It is increasingly clear that delaying the onset of Alzheimer’s disease (AD) dementia by several years can meaningfully lower its prevalence. The goal of the present study is to examine the relationship between lifestyle activities and cognition function as well as cerebrospinal fluid (CSF) biomarkers of AD to determine whether these activities can serve as protective factors for AD resistance and resilience. 173 cognitively normal older individuals (mean ± SD, 69 ± 6.4 years) were recruited to the Stanford Aging and Memory Study (SAMS) and completed the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire regarding current social, cognitive, and physical activity (Table 1). They also underwent APOE genetic testing and a detailed neuropsychological evaluation. The following cognitive domains were evaluated after conversion to z-scores: global cognition (cognitive composite), executive function, working memory, attention, episodic memory, visuospatial function, and language (see Table 2 for definitions). 127 participants completed lumbar punctures, and levels of Aβ-40, Aβ-42, p-tau181, and total tau were measured in the CSF. Cross-sectional regression models included age, sex, years of education, and APOE status as co-variates. Benjamini-Hochberg corrections for multiple hypotheses were completed. There was a significant association between social activity (frequency/week) and global cognition (β = 0.20, p = 0.03), executive function (β = 0.15, p<0.05), and working memory (β = 0.26, p = 0.01) but not episodic memory, visuospatial function, or language function. There was also a significant association with attention prior to correction for multiple hypotheses (β = 0.17, p = 0.04) but not afterward (Table 2). Additionally, there was a significant association between cognitive activity (hours/week) and global cognition (β = 0.19, p = 0.03) as well as executive function (β = 0.25, p = 0.007) but not with other cognitive domains tested (Table 3). There was no association between light or moderate caloric expenditure and cognitive measures. There was also no significant relationship between CSF biomarkers and levels of social, cognitive, and physical activity. In a well-characterized cohort of cognitively normal older adults, higher levels of social and cognitive activity were associated with higher cognitive scores on tasks of executive function but not episodic memory. The mechanism mediating this relationship appears to be independent of both Aβ and tau burden.

The medial temporal lobe (MTL) has distinct cortical subregions that are differentially vulnerable to pathology and neurodegeneration in diseases such as Alzheimer’s disease. However, previous protocols for segmentation of MTL cortical subregions on magnetic resonance imaging (MRI) vary substantially across research groups, and have been informed by different cytoarchitectonic definitions, precluding consistent interpretations. The Hippocampal Subfields Group aims to create a harmonized, histology-based protocol for segmentation of MTL cortical subregions that can reliably be applied to T2-weighted MRI with high in-plane resolution. Nissl-stained sections from the temporal lobes of three human specimens (66-90 years old; 2 female) were annotated by four expert neuroanatomists for the following MTL subregions: entorhinal cortex (ERC), Brodmann’s Area 35 (BA35; largely corresponding to “transentorhinal” cortex), Brodmann’s Area 36 (BA36), and parahippocampal cortex (PHC). On each histology section, the number of annotations and the spatial overlap of annotations were analyzed to determine the consensus of the anterior to posterior range of each structure. Gross anatomical landmarks, detectable on MRI and reliably corresponding with each range, were then selected to create an MRI ranging protocol. Feasibility of this MRI protocol was tested by two independent raters across four MRI scans (two healthy adults, two older adults), and agreement in range selection was assessed using Cohen’s kappa statistic. The proposed MTL ranging protocol is shown in Fig. 1 , and corresponding histology data substantiating the protocol is shown in Fig. 2 . MRI-visible gross anatomical landmarks that reliably corresponded with the anterior or posterior range of each subregion on histology included the anterior-most appearance of the collateral sulcus ( Fig. 3A ), hippocampal head ( Fig. 3B ), hippocampal body, and anterior calcarine fissure ( Fig. 3C ). This protocol demonstrated high feasibility when applied to MRI, with average kappa values of 0.75 ± 0.07, representing a “substantial” level of agreement of range selection. Future directions include obtaining consensus on this protocol from the larger research community through a Delphi procedure, and expansion of the protocol to include slice-by-slice segmentation guidelines for full delineation. This harmonized, histology-based protocol will facilitate critical research on MTL subregion vulnerability and their contributions to memory deficits in Alzheimer’s disease.

Non-pharmacological approaches may guide prevention and treatment strategies for patients with Alzheimer's disease (AD), but little is known about the “dose” and “type” required. The goal of this study is to examine what types of social and cognitive activities are associated with cognitive performance and AD biomarkers. 173 cognitively normal participants (69.0 ± 6.4 years) completed a questionnaire regarding frequency and hours per week of 7 social and 5 cognitively engaging activities. Participants underwent neuropsychological testing (z-scored composites of executive function, working memory, attention, episodic memory, visuospatial function, and language as well as a global cognitive composite), CSF biomarker testing (127 individuals: Aβ-42/Aβ-40, p -tau181, and t-tau), and plasma testing (127: Aβ-42/Aβ-40 and pTau181). Regression co-variates included age, sex, education, and APOE. Because this was a hypothesis-driven analysis, multiple comparisons corrections were deferred. Visiting loved ones more frequently was associated with higher global cognition (β=0.20, p  = 0.0097), executive function (β=0.17, p  = 0.037), and working memory (β=0.20, p  = 0.021) scores. More hours spent on these visits was associated with higher executive function scores (β =0.15, p  = 0.049). Volunteering more frequently was positively associated with global cognition (β=0.20, p  = 0.0069), executive (β=0.17, p  = 0.031), and working memory (β=017, p  = 0.046); volunteering for more hours per week was positively associated with executive function (β=0.18, p  = 0.016). There was a negative association between cognitive performance and senior center attendance (executive function: β=-0.17, p  = 0.033) and church attendance (language and frequency: β=-0.21, p  = 0.012; language and hours: β=-0.19, p  = 0.020). Attending clubs more frequently was positively associated with working memory (β=0.17, p  = 0.047). Using computers for longer was significantly associated with global cognition (β=0.26, p  <0.001), executive function (β=0.29, p  <0.001), working memory (β=0.17, p  = 0.045), attention (β=0.18, p  = 0.026), and language (β=0.18, p  = 0.029). Additionally, doing woodworking, needlework, drawing, or other crafts for longer was positively associated with executive function (β=0.15, p  = 0.048). Games, billiards, attending events, playing an instrument, and reading were not associated with cognitive performance. There was no association between these activities and AD biomarkers. In a comprehensive analysis of the associations between types of social and cognitive activities on cognitive scores, social visits, volunteering, clubs, computer use, and crafts were associated with higher cognitive performance.

The hippocampus is a heterogeneous structure with cytoarchitectonically distinct subfields that exhibit heterogeneous lifespan trajectories and are differentially susceptible to diseases. Advances in high-resolution imaging have accelerated research on these structures, yet variability in segmentation protocols limits cross-study comparability. The Hippocampal Subfields Group (HSG) is an international consortium addressing this challenge by developing a reliable, accessible, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI scans (http://www.hippocampalsubfields.com). Here, we present the harmonized protocol for the posterior portion of the hippocampus (the "tail"), complementing the previously established "body" protocol, and with an anterior "head" protocol under development. The tail protocol provides standardized definitions of the external boundaries for the posterior-most extent of the hippocampus, facilitating consistent segmentation from surrounding tissues. The research community was extensively involved through an online survey that incorporated comprehensive protocol details, feasibility assessments, tutorial videos, and illustrative segmentations. Through this collaborative process, consensus emerged to exclude subfield labeling in the hippocampal tail due to limited visibility of internal landmarks and substantial anatomical variability in this region. All proposed boundary guidelines were deemed clear and agreed upon via a Delphi procedure. The harmonized tail protocol has high intra- (Averaged ICC(2,1) > 0.98; Averaged Dice Similarity Coefficient = 0.92) and inter-rater reliability (Averaged ICC(2,k) > 0.98; Averaged Dice Similarity Coefficient = 0.86) and offers a practical framework for replicable segmentation. By establishing standardized guidelines, this protocol enhances comparability of findings across developmental, aging, and clinical research and is compatible with ongoing technological advances.

BACKGROUND:Non-pharmacological approaches may guide prevention and treatment strategies for patients with Alzheimer's disease (AD), but little is known about the "dose" and "type" required. The goal of this study is to examine what types of social and cognitive activities are associated with cognitive performance and AD biomarkers. METHOD:173 cognitively normal participants (69.0 ± 6.4 years) completed a questionnaire regarding frequency and hours per week of 7 social and 5 cognitively engaging activities. Participants underwent neuropsychological testing (z-scored composites of executive function, working memory, attention, episodic memory, visuospatial function, and language as well as a global cognitive composite), CSF biomarker testing (127 individuals: Aβ-42/Aβ-40, p-tau181, and t-tau), and plasma testing (127: Aβ-42/Aβ-40 and pTau181). Regression co-variates included age, sex, education, and APOE. Because this was a hypothesis-driven analysis, multiple comparisons corrections were deferred. RESULT:Visiting loved ones more frequently was associated with higher global cognition (β=0.20, p = 0.0097), executive function (β=0.17, p = 0.037), and working memory (β=0.20, p = 0.021) scores. More hours spent on these visits was associated with higher executive function scores (β =0.15, p = 0.049). Volunteering more frequently was positively associated with global cognition (β=0.20, p = 0.0069), executive (β=0.17, p = 0.031), and working memory (β=017, p = 0.046); volunteering for more hours per week was positively associated with executive function (β=0.18, p = 0.016). There was a negative association between cognitive performance and senior center attendance (executive function: β=-0.17, p = 0.033) and church attendance (language and frequency: β=-0.21, p = 0.012; language and hours: β=-0.19, p = 0.020). Attending clubs more frequently was positively associated with working memory (β=0.17, p = 0.047). Using computers for longer was significantly associated with global cognition (β=0.26, p <0.001), executive function (β=0.29, p <0.001), working memory (β=0.17, p = 0.045), attention (β=0.18, p = 0.026), and language (β=0.18, p = 0.029). Additionally, doing woodworking, needlework, drawing, or other crafts for longer was positively associated with executive function (β=0.15, p = 0.048). Games, billiards, attending events, playing an instrument, and reading were not associated with cognitive performance. There was no association between these activities and AD biomarkers. CONCLUSION:In a comprehensive analysis of the associations between types of social and cognitive activities on cognitive scores, social visits, volunteering, clubs, computer use, and crafts were associated with higher cognitive performance.

The nation's expanding digital workplace requires more computing professionals as well as workers with both domain and computing skills.Several universities have developed new interdisciplinary computing programs to meet these demands, but many lower-division students, especially those at community colleges, are not aware of these programs.Moreover, many students may not encounter learning experiences that foster their self-efficacy in pursuing these programs, creating an inequitable lack of opportunity for students at two-year institutions.In this paper we describe our approach to addressing these issues: the Applied Programming Experiences (APEX) program, which embeds computing modules into existing introductory statistics and biology courses.These modules use Python and are accessed via Google Colab, a free, web-based version of Jupyter Notebook.Critically, the success of the program requires instructors who feel comfortable teaching APEX content, particularly when they have little or no prior experience with computer programming.To this end, we created two Canvas courses, the first of which introduces faculty to Colab and Python, and the second of which contains APEX statistics and biology modules plus instructor solutions.We also piloted a faculty learning community (FLC) with a local two-year institution to foster a collaborative community and support faculty in adopting APEX materials, which included helping them to consider, plan, apply, and reflect on effective practices for integrating computing into their courses.Building upon these pilot efforts, we are actively expanding adoption of the APEX program in several ways.First, we have begun holding summer and winter training workshops for faculty at several additional community colleges.Second, we are refining and improving the FLC experience as we initiate new FLCs with these institutional partners.Finally, we will continue to assess the program's efficacy through a research plan that evaluates student and faculty experiences, allowing us to optimize the program and encourage faculty across the country to adopt our model of embedding computing experiences in lower division courses.

Cortical reinstatement is a key neural correlate of episodic remembering across the lifespan and explains significant variability in memory performance among older adults. We assessed whether Alzheimer’s disease (AD) risk factors – cerebrospinal fluid (CSF) Aβ 42 /Aβ 40, CSF pTau 181 , plasma pTau 181 , and APOE genotype – impact cortical reinstatement in clinically unimpaired older adults. Participants were 150 clinically unimpaired older adults enrolled in the Stanford Aging and Memory Study (SAMS). APOE genotype was determined from whole-genome sequencing and participants were classified as ε4 carriers (N = 38) or non-carriers (N = 112). CSF Aβ 42 /Aβ 40 and pTau 181 and plasma pTau 181 were quantified using the automated Lumipulse G system. Cortical reinstatement was quantified during successful retrieval of word-picture associations using fMRI multivoxel pattern analysis (MVPA) in five regions of interest, including parahippocampal gyrus (PHG), ventral temporal cortex (VTC), middle temporal gyrus (MTG), angular gyrus (ANG), and posterior medial cortex (PMC). Regression analyses examined cross-sectional relationships between regional cortical reinstatement and a) APOE genotype (N = 150), b) CSF Aβ 42 /Aβ 40 and pTau 181 (N = 113), and (c) plasma pTau 181 (N = 140), as well as associations of these variables with associative memory discrimination ( d’ ). All models included age, sex, and regional MVPA classifier accuracy during memory encoding. APOE ε4 genotype was negatively associated with reinstatement strength in VTC (β = -0.54, p < .005), MTG (β = -0.32, p < .05), and ANG (β = -0.32, p < .05) and CSF Aβ 42 /Aβ 40 burden was linked to weaker reinstatement in ANG (β = 0.16, p < .05). In VTC, the effect of APOE ε4 on reinstatement remained significant after controlling for CSF Aβ 42 /Aβ 40 (β = -0.47, p < .05); a similar pattern was observed in MTG and ANG. Although CSF pTau 181 was unrelated to reinstatement strength, both pTau 181 and cortical reinstatement explained unique variance in memory performance (pTau 181 : β = -0.26, p < .005, reinst VTC : β = 0.39, p < .001). Analogous findings were observed with plasma pTau 181 . These results suggest that APOE ε4 impacts cortical reinstatement, and that this effect may be independent of amyloid burden. These effects of APOE ε4 may be distinct from tau-mediated effects on episodic memory in human aging.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo , the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

Prior work has demonstrated that elevated CSF biomarkers in older adults are associated with diminished performance across several hippocampally-dependent memory tasks. It is unknown whether early structural changes in medial temporal lobe subfields (1) may be impacted by elevated p-tau 181 , and (2) mediate the effect of p-tau 181 on memory performance in older adults. The current study draws on a cohort of 147 cognitively unimpaired older adults (Stanford Aging and Memory Study) that completed both 3T MRI and lumbar punctures. To examine memory performance, participants completed two hippocampally dependent tasks: a paired associate cued recall task and a mnemonic discrimination task (MST) that examined discrimination between previously studied “old” objects, novel “foil” objects and perceptually similar “lure” objects. Lure trials were binned in five difficulty levels, ranging from low to high similarity compared to previously presented stimuli. Hippocampal subregions (CA1, CA3/DG, subiculum) were manually delineated on T2 * weighted images following Carr et al., (2017). CSF was processed with Lumipulse to measure Ab 42 :Ab 40 ratio and p-tau 181. Multiple regression was used to assess the associative memory d’ from the paired associate task. Given the repeated measures design of the MST task, linear mixed models were conducted to understand the association between hippocampal subfields and p-tau 181 on performance as a function of similarity strength (Trelle et al., 2021). Age, sex, and education were controlled in all models. P-tau 181 was correlated with reduced left CA1 volume (partial r 2 =0.043, p = 0.01), but not with volume in other hippocampal subfields. Increased CA1 volume was positively associated with better memory performance, including higher associative memory recall and old-lure discrimination. After controlling for p-tau 181, CA1 volume was no longer associated with performance on the associative memory task but remained significantly correlated with old/lure discrimination. Notably, increased CA1 volume improved overall discrimination for old/lure trials, independent of the difficulty level, while the association between p-tau 181 and performance was strongest at the lower similarity level. Reduced CA1 volume and p-tau explain unique variance in memory performance in older adults. This combination of biofluid biomarkers and high-resolution MRI has the potential to understand mechanisms underlying age-related memory decline.

The structure and computations associated with specific hippocampal subfields decline in aging and are also initial sites of Alzheimer’s disease pathology. The degree to which age-associated changes in hippocampal-dependent memory are driven by early AD pathology among older normal adults remains unclear. We enrolled one hundred ninety-nine clinically unimpaired (CU) older individuals into the Stanford Aging and Memory Study (SAMS, 117 Female, mean age= 68.9±6.2). Participants completed a lumbar puncture to collect cerebrospinal fluid (CSF), high-resolution fMRI (at 3T) during a visual associative memory paradigm, and ultra high-resolution structural MRI (at 7T) to assess MTL subregion integrity, as well as extensive cognitive assessment. Data collection is complete, and analysis of fMRI and 7T structural data of the 199 participants is currently underway. To examine neuronal computations underlying hippocampal dependent memory, we focused on fMRI metrics in a subset of 78 participants that quantify cortical reinstatement (the degree to which voxelwise patterns of activation during retrieval match activation patterns during encoding) in two a priori regions known to be important for visual associative memory (ventral temporal cortex, VTC; and angular gyrus, ANG). Additionally, we extracted univariate fMRI signal from the hippocampus during successful retrieval. Finally, hippocampal thickness from CA1 in a subset of 77 participants was manually delineated on 7T scans, and CSF was processed with Lumipulse to measure Ab 42 :Ab 40 ratio and p-tau 181. Elevated p-tau 181 was associated with worse performance on the fMRI-scanned visual associative memory task (Figure A), reduced cortical reinstatement strength in both VTC (r = -0.25, p = .027, Figure B) and ANG (r = -0.22, p = .048), as well as reduced CA1-SRLM thickness (r = -0.32, p = .004, Figure C). Although Ab 42 :Ab 40 ratios were related to p-tau 181, they were not independently associated with neuronal indices of hippocampal-dependent memory. CU with evidence of early tau abnormalities show worse hippocampal-dependent memory and differences in fMRI and structural measurements in regions critical for successful associative memory. Initial consequences of AD pathology target specific hippocampal-cortical circuits, and this is measurable using advanced MRI techniques.

Identifying biomarkers that predict current and future cognition may improve estimates of Alzheimer’s disease risk among cognitively unimpaired older adults (CU). In vivo measures of amyloid and tau protein burden and task-based functional MRI measures of core memory mechanisms, such as the strength of cortical reinstatement during remembering, have each been linked to individual differences in memory in CU. This study assesses whether combining CSF biomarkers with fMRI indices of cortical reinstatement improves estimation of memory function in CU, assayed using three unique tests of hippocampal-dependent memory. Participants were 157 CU (90F, aged 60-88 years, CDR=0) enrolled in the Stanford Aging and Memory Study (SAMS). Cortical reinstatement was quantified using multivoxel pattern analysis of fMRI data collected during completion of a paired associate cued recall task. Memory was assayed by associative cued recall, a delayed recall composite, and a mnemonic discrimination task that involved discrimination between studied ‘target’ objects, novel ‘foil’ objects, and perceptually similar ‘lure’ objects. CSF Aβ42, Aβ40, and p-tau181 were measured with the automated Lumipulse G system (N=115). Regression analyses examined cross-sectional relationships between memory performance in each task and a) the strength of cortical reinstatement in the Default Network (comprised of posterior medial, medial frontal, and lateral parietal regions) during associative cued recall and b) CSF Aβ42/Aβ40 and p-tau181, controlling for age, sex, and education. For mnemonic discrimination, linear mixed effects models were used to examine the relationship between discrimination ( d’) and each predictor as a function of target-lure similarity. Stronger cortical reinstatement was associated with better performance across all three memory assays. Age and higher CSF p-tau181 were each associated with poorer associative memory and a diminished improvement in mnemonic discrimination as target-lure similarity decreased. When combined in a single model, CSF p-tau181 and Default Network reinstatement strength, but not age, explained unique variance in associative memory and mnemonic discrimination performance, outperforming the single-modality models. Combining fMRI measures of core memory functions with protein biomarkers of Alzheimer’s disease significantly improved prediction of individual differences in memory performance in CU. Leveraging multimodal biomarkers may enhance future prediction of risk for cognitive decline.

The rapid growth of the digital economy and an associated increase in user-generated data has created a strong need for interdisciplinary computing professionals possessing both technical skills and knowledge of human behavior. To help meet this need and with funds from NSF IUSE, we developed an academic minor in Applied Computing for Behavioral and Social Sciences at San Jose State University. The minor involves a four-course sequence that includes programming fundamentals, data structures and algorithms, data cleaning and management, and a culminating project. At our institution and nationwide, social science students are more diverse than engineering students, with respect to gender, race, and ethnicity. By providing social science students with computing skills that complement their domain expertise, we aim to expand their career options and address the nation's need for a diverse, technology-capable workforce. We administered an exit survey on student learning experiences to two cohorts of students completing the minor. Given that the minor is new and that the first cohorts were relatively small, the number of students completing the survey was modest (n = 15). Results indicate that students were motivated to minor in Applied Computing by a desire to improve their data analysis skills and better prepare themselves for the job market / graduate school, as well as a belief that programming is a necessary skill for the future. A large majority of students indicated that their peers, instructors, and homework assignments supported their learning very well, whereas they found topics covered and course projects to be less supportive, followed by pacing of course content. With respect to career plans, a majority of students agreed that the minor provided them with their desired skills and allowed them to learn about careers in applied computing, and a large majority indicated that they planned to pursue a career utilizing applied computing. They expressed interest in fields such as human factors, data analytics, project management, teaching, clinical psychology, and various types of research. Finally, common themes that arose when providing advice to future students included not being shy in seeking help, tips for managing the level of course difficulty, encouragement to regularly practice, suggestions for how to master course content, and advice for adopting a successful mindset. These results will be instrumental in helping to optimize students' experiences in the minor, ranging from how we recruit new students to how we can better support their professional development. Given the largely positive experiences of our students and their plans to pursue careers involving applied computing, we believe that our approach of adding computing education alongside a social science degree demonstrates a promising model for meeting the increasing demand for diverse interdisciplinary computing workers in this digital age.

Objective To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF beta-amyloid (A beta)(42)/A beta(40) and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). Methods CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 +/- 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF A beta(42), A beta(40), and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (wordpicture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. Results Age and lower A beta(42)/A beta(40) were independently associated with elevated p-tau181. Age, A beta 42/A beta 40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of A beta(42)/A beta(40) on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF A beta(42) was not significantly associated with p-tau181 or memory. Conclusions Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

With an exponential increase in user-generated data, there is a strong and increasing demand for employees possessing both technical skills and knowledge of human behavior. Supported by funds from the National Science Foundation Division of Undergraduate Education, we have begun to address this need by developing a technology pathway program in data technology and applications at a large, minority-serving public university. As part of this program, an interdisciplinary team of faculty created a new minor in Applied Computing for Behavioral and Social Sciences. A large number of diverse students are studying behavioral and social sciences, and the ability to model human behaviors and social interactions is a highly valuable skill set in our increasingly data-driven world. Applied Computing students complete a four-course sequence that focuses on data analytics and includes data structures and algorithms, data cleaning and management, SQL, and a culminating project. Our first full cohort of students completed the Applied Computing minor in Spring 2019. To assess the success of the minor, we conduct student surveys and interviews in each course. Here, we focus on survey data from the beginning and end of the first course, given that it served as a particularly important feedback loop to optimize the course and to inform the design and execution of subsequent courses. The data reflect a significant increase in confidence in programming abilities over time, as well as a shift in attitudes about programming that more closely matches those of experts. The data did not show a significant change in mindset over time, such that students maintained a growth mindset across the semester. Finally, with respect to goals, students placed a greater emphasis on data and tech at the end of the semester, highlighting specific career paths such as user experience and human factors. In the future, we plan to administer this same survey to social science students not involved in the minor to serve as a control group and to begin exploring the large dataset obtained from other courses in the minor. We believe that embedding computing education into the social sciences is a promising means of diversifying the technical workforce and filling the need for interdisciplinary computing professionals, as evidenced by high rates of female and underrepresented minority enrollment in our courses, as well as promising shifts in student confidence, attitudes, and career goals as a result of taking Applied Computing courses.

Spurred by availability of automatic segmentation software, in vivo MRI investigations of human hippocampal subfield volumes have proliferated in the recent years. However, a majority of these studies apply automatic segmentation to MRI scans with approximately 1 × 1 × 1 mm3 resolution, a resolution at which the internal structure of the hippocampus can rarely be visualized. Many of these studies have reported contradictory and often neurobiologically surprising results pertaining to the involvement of hippocampal subfields in normal brain function, aging, and disease. In this commentary, we first outline our concerns regarding the utility and validity of subfield segmentation on 1 × 1 × 1 mm3 MRI for volumetric studies, regardless of how images are segmented (i.e., manually or automatically). This image resolution is generally insufficient for visualizing the internal structure of the hippocampus, particularly the stratum radiatum lacunosum moleculare, which is crucial for valid and reliable subfield segmentation. Second, we discuss the fact that automatic methods that are employed most frequently to obtain hippocampal subfield volumes from 1 × 1 × 1 mm3 MRI have not been validated against manual segmentation on such images. For these reasons, we caution against using volumetric measurements of hippocampal subfields obtained from 1 × 1 × 1 mm3 images.

The hippocampus (HC) and surrounding medial temporal lobe (MTL) cortical regions play a critical role in spatial navigation and episodic memory. However, it remains unclear how the interaction between the HC’s conjunctive coding and mnemonic differentiation contributes to neural representations of spatial environments. Multivariate functional magnetic resonance imaging (fMRI) analyses enable examination of how human HC and MTL cortical regions encode multidimensional spatial information to support memory-guided navigation. We combined high-resolution fMRI with a virtual navigation paradigm in which participants relied on memory of the environment to navigate to goal locations in two different virtual rooms. Within each room, participants were cued to navigate to four learned locations, each associated with one of two reward values. Pattern similarity analysis revealed that when participants successfully arrived at goal locations, activity patterns in HC and parahippocampal cortex (PHC) represented room-goal location conjunctions and activity patterns in HC subfields represented room-reward-location conjunctions. These results add to an emerging literature revealing hippocampal conjunctive representations during goal-directed behavior.

AbstractBackgroundThe medial temporal lobe (MTL, i.e. hippocampus and adjacent cortices) is particularly vulnerable to age‐related diseases: Alzheimer’s disease, other age‐related proteinothies (TDP‐43, AGD, etc) and vascular injury. Yet, the subregional pattern of vulnerability is thought to differ across etiologies; characterizing these differences using high‐resolution MRI may provide more insight in disease processes and better biomarkers. However, substantial differences in subfield definition has hindered the ability to compare results across laboratories or draw robust conclusions (Figure 1). The Hippocampal Subfields Group (HSG) is an international group seeking to remedy this problem by developing a histologically‐valid, reliable, and freely available segmentation protocol for high‐resolution T2‐weighted 3T MRI (http://www.hippocampalsubfields.com)MethodOur workflow consists of five steps: 1) collecting histology samples labeled by multiple expert neuroanatomists to form a novel reference dataset to guide the development of the MRI segmentation protocol, 2) developing boundary definitions for each segment of the hippocampus, (head, body, and tail) and MTL cortices), 3) assessing HSG community agreement with boundary rules via online questionnaires and revising boundary rules based on questionnaire responses, and 4) testing reliability of the protocol definitions on multiple MRI datasets.ResultFor both the hippocampal body and head, we have developed a preliminary subfield segmentation protocol (i.e. completed steps 1‐2, see Figure 2 for a histology slice segmented by three anatomists). Step 3 was piloted for the outer boundaries of the body (i.e., the anterior/posterior, medial/lateral, and superior/inferior boundaries) using an online questionnaire describing each of the proposed rules. 29 labs participated and consensus agreement was reached for all rules, with only minor changes being made to improve comprehension and clarity. We are now creating and administering additional questionnaires for assessing agreement of the hippocampal body and head inner boundary rules (e.g., between the CA fields and dentate gyrus). Upon completion of the assessment/revision process for each set of rules, the final phase – reliability testing of the protocol – should begin mid 2020 for the body.ConclusionOnce completed, the harmonized protocol will significantly facilitate cross‐study comparisons thus advancing insight in the role of hippocampal subfields across the lifespan in aging and disease.

As the digital economy grows, so does the demand for technology-capable workers who have both computing skills and domain expertise. Growing such a workforce is critical to ensuring the nation's competitiveness, according to a recent National Science Board publication. To address this need, faculty from the Colleges of Engineering and Social Sciences at San Jóse State University worked together to create the Applied Computing for Behavioral and Social Sciences minor degree. The minor targets students in majors such as Psychology and Economics, which have a more diverse student population than that of Computer Science or Engineering. The minor, designed with industry input, includes a four-course sequence that focuses on Python and R and includes topics such as data structures, algorithms, data cleaning and management, and data analysis. Our cohort-based program was built specifically for social science students using social science content, helping to foster a sense of community and belongingness among students. The first full cohort of 26 students graduated in Spring 2019, 48% of whom were female and 23% of whom were underrepresented minorities. Our approach of embedding computing education into the social sciences demonstrates a promising model of broadening participation in computing and meeting the nation's increasing demand for interdisciplinary computing workers in the digital age.

Abstract Introduction Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. Methods Our international working group, funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. Results This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. Discussion A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.