Life Sciences Commons^™

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Publications

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …

Neurocounseling And The Counseling Profession: Integrating Neuroscience Into The Practice Of Counseling, Sherri Clark

Dissertations, Theses, and Projects

Neurocounseling integrates Neuroscience into mental health counseling by using psychoeducation, teaching, and illustrations as well as other forms of therapy (CBT, Interpersonal Psychotherapy, Narrative Therapy, etc.) to assist clients in understanding the neurological basis of many mental and behavioral health concerns. Clients can benefit from Neurocounseling as they gain a more comprehensive understanding of the central nervous system and brain function in connection to the body, cognition, mood, and behaviors, also known as the mind and body connection. Neuroplasticity and neurogenesis allow us to understand the brain’s amazing capability to grow and change. Understanding neuroscience allows for more integrated case …

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

Testosterone Undecanoate Effects On Behavior And Cognitive Functions In Male Swiss Albino Mice Exposed To Chronic Social Defeat, Micheal K. Ibrahim, Rajiv Tikamdas, Mohamed M. Kamal, Roua Aref Nouh, Mostafa H. Sayed

Pharmacy

Objective: To examine the impact of exogenous testosterone undecanoate (TU) on chronic stress-induced behavioral changes of sensory contact model in adolescent male Swiss Albino mice. Design: Stress was induced by sensory contact model (SCM) for 12 consecutive days. Defeated mice were randomly assigned to control group (vehicle), testosterone undecanoate (100mg/Kg) (TU 100) or testosterone undecanoate (500mg/Kg) (TU 500) given intramuscular once for 45 days administered 2 hours after the last SCM session. Results: SCM significantly reduced distance traveled, time spent in the center, average speed in the open field test compared to negative control group. In addition, SCM significantly reduced …

Multimodal Computational Modeling Of Visual Object Recognition Deficits But Intact Repetition Priming In Schizophrenia, Pejman Sehatpour, Anahita Bassir Nia, Devin Adair, Zhishun Wang, Heloise M. Debaun, Gail Silipo, Antigona Martinez, Daniel C. Javitt

Publications and Research

The term perceptual closure refers to the neural processes responsible for “filling-in” missing information in the visual image under highly adverse viewing conditions such as fog or camouflage. Here we used a closure task that required the participants to identify barely recognizable fragmented line-drawings of common objects. Patients with schizophrenia have been shown to perform poorly on this task. Following priming, controls and importantly patients can complete the line-drawings at greater levels of fragmentation behaviorally, suggesting an improvement in their ability to performthe task. Closure phenomena have been shown to involve a distributed network of cortical regions, notably the lateral …

Historical Trauma Response Scores As A Function Of Unresolved Grief And Substance Use Disorder In American Indian Populations, Andrew R. Saunders

Undergraduate Research Symposium

Abstract

Researchers are interested in the outcomes of interventions, specifically, measuring historical trauma (HT) among American Indian/Alaska Native communities and the long-term distress and substance abuse as a result of historical trauma response (HTR). Previous literature has implicated limitations in the clinical conceptualization of the relationship between intergenerational transfer of HTR and substance abuse. The aim of the current study is to examine treatment efficacy of 50 homosexual, American Indian males randomized to a culturally-adapted juxtaposition of (1) Group Interpersonal Psychotherapy (IPT), (2) Cognitive Processing Therapy (CPT), and (3) Historical Trauma and Unresolved Grief Intervention (HTUG), or (4) waitlisted on …

Examining The Structure Of Symbolic Number Representations In The Parietal Cortex: An Rsa Study, Aymee Alvarez Rivero

Electronic Thesis and Dissertation Repository

Previous studies using fMRI adaptation to investigate the neural substrate of symbolic number processing have found ratio-dependent responses in regions of the parietal cortex, suggesting that number symbols are coded by overlapping neuronal populations: the larger the ratio between two numerals, the more their representation overlap. The current study analyzed the distributed patterns of activation associated with numerals presented during this task. I could not find substantial evidence supporting the ratio-dependent structure of the similarity space predicted by the univariate adaptation analyses. I also failed to find evidence in favor of the alternative model that similarities were driven by lexical …

Is Executive Function The Universal Acid?, Stephen J. Morse

All Faculty Scholarship

This essay responds to Hirstein, Sifferd and Fagan’s book, Responsible Brains (MIT Press, 2018), which claims that executive function is the guiding mechanism that supports both responsible agency and the necessity for some excuses. In contrast, I suggest that executive function is not the universal acid and the neuroscience at present contributes almost nothing to the necessary psychological level of explanation and analysis. To the extent neuroscience can be useful, it is virtually entirely dependent on well-validated psychology to correlate with the neuroscientific variables under investigation. The essay considers what executive function is and what the neuroscience adds to our …

Cognitive Resources Are Recruited Consistently Across People During Story Listening, Matthew T. Bain

Electronic Thesis and Dissertation Repository

Degraded speech encoding as a result of hearing loss increases cognitive load and makes listening effortful. Standard hearing assessment does not capture this cognitive impact of hearing impairment. Speech-in-noise testing measures intelligibility for isolated sentences that are typically not engaging and lack meaningful context. These materials may not capture the processes involved in everyday listening situations, in which people are often intrinsically motivated to comprehend the speech they are hearing. The current study explored a novel approach using natural, spoken stories. We first characterized time courses of executive load during story listening in young individuals with normal hearing using a …

Investigating Cognitive Impairment In Tdp-43 Mouse Models Of Ftd-Als Using Automated Touchscreens, Keon Coleman

Electronic Thesis and Dissertation Repository

TAR-DNA-binding protein 43 (TDP-43) misfolding and aggregation is a major pathological hallmark of frontotemporal dementia-amyotrophic lateral sclerosis (FTD/ALS). FTD/ALS is characterized by motor and cognitive impairment, with cognitive impairment frequently reported before the onset of classical motor symptoms. Yet, treatment for cognitive decline in FTD/ALS is lacking, and robust cognitive phenotypes related to TDP-43 proteinopathy have not been established for most mouse models of FTD/ALS. Herein, we used automated touchscreen technology to assess executive function (affected in FTD/ALS) in male TDP-43^Q331Klow and ^-G348C FTD/ALS transgenic mice. The touchscreen pairwise visual discrimination task revealed impairments in 4-5-month-old TDP-43^Q331Klow and …

An Acute Application Of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance In Parkinson’S Disease, Lidio Lima De Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari, Brach Poston

Integrated Health Sciences Faculty Publications

Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson’s disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) …

Modeling Self-Organization In Human Crowds, Trenton D. Wirth

Link Foundation Modeling, Simulation and Training Fellowship Reports

Developing an understanding of human crowd movement is critical for optimizing crowd safety, both on the streets and in buildings. It is well understood from the study of animal collective motion that individuals are better able coordinate and respond to perturbations by perceiving movements from their neighbors (Ballerini et al., 2008; Couzin & Krause, 2003; Partridge, 1982). Thus, modeling and simulating human crowd behavior depends on the modeler’s ability to accurately characterize how an individual is influenced by his or her neighbors (Ballerini et al., 2008); i.e., identifying the local rules of engagement that lead to self-organization (Rio et al., …

Optimizing Preprocessing Of Fmri Data To Maximize Correspondence Of Functional Anatomy Across Individuals, Nargess Ghazaleh

Electronic Thesis and Dissertation Repository

In movie-activation fMRI, intersubject correlation (ISC) indicates a functional correspondence across viewers. Brains di↵er in shape; spatial normalization and smoothing enhance inter-subject functional overlap. We compare three normalization methods and six smoothing levels to discover which method yields the best functional overlap, indexed by ISC. This is key to optimizing data analysis in clinical studies using movie-activation fMRI in future. In a 3T scanner, 44 healthy subjects watched an 8-min movie. Both normalization and smoothing a↵ected the strength and extent of the ISC. ISC values were more robust for ANTs and DARTELthanforSPM12andwere(asymptotically)thestrongestat12mmsmoothing. When image data are preprocessed with high-dimensional volumetric …

A Glance At The Mirror: Ensemble Perception Of Symmetry, Gene Jerskey

Dissertations, Theses, and Capstone Projects

A growing body of research has demonstrated the ability of subjects to extract representative statistics from visual ensembles, images of similar but distinct groups of objects, without conscious effort or attention focused on individual members of the ensemble. When presented with ensembles, subjects have been able to accurately report the mean, range, and even distribution of various features in the ensemble. Research into ensemble perception, as it has become known, has divided mainly into studies of either low-level features, such as orientation, motion, and color, which are processed in early visual areas, at least for individual objects, or high-level features, …

Rehabilitative Movement Approaches And Dance Interventions In Parkinson’S Disease, Cecilia Fontanesi

Dissertations, Theses, and Capstone Projects

The scope of this work is to address the functional deficits and symptoms experienced by those living with Parkinson’s Disease through movement interventions.

Chapter 1 offers a brief overview of current pharmacotherapy and rehabilitation approaches in Parkinson’s, focusing on dance in particular as a movement intervention that may be particularly suited to this population.

Chapter 2 focuses on brain plasticity and motor learning in PD, reporting the effects of rTMS applied after the acquisition of a motor skill. In this study, adaptation tested in patients with PD was comparable in the sham and TMS sessions, while retention indices tested on …

Investigating The Neural Mechanisms Of Unconscious And Illusory Touch Perception, Lua Koenig

Dissertations, Theses, and Capstone Projects

Despite our everyday reliance on touch, from manipulating tools to dressing ourselves, relatively little is known about the neural correlates of tactile perception. As with other modalities, our conscious, reportable experiences of touch can dissociate from the physical tactile stimulation processed by the skin. In unconscious touch perception, tactile stimuli can be processed and guide our behavior without an accompanying conscious percept. For example, we may swat away a mosquito without having consciously registered its presence on our skin. In tactile illusions, conscious tactile experiences occur without a corresponding tactile stimulus. Multisensory tactile illusions arise when stimulation of a different …

Sex/Gender Differences In Serial Position Profiles In Patients With Mild Cognitive Impairment And Healthy Controls, Emnet Z. Gammada

Dissertations, Theses, and Capstone Projects

Introduction: Alzheimer’s disease disproportionately affects more women, but paradoxically, men have a higher incidence of Mild Cognitive Impairment (MCI). Researchers have suggested that women’s verbal memory advantage across the lifespan reflects better premorbid skills, which then require more neurodegeneration to manifest early clinical impairment. To date, measurement of sex differences in verbal memory have used total list scores. We proposed that a granular examination of serial position effects (SPE) in list-learning can refine the source of sex/gender differences.

Methods: A cross-sectional analysis of participants with Mild Cognitive Impairment (MCI) and Healthy Controls (HC) was examined from the Alzheimer’s Disease Neuroimaging …

The Temporal Dynamics Of Ensemble Perception, Michael L. Epstein

Dissertations, Theses, and Capstone Projects

The striking disparity between the subjective richness of experience and the considerable limitations of perceptual processing has emerged as an essential, enduring question in both vision science and philosophy of mind. A potential solution to this issue is ensemble perception: the ability for the visual system to compute the statistical summaries of object groups, effectively compressing an otherwise overwhelming amount of information. Previous work has supported that ensemble statistics can be perceived quickly and accurately for a wide range of object features. This has motivated models of ensemble perception as an early process in vision, providing an initial sense of …

Structural And Functional Brain Markers Of Trauma-Related Symptoms, Glenn Blessington

Dissertations, Theses, and Capstone Projects

The neurocircuitry model of posttraumatic stress disorder suggests an association between trauma-related symptoms and abnormalities in the structure and function of limbic and prefrontal brain regions. Evidence also suggests that these structural and functional abnormalities are related. We tested the relation between whole brain white matter integrity, resting-state functional connectivity of a fronto-limbic network, and trauma-related symptoms in 22 trauma-exposed women. We hypothesized that components of whole brain white matter would correlate with components of resting connectivity within a fronto-limbic network. We used parallel independent component analysis (pICA) to test the associations between whole brain fractional anisotropy (FA) maps and …

The Cognitive Thalamus: Source Analysis Of Scene Working Memory Delay Activity, Bernard A. Gomes

Dissertations, Theses, and Capstone Projects

Working Memory represents a limited-capacity store for maintaining information and manipulating the store's contents over a short period for the guidance of goal-directed behavior. Working Memory is an essential component of executive functions that are intricately associated with the prefrontal cortex (PFC). The PFC has been implicated in maintaining task-related information online for brief periods in the absence of relevant information. This active maintenance phase is called the delay period that occurs between encoding and retrieval of the stimulus. Previous studies have attempted to understand the relationship between working memory and the PFC, especially during the delay or maintenance phase …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Early Markers Of Dysfunction In Frontotemporal Dementia, Tamara P. Tavares

Electronic Thesis and Dissertation Repository

Frontotemporal Dementia (FTD) is a neurodegenerative disorder that results in atrophy within the frontal and/or temporal lobes. Clinically, patients with FTD present with progressive deterioration in behaviour and/or language abilities. FTD has a strong genetic component with approximately 40% of patients reporting a family history. Specifically, mutations in microtubule-associated protein tau (MAPT), progranulin (GRN) and expanded repeats in the chromosome 9 open reading frame 72 (C9orf72) are the main genetic causes of FTD. Currently, no disease-modifying treatments exist, and off-label medications have been used for symptomatic management of behaviours. Substantial progress has been made to …

Feeling-Of-Knowing Experiences Breed Curiosity, Gregory Brooks

Electronic Thesis and Dissertation Repository

It is well-established that curiosity has benefits for learning. Less is known about potential links between curiosity and memory retrieval. In theoretical work on metacognition it has been argued that retrieval experiences that occur during memory search can exert control over behaviour. States of curiosity, which can be defined as behavioural tendencies to seek out information, may play a critical role in this control function. We conducted two experiments to address this idea, focusing on links between feeling-of knowing (FOK) experiences, memory-search duration, and subsequent information-seeking behaviour. We administered an episodic FOK paradigm that probed memory for previously studied arbitrary …

The Impact Of Multiliteracies And Multimodality On Esl Learners: Using Neuroimaging Technologies, Wenyu Huang

Electronic Thesis and Dissertation Repository

Educational neuroscience has become an important role in understanding education and the association with brain development. However, few previous studies have applied neuroimaging techniques to multiliteracies research, which is an important literacy pedagogy addressing multimodal learning and cultural and linguistic diversity. This study used functional near infrared spectroscopy (fNIRS) to investigate the association of multiliteracies learning on adult English Second Language (ESL) students’ performance through multimodal tasks.

Students’ multimodality background was collected through a technology questionnaire. Behavioural and fNIRS data were collected before and after multiliteracies learning. Results showed that there was no significance change in behavioural responses while the …

Optimization And Validation Of A Modified Radial-Arm Water Maze Protocol Using A Murine Model Of Mild Closed Head Traumatic Brain Injury, Teresa Macheda, Kelly N. Roberts, Josh M. Morganti, David J. Braun, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues …

The Impact Of Emotional Information On Task Performance In Unimodal Vs. Cross-Modal Paradigms, Emma K. Stewart

Electronic Thesis and Dissertation Repository

Emotional stimuli can disrupt or enhance task performance, and this may depend on the sensory modality involved. In unimodal paradigms (e.g. visual task-irrelevant stimuli during a visual task) emotional stimuli frequently produce distraction effects; it is unclear how emotion affects task performance in cross-modal paradigms (e.g. auditory stimuli during a visual task). This project explored task performance as a function of sensory modality and emotional valence. In Study 1, participants (N=50) completed a visual task in the presence of task-irrelevant negative and neutral images and sounds. Response times and accuracy were disrupted in the presence of visual but not auditory …

Preliminary Evidence Of The Role Of Medial Prefrontal Cortex In Self-Enhancement: A Transcranial Magnetic Stimulation Study, Birgitta Taylor-Lillquist, Vivek Kanpa, Maya Crawford, Mehdi El Filali, Julia Oakes, Alex Jonasz, Amanda Disney, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

Humans employ a number of strategies to improve their position in their given social hierarchy. Overclaiming involves presenting oneself as having more knowledge than one actually possesses, and it is typically invoked to increase one’s social standing. If increased expectations to possess knowledge is a perceived social pressure, such expectations should increase bouts of overclaiming. As the medial prefrontal cortex (MPFC) is sensitive to social pressure and disruption of the MPFC leads to decreases in overclaiming, we predicted that transcranial magnetic stimulation (TMS) applied to the MPFC would reduce overclaiming and the effects would be enhanced in the presence of …

Brainwaves And Intentions: The Readiness Potential And Its Relation To Free Will, Joanna Pak, Aaron Schurger, Adina Roskies, Pengbo Hu

SURF Posters and Papers

First discovered in 1965 by Kornhuber and Deecke, the readiness potential (RP) is a distinctive buildup of neural activity in motor areas of the brain that begins ~500 ms before voluntary movements. In 1983, Libet used the RP as the foundation for his argument against the existence of conscious free will. This argument became known as the classic model of the RP, which interprets the RP as a precursor to the conscious experience of volition and a quantifiable representation of unconscious brain activity preceding spontaneous movements. Although the classic model connected the RP to free will, the significance of the …

Nutraceutical Potential For Alzheimer's Disease Treatment, Alex Gewecke

Undergraduate Research Journal

Alzheimer’s disease (AD) is a progressive disorder involving buildup of excessive amounts of proteins such as beta amyloid in the brain that leads to memory loss, inability to perform daily functions, and an early death. By 2060, the number of cases is forecast to nearly triple current numbers. Age is the primary risk factor for AD and no new drugs have been approved since 2003. Nutraceuticals, a broad category of substances that can be utilized for both medicinal and nutritional purposes may be able to help, which is why they are being more widely researched. Overall, a number of attempts …

Consider The Agent In The Arthropod, Nicolas Delon, Peter Cook, Gordon Bauer, Heidi Harley

Animal Sentience

Whether or not arthropods are sentient, they can have moral standing. Appeals to sentience are not necessary and retard progress in human treatment of other species, including invertebrates. Other increasingly well-documented aspects of invertebrate minds are pertinent to their welfare. Even if arthropods are not sentient, they can be agents whose goals—and therefore interests—can be frustrated. This kind of agency is sufficient for moral status and requires that we consider their welfare.