Medicine and Health Sciences Commons^™

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …

No Statistical Learning Advantage In Children Over Adults: Evidence From Behaviour And Neural Entrainment., Christine N Moreau, Marc F. Joanisse, Jerrica Mulgrew, Laura J. Batterink

Brain and Mind Institute Researchers' Publications

Explicit recognition measures of statistical learning (SL) suggest that children and adults have similar linguistic SL abilities. However, explicit tasks recruit additional cognitive processes that are not directly relevant for SL and may thus underestimate children's true SL capacities. In contrast, implicit tasks and neural measures of SL should be less influenced by explicit, higher-level cognitive abilities and thus may be better suited to capturing developmental differences in SL. Here, we assessed SL to six minutes of an artificial language in English-speaking children (n = 56, 24 females, M = 9.98 years) and adults (n = 44; 31 females, M …

A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these …

Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos

Department of Occupational Therapy Faculty Papers

BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.

METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …

Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et …

Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker

Neurology Faculty Publications

Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of …

Modified Origins Of Cortical Projections To The Superior Colliculus In The Deaf: Dispersion Of Auditory Efferents., Blake E Butler, Julia K Sunstrum, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (

Seeing The Forest And The Trees: Default Local Processing In Individuals With High Autistic Traits Does Not Come At The Expense Of Global Attention., Ryan A Stevenson, Sol Z Sun, Naomi Hazlett, Jonathan S Cant, Morgan D Barense, Susanne Ferber

Brain and Mind Institute Researchers' Publications

Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals' levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

Nutrient Intake In The First Two Weeks Of Life And Brain Growth In Preterm Neonates., Juliane Schneider, Céline J Fischer Fumeaux, Emma G Duerden, Ting Guo, Justin Foong, Myriam Bickle Graz, Patric Hagmann, M Mallar Chakravarty, Petra S Hüppi, Lydie Beauport, Anita C Truttmann, Steven P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes.

METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, …

Early Procedural Pain Is Associated With Regionally-Specific Alterations In Thalamic Development In Preterm Neonates., Emma G Duerden, Ruth E Grunau, Ting Guo, Justin Foong, Alexander Pearson, Stephanie Au-Young, Raphael Lavoie, M Mallar Chakravarty, Vann Chau, Anne Synnes, Steven P Miller

Brain and Mind Institute Researchers' Publications

Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median …

Human Neuroimaging Reveals The Subcomponents Of Grasping, Reaching And Pointing Actions., Cristiana Cavina-Pratesi, Jason D Connolly, Simona Monaco, Teresa D Figley, A David Milner, Thomas Schenk, Jody C Culham

Brain and Mind Institute Researchers' Publications

Although the neural underpinnings of visually guided grasping and reaching have been well delineated within lateral and medial fronto-parietal networks (respectively), the contributions of subcomponents of visuomotor actions have not been explored in detail. Using careful subtraction logic, here we investigated which aspects of grasping, reaching, and pointing movements drive activation across key areas within visuomotor networks implicated in hand actions. For grasping tasks, we find activation differences based on the precision required (fine > coarse grip: anterior intraparietal sulcus, aIPS), the requirement to lift the object (grip + lift > grip: aIPS; dorsal premotor cortex, PMd; and supplementary motor area, SMA), …

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …

Microrna Expression Patterns In Human Anterior Cingulate And Motor Cortex: A Study Of Dementia With Lewy Bodies Cases And Controls, Peter T. Nelson, Wang-Xia Wang, Sarah A. Janse, Katherine L. Thompson

Sanders-Brown Center on Aging Faculty Publications

Overview

MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB).

Methods

RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals. RNA was profiled using Exiqon miRNA microarrays. Quantitative PCR for post-hoc replication was performed on separate cases (n=6 controls) and included RNA isolated from gray matter of MO, AC, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions.

Results

The miRNA expression patterns differed substantially according to …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …

Higher And Lower Order Factor Analyses Of The Temperament In Middle Childhood Questionnaire., Yuliya Kotelnikova, Thomas M Olino, Daniel N Klein, Sarah V M Mackrell, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent-report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings ≥.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure's authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative …

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu

Russell W. Brown

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and …

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Vocabulary Learning Benefits From Rem After Slow-Wave Sleep., Laura J Batterink, Carmen E Westerberg, Ken A Paller

Brain and Mind Institute Researchers' Publications

Memory reactivation during slow-wave sleep (SWS) influences the consolidation of recently acquired knowledge. This reactivation occurs spontaneously during sleep but can also be triggered by presenting learning-related cues, a technique known as targeted memory reactivation (TMR). Here we examined whether TMR can improve vocabulary learning. Participants learned the meanings of 60 novel words. Auditory cues for half the words were subsequently presented during SWS in an afternoon nap. Memory performance for cued versus uncued words did not differ at the group level but was systematically influenced by REM sleep duration. Participants who obtained relatively greater amounts of REM showed a …

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Rapid Statistical Learning Supporting Word Extraction From Continuous Speech., Laura J Batterink

Brain and Mind Institute Researchers' Publications

The identification of words in continuous speech, known as speech segmentation, is a critical early step in language acquisition. This process is partially supported by statistical learning, the ability to extract patterns from the environment. Given that speech segmentation represents a potential bottleneck for language acquisition, patterns in speech may be extracted very rapidly, without extensive exposure. This hypothesis was examined by exposing participants to continuous speech streams composed of novel repeating nonsense words. Learning was measured on-line using a reaction time task. After merely one exposure to an embedded novel word, learners demonstrated significant learning effects, as revealed by …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Online Neural Monitoring Of Statistical Learning., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

The extraction of patterns in the environment plays a critical role in many types of human learning, from motor skills to language acquisition. This process is known as statistical learning. Here we propose that statistical learning has two dissociable components: (1) perceptual binding of individual stimulus units into integrated composites and (2) storing those integrated representations for later use. Statistical learning is typically assessed using post-learning tasks, such that the two components are conflated. Our goal was to characterize the online perceptual component of statistical learning. Participants were exposed to a structured stream of repeating trisyllabic nonsense words and a …