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ItemThe effects of 40 Hz gamma flicker stimulation on spatial memory, perceptual discrimination, and recall(Georgia Institute of Technology, 2022-08) Salen, AshleyThe rising prevalence of Alzheimer's Disease (AD), which leads to progressively deteriorating memory and thinking skills is alarming. A preliminary data analysis was performed to predict potential behavioral changes that may occur in cognitively healthy older adults between conditions as a result of using the flicker for 8 weeks. Although the preliminary data analysis has not yet yielded any statistically significant effects induced by the 40 Hz gamma flicker on the memory of the flicker group compared to the control group, it may provide insight into what the results could look like further down the line. Based on graph analysis, it could be predicted that the flicker group may have fewer spatial memory deficits.
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ItemCyclic mechanical stretch upregulates Akt, MAPK, and NF-kappaB signaling pathways in BV2 microglia(Georgia Institute of Technology, 2022-05-24) Udeshi, Kareena JaydeepMild traumatic brain injury (mTBI) is prevalent in contact sports. Post injury, microglia in the central nervous system are known to produce an inflammatory response. Moreover, with repeated injuries, chronic inflammation may be sustained, which is detrimental to the host. This study focuses on the signaling pathways that are activated with brain injury-induced injury. We hypothesize that mechanical stretch activates inflammatory signaling pathways in microglia. This experiment utilized impulse, cyclic, and sham-stretch conditions in the presence or absence of the mechanosensitive channel inhibitor GSMTx4. Afterwards, the cell lysate was collected, and the samples were analyzed by a Luminex multiplexed ELISA to determine if there was a change in protein phosphorylation across 27 phosphoproteins in three main signaling pathways: Akt, MAPK, and NFkB. My data showed that GSMTx4 had little impact on phosphorylation, but it did increase the expression of the Akt pathway proteins. Nonetheless, the minimal role GSMTx4 played in the measured phospho-protein signaling pathways at acute timepoints could imply that Piezo1 does not play a direct role in acute pathway activation. Of note, however, a control 20% cyclic stretch resulted in an upregulation in phosphorylation in all signaling pathways. As such, future studies will include GSMTx4-treated BV2 microglia that undergo cyclic stretch at varying degrees. Clinically, this data is useful in understanding how sustained injury can force the progression of neurodegenerative diseases.
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ItemMeasuring Cerebral Blood Flow in a Mouse Model of Alzheimer's Disease(Georgia Institute of Technology, 2022-05) Daniel, ChristyMild traumatic brain injuries (mTBIs), which are defined by an absence of overt structural damage in the brain have been associated with an increased risk of Alzheimer's Disease when sustained multiple times over an interval. Within mTBI, indirect evidence suggests that persistent post-concussive symptoms may be linked to reduced cerebral blood flow (CBF), of which deficits have been observed in cases of Alzheimer's Disease. Diffuse correlation spectroscopy (DCS) is a non-invasive optical method that uses near-infrared light to measure fluctuations in intensity that are caused by moving red blood cells that can be used to measure cerebral blood flow (CBF) in C57bl/6 mice. This dissertation will adapt this novel protocol to a mouse model of Alzheimer’s Disease (3xTg). This strain will be utilized due to its accelerated AD pathology and the presence of literature that have observed impairments in CVR, CBF, among other biomarkers of Alzheimer’s Disease and traumatic brain injury. Given the smaller size of the 3xTg mice compared to C57bl/6, the DCS optical sensor must be modified. Herein, the design of a smaller sensor is detailed, along with a series of validation tests, which include measurements on a liquid phantom with known flow properties and on a pilot cohort of four 6–7-month-old 3xTg mice (2 males, 2 females). This data provides the foundational work to characterize the feasibility of DCS as a technique to monitor CBF and CVR in 3xTg mice for future experiments.
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ItemThe Effects of Nerve Injury and Synaptic Preservation on Motoneuron Activity(Georgia Institute of Technology, 2022-05) Garcia, VioletPeripheral nerve injury currently has a poor prognosis that often results in motor deficits such as discoordination and co-contraction of muscle antagonists (Brushart, 2011; Horstman et al., 2019). Because of this, studying the effects of peripheral nerve injury on the morphology and functional connectivity of the central nervous system (CNS) is of utmost importance. Our study centers around the anatomical changes that occur after peripheral nerve injury in the rat spinal cord, namely the degradation of Ia input defined by the expression of the vesicular glutamate transporter 1 (VGLUT1). This study is based on the proposed microglia-dependent mechanism of permanent synaptic loss from the Rotterman et al. (2019) paper. We ask if 1) we can suppress microglia accumulation with minocycline, a tetracycline antibiotic, and 2) if using minocycline can help preserve the Ia sensory afferent synapses after nerve injury. We first retrogradely labeled the medial gastrocnemius motor pool in 15 adult Wistar rats. One week later, we transected the medial gastrocnemius nerve in the left hindlimb. Rats were either treated with vehicle or minocycline for 14 days following injury. Control animals were also produced. At 14 days post injury, animals were perfused, spinal cords were collected and subsequently sectioned. Using immunohistochemistry (IHC), we labeled VGLUT1 synapses on these injured motor neurons and imaged them with confocal microscopy for subsequent reconstruction and analysis. We found four main results: 1) treatment with minocycline for 14 days after nerve injury does not seem to prevent microglia proliferation, 2) the chromalytic reaction (somatic expansion) that commonly occurs after axotomy did not seem to occur in the minocycline- treated animals, 3) there was partial preservation of somatic VGLUT1 synapses in the minocycline-treatment animals, and 4) there was complete dendritic VGLUT1 synapse preservation in the minocycline-treated animals. Although there were limitations to the study with regards to the methods of counting microglia, the study produced robust conclusions that will aid in the development of further research. Future studies should be conducted on the efficacy of minocycline preserving the synapses, the molecular mechanisms underlying minocycline’s effects, and the potential recovery of nerve function.
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ItemImproving Online Instructional Design using Memory, Attention, and Engagement(Georgia Institute of Technology, 2022-05) Chanda, RitikaNeuroscience research supports a relationship between the psychological constructions of attention and engagement. The level of selective attention and engagement present during the learning process correlates with increased memory and recall. With the recent rise in online learning, new questions regarding the improvement of educational design, teaching techniques, and learning have created a new avenue of investigation within the field of Neuroeducation. The objective of this study is to identify whether attentional brain networks related to Gagné’s Nine Events of Instruction and engagement can predict learning in an online setting by using fMRI and behavioral techniques. Overall, we found fMRI evidence of engagement, verified engagement’s role in memory and retrieval, and identified three Gagné events (Events 5, 6 and 7) that increase learning among students. This investigation allows for further advancements in online educational design as it will provide instructors with guidance on how to properly build their curriculum and modify the content structure of online classes to highlight techniques that promote successful learning.
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ItemRelating Neural Mechanisms for Learning to Instructional Techniques in Online Learning Environments(Georgia Institute of Technology, 2022-05) Joshi, Jenna GerdesThe virtual learning experience is fundamentally different from the traditional classroom because of the challenges of maintaining learners’ attention amid distractions in their environment. This study aims to study how the established Nine Events of Instruction can be most effective at maintaining engagement in learners in the online classroom. To test this, participants watched a 1-hour course on Human-Computer Interaction while in a functional magnetic resonance imaging (fMRI) scanner, rated how engaged they felt with the course, and were tested on the information they learned later. The participants then came back for a second session where they watched the same course and used a slider mouse scale to rate their engagement with the videos. Β-values were regressed from the fMRI data after being processed and analyzed extensively. Results revealed that brain activation in the lateral occipito-temporal cortex and ventral attention network occurred during times that participants reported increasing engagement. These regions of brain activation, among others, were also applied to which of the Events of Instruction were being employed by the instructor at that time. This experiment will link successful learning and cognitive engagement to the Nine Events of Instruction and will be applied to improve the virtual classroom experience in the near future.
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ItemSleep and Quasi-Periodic Patterns During Rest(Georgia Institute of Technology, 2022-05) Karkare, Maya C.In this preliminary study, researchers attempted to determine the relationship between sleep and quasi-periodic pattern strength. Three participants wore actigraphy watches for three nights prior to a resting-state functional MRI (rs-fMRI) scan. Actigraphy data was analyzed using the Cole Kripke analysis method. Functional connectivity was analyzed for quasi-periodic patterns (QPPs) between the default mode network (DMN) and the task-positive network (TPN). Due to errors involving preprocessing of rs-fMRI data, proper QPP analyses were unable to be conducted as the QPP template was abnormal. Further analysis of the data collected in the future will yield more conclusive results.
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ItemExploring Relationships in Alzheimer’s APOE Transgenic Mice(Georgia Institute of Technology, 2022-05) Hernandez Kluesner, JamieBackground: Apolipoprotein E (APOE) genotypes typically increase risk of amyloid-β deposition and onset of clinical Alzheimer's disease (AD). However, cognitive assessments in APOE transgenic AD mice have resulted in discord. Objective: Analysis of 31 peer-reviewed AD APOE mouse publications (n = 3,045 mice) uncovered aggregate trends between age, APOE genotype, gender, modulatory treatments, and cognition. Methods: T-tests with Bonferroni correction (significance = p < 0.002) compared age-normalized Morris water maze (MWM) escape latencies in wild type (WT), APOE2 knock-in (KI2), APOE3 knock-in (KI3), APOE4 knock-in (KI4), and APOE knock-out (KO) mice. Positive treatments (t+) to favorably modulate APOE to improve cognition, negative treatments (t-) to perturb etiology and diminish cognition, and untreated (t0) mice were compared. Machine learning with random forest modeling predicted MWM escape latency performance based on 12 features: mouse genotype (WT, KI2, KI3, KI4, KO), modulatory treatment (t+, t-, t0), mouse age, and mouse gender (male = g_m; female = g_f, mixed gender = g_mi). Results: KI3 mice performed significantly better in MWM, but KI4 and KO performed significantly worse than WT. KI2 performed similarly to WT. KI4 performed significantly worse compared to every other genotype. Positive treatments significantly improved cognition in WT, KI4, and KO compared to untreated. Interestingly, negative treatments in KI4 also significantly improved mean MWM escape latency. Random forest modeling resulted in the following feature importance for predicting superior MWM performance: [KI3, age, g_m, KI4, t0, t+, KO, WT, g_mi, t-, g_f, KI2] = [0.270, 0.094, 0.092, 0.088, 0.077, 0.074, 0.069, 0.061, 0.058, 0.054, 0.038, 0.023]. Conclusion: APOE3, age, and male gender was most important for predicting superior mouse cognitive performance.
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ItemMediating Age-Related Changes in Memory with Recall Intervention(Georgia Institute of Technology, 2022-05) Allen, JadaMemory- the lifeform that gives life its meaning and stores valuable information key to the success of our species. As far as we know, aging, a natural and unavoidable process, causes aspects of our memory to decline. Prospective memory is involved with remembering to complete an action or task at a future date and time while retrospective memory is involved in the remembrance, or perhaps not remembering, key details about items, places, or people experienced in the past. Different neural processes underlie each type and in exposing the neural process and further research, the factor to which aging impacts each memory is revealed. By conducting an exploratory study of autobiographical and declarative memory, researchers Carol Wilkinson and Ira Hyman revealed inconsistencies between memory errors experienced when asked to recall autobiographical information as opposed to when participants were asked to recall words in a list such as in a declarative memory task. When using the Dissociative Experience Scale to quantify memory errors, the inability to correctly source monitor a particular memory was different for autobiographical memory errors as opposed to declarative memory errors. This suggests that different processes may underlie different types of memory (Wilkinson & Hyman, 1999).
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ItemHow Stress Affects Concurrent Learning and Memory Integration during Decision-Making(Georgia Institute of Technology, 2022-05) Beveridge, ElizabethSpatial navigation presents as a realistic way to measure decision-making as acute stress has been shown to disrupt the hippocampal network involved in planning during navigation (Gagnon et al., 2018) and encourage the use of familiar routes over short-cuts (Brown et al., 2020). This planning during decision-making requires both memory retrieval and memory integration, the placement of weight on recalled past memories (He et al., 2022). While existing literature suggests acute stress impairs memory retrieval, there is no research on how stress affects memory integration during decision-making. To fill this critical gap in the literature, this study exposes half of its participants to stress via an electrical shock and uses a spatial navigation paradigm to measure how stress affects memory integration during decision-making. All 82 participants, divided roughly equally between gender and condition, navigated a virtual environment searching for goal objects. For each trial, the participant was prompted to decide between a familiar route with a lower payout or an unfamiliar route with a higher payout. For each participant, we used computational modeling to measure the degree of memory integration. We suspect that since stress impairs memory retrieval and decreases the use of shortcuts in spatial navigation, the degree of memory integration will decrease in the stress group. As hypothesized, participants in the stress group had significantly decreased memory integration than individuals in the control group (p=0.002), both expanding and validating the existing literature that acute stress impacts the prospective planning in decision-making during spatial navigation.