Exploring the Neural Mechanisms of Physics Learning

This dissertation presents a series of neuroimaging investigations and achievements that strive to deepen and broaden our understanding of human problem solving and physics learning. Neuroscience conceives of dynamic relationships between behavior, experience, and brain structure and function, but how neural changes enable human learning across classroom instruction remains an open question. At the same time, physics is a challenging area of study in which introductory students regularly struggle to achieve success across university instruction. Research and initiatives in neuroeducation promise a new understanding into the interactions between biology and education, including the neural mechanisms of learning and development. These insights may be particularly useful in understanding how students learn, which is crucial for helping them succeed. Towards this end, we utilize methods in functional magnetic resonance imaging (fMRI), as informed by education theory, research, and practice, to investigate the neural mechanisms of problem solving and learning in students across semester-long University-level introductory physics learning environments. In the first study, we review and synthesize the neuroimaging problem solving literature and perform quantitative coordinate-based meta-analysis on 280 problem solving experiments to characterize the common and dissociable brain networks that underlie human problem solving across different representational contexts. Then, we describe the Understanding the Neural Mechanisms of Physics Learning project, which was designed to study functional brain changes associated with learning and problem solving in undergraduate physics students before and after a semester of introductory physics instruction. We present the development, facilitation, and data acquisition for this longitudinal data collection project. We then perform a sequence of fMRI analyses of these data and characterize the first-time observations of brain networks underlying physics problem solving in students after university physics instruction. We measure sustained and sequential brain activity and functional connectivity during physics problem solving, test brain-behavior relationships between accuracy, difficulty, strategy, and conceptualization of physics ideas, and describe differences in student physics-related brain function linked with dissociations in conceptual approach. The implications of these results to inform effective instructional practices are discussed. Then, we consider how classroom learning impacts the development of student brain function by examining changes in physics problem solving-related brain activity in students before and after they completed a semester-long Modeling Instruction physics course. Our results provide the first neurobiological evidence that physics learning environments drive the functional reorganization of large-scale brain networks in physics students. Through this collection of work, we demonstrate how neuroscience studies of learning can be grounded in educational theory and pedagogy, and provide deep insights into the neural mechanisms by which students learn physics

A genomic analysis and transcriptomic atlas of gene expression in Psoroptes ovis reveals feeding- and stage-specific patterns of allergen expression

Background: Psoroptic mange, caused by infestation with the ectoparasitic mite, Psoroptes ovis, is highly contagious, resulting in intense pruritus and represents a major welfare and economic concern for the livestock industry Worldwide. Control relies on injectable endectocides and organophosphate dips, but concerns over residues, environmental contamination, and the development of resistance threaten the sustainability of this approach, highlighting interest in alternative control methods. However, development of vaccines and identification of chemotherapeutic targets is hampered by the lack of P. ovis transcriptomic and genomic resources. Results: Building on the recent publication of the P. ovis draft genome, here we present a genomic analysis and transcriptomic atlas of gene expression in P. ovis revealing feeding- and stage-specific patterns of gene expression, including novel multigene families and allergens. Network-based clustering revealed 14 gene clusters demonstrating either single- or multi-stage specific gene expression patterns, with 3075 female-specific, 890 male-specific and 112, 217 and 526 transcripts showing larval, protonymph and tritonymph specific-expression, respectively. Detailed analysis of P. ovis allergens revealed stage-specific patterns of allergen gene expression, many of which were also enriched in "fed" mites and tritonymphs, highlighting an important feeding-related allergenicity in this developmental stage. Pair-wise analysis of differential expression between life-cycle stages identified patterns of sex-biased gene expression and also identified novel P. ovis multigene families including known allergens and novel genes with high levels of stage-specific expression. Conclusions: The genomic and transcriptomic atlas described here represents a unique resource for the acarid-research community, whilst the OrcAE platform makes this freely available, facilitating further community-led curation of the draft P. ovis genome

Extended Functional Connectivity of Convergent Structural Alterations Among Individuals with PTSD: A Neuroimaging Meta-Analysis

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. Methods: Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. Results: We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. Conclusions: Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD

A genomic analysis and transcriptomic atlas of gene expression in Psoroptes ovis reveals feeding- and stage-specific patterns of allergen expression

Background: Psoroptic mange, caused by infestation with the ectoparasitic mite, Psoroptes ovis, is highly contagious, resulting in intense pruritus and represents a major welfare and economic concern for the livestock industry Worldwide. Control relies on injectable endectocides and organophosphate dips, but concerns over residues, environmental contamination, and the development of resistance threaten the sustainability of this approach, highlighting interest in alternative control methods. However, development of vaccines and identification of chemotherapeutic targets is hampered by the lack of P. ovis transcriptomic and genomic resources. Results: Building on the recent publication of the P. ovis draft genome, here we present a genomic analysis and transcriptomic atlas of gene expression in P. ovis revealing feeding- and stage-specific patterns of gene expression, including novel multigene families and allergens. Network-based clustering revealed 14 gene clusters demonstrating either single- or multi-stage specific gene expression patterns, with 3075 female-specific, 890 male-specific and 112, 217 and 526 transcripts showing larval, protonymph and tritonymph specific-expression, respectively. Detailed analysis of P. ovis allergens revealed stage-specific patterns of allergen gene expression, many of which were also enriched in "fed" mites and tritonymphs, highlighting an important feeding-related allergenicity in this developmental stage. Pair-wise analysis of differential expression between life-cycle stages identified patterns of sex-biased gene expression and also identified novel P. ovis multigene families including known allergens and novel genes with high levels of stage-specific expression. Conclusions: The genomic and transcriptomic atlas described here represents a unique resource for the acarid-research community, whilst the OrcAE platform makes this freely available, facilitating further community-led curation of the draft P. ovis genome

Neural Systems Underlying RDoC Social Constructs: An Activation Likelihood Estimation Meta-Analysis

Neuroscientists have sought to identify the underlying neural systems supporting social processing that allow interaction and communication, forming social relationships, and navigating the social world. Through the use of NIMH’s Research Domain Criteria (RDoC) framework, we evaluated consensus among studies that examined brain activity during social tasks to elucidate regions comprising the “social brain”. We examined convergence across tasks corresponding to the four RDoC social constructs, including Affiliation and Attachment, Social Communication, Perception and Understanding of Self, and Perception and Understanding of Others. We performed a series of coordinate-based meta-analyses using the activation likelihood estimate (ALE) method. Meta-analysis was performed on whole-brain coordinates reported from 864 fMRI contrasts using the NiMARE Python package, revealing convergence in medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, temporoparietal junction, bilateral insula, amygdala, fusiform gyrus, precuneus, and thalamus. Additionally, four separate RDoC-based meta-analyses revealed differential convergence associated with the four social constructs. These outcomes highlight the neural support underlying these social constructs and inform future research on alterations among neurotypical and atypical populations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Meta-analytic evidence for a core problem solving network across multiple representational domains

Problem solving is a complex skill engaging multi-stepped reasoning processes to find unknown solutions. The breadth of real-world contexts requiring problem solving is mirrored by a similarly broad, yet unfocused neuroimaging literature, and the domain-general or context-specific brain networks associated with problem solving are not well understood. To more fully characterize those brain networks, we performed activation likelihood estimation meta-analysis on 280 neuroimaging problem solving experiments reporting 3,166 foci from 1,919 individuals across 131 papers. The general map of problem solving revealed broad fronto-cingulo-parietal convergence, regions similarly identified when considering separate mathematical, verbal, and visuospatial problem solving domain-specific analyses. Conjunction analysis revealed a common network supporting problem solving across diverse contexts, and difference maps distinguished functionally-selective sub-networks specific to task type. Our results suggest cooperation between representationally specialized sub-network and whole-brain systems provide a neural basis for problem solving, with the core network contributing general purpose resources to perform cognitive operations and manage problem demand. Further characterization of cross-network dynamics could inform neuroeducational studies on problem solving skill development

Toward a Neurobiological Basis for Understanding Learning in University Modeling Instruction Physics Courses

Modeling Instruction (MI) for University Physics is a curricular and pedagogical approach to active learning in introductory physics. A basic tenet of science is that it is a model-driven endeavor that involves building models, then validating, deploying, and ultimately revising them in an iterative fashion. MI was developed to provide students a facsimile in the university classroom of this foundational scientific practice. As a curriculum, MI employs conceptual scientific models as the basis for the course content, and thus learning in a MI classroom involves students appropriating scientific models for their own use. Over the last 10 years, substantial evidence has accumulated supporting MI's efficacy, including gains in conceptual understanding, odds of success, attitudes toward learning, self-efficacy, and social networks centered around physics learning. However, we still do not fully understand the mechanisms of how students learn physics and develop mental models of physical phenomena. Herein, we explore the hypothesis that the MI curriculum and pedagogy promotes student engagement via conceptual model building. This emphasis on conceptual model building, in turn, leads to improved knowledge organization and problem solving abilities that manifest as quantifiable functional brain changes that can be assessed with functional magnetic resonance imaging (fMRI). We conducted a neuroeducation study wherein students completed a physics reasoning task while undergoing fMRI scanning before (pre) and after (post) completing a MI introductory physics course. Preliminary results indicated that performance of the physics reasoning task was linked with increased brain activity notably in lateral prefrontal and parietal cortices that previously have been associated with attention, working memory, and problem solving, and are collectively referred to as the central executive network. Critically, assessment of changes in brain activity during the physics reasoning task from pre- vs. post-instruction identified increased activity after the course notably in the posterior cingulate cortex (a brain region previously linked with episodic memory and self-referential thought) and in the frontal poles (regions linked with learning). These preliminary outcomes highlight brain regions linked with physics reasoning and, critically, suggest that brain activity during physics reasoning is modifiable by thoughtfully designed curriculum and pedagogy

Data_Sheet_1_Toward a Neurobiological Basis for Understanding Learning in University Modeling Instruction Physics Courses.DOCX

<p>Modeling Instruction (MI) for University Physics is a curricular and pedagogical approach to active learning in introductory physics. A basic tenet of science is that it is a model-driven endeavor that involves building models, then validating, deploying, and ultimately revising them in an iterative fashion. MI was developed to provide students a facsimile in the university classroom of this foundational scientific practice. As a curriculum, MI employs conceptual scientific models as the basis for the course content, and thus learning in a MI classroom involves students appropriating scientific models for their own use. Over the last 10 years, substantial evidence has accumulated supporting MI's efficacy, including gains in conceptual understanding, odds of success, attitudes toward learning, self-efficacy, and social networks centered around physics learning. However, we still do not fully understand the mechanisms of how students learn physics and develop mental models of physical phenomena. Herein, we explore the hypothesis that the MI curriculum and pedagogy promotes student engagement via conceptual model building. This emphasis on conceptual model building, in turn, leads to improved knowledge organization and problem solving abilities that manifest as quantifiable functional brain changes that can be assessed with functional magnetic resonance imaging (fMRI). We conducted a neuroeducation study wherein students completed a physics reasoning task while undergoing fMRI scanning before (pre) and after (post) completing a MI introductory physics course. Preliminary results indicated that performance of the physics reasoning task was linked with increased brain activity notably in lateral prefrontal and parietal cortices that previously have been associated with attention, working memory, and problem solving, and are collectively referred to as the central executive network. Critically, assessment of changes in brain activity during the physics reasoning task from pre- vs. post-instruction identified increased activity after the course notably in the posterior cingulate cortex (a brain region previously linked with episodic memory and self-referential thought) and in the frontal poles (regions linked with learning). These preliminary outcomes highlight brain regions linked with physics reasoning and, critically, suggest that brain activity during physics reasoning is modifiable by thoughtfully designed curriculum and pedagogy.</p