Neurosciences Commons^™

A Spatiotemporal Map Of Reading Aloud, Oscar Woolnough, Cristian Donos, Aidan Curtis, Patrick S Rollo, Zachary J Roccaforte, Stanislas Dehaene, Simon Fischer-Baum, Nitin Tandon

Faculty, Staff and Student Publications

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans (26 male, 20 female) as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband γ activity varies with multiple word attributes critical to reading speed: lexicality, word frequency, and orthographic neighborhood. We found that lexicality is encoded …

Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and …

Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores In Older Adults, Timothy J. Libecap, Valentinos Zachariou, Christopher E. Bauer, Donna M. Wilcock, Gregory A. Jicha, Flavius D. Raslau, Brian T. Gold

Sanders-Brown Center on Aging Faculty Publications

Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56–86) underwent neuroimaging and MoCA testing. Quantification of region-specific ePVS burden was performed using a previously validated visual rating method and WMH volumes were computed using the standard ADNI pipeline. Separate …

Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L. Hartley, Victoria Fleming, Brianna Piro-Gambetti, Annie Cohen, Beau M. Ances, Michael A. Yassa, Adam M. Brickman, Benjamin L. Handen, Elizabeth Head, Mark Mapstone, Bradley T. Christian, Ira T. Lott, Eric Doran, Shahid Zaman, Sharon Krinsky-Mchale, Frederick A. Schmitt, Christy L. Hom, Nicole Schupf

Sanders-Brown Center on Aging Faculty Publications

Background: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.

Objective/hypothesis: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.

Methods: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged …

Using Noise For The Better: The Effects Of Transcranial Random Noise Stimulation On The Brain And Behavior, Onno Van Der Groen, Weronika Potok, Nicole Wenderoth, Grace Edwards, Jason B. Mattingley, Dylan Edwards

Research outputs 2022 to 2026

NEUROSCI BIOBEHAV REV X (X) XXX-XXX 2021.- Transcranial random noise stimulation (tRNS) is a non-invasive electrical brain stimulation method that is increasingly employed in studies of human brain function and behavior, in health and disease. tRNS is effective in modulating perception acutely and can improve learning. By contrast, its effectiveness for modulating higher cognitive processes is variable. Prolonged stimulation with tRNS, either as one longer application, or multiple shorter applications, may engage plasticity mechanisms that can result in long-term benefits. Here we provide an overview of the current understanding of the effects of tRNS on the brain and behavior and …

Concurrent Exposure To (Acute Intermittent) Hypoxia And Hypercapnia: A Promising Therapeutic Cocktail For Neuroplasticity?, Ricardo N. O. Mesquita

Research outputs 2022 to 2026

Pioneering experiments revealed that intermittent stimulation of afferent neurons from the carotid bodies elicits long-lasting increased activity of respiratory nerves, a phenomenon known as respiratory long-term facilitation (LTF). Initially observed with episodic electrical stimulation of the carotid sinus nerve, this phenomenon was then extensively demonstrated in rodent experiments via protocols of brief, episodic exposures to periods of hypoxia (i.e. acute intermittent hypoxia; AIH). Then, the realization that AIH could be used as a therapeutic modality to induce neuroplasticity and restore both respiratory and non-respiratory motor function in rats with spinal cord injuries (SCI) motivated translation to human studies. AIH has …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer’S Disease, Jaclyn M. Eissman, Logan Dumitrescu, Emily R. Mahoney, Alexandra N. Smith, Shubhabrata Mukherjee, Michael L. Lee, Phoebe Scollard, Seo Eun Choi, William S. Bush, Corinne D. Engelman, Qiongshi Lu, David W. Fardo, Emily H. Trittschuh, Jesse Mez, Catherine C. Kaczorowski, Hector Hernandez Saucedo, Keith F. Widaman, Rachel F. Buckley, Michael J. Properzi, Elizabeth C. Mormino, Hyun Sik Yang, Theresa M. Harrison, Trey Hedden, Kwangsik Nho, Shea J. Andrews, Douglas Tommet, Niran Hadad, R. Elizabeth Sanders, Douglas M. Ruderfer, Katherine A. Gifford, Xiaoyuan Zhong, Neha S. Raghavan, Badri Vardarajan, Margaret A. Pericak-Vance, Lindsay A. Farrer, Li San Wang, Carlos Cruchaga, Gerard D. Schellenberg, Nancy J. Cox, Jonathan L. Haines, C. Dirk Keene, Andrew J. Saykin, Eric B. Larson, Reisa A. Sperling, Richard Mayeux, Michael L. Cuccaro, David A. Bennett, Julie A. Schneider, Paul K. Crane, Angela L. Jefferson, Timothy J. Hohman

Sanders-Brown Center on Aging Faculty Publications

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience.

We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Frontal-Cerebellar Eeg As An Index Of Risk For Alzheimer's Disease In Healthy Elders, Elizabeth Paitel

Dissertations (1934 -)

The Apolipoprotein-E (APOE) ε4 allele is the greatest genetic risk factor for late-onset Alzheimer’s disease (AD), but alone it is not sufficiently predictive. Because neuropathological changes associated with AD begin decades before cognitive symptoms, neuroimaging of healthy, cognitively intact ε4 carriers (ε4+) may enable early characterization of neural patterns associated with risk for future cognitive decline. Research has typically focused on the cerebral cortex, where elders and ε4+ tend to exhibit ‘recruitment’ (i.e., hyperactivation) to maintain cognitive functioning. Yet, recent evidence suggests that AD-related changes may occur even earlier in the cerebellum. Moreover, advances in electroencephalography (EEG) source localization now …

Contributions Of Semantic And Phonological Working Memory To Narrative Language Independent Of Single Word Production: Evidence From Acute Stroke, Rachel Zahn, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

Neuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. …

Tfeb Induces Mitochondrial Itaconate Synthesis To Suppress Bacterial Growth In Macrophages, Ev-Marie Schuster, Maximilian W Epple, Katharina M Glaser, Michael Mihlan, Kerstin Lucht, Julia A Zimmermann, Anna Bremser, Aikaterini Polyzou, Nadine Obier, Nina Cabezas-Wallscheid, Eirini Trompouki, Andrea Ballabio, Jörg Vogel, Joerg M Buescher, Alexander J Westermann, Angelika S Rambold

Duncan NRI Faculty and Staff Publications

Successful elimination of bacteria in phagocytes occurs in the phago-lysosomal system, but also depends on mitochondrial pathways. Yet, how these two organelle systems communicate is largely unknown. Here we identify the lysosomal biogenesis factor transcription factor EB (TFEB) as regulator for phago-lysosome-mitochondria crosstalk in macrophages. By combining cellular imaging and metabolic profiling, we find that TFEB activation, in response to bacterial stimuli, promotes the transcription of aconitate decarboxylase (Acod1, Irg1) and synthesis of its product itaconate, a mitochondrial metabolite with antimicrobial activity. Activation of the TFEB-Irg1-itaconate signalling axis reduces the survival of the intravacuolar pathogen Salmonella enterica serovar Typhimurium. TFEB-driven …

The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …

Static And Group-Based Trajectory Analyses Of Factors Associated With Non-Adherence In Patients With Multiple Sclerosis Newly-Initiating Once- Or Twice-Daily Oral Disease-Modifying Therapy., Jacqueline A Nicholas, Natalie C Edwards, Roger A Edwards, Anna Dellarole, Luigi Manca, Danielle E Harlow, Amy L Phillips

Ambulatory and Primary Care Articles

BACKGROUND: Increased understanding of adherence may facilitate optimal targeting of interventions.

OBJECTIVE: To utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide).

METHODS: Commercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence. GBTM clustered patient subgroups with similar longitudinal patterns of adherence measured by monthly PDC (≥80%) and multinomial logistic regression identified factors associated with adherence trajectory subgroups.

RESULTS: Among 7689 patients, 39.5% were non-adherent to once-/twice-daily oral …

Podium Presentation: Spontaneous Intraventricular Empyema In A Patient With Bacterial Sinusitis, Rachel Freedberg, Brian J. Carlson, Cynthia Murphy, Teresa Bigand

2022 Providence Nurse Research Conference

No abstract provided.

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel B Zamler, Takashi Shingu, Laura M Kahn, Kristin Huntoon, Cynthia Kassab, Martina Ott, Katarzyna Tomczak, Jintan Liu, Yating Li, Ivy Lai, Rocio Zorilla-Veloz, Cassian Yee, Kunal Rai, Betty Ys Kim, Stephanie S Watowich, Amy B Heimberger, Giulio F Draetta, Jian Hu

Faculty, Staff and Student Publications

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that …

Chemotherapy Coupled To Macrophage Inhibition Induces T-Cell And B-Cell Infiltration And Durable Regression In Triple-Negative Breast Cancer, Swarnima Singh, Nigel Lee, Diego A Pedroza, Igor L Bado, Clark Hamor, Licheng Zhang, Sergio Aguirre, Jingyuan Hu, Yichao Shen, Yitian Xu, Yang Gao, Na Zhao, Shu-Hsia Chen, Ying-Wooi Wan, Zhandong Liu, Jeffrey T Chang, Daniel Hollern, Charles M Perou, Xiang H F Zhang, Jeffrey M Rosen

Duncan NRI Faculty and Staff Publications

Immunosuppressive elements within the tumor microenvironment, such as tumor-associated macrophages (TAM), can present a barrier to successful anti-tumor responses by cytolytic T cells. Here we employed preclinical syngeneic p53 null mouse models of triple-negative breast cancer (TNBC) to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose cyclophosphamide coupled with the pharmacologic inhibition of TAMs using either a small molecule CSF1R inhibitor or an anti-CSF1R antibody. This therapeutic combination was effective in treating several highly aggressive TNBC murine mammary tumor and lung metastasis models. Single cell RNA sequencing characterized tumor-infiltrating lymphocytes (TIL) including helper T cells and antigen-presenting …

Gut Dysbiosis And Age-Related Neurological Diseases In Females, Janelle M Korf, Bhanu P Ganesh, Louise D Mccullough

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

Norepinephrine Regulation Of Spatial Memory Using The Barnes Maze In Male And Female Rats, Serena Simpson, Ali Gheidi Phd, Nareen Sadik, Cameron J. Davidson Phd, Shane A. Perrine Phd

Medical Student Research Symposium

The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution remains to be clarified. This study aimed to investigate the role of NE on spatial learning and memory in female and male rats using a Barnes maze assay. We used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a specific noradrenergic neurotoxin that can cross the blood brain barrier, to deplete NE stores. We hypothesized that brain NE ablation would attenuate spatial learning and memory in rats. Loss of NE by DSP-4 was determined by measuring NE (and dopamine and serotonin) levels in several brain regions using HPLC. For the …

Intrabody-Mediated Postsynaptic Recruitment Of Camkiiα Improves Memory, Anthony Chifor, Jeongyoon Choi Dr., Joongkyu Park Dr.

Medical Student Research Symposium

Long-term potentiation (LTP), the selective strengthening of specific synapses based on recent activity, has widely been accepted as the biological mechanism responsible for learning and memory. N-methyl-D-aspartate receptors (NMDARs) play a critical role in LTP, which when activated, result in a surge of postsynaptic intracellular calcium levels. The calcium rise during LTP results in the activation of Ca²⁺/calmodulin-dependent kinase II alpha (CaMKIIa), which consequently enacts multiple cellular effects that ultimately result in the strengthening of synaptic connections. Previous work has examined the effects of CaMKIIa overexpression in rat hippocampi on spatial memory, however, significant but limited improvement in …

Il-10 And Tgf-Β Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox, Mike Castro, Thomas L. Brown, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

Cardiac resident macrophages facilitate electrical conduction by interacting with cardiomyocytes via connexin-43 (Cx43) hemichannels. Cx43 is critical for impulse propagation and coordination between muscle contractions. Cardiomyocyte electrophysiology can be altered when coupled with noncardiomyocyte cell types such as M2c tissue-resident macrophages. Using cocultures of murine HL-1 cardiomyocytes and RAW 264.7 macrophages, we examined the hypothesis that cytokine signals, TGF-β1 and IL-10, upregulate Cx43 expression at points of contact between the two cell types. These cytokine signals maintain the macrophages in an M2c anti-inflammatory phenotype, mimicking cardiac resident macrophages. The electrophysiology of cardiomyocytes was examined using di-8-ANEPPS potentiometric dye, which reflects …