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Item Basal ganglia role in learning rewarded actions and executing previously learned choices: Healthy and diseased states(Public Library of Science, 2020-02-10) Mulcahy, Garrett; Atwood, Brady; Kuznetsov, Alexey; Psychiatry, School of MedicineThe basal ganglia (BG) is a collection of nuclei located deep beneath the cerebral cortex that is involved in learning and selection of rewarded actions. Here, we analyzed BG mechanisms that enable these functions. We implemented a rate model of a BG-thalamo-cortical loop and simulated its performance in a standard action selection task. We have shown that potentiation of corticostriatal synapses enables learning of a rewarded option. However, these synapses became redundant later as direct connections between prefrontal and premotor cortices (PFC-PMC) were potentiated by Hebbian learning. After we switched the reward to the previously unrewarded option (reversal), the BG was again responsible for switching to the new option. Due to the potentiated direct cortical connections, the system was biased to the previously rewarded choice, and establishing the new choice required a greater number of trials. Guided by physiological research, we then modified our model to reproduce pathological states of mild Parkinson's and Huntington's diseases. We found that in the Parkinsonian state PMC activity levels become extremely variable, which is caused by oscillations arising in the BG-thalamo-cortical loop. The model reproduced severe impairment of learning and predicted that this is caused by these oscillations as well as a reduced reward prediction signal. In the Huntington state, the potentiation of the PFC-PMC connections produced better learning, but altered BG output disrupted expression of the rewarded choices. This resulted in random switching between rewarded and unrewarded choices resembling an exploratory phase that never ended. Along with other computational studies, our results further reconcile the apparent contradiction between the critical involvement of the BG in execution of previously learned actions and yet no impairment of these actions after BG output is ablated by lesions or deep brain stimulation. We predict that the cortico-BG-thalamo-cortical loop conforms to previously learned choice in healthy conditions, but impedes those choices in disease states.Item The charismatic journey of mastery learning(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2015-11) Inui, Thomas S.; Department of Medicine, IU School of MedicineA collection of articles in this issue examine the concept of mastery learning, underscoring that our journey is from a 19th-century construct for assuring skill development (i.e., completing a schedule of rotations driven by the calendar) to a 21st-century sequence of learning opportunities focused on acquiring mastery of special key competencies within clerkships or other activities. Mastery learning processes and standards have the potential to clarify learning goals and competency measurement issues in medical education. Although mastery learning methods originally focused on developing learners' competency with skillful procedures, the author of this Commentary posits that mastery learning methods may be usefully applied more extensively to broader domains of skillful practice, especially those practices that can be linked to outcomes of care. The transition to mastery-focused criteria for educational advancement is laudatory, but challenges will be encountered in the journey to mastery education. The author examines several of these potential challenges, including expansion of mastery learning approaches to effective but relational clinician advice-giving and counseling behaviors, developing criteria for choosing critical competencies that can be linked to outcomes, avoiding a excessively fragmented approach to mastery measurement, and dealing with "educational comorbidity."Item Criterion Validation of Tau PET Staging Schemes in Relation to Cognitive Outcomes(IOS Press, 2023) Hammers, Dustin B.; Lin, Joshua H.; Polsinelli, Angelina J.; Logan, Paige E.; Risacher, Shannon L.; Schwarz, Adam J.; Apostolova, Liana G.; Alzheimer’s Disease Neuroimaging Initiative; Neurology, School of MedicineBackground: Utilization of NIA-AA Research Framework requires dichotomization of tau pathology. However, due to the novelty of tau-PET imaging, there is no consensus on methods to categorize scans into "positive" or "negative" (T+ or T-). In response, some tau topographical pathologic staging schemes have been developed. Objective: The aim of the current study is to establish criterion validity to support these recently-developed staging schemes. Methods: Tau-PET data from 465 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90) were classified as T+ or T- using decision rules for the Temporal-Occipital Classification (TOC), Simplified TOC (STOC), and Lobar Classification (LC) tau pathologic schemes of Schwarz, and Chen staging scheme. Subsequent dichotomization was analyzed in comparison to memory and learning slope performances, and diagnostic accuracy using actuarial diagnostic methods. Results: Tau positivity was associated with worse cognitive performance across all staging schemes. Cognitive measures were nearly all categorized as having "fair" sensitivity at classifying tau status using TOC, STOC, and LC schemes. Results were comparable between Schwarz schemes, though ease of use and better data fit preferred the STOC and LC schemes. While some evidence was supportive for Chen's scheme, validity lagged behind others-likely due to elevated false positive rates. Conclusions: Tau-PET staging schemes appear to be valuable for Alzheimer's disease diagnosis, tracking, and screening for clinical trials. Their validation provides support as options for tau pathologic dichotomization, as necessary for use of NIA-AA Research Framework. Future research should consider other staging schemes and validation with other outcome benchmarks.Item Demographically-corrected normative data for the RBANS Learning Ratio in a sample of older adults(Taylor & Francis, 2022) Hammers, Dustin B.; Duff, Kevin; Spencer, Robert J.; Neurology, School of MedicineBackground: A novel learning slope score - the Learning Ratio (LR) - has recently been developed that appears to be sensitive to memory performance and AD pathology more optimally than traditional learning slope calculations. While promising, this research to date has been both experimental and based on group differences, and therefore does not aid in the interpretation of individual LR performance for either clinical or research settings. The objective of the current study was to develop demographically-corrected normative data on these LR learning slopes on verbal learning measures from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Method: The current study examined the influence of age and education on LR metrics for the List Learning, Story Memory, and an Aggregated RBANS score in 200 cognitively intact adults aged 65 or older using linear regression. Results: Age and education correlated with most LR metrics, but no sex differences were observed. Linear regression permitted the prediction of LR values from age and education, which are then compared to observed LR values. The result is demographically-corrected T scores for these LR metrics. Conclusions: By comparing observed and predicted LR scores calculated from regression-based prediction equations, this represents the first step towards interpretation of individual performances on this metric for clinical decision making and treatment planning purposes. With future replication in diverse and heterogenous samples, we hope to offer a new clinical tool for the examination of learning slopes in older adults.Item Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans(Karger, 2016-05) Katner, S.K.; Neal-Beliveau, B.S.; Engleman, E.A.; Psychology, School of ScienceMethamphetamine (MAP) addiction is substantially prevalent in today's society, resulting in thousands of deaths and costing billions of dollars annually. Despite the potential deleterious consequences, few studies have examined the long-term effects of embryonic MAP exposure. Using the invertebrate nematode Caenorhabditis elegans allows for a controlled analysis of behavioral and neurochemical changes due to early developmental drug exposure. The objective of the current study was to determine the long-term behavioral and neurochemical effects of embryonic exposure to MAP in C. elegans. In addition, we sought to improve our conditioning and testing procedures by utilizing liquid filtration, as opposed to agar, and smaller, 6-well testing plates to increase throughput. Wild-type N2 C. elegans were embryonically exposed to 50 μM MAP. Using classical conditioning, adult-stage C. elegans were conditioned to MAP (17 and 500 μM) in the presence of either sodium ions (Na+) or chloride ions (Cl-) as conditioned stimuli (CS+/CS-). Following conditioning, a preference test was performed by placing worms in 6-well test plates spotted with the CS+ and CS- at opposite ends of each well. A preference index was determined by counting the number of worms in the CS+ target zone divided by the total number of worms in the CS+ and CS- target zones. A food conditioning experiment was also performed in order to determine whether embryonic MAP exposure affected food conditioning behavior. For the neurochemical experiments, adult worms that were embryonically exposed to MAP were analyzed for dopamine (DA) content using high-performance liquid chromatography. The liquid filtration conditioning procedure employed here in combination with the use of 6-well test plates significantly decreased the time required to perform these experiments and ultimately increased throughput. The MAP conditioning data found that pairing an ion with MAP at 17 or 500 μM significantly increased the preference for that ion (CS+) in worms that were not pre-exposed to MAP. However, worms embryonically exposed to MAP did not exhibit significant drug cue conditioning. The inability of MAP-exposed worms to condition to MAP was not associated with deficits in food conditioning, as MAP-exposed worms exhibited a significant cue preference associated with food. Furthermore, our results found that embryonic MAP exposure reduced DA levels in adult C. elegans, which could be a key mechanism contributing to the long-term effects of embryonic MAP exposure. It is possible that embryonic MAP exposure may be impairing the ability of C. elegans to learn associations between MAP and the CS+ or inhibiting the reinforcing properties of MAP. However, our food conditioning data suggest that MAP-exposed animals can form associations between cues and food. The depletion of DA levels during embryonic exposure to MAP could be responsible for driving either of these processes during adulthood.Item Enhancing Creativity in Teaching and Learning in Online, Face-to-Face and Hybrid Courses(2014-10-10) Hook, Sara Anne; Tennant, Felisa; Jones, Josette; Defazio, JosephThis engaging session will feature four faculty members from one school who have incorporated a number of pedagogical and technological approaches into their courses to encourage creativity in their students while continuing to nurture their own creativity as a way to stay motivated, innovative and engaged as teachers. It will include an interactive online activities for participants with an opportunity for self-reflection and illustrate some options for encouraging and assessing creativity in higher education. The session will review current research on creativity and distill the findings into practical applications for generating a learner-centered environment in any kind of classroom setting.Item Eternal Age: Art Therapy as a Means of Improving Quality of Life(2019) Rush, Haley; Misluk, EileenThis human-subject study used a mixed methods research design to identify if participation in individual, group, and open studio art therapy sessions would improve the quality of life for older adults. Person centered care was used as a framework for the art therapy programming. The Brunnsviken Brief Quality of life scale (BBQ) was used as a pre and mid test intervention and provided a baseline measure of quality of life. It was hypothesized that there would be an increase in the BBQ scores after participation in a 16-week art therapy program. The average difference of individuals pre and mid BBQ scores were used to identify if a change in quality of life had occurred in the life areas of leisure, creativity, and learning through the art making process. This study assessed creativity and learning through art making and leisure as the time spent in the process. The results showed that the overall BBQ scores were not representative of the gains demonstrated, although there were notable increases in leisure, creativity, and learning. Additionally, companionship was found to be a key factor in quality of life. These findings provided support for the use of a person-centered approach to art therapy which may lead to an increase in quality of life for older adults. Future implications of this study include continuing to explore the correlations between art therapy and quality of life as a means of engaging older adults in meaningful and productive activities that foster self-esteem, autonomy, empowerment, and problem-solving skills.Item Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning(Springer Nature, 2022) Lahti, Jari; Tuominen, Samuli; Yang, Qiong; Pergola, Giulio; Ahmad, Shahzad; Amin, Najaf; Armstrong, Nicola J.; Beiser, Alexa; Bey, Katharina; Bis, Joshua C.; Boerwinkle, Eric; Bressler, Jan; Campbell, Archie; Campbell, Harry; Chen, Qiang; Corley, Janie; Cox, Simon R.; Davies, Gail; De Jager, Philip L.; Derks, Eske M.; Faul, Jessica D.; Fitzpatrick, Annette L.; Fohner, Alison E.; Ford, Ian; Fornage, Myriam; Gerring, Zachary; Grabe, Hans J.; Grodstein, Francine; Gudnason, Vilmundur; Simonsick, Eleanor; Holliday, Elizabeth G.; Joshi, Peter K.; Kajantie, Eero; Kaprio, Jaakko; Karell, Pauliina; Kleineidam, Luca; Knol, Maria J.; Kochan, Nicole A.; Kwok, John B.; Leber, Markus; Lam, Max; Lee, Teresa; Li, Shuo; Loukola, Anu; Luck, Tobias; Marioni, Riccardo E.; Mather, Karen A.; Medland, Sarah; Mirza, Saira S.; Nalls, Mike A.; Nho, Kwangsik; O'Donnell, Adrienne; Oldmeadow, Christopher; Painter, Jodie; Pattie, Alison; Reppermund, Simone; Risacher, Shannon L.; Rose, Richard J.; Sadashivaiah, Vijay; Scholz, Markus; Satizabal, Claudia L.; Schofield, Peter W.; Schraut, Katharina E.; Scott, Rodney J.; Simino, Jeannette; Smith, Albert V.; Smith, Jennifer A.; Stott, David J.; Surakka, Ida; Teumer, Alexander; Thalamuthu, Anbupalam; Trompet, Stella; Turner, Stephen T.; van der Lee, Sven J.; Villringer, Arno; Völker, Uwe; Wilson, Robert S.; Wittfeld, Katharina; Vuoksimaa, Eero; Xia, Rui; Yaffe, Kristine; Yu, Lei; Zare, Habil; Zhao, Wei; Ames, David; Attia, John; Bennett, David A.; Brodaty, Henry; Chasman, Daniel I.; Goldman, Aaron L.; Hayward, Caroline; Ikram, M. Arfan; Jukema, J. Wouter; Kardia, Sharon L.R.; Lencz, Todd; Loeffler, Markus; Mattay, Venkata S.; Palotie, Aarno; Psaty, Bruce M.; Ramirez, Alfredo; Ridker, Paul M.; Riedel-Heller, Steffi G.; Sachdev, Perminder S.; Saykin, Andrew J.; Scherer, Martin; Schofield, Peter R.; Sidney, Stephen; Starr, John M.; Trollor, Julian; Ulrich, William; Wagner, Michael; Weir, David R.; Wilson, James F.; Wright, Margaret J.; Weinberger, Daniel R.; Debette, Stephanie; Eriksson, Johan G.; Mosley, Thomas H., Jr.; Launer, Lenore J.; van Duijn, Cornelia M.; Deary, Ian J.; Seshadri, Sudha; Räikkönen, Katri; Radiology and Imaging Sciences, School of MedicineUnderstanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Item Impact of Multi-Night Experimentally Induced Short Sleep on Adolescent Performance in a Simulated Classroom(Oxford University Press, 2017-02-01) Beebe, Dean W.; Field, Julie; Milller, Megan M.; Miller, Lauren E.; LeBlond, Elizabeth; Psychology, School of ScienceStudy Objectives: Investigate whether a realistic "dose" of shortened sleep, relative to a well-rested state, causes a decline in adolescents' learning and an increase in inattentive and sleepy behaviors in a simulated classroom setting. Methods: Eighty-seven healthy 14.0- to 16.9-year olds underwent a 3-week sleep manipulation protocol, including two 5-night sleep manipulation conditions presented in a randomly counterbalanced within-subjects cross-over design. Wake time was held constant. Bedtimes were set to induce Short Sleep (SS; 6.5 hours in bed) versus Healthy Sleep (HS; 10 hours in bed). During the morning at the end of each condition, participants underwent a simulated classroom procedure in which they viewed lecture-based educational videotapes and completed relevant quizzes. Their behaviors in the simulated classroom were later coded by condition-blind raters for evidence of inattention and sleepiness. Results: Adolescents had a longer average sleep period during HS (9.1 hours) than SS (6.5 hours). Compared to scores during HS, adolescents scored significantly lower on the quiz, showed more behaviors suggestive of inattention and sleepiness in the simulated classroom, and were reported by adolescents themselves and by their parents to be more inattentive and sleepy during SS. However, the impact of the manipulation on quiz scores was not mediated by changes in attention or sleepiness. Conclusions: Although effect sizes were modest, these findings suggest that previously-reported correlations between sleep duration and academic performance reflect true cause-effect relationships. Findings add to the growing evidence that the chronically shortened sleep experienced by many adolescents on school nights adversely impacts their functioning and health.Item Learning curve for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions in a novel ex-vivo simulation model(Thieme, 2016-12) Gonzalez, J.M.; Cohen, J.; Gromski, M.A.; Saito, K.; Loundou, A.; Matthes, K.; Department of Medicine, IU School of MedicineBackground: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is essential in the management of digestive cancers. However, teaching and learning this technique remain challenging due to the lack of cost-effective models. Material and methods: This was a prospective experimental study using a complete porcine upper gastrointestinal ex-vivo organ package, placed in an Erlangen Active Simulator for Interventional Endoscopy (EASIE-R), and prepared with one cyst and two solid masses (2 cm). Five fellows inexperienced in EUS-FNA were enrolled, performing 10 procedures on each lesion, alternatively. The total time, number of attempts for success, of needle view losses, and of scope handling were recorded, associated with an independent skills rating by procedure. We compared the first 15 procedures with the last 15 for each fellow. Results: The fellows successfully performed all procedures in 2 to 40 minutes, requiring 1 to 6 attempts. All (5/5) improved their total time taken (P < 0.001), number of times when the EUS view of the needle was lost (P < 0.05), scope handling (P < 0.005), and skills rating (P < 0.001), whereas 4/5 (80 %) improved their number of attempts. The overall evaluation showed a significant decrease (P < 0.001) in the total time taken (11.2 ± 7.8 vs 4.3 ± 2.2 minutes), number of attempts (2.6 ± 1.2 vs 1.2 ± 0.7), number of times when the EUS view of the needle was lost (2.3 ± 2 vs 0.5 ± 0.7), and need for scope handling (1.1 ± 1.7 vs 0.1 ± 0.2). We also observed an improvement in skills rating (5 ± 1.9 vs. 7.7 ± 1.1). Conclusion: This newly designed ex-vivo model seems to be an effective way to improve the initial learning of EUS-FNA, by performing 30 procedures.
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