Cognitive Neuroscience Commons^™

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Research

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Visual Modulation Of Resting State Α Oscillations, Kelly Webster, Tony Ro

Publications and Research

Once thought to simply reflect passive cortical idling, recent studies have demonstrated that α oscillations play a causal role in cognition and perception. However, whether and how cognitive or sensory processes modulate various components of the α rhythm is poorly understood. Sensory input and resting states were manipulated in human subjects while electroencephalography (EEG) activity was recorded in three conditions: eyes-open fixating on a visual stimulus, eyes-open without visual input (darkness), and eyes-closed without visual input (darkness). We show that α power and peak frequency increase when visual input is reduced compared to the eyes open, fixating condition. These results …

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Functional Analysis In The Home Setting Of An Older Adult With Neurocognitive Disorder, Emily Norton

Masters Theses

Currently within the behavioral gerontology literature there are no published studies that include a functional assessment in the home setting. The primary goal of the present study was to address this gap by conducting a functional analysis on a challenging behavior of an older adult with neurocognitive disorder in the home. This study occurred in two phases. During phase one, researchers conducted an antecedent functional analysis on the bizarre speech of an 81-year-old female with suspected dementia across four conditions (television on, no interactions initiated; television on, interactions initiated; television off, no interactions initiated; television off, interactions initiated). Results from …

The Feedback-Related Negativity Is A Time-Dependent Brain Mechanism That Facilitates Aversive Learning: Implications For The Reinforcement Learning Frn Hypothesis, Eric Rawls

Graduate Theses and Dissertations

Organisms encode rewarding and aversive experiences through reinforcement learning, capitalizing on prediction errors (PEs), which adapt action strategies over time. Computational theories are explicit that PE signals should update action weights continuously over the course of a behavioral task, an important time-dependent variation that is eschewed in traditional neuroscience studies that average over large numbers of trials. I examined variation in reaction times and feedback-locked cortical activity over time as a function of PE to critically examine theories indicating that PE signals drive time-dependent learning. We recorded EEG while participants completed a novel reinforcement task that varied prediction error on …

The Role Of Gamma Oscillations And Cortical Inhibition In The Development Of Working Memory In Adolescence, Christopher P. Walker

Dissertations and Theses (Open Access)

Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric …

Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei

School of Medicine Faculty Research

Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in …

Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh

School of Medicine Faculty Research

Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer’s disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development. Areas covered: We provide an overview of the DLB drug …

Neural Correlates Of Decision Making Related To Information Security: Self-Control And Moral Potency, Robert West, Emily Budde, Qing Hu

Publications and Research

Security breaches of digital information represent a significant threat to the wellbeing of individuals, corporations, and governments in the digital era. Roughly 50% of breaches of information security result from the actions of individuals inside organizations (i.e., insider threat), and some evidence indicates that common deterrence programs may not lessen the insiders’ intention to violate information security. This had led researchers to investigate contextual and individual difference variables that influence the intention to violate information security policies. The current research builds upon previous studies and explores the relationship between individual differences in self-control and moral potency and the neural correlates …

Visual Entrainment Of Perception-Related Neural Oscillations As A Mechanism For Maintaining Rhythmic Temporal Expectations Across A Wide Range Of Frequencies, Michael James Gray

Dissertations, Theses, and Capstone Projects

Visual sensitivity fluctuates rhythmically, in-synch with ongoing, EEG-recorded neural oscillations across a wide range of frequencies (~1-25hz). Some recent work has suggested that these perception-related neural oscillations can be entrained by rhythmic visual stimulation. Evidence is also emerging that the entrainment of ongoing oscillations in visual and auditory cortices is involved in rhythmic temporal expectations. In the introduction chapter, I attempt to bridge these bodies of literature and hypothesize that rhythmic visual stimuli automatically entrain ongoing, perception-related neural oscillations and that this mechanism supports the maintenance of rhythmic temporal expectations. Chapters 2 and 3 address this hypothesis from different angles. …

Neural Correlates Of Automatic Emotional Processing And Emotion Regulation In Empathy And Psychopathy-Related Coldheartedness, Danielle Difilipo

Dissertations, Theses, and Capstone Projects

Psychopathy is a personality disorder that is defined, in part, by a lack of empathy. Psychopathy-related empathic deficits have been associated with atypical behavioral and neural responses to emotional facial expressions. Although the mirror neuron system (MNS) has been implicated in empathy, very few studies have examined the role of MNS functioning as it pertains to empathy impairments in psychopathy. Moreover, there is very little empirical research regarding emotion regulation in psychopathy, and specifically whether emotional responses can be intentionally upregulated. The present study sought to clarify whether the MNS is functionally intact in adults with subclinical psychopathic traits, particularly …

The Interaction Of Attention And Memory On The Reorienting Negativity, John C. Moses

Dissertations, Theses, and Capstone Projects

The three-stage model of distraction asserts that when we are presented with salient but task-irrelevant information, our sensory systems first detect the distracting stimulus by way of sensory memory buffers, which is indicated electrophysiologically by the mismatch negativity (MMN). Following detection, attentional resources are involuntarily allocated towards the processing of the distraction, as represented by the P3a. Finally, attentional resources are shifted away from the distracting stimulus and returned to the task-relevant information, as indicated by the reorienting negativity (RON). A great deal of research has focused on this last step in the model, largely centering around defining the mechanisms …

Emotion Processing Deficits In Psychopathy: Does Cueing To Relevant Facial Features Increase Cognitive And Emotional Empathy?, Shawn E. Fagan

Dissertations, Theses, and Capstone Projects

Psychopathy is a multifaceted disorder characterized by a lack of cognitive and emotional empathy. The traditional model of psychopathy divides the disorder into two factors: Factor 1 consists of the interpersonal and affective traits of psychopathy while Factor 2 measures antisocial behaviors and lifestyle choices. The attention-to-the-eyes hypothesis argues that psychopathic individuals have impaired emotion recognition (specifically for fear) due to deficits in orienting attention to salient facial features like the eyes. Psychopathic individuals also display blunted autonomic responding to emotional stimuli, though whether this is due to attention-orienting deficits remains to be clarified. The present project investigated whether empathy-related …

Voluntary Oral Methamphetamine Reveals Susceptibilities To Spatial Memory Deficits, Decreased Dopamine Marker Expression And Increased Neuroinflammation In The Hippocampus Of Male And Female Mice, Jorge A. Avila

Dissertations, Theses, and Capstone Projects

Methamphetamine is an addictive illicit psychostimulant that produces lasting neurochemical and behavioral changes. The mechanisms underlying these deficits have been characterized in animal models using extremely high doses. Currently, better translational models are needed to understand the onset and progression of these deficits that more accurately reflect the gradual and voluntary dosing parameters as chosen by an abuser. To that end, a new model of methamphetamine administration, labeled Voluntary Oral Methamphetamine Administration (VOMA), offers a means to examine the progression of neurotoxicity, behavioral deficits, and the addiction process through a voluntary consumption framework.

Female populations show consistent vulnerabilities to methamphetamine, …

Sex Moderates Amyloid And Apolipoprotein Ε4 Effects On Default Mode Network Connectivity At Rest, Jessica Z.K. Caldwell, Xiaowei Zhuang, Mackenzie J. Leavitt, Sarah J. Banks, Jeffery Cummings, Dietmar Cordes

School of Medicine Faculty Research

Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men—an advantage that has been termed “memory reserve.” Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might …

Souvenaid In The Management Of Mild Cognitive Impairment: An Expert Consensus Opinion, Jeffrey Cummings, Peter Passmore, Bernadette Mcguinness, Vincent Mok, Christopher Chen, Sebastiaan Engelborghs, Michael Woodward, Sagrario Manzano, Guillermo Garcia-Ribas, Stefano Cappa, Paulo Bertolucci, Leung-Wing Chu

School of Medicine Faculty Research

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, …

Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of …

Impact Of Excitation-Inhibition Balance/Imbalance On Dynamics Of Cortical Neural Networks, Vidit Agrawal

Graduate Theses and Dissertations

The purpose of this research is to study the implications of Excitation/Inhibition balance and imbalance on the dynamics of ongoing (spontaneous) neural activity in the cerebral cortex region of the brain.

The first research work addresses the question that why among the continuum of Excitation-Inhibition balance configurations, particular configuration should be favored? We calculate the entropy of neural network dynamics by studying an analytically tractable network of binary neurons. Our main result from this work is that the entropy maximizes at regime which is neither excitation-dominant nor inhibition-dominant but at the boundary of both. Along this boundary we see there …

Alpha Oscillations And Feedback Processing In Visual Cortex For Conscious Perception, Tony Ro

Publications and Research

Variability in perception between individuals may be a consequence of different inherent neural processing speeds. To assess whether alpha oscillations systematically reflect a feedback pacing mechanism for cortical processing during visual perception, comparisons were made between alpha oscillations, visual suppression from TMS, visual evoked responses, and metacontrast masking. Peak alpha oscillation frequencies, measured through scalp EEG recordings, significantly correlated with the optimum latencies for visual suppression from TMS of early visual cortex. Individuals with shorter alpha periods (i.e., higher peak alpha frequencies) processed visual information faster than those with longer alpha periods (i.e., lower peak alpha frequencies). Moreover, peak alpha …

The Dissociable Impact Of Auditory Vs. Visual Emotional Cues On Visual Processing, Emma K. Stewart Bsc, Derek Gv Mitchell Phd

Western Research Forum

Background: Emotional information has privileged access to processing resources, which can cause it to have a distracting or facilitating effect on task performance for reasons that are poorly understood. The sensory modality through which it is presented may be one determining factor. Some findings suggest that auditory stimuli facilitate visual task performance while visual stimuli interfere with it, but there are conflicting findings.

Hypothesis: We hypothesize that emotional content of a different sensory modality from the task improves task-related performance via a general alerting and arousing effect for all stimuli, while emotional content of the same modality disrupts performance when …

Optimization Of The Touchscreen-Based Visuomotor Conditional Learning Task In Mice, Oren Princz-Lebel, David I. Wasserman, Miguel Skirzewski, Penny A. Macdonald, Lisa M. Saksida, Tim J. Bussey

Western Research Forum

The translational gap between animal models and clinical trials is a longstanding, yet largely unresolved, limitation in the study of cognition. This discrepancy is largely due to the differences in how cognition is assessed in animal models compared to those in clinical populations. In the stimulus-response (S-R) learning literature, for example, the techniques used to assess the acquisition of habitual behaviour differ greatly across species, leading to poor cross-species translation and often conflicting results. As a result, we set out to optimize a S-R learning task in mice using the touchscreen-based operant technologies. Similar to human studies, this touchscreen technique …

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

Spontaneous Mimicry Of Emotional Facial Expressions As A Function Of Trait Sadism, Cathleen Fleury, Mary Ritchie, Derek Mitchell

Western Research Forum

Using electromyography (EMG), it has been shown that facial muscles imperceptibly mirror the facial expressions of others, a phenomenon referred to as spontaneous facial mimicry. Facial mimicry may be involved in empathy processing, and is impaired in several empathy deficit disorders. It was previously believed to follow the direct-matching principle, a theory postulating that spontaneous facial mimicry involves the observer mirroring their partner’s expression exactly. However, several recent studies have demonstrated that context and individual differences may be influencing factors of spontaneous facial mimicry. In the present study, we propose to investigate the relationship between facial mimicry and empathy through …

Associations Between Comorbid Tdp-43, Lewy Body Pathology And Neuropsychiatric Symptoms In Alzheimer's Disease, Ece Bayram, Guogen Shan, Jeffrey L. Cummings

School of Public Health Faculty Research

More than half of the patients with Alzheimer’s disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer’s Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.

Becoming The Good Shepherds, Eze Paez

Animal Sentience

It is very important that we clarify what we owe to nonhuman animals. To that end, we need a better understanding of animal cognition and emotion. Marino & Merskin’s target article is a welcome contribution to this project. Sheep, like most other animals, are sentient beings with interests of their own. It is wrong to discriminate against them based on species-membership or cognitive sophistication. We are morally required not to harm them, and to help them have the best possible lives, just as we would be in the case of human beings with similar interests. We must become the good …

How Music Therapy Effects The Traumatized Brain: Neurorehabilitation For Posttraumatic Stress Disorder Through Music Therapy, Jordan Winter Payne

Honors Projects

This review discusses the neurological components of posttraumatic stress disorder (PTSD) and how both structures and processes in the brain are altered in individuals with the disorder, specifically the neural network that includes the prefrontal cortex, the hippocampus, and the amygdala. This impacts awareness and responsiveness to stimuli. After examining these aspects, invasive and non-invasive treatment approaches are examined, with a specific emphasis on the treatment approach of music therapy. Musical stimuli are processed in many areas of the brain, so it has therapeutic potential for modulating neurological changes. Music therapy applies music clinically to address a variety of goals …

Sensory Perception, Adrian Rodriguez-Contreras

Open Educational Resources

Different types of sensory systems with their functional modalities will be presented. The biological bases for how these functions are generated and modified will then be described. As vision is the principal means of perception, we will focus in this course most on visual processing. Scientific data will be integrated into the lectures, such that students develop critical skills in analyzing data and proposing hypotheses.

Changes In Hemodynamic Response To Faces, Scenes, And Objects In A Visual Statistical Learning Task: An Fmri Analysis, Aaron T. Halvorsen

Honors Program: Senior Projects (Public)

Learning causes changes in brain activity and neural connections. Statistical learning is an implicit learning process that involves extracting regularities from the environment and finding patterns in stimuli based on their transitional probabilities. The following study describes an attempt to elucidate temporal changes in hemodynamic activity for three category-specific brain areas using functional magnetic resonance imaging (fMRI). Blood oxygen-level dependent signal (BOLD) responses were collected while subjects viewed faces, scenes, and objects with high and low transitional probabilities in an fMRI scanner. We expected brain activity to show a temporal shift in timing of activation when comparing BOLD signal responses …