provide further constraints, the same people will also be imaged as they perform simpler "pure function" tasks. Models will be developed in the various cognitive architectures that address both the brain imaging data and the behavioral data from these tasks.

The mapping and computational understanding of human brain function can have important implications for education, artificial intelligence, and treatment of mental disorders. Understanding the brain structures involved in higher level cognition and how they interact will provide a better foundation for optimizing human performance and duplicating those functions in computers. An understanding of the neural basis of complex cognition has the potential for making brain research enhance education in the critical areas of skill acquisition and learning. It will also assist in the diagnosis and correction of brain dysfunction such as dyslexia and learning disabilities.

DESCRIPTION (provided by applicant): Working memory, defined as the information processes dedicated to holding and actively manipulating information on-line, serves as a "mental scratchpad" that is integral to complex cognition. The focus of this proposal is on the underlying phonological and articulatory representations and processes that support the maintenance of verbal information. Our prior work and recent behavioral findings by other investigators have generated results that are difficult to reconcile with a highly influential model of verbal working memory proposed by Baddeley and colleagues. In this competitive renewal, we will test an alternative neurally-based account through convergent behavioral, neuroimaging, and neuropsychological studies. Aim 1 will evaluate the maintenance of information via rehearsal-based and attention-based strategies supported, respectively, by speech motor areas and the inferior parietal cortex. Aim 2 will examine a novel hypothesis about the interplay between articulation and activated phonological representations supported by temporoparietal cortex. Aim 3 will seek to delineate the specific contributions of three different regions - the left frontal operculum, premotor cortex, and the cerebellum - to subvocal rehearsal. This work is a unique use of neuroimaging to inform cognitive theoretical models. It has the potential to impact our broader understandings of attention, the representation of serial order, and the joint influence of phonological processing on language and working memory.

DESCRIPTION: (provided by applicant) Drug abuse and addiction are major societal problems. Much of the previous research in this area has focused on understanding drug action at a cellular and molecular level. This research has helped to identify a basic neural circuit that appears to mediate reward-related processing. Key components of this system include brainstem dopamine neurons, the striatum, and orbitofrontal cortex. However, comparatively little research has focused on understanding, how these areas they interact with each other, and with other brain regions that are involved in non-affective cognitive processing. This is an important gap in our knowledge, since there are clear indications that interactions between affective and cognitive processes are critical components of drug abuse and addiction. Neuroimaging offers the opportunity to make important advances in this area, because it is a technique that allows activity changes in the reward-related circuitry to be monitored throughout the entire brain at once, and humans can be used as subjects. The overall objective of this research proposal is to use neuroimaging to advance our knowledge of how human behavior and brain function is influenced by rewards. Our work will be based upon an initial model of frontal-striatal interaction that is derived from previous research in animals and brain-damaged humans. We propose to evaluate our theoretical framework through a series of 6 inter-related sets of neuroimaging studies that will: 1) build bridges to previous animal research on the role of the striatum and brainstem dopamine neurons, 2) examine state and trait dependent differences in decision making and associated activity in ventral frontal cortex and the striatum, and 3) assess how this core circuitry involved in reward-related processing and decision-making influences cognitive task performance and patterns of functional brain activation in the domains of working memory and perceptual learning. The proposed research will advance our understanding of the brain regions that participate in reward-related processing, and it will demonstrate the relevance of a theoretical model derived mainly from prior research in animals for understanding human behavior. The enhanced understanding of the normal cognitive processes and neural systems involved in motivation and reinforcement provided by our work should be critical for efforts to understand how dysfunction of this same system can lead to drug abuse and addiction.

DESCRIPTION (provided by applicant): The primary purpose of this project is to examine basic neurobiological and cognitive processes related to smoking relapse. There are two premises underlying the proposed studies. First, exposure to smoking cues can elicit a set of neurobiological and cognitive responses that systematically increases the likelihood that one will smoke. Second, attempts to regulate such cue-elicited affective responses in abstinent-seeking subjects will typically recruit executive control processes mediated by dorsolateral prefrontal cortex. Thus, smokers with low levels of working memory will be more vulnerable to these effects, because they are less able to execute coping responses to forestall relapse than smokers with high working memory capacity. The proposed laboratory functional magnetic resonance imaging (fMRI) studies will merge the research approaches and theoretical perspectives of human neuroscience, cognitive psychology, and drug cue reactivity to examine the effects of treatment-seeking status, perceived opportunity to smoke, and alternative coping techniques on the regulation of smoking cue reactivity. Active smokers and smokers interested in participating in a smoking cessation program will be exposed to smoking or control cues, while deprived of nicotine. Study 1 (n=100) will test whether cue exposure activates regions of the prefrontal cortex supporting cognitive control processes. Study 2 (n = 50) will investigate the impact of coping with smoking cues across cognitive, behavioral, and neurobiological response domains, and link changes in working memory to levels of activation in the dorsolateral prefrontal cortex. Study 3 (n= 100) will test the effects of working memory capacity (high vs. low) and specific coping technique (high self-relevance vs. low self-relevance) on cognitive and neurobiological responding. This model-driven experimental research will examine neurobiological and cognitive mechanisms that may link cue-elicited craving to relapse. By integrating fMRI methods with measures derived from basic psychology, this interdisciplinary project aims to advance knowledge of neurobiological and cognitive processes in addiction. Regardless of the outcome, the studies will provide critical data regarding observable effects of cue-elicited craving on smokers, which will improve understanding of factors contributing to the etiology, maintenance, and treatment of nicotine addiction.

DESCRIPTION (provided by applicant): The objective of the proposed predoctoral training program is to train the next generation of behavioral science researchers to skillfully incorporate neuroscience perspectives and methods into their programs of research, based on an understanding of brain structure and function that extends across traditional areas of behavioral research. The Behavioral Brain (B2) Research Training Program has the specific aim of providing graduate students committed to research at the interface of the behavioral and brain sciences with foundational training in neuroscience methods and perspectives, through coursework and laboratory-based research experiences. Moreover, trainees receive deep training in behavioral science research, via courses and independent programs of research. Finally, we aim for continued infusion of cross- cutting perspectives, through co-mentoring, laboratory rotation experiences, and program forums that foster exposure to behavioral and brain science research. We believe that basic research focused on the interface between behavior and the brain is crucial for understanding the mechanisms and treatment of a large number of human health issues that cut across NIH Institutes. Because NIGMS has a broad mission, it is the natural home of a training program that aims to bridge behavioral and biomedical approaches across traditionally separate lines of inquiry in the behavioral sciences. By focusing upon the brain as a common substrate, we believe progress in different subfields of behavioral research can be most effectively integrated, thus leveraging advances in one area into other domains of study. This training program focuses on three major research themes to accomplish integration: Representation & Communication; Evaluation & Control; Learning, Memory, & Plasticity. The training program is jointly coordinated by the University of Pittsburgh and Carnegie Mellon University. Situated within blocks of one another and possessing excellence in both behavioral research and neuroscience, the institutions share a long history of collegiality and cooperation in graduate training that can be leveraged to broaden and deepen the neuroscience training of the next generation of behavioral science students.

This work involves a new training approach to help adults learn to quickly and accurately solve multi-digit addition and subtraction problems (e.g., 34 + 29). We will use behavioral measures of skill to demonstrate that the training program improves the ability to solve addition and subtraction problems, and to determine whether the benefits extend to other types of mathematical tasks (e.g., solving an algebra problem, or comparing the magnitude of two numbers). Measures of brain function will be used to test the idea that our training approach leads to adaptive changes in a core brain region involved in "basic number sense."

DESCRIPTION (provided by applicant): Years of interdisciplinary research have significantly advanced our understanding of optimal methods for reading instruction, orthographic and phonological variables that interact with word identification, and the neural substrates that support reading. However, core theoretical issues remain unresolved. For instance, a specific region in the left fusiform cortex, termed the Visual Word Form Area (VWFA), has been strongly implicated in orthographic processing. Overall, the current findings suggest the region is a core - perhaps even obligatory -- part of the pathway by which the perceptual analysis of written words ultimately provides fluent access to representations of phonology and meaning. In this proposal, we consider an alternative possibility: namely, that the right fusiform cortex can provide an alternative route through which print can gain access to the language system. We will test this hypothesis by examining the effect of cultural (Aim 1), individual (Aim 2), and orthographic (Aim 3) differences on the magnitude, time course, and functional connectivity of the right and left fusiform cortex. We will relate fusiform activity to measures of reading skill, and to behavioral markers for different types of orthographic analysis. The results should inform the theoretical debate about the VWFA, and they may lead to new approaches for the treatment of acquired and developmental reading disorders. PUBLIC HEALTH RELEVANCE: The overarching goal of the proposed research is to determine whether the right fusiform can provide an alternative route into the language system, a possibility that is raised by our findings with native Chinese speakers. The answer will shed light on the ongoing debate about the nature of the Visual Word Form Area (VWFA) and the impact of perceptual analysis upon phonological coding during reading. Longer term, the answer may also have important clinical implications: if the right fusiform can support reading independently from the left fusiform (i.e., VWFA), then it may be possible to design new approaches to the treatment of individuals with acquired or developmental dysfunction of the VWFA.

This research project is investigating the role of the cerebellum in language processing. The cerebellum, which is Latin for 'the little brain,' sits below the left and right hemispheres of the cerebrum (the largest and most commonly depicted part of the brain). While the cerebellum may be small, it is densely packed with brain cells, and it is thought to play a crucial role in motor control and learning. With funding from the National Science Foundation, Dr. Julie Fiez of the University of Pittsburgh is using functional brain imaging to identify specific regions in the cerebrum and cerebellum that are important for processing phonological (word sound), semantic (word meaning), and articulatory (speech production) attributes of spoken and written words. The research builds on evidence that portions of the cerebellum are expanded in humans, and that these newer portions of the cerebellum are interconnected with portions of the cerebrum that support human thought and language. But scientists still have a poor understanding of exactly how the cerebellum contributes to cognition, in part, because the prior research on this brain structure has focused mainly on its motor functions. This project is using cutting-edge brain imaging techniques to address the gap in current knowledge. A newly developed technique (diffusion weighted imaging) for studying the neural fiber pathways of the human brain is being used to determine whether regions with the same functional specializations are interconnected with each other, forming cerebro-cerebellar processing loops that are dedicated to different language functions. The research is being carried out with healthy young participants and then with participants who have a history of a stroke that has damaged part of their cerebellum. The project is examining whether damage to specific processing loops for language cause corresponding problems with specific types of language tasks.

The broader impacts of the research are diverse. First, the methods being used are still under development, and their use in this project provides an opportunity to validate them as research tools and to push the technology forward. These methods are a major scientific breakthrough, because until now there has been no suitable technique for studying, with high definition, the fiber pathways of the human brain. The specific application of these methods to the cerebellum is expected to have a significant impact. For more than 20 years scientists have speculated about what the cerebellum contributes to cognition, but the results across different research labs have been inconsistent, and existing theories are overly general. By gaining a more solid understanding of specific processing loops within the cerebellum, apparent discrepancies within the scientific literature can be resolved and more accurate and precise theoretical models can be developed. While the research is not directed towards a clinical application, it is important to note that the cerebellum has been implicated in several clinical disorders, such as autism, dyslexia, and schizophrenia. An increased understanding of the cerebellum's contributions to human thought and language could point the way towards more effective clinical diagnoses and treatments. The project is also providing an opportunity for undergraduate and graduate students interested in cognitive neuroscience to gain experience in this field of study, and efforts are being made to communicate the results to both the scientific community and lay audiences.

DESCRIPTION (provided by applicant): Stroke is a leading cause of adult disability with a large portion of stroke survivors confronting a communication disorder that significantly diminishes the quality of their lives. Clinical and basic researchers rely upon neuropsychological testing to evaluate the neurologic and behavioral status of stroke survivors. The difficulties involved in obtaining neuropsychological data hinder basic and clinical research involving this population. This proposal responds to the need for innovative approaches to neuropsychological testing. Standard neuropsychological test administration relies upon face-to-face (F2F) interactions. This imposes geographic constraints and data acquisition burdens that reduce research efficiency and lead to disparities in research involvement. To overcome these barriers, we will develop tools and protocols that will allow stroke survivors to complete neuropsychological tests in their own homes, through the virtual support of a geographically distant investigator. We will use wireless collaborative videoconferencing software and easy-to-operate tablet computers (iPads). Our test battery will probe core language functions and our participants will have left-hemisphere lesions. This initial direction was chosen because the personal and societal burden of post-stroke aphasia is significant, many tasks used for aphasia research are straightforward, prior data permits predictions about expected results, and there is a clear need for tools that can monitor aphasia status and treatment outcomes. Formative usability tests of our technology and protocols will be used to optimize the administration of our battery under three different conditions: 1) a virtual, investigator-guided protocol that is designd to emulate standard F2F neuropsychological testing, 2) a virtual, self- administered protocol that is designed to emulate computerized approaches to test administration, and 3) a standard face-to-face protocol that is intended as a performance benchmark. Once our protocols are in place, data will be acquired from three groups of participants with focal left-hemisphere lesions. Each group will complete our battery of language tasks in their home, via one of our two virtual protocols or a standard F2F protocol. All groups will complete a standard F2F protocol in our research laboratory. A variety of usability metrics will be used to evaluate participant and researcher satisfaction, confidence, and success with our virtual protocols. The behavioral data will be used to test whether comparable results are obtained when our tasks are administered under versus F2F testing conditions. Measures of efficiency and equipment reliability will provide a practical perspective on the benefits and limitations of home-based remote neuropsychological assessment. Overall, we aim to develop an innovative method for home-based remote neuropsychological testing that can be readily adapted and adopted by other investigators to meet a diverse set of research needs.

? DESCRIPTION (provided by applicant): Our environment is composed of pervasive deterministic and quasi-deterministic (very high- probability) relationships. A basal ganglia (BG) reinforcement learning system plays a key role in optimizing probabilistic decisions based upon an accrued history of experience, but it is unknown if this system contributes to deterministic decision-making. A medial temporal lobe (MTL) associative memory system could play a dominant role, since experiencing a deterministic choice outcome even once can provide sufficient information to optimize future decisions. We will use functional neuroimaging (fMRI) and neuropsychological methods to investigate how the BG and MTL systems work together to support deterministic decision- making. There is a crucial need to understand this question. Normal aging slows down memory- retrieval processes, leading to slower, inefficient, or impaired decision-making skills for even simple judgments. In patient populations with memory disorders, severely affected individuals can become unable to utilize information from deterministic outcomes, leading to a reduced ability to learn from basic everyday experiences. To address our research questions, we will use an innovative approach that will (a) incorporate factors drawn from both the decision and memory literatures, (b) allow us to investigate alternative computational models of deterministic decision-making, and (c) unmask effects of medication state on the cognitive performance of patients with Parkinson's disease. Experiment 1 will test how two factors differentially linked to reinforcement learning and associative memory are encoded and subsequently used to guide deterministic decision-making. The main objectives are to determine what information is gained from an initial decision event, and how this information influences a subsequent choice (Aim 1a) and value learning (Aim 1b). We expect activity in the BG and the MTL during an initial choice will predict subsequent choice-making ability across changes in value and associative context, respectively. This would indicate that these two systems make separable contributions to deterministic decision-making, a finding with significant theoretical impact. We will use computational agents to evaluate whether value learning from repeated choice experiences is best described as model-based or model-free, a question that has critical implications for how individuals learn from sampling their environment. Experiment 2 will involve a neuropsychological investigation of deterministic decision-making behavior in Parkinson's Disease (PD) and Mild Cognitive Impairment (MCI) patients. Deficits arising from problems with BG-mediated reinforcement learning in PD and MTL-mediated associative memory in MCI should reflect an inability to update value or encode associative information, respectively. This leads us to predict that subjects with PD will show reduced effects of value updating, but intact effects of experience (e.g., context) on choice accuracy. The converse is expected for MCI subjects. Such findings would point toward preserved learning and memory mechanisms that could be exploited to reduce the functional impact of these disorders.

? DESCRIPTION (provided by applicant): Training in lesion-symptom mapping for speech-language research Abstract: Researchers rely upon the lesion method to evaluate the speech-language status of stroke survivors and draw inferences about underlying brain function. This use of neuropsychology is highly valued in basic speech- language research because it can support causal inferences about brain structure/function relationships. Crucially, advances in analytic techniques and brain image computing are creating a new landscape for neuropsychological research. In this new landscape, the lesion method represents a form of big-data science that requires large sample sizes and complex image computing to implement lesion-symptom mapping (LSM) across the entire brain, without prior regions of interest. Expertise in these new techniques is becoming critical for high impact speech-language research. The career enhancement plan will provide the candidate with training in cutting-edge LSM. The candidate is an established speech-language investigator with a basic program of multidisciplinary research that includes populations with communication disorders due to stroke. The career enhancement will come at an ideal point, because it will build on the candidate's success in establishing an open-access research registry of stroke survivors (the Western Pennsylvania Patient Registry, WPPR), and current work to develop and validate collaborative videoconferencing for remote neuropsychological assessment. These efforts have created the recruitment pool and datasets that are needed for LSM. The career enhancement will provide the training needed to leverage these resources, thereby augmenting the candidate's program of research and career trajectory. The overarching objectives are to: (1) retool the skills of the candidate to infuse LSM into her program of speech-language research, (2) seed data sharing and data science partnerships to boost the candidate's leadership of WPPR as a national resource, and (3) advance understanding of LSM methods and the neural substrates for speech and language to improve the knowledge base of the candidate and other investigators. The candidate proposes a synergistic set of activities. Didactic activities will give training in machie learning and brain image computing, scholarly travel experiences will afford opportunities to network with speech-language researchers and data scientists whose work is relevant for LSM, and two research studies will provide a hands-on opportunity for the candidate to acquire, apply, and extend LSM methods under the guidance of a superb mentoring team. Study 1 will use univariate and multivariate LSM analysis to investigate the neural substrates of chronic Broca's aphasia and the factors that influence the reproducibility of LSM results. Study 2 will develop and evaluate a workflow for automated lesion segmentation, using a software platform (3D Slicer) that involves two NIH-supported data science centers. Overall, the career enhancement will retool the skills, research network, and knowledge base of an established investigator, allowing the candidate to significantly augment her program of speech-language research and advance the utility of WPPR as a national resource for speech-language research.

This project, conducted by a team of researchers at the University of Pittsburgh, will address the need to improve math abilities in American children and adults. According to the 2015 National Assessment of Educational Progress, only 40% of 4th graders, and 33% of 8th graders score at, or above, proficiency level in math, and only about 30% of US adults can complete basic mathematical processes in real-world scenarios such as looking at a thermometer and figuring out the temperature. Such poor math achievement outcomes impose significant burdens, such as in securing employment, on individuals who enter adulthood without achieving basic proficiency, and challenges the capacity of the US to remain competitive in a global economy that is strongly driven by the intellectual capital of its citizens. This project will investigate a foundational skill that underlies math achievement: the ability to recognize visual number symbols by connecting them with the quantities they represent. Using functional magnetic resonance imaging (fMRI) and behavioral measures, the project team will characterize the neural constituents of number knowledge and will test for pathways within this number network that contribute to this "symbolic integration" and math ability. Finally, by studying adults and 8-year-old children, they will test whether the neural substrates of symbolic integration change with age, and if so, whether these changes correspond to shifts in the behavioral profile of symbolic integration and individual difference in math ability. Overall, by focusing on the widely used, but poorly understood, construct of symbolic integration, the proposed work will have broad impact on theories of math ability that make assumptions about these underlying processes and will inform future studies examining math learning trajectories and remediation strategies for struggling math learners. This project is funded by Integrative Strategies for Understanding Neural and Cognitive Systems (NSF-NCS), a multidisciplinary program jointly supported by the Directorates for Computer and Information Science and Engineering (CISE), Education and Human Resources (EHR), Engineering (ENG), and Social, Behavioral, and Economic Sciences (SBE).


The overarching objective of the project is to investigate whether symbolic integration is foundational to math ability in adults and children. The project leverages the larger and more established literature on word recognition to develop and test a symbolic integration hypothesis of number processing. This model posits that formal math ability rests in part upon the integration of visual symbols (i.e., Arabic numerals) with the magnitudes they represent, via both direct (visual-semantic) and indirect (visual-verbal, visual-manual) pathways. An innovative combination of neurobehavioral measures will be used to test the model, through an individual differences study involving 100 adults and 125 8-year-old children. The project team will develop a novel neuroimaging protocol and will use cutting-edge multivariate methods to efficiently and broadly identify and characterize the neural constituents of a number processing network. A likely set of regions includes those involved in visual (fusiform gyrus), verbal (angular gyrus), manual (precental gyrus), and semantic (inferior parietal cortex) coding of number. In addition, resting state data will be acquired from each participant, and used to extract a metric of connectivity between identified visual, verbal, manual, and semantic constituents of number knowledge. A pair of behavioral tasks will measure the associative strength between visual and semantic codes for number (i.e., symbolic integration) in each participant. Using general linear models (GLM), the investigators will then test the prediction that both direct (visual-semantic) and mediated (visual-verbal-semantic; visual-manual-semantic) pathways significantly contribute to symbolic integration skill. Finally, standardized measures of math ability will be obtained from each participant. A GLM will be used to test for a predicted positive relation between individual differences in symbolic integration and math ability. Overall, the work will have a broad impact on theories of math ability and will inform future studies of math learning and intervention.

ABSTRACT The predominant theories of developmental dyslexia view the underlying disorder as arising from dysfunction in the cerebral cortex. Similarly, efforts to understand the neural basis of reading development have focused largely upon the cerebral cortex. However, because predominant theories of dyslexia do not capture its full behavioral phenotype, there has been continued consideration of alternative perspectives on the neural substrates of reading development and dyslexia. The current proposal evaluates one such alternative theory, the ?cerebellar deficit hypothesis? proposed by Nicolson and colleagues. We propose a variant of this hypothesis that arose from a meta-analytic review of the reading literature, the CDH* model. In the CDH* model, a fusiform-parietal-frontal (dorsal) pathway supports the decoding of unfamiliar printed words, with cerebellar connectivity into this pathway improving the representational similarity between the parietal and frontal nodes. This increases the likelihood that a given item will be decoded successfully, and thus induce orthographic learning. A ventrally connected cerebellar-cerebral circuit involving a fusiform-temporal-frontal pathway is proposed to play an assistive role, by providing lexical-semantic constraints when decoding demands are high. We investigate the CDH* model across three aims involving functional magnetic resonance imaging and behavioral studies in adult subjects, and the use of orthographic learning protocols to study reading development from an item-based (rather than stage-based) perspective. In Aim 1, we study adults reading words printed in a newly learned artificial orthography, and test for predicted relationships between cerebellar-cerebral connectivity, representational similarity, decoding success, and orthographic learning, and the impact of phonological demands on these relationships. In Aim 2, we will test whether individuals with and without dyslexia have differences in cerebellar- cerebral connectivity that can account for group differences in effective connectivity, decoding ability, and orthographic learning. In Aim 3, we will use the lesion method to test for a causal relationship between acquired cerebellar damage and impairments in decoding and orthographic learning. By advancing current understanding of how the cerebellum ? one of the brain's core learning systems ? interfaces with a cerebral reading network, the work has the potential to widely influence theories of reading development and dyslexia.

The ability to engage in mathematical thought is central to an individual's ability to thrive modern society. This project will investigate the neural basis of this ability by studying individuals with brain injury due to stroke. The goal is to understand how and where localized brain injury leads to impairments in math skills, thereby revealing the parts of the brain that are crucial for normal function. The work will examine the ability to make judgments about magnitude, a fundamental skill thought to rest upon an innate approximate number system, as well the abilities that rest upon cultural transmission of symbol systems for number (e.g., through classroom instruction). The relationship between these different types of skills, and their neural substrates, remains a point of significant debate. To make progress, stroke survivors will participate in the study. All participants will complete a magnetic resonance imaging (MRI) session to acquire images of their brain, and a set of behavioral tasks probing sensory, motor, language, general cognitive, and mathematical abilities. A series of statistical analyses will combine the brain and behavioral data, in order to identify sites of brain injury that are associated with: (1) specific impairments in approximate number representation and estimation, (2) specific impairments in precise number representation and calculation, and (3) impairments in math ability that are secondary to impairments in language or more general cognitive functions. The work should help to adjudicate between theories of math ability and inform future studies examining math learning and intervention strategies for struggling learners. Importantly, the project will be deeply intertwined with undergraduate education and research mentorship. This will occur by embedding the data collection into an advanced undergraduate laboratory course and summer research internship programs, with graduate students contributing to the instruction. The result will be a multilayered, interdisciplinary, and diverse learning context for experiential science learning that will be of broad educational impact. Additionally, at the conclusion of the project the data (without identifying information) will be placed into an open repository for neuroscience research. No other dataset like this currently exists, and so this will give researchers access to unique and highly valuable dataset that will be suitable for addressing many research questions.

The lesion method involves studying patterns of preserved and impaired abilities in participants with brain damage. By combining information about patterns of behavioral performance and corresponding locations of neural damage, causal inferences can be drawn about the functions supported by particular brain regions and their white matter connections. This project will use the lesion method to investigate the relationship between different aspects of numeracy. The participants in the study will be ~ 160 individuals with left-hemisphere focal brain lesions, and an exploratory group of ~ 40 individuals with right-hemisphere lesions. All participants will complete a neuroimaging session to acquire structural and functional brain volumes, and a battery of behavioral tasks probing sensory, motor, general cognitive, linguistic, and mathematical abilities. Participants with evidence of impaired numeracy, or aphasia without intact numeracy, will be invited to return for a second behavioral-only session. This secondary assessment will involve a battery of tasks that will probe numeracy skills in greater depth, as well as general cognitive abilities relevant for skilled math performance. For the primary analyses, voxelwise lesion symptom mapping (VLSM) analyses will be used to test predictions derived from theoretical models of numeracy. These include the predictions that impairments in number comparison will be associated with damage to the inferior parietal sulcus, impairments in verbal fact retrieval will be associated with damage to the angular gyrus, and impairments in ordinality will be associated with damage to premotor cortex. Secondary analyses will permit more detailed examination of associations and dissociations across our numeracy, language, and cognitive tasks. This will include the use of principal components analysis and other data-driven techniques to discover patterns of impairments across our battery of tasks and test for associated loci of neural damage. Finally, exploratory analyses will probe for hemispheric differences in the representation of number.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.