Neuroscience and Neurobiology Commons^™

Elucidating Neuroinflammation In Multiple Sclerosis By Network Analysis, Nora C. Welsh

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a heterogeneous disease, differing on many variables, including disease course, sex, and overall activity. Key characteristics of the disease encompass demyelination, axonal damage, neuronal loss, glial cell activation, and the infiltration of peripheral immune cells. Molecular proxies of these functions are secreted proteins, including cytokines and immunoglobulins, which, in the central nervous system (CNS), can be secreted into the cerebrospinal fluid (CSF). A detailed analysis of these secreted proteins can offer insights into the evolving immunological and neurodegenerative features as the disease progresses. To understand the dynamic biological processes involved in MS, I used network analysis …

Target Selection And Enhancement During Attentional Tracking, Marvin R. Maechler

Dartmouth College Ph.D Dissertations

At any waking moment, we are bombarded with more sensory information than we can fully process. Attention is necessary to deal with the dynamic world we live in. One fundamental function of vision and attention is to keep track of moving objects, but what are the targets of attention during tracking?

One of the first theories of attentional tracking predicted that targets would be selected at early processing stages. By employing the double-drift illusion, which dissociates physical and perceived positions of moving objects, we investigated which of these positions is selected for tracking. Contrary to earlier theories and in line …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Oligodendrocyte 2phatal Reveals Dynamics Of Myelin Degeneration And Repair, Timothy W. Chapman

Dartmouth College Ph.D Dissertations

Oligodendrocytes are responsible for producing myelin in the central nervous system. This lipid-rich coating along axons helps to increase action potential velocity, provide metabolic support to axons, and facilitate fine-tuning of neuronal circuitry. Demyelination and/or myelin dysfunction is widespread in neurodegenerative diseases and aging. Despite this, we know very little about how individual oligodendrocytes, or the myelin sheaths they produce, degenerate. Myelin repair, carried out by resident oligodendrocyte precursor cells (OPCs), is known to occur following myelin damage in certain contexts. We sought to investigate the cellular dynamics of oligodendrocyte degeneration and repair by developing a non-inflammatory demyelination model, combining …

Self-Supervised Pretraining And Transfer Learning On Fmri Data With Transformers, Sean Paulsen

Dartmouth College Ph.D Dissertations

Transfer learning is a machine learning technique founded on the idea that knowledge acquired by a model during “pretraining” on a source task can be transferred to the learning of a target task. Successful transfer learning can result in improved performance, faster convergence, and reduced demand for data. This technique is particularly desirable for the task of brain decoding in the domain of functional magnetic resonance imaging (fMRI), wherein even the most modern machine learning methods can struggle to decode labelled features of brain images. This challenge is due to the highly complex underlying signal, physical and neurological differences between …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Behavioral And Neural Mechanisms Of Serotonin Modulation Of Impulsivity And Reward, Stephanie S. Desrochers

Dartmouth College Ph.D Dissertations

Despite its prevalence in many psychiatric disorders, such as attention deficit hyperactivity disorder, suicidal depression, schizophrenia, and aggression and motivational disorders, impulsivity and its biological bases remain poorly understood. Subdivisions of impulsivity, including impulsive action (reduced response inhibition) and impulsive choice (reduced delay of gratification), sometimes present in an uncorrelated manner. This complexity renders pathological impulsivity difficult to treat, as different underlying causes likely result in different phenotypic presentations, despite being placed under one umbrella term. In order to study the behavior and biology of one particular facet of impulsivity, this dissertation utilizes the serotonin 1B receptor (5-HT1BR; an inhibitory …

Gabaergic Interneurons And Prenatal Ethanol Exposure: From Development To Aging, Adelaide R. Tousley

Dartmouth College Ph.D Dissertations

Fetal Alcohol Spectrum Disorders are the most common non-genetic cause of neurodevelopmental disability worldwide. Individuals with Fetal Alcohol Spectrum Disorder experience clinical symptoms including differences in physical, cognitive and behavioral development beginning in early childhood, but continue to face challenges into adulthood. There is a critical need to examine the effects of prenatal ethanol exposure across early development, and to establish how the developmental effects of prenatal ethanol exposure may or may not progress in aging individuals. To contribute to these two areas, I asked how a binge-type prenatal ethanol exposure might affect: (1) early postnatal development of striatal neurons …

Accelerated Forgetting In People With Epilepsy: Pathologic Memory Loss, Its Neural Basis, And Potential Therapies, Sarah Ashley Steimel Phd

Dartmouth College Ph.D Dissertations

While forgetting is vital to human functioning, delineating between normative and disordered forgetting can become incredibly complex. This thesis characterizes a pathologic form of forgetting in epilepsy, identifies a neural basis, and investigates the potential of stimulation as a therapeutic tool. Chapter 2 presents a behavioral characterization of the time course of Accelerated Long-Term Forgetting (ALF) in people with epilepsy (PWE). This chapter shows evidence of ALF on a shorter time scale than previous studies, with a differential impact on recall and recognition. Chapter 3 builds upon the work in Chapter 2 by extending ALF time points and investigating the …

Mapping The Malleable Self: How Self-Views Are Represented And Learned Within The Social Brain, Sasha Carmela Brietzke

Dartmouth College Ph.D Dissertations

Humans possess a unique and wide-ranging ability to self-reflect that takes center stage in our everyday cognition. While many people believe their own self to be immutable, different contexts may warp how we perceive the self. The goal of this dissertation is to investigate two lenses through which we may view the self: (1) across time in the past and future, and (2) through the eyes of others via evaluative feedback. In Studies 1-3, I demonstrate that people’s ratings of their own personality become increasingly less differentiated as they consider more distant past and future selves. This effect was preferential …

Spatial Representation In Postrhinal Cortex, Patrick Lachance

Dartmouth College Ph.D Dissertations

Animals rely on a variety of internal and external cues to orient themselves when navigating their environments and determining their current spatial context. Information regarding these cues enters the brain from the navigator’s first-person perspective. Information of this type is considered to be egocentric, or self-centered. However, decades of behavioral, electrophysiological, and imaging research suggest that the brain contains a rich collection of spatial representations that are unrestricted by the animal’s first-person perspective, and instead are defined relative to the surrounding environment. These representations are considered allocentric, or world-centered. Despite an abundance of promising modeling work, the specific mechanisms by …

Genetic Heterogeneity In Schizophrenia And Contribution Of Context To Vowel Recognition, Eva Childers

Dartmouth College Ph.D Dissertations

This dissertation is composed of three chapters that address two distinct topics. Chapter 2 addresses the use of consonantal context in vowel perception. Previous studies have demonstrated that context is important for vowel identification, however, this effect may be an artifact of stimuli production. To address this potential confound, we used stimuli extracted from an audiobook and asked subjects to identify vowels encased in consonants and isolated by themselves. We show that subjects had improved vowel identification when the vowel is presented with a consonantal framing, suggesting there is information contained in the surrounding context that is important for phoneme …

Application Of Cycle-By-Cycle Analysis To Eeg Data From Individuals With Phelan-Mcdermid Syndrome, Naomi Miller

ENGS 88 Honors Thesis (AB Students)

This study aimed to analyze a novel method of processing data from electroencephalography (EEG) recordings, which implements time-domain cycle-by-cycle analysis. This "bycycle" method, developed by the Cole & Voytek laboratory, was implemented on a EEG dataset of children with and without Phelan-McDermid Syndrome in the hopes of uncovering network-level explanations for the genetic disorder. A supplemental Python pipeline was developed to organize and visualize the data. This led to the discovery of group-level differences in measures of cycle symmetry in alpha band waves over the sensorimotor electrodes. Through the same pipeline, the bycycle tool was validated as a sound EEG …

Nmda Receptors Enhance The Fidelity Of Synaptic Integration, Chenguang Li, Allan Gulledge

Dartmouth Scholarship

Excitatory synaptic transmission in many neurons is mediated by two coexpressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in kinetics, ion selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here, we report that the voltage dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of EPSPs across spatial and volt- age domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees re- vealed that the combined presence of AMPA and NMDA conductances reduce the variability of …

Idiosyncratic, Retinotopic Bias In Face Identification Modulated By Familiarity, Matteo Visconti Di Oleggio Castello, Morgan Taylor, Patrick Cavanagh, Maria Ida Gobbini

Dartmouth Scholarship

The perception of gender and age of unfamiliar faces is reported to vary idiosyncratically across retinal locations such that, for example, the same androgynous face may appear to be male at one location but female at another. Here we test spatial heterogeneity for the recognition of the identity of personally familiar faces in human participants. We found idiosyncratic biases that were stable within participants and that varied more across locations for low as compared to high familiar faces. These data suggest that like face gender and age, face identity is processed, in part, by independent populations of neurons monitoring restricted …

Modeling Semantic Encoding In A Common Neural Representational Space, Cara E. Van Uden, Samuel A. Nastase, Andrew C. Connolly, Ma Feilong, Isabella Hansen, M Ida Gobbini, James V. Haxby

Dartmouth Scholarship

Encoding models for mapping voxelwise semantic tuning are typically estimated separately for each individual, limiting their generalizability. In the current report, we develop a method for estimating semantic encoding models that generalize across individuals. Functional MRI was used to measure brain responses while participants freely viewed a naturalistic audiovisual movie. Word embeddings capturing agent-, action-, object-, and scene-related semantic content were assigned to each imaging volume based on an annotation of the film. We constructed both conventional within-subject semantic encoding models and between-subject models where the model was trained on a subset of participants and validated on a left-out participant. …

Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge

Dartmouth Scholarship

Serotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT_2A (2A) receptors coupled to G_q subtype G-protein alpha subunits. G_q-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by K_V7 potassium channels (i.e., the M-current), or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation …

Feature-Based Learning Improves Adaptability Without Compromising Precision, Shiva Farashahi, Katherine Rowe, Zohra Aslami, Daeyeol Lee, Alireza Soltani

Dartmouth Scholarship

Learning from reward feedback is essential for survival but can become extremely challenging with myriad choice options. Here, we propose that learning reward values of individual features can provide a heuristic for estimating reward values of choice options in dynamic, multi-dimensional environments. We hypothesize that this feature-based learning occurs not just because it can reduce dimensionality, but more importantly because it can increase adaptability without compromising precision of learning. We experimentally test this hypothesis and find that in dynamic environments, human subjects adopt feature-based learning even when this approach does not reduce dimensionality. Even in static, low-dimensional environments, subjects initially …

The Neural Representation Of Personally Familiar And Unfamiliar Faces In The Distributed System For Face Perception, Matteo Visconti Di Oleggio Castello, Yaroslav O. Halchenko, J. Swaroop Guntupalli, Jason D. Gors, Ida M. Gobbini

Dartmouth Scholarship

Personally familiar faces are processed more robustly and efficiently than unfamiliar faces. The human face processing system comprises a core system that analyzes the visual appearance of faces and an extended system for the retrieval of person-knowledge and other nonvisual information. We applied multivariate pattern analysis to fMRI data to investigate aspects of familiarity that are shared by all familiar identities and information that distinguishes specific face identities from each other. Both identity-independent familiarity information and face identity could be decoded in an overlapping set of areas in the core and extended systems. Representational similarity analysis revealed a clear distinction …

Medial Prefrontal Cortical Thinning Mediates Shifts In Other-Regarding Preferences During Adolescence, Sunhae Sul, Berna Güroğlu, Eveline A. Crone, Luke J. Chang

Dartmouth Scholarship

Adolescence is a time of significant cortical changes in the ‘social brain’, a set of brain regions involved in sophisticated social inference. However, there is limited evidence linking the structural changes in social brain to development of social behavior. The present study investigated how cortical development of the social brain relates to other-regarding behavior, in the context of fairness concerns. Participants aged between 9 to 23 years old responded to multiple rounds of ultimatum game proposals. The degree to which each participant considers fairness of intention (i.e., intention-based reciprocity) vs. outcome (i.e., egalitarianism) was quantified using economic utility models. We …

Motion-Induced Position Shifts Activate Early Visual Cortex, Peter J. Kohler, Patrick Cavanagh, Peter U. Tse

Dartmouth Scholarship

The ability to correctly determine the position of objects in space is a fundamental task of the visual system. The perceived position of briefly presented static objects can be influenced by nearby moving contours, as demonstrated by various illusions collectively known as motion-induced position shifts. Here we use a stimulus that produces a particularly strong effect of motion on perceived position. We test whether several regions-of-interest (ROIs), at different stages of visual processing, encode the perceived rather than retinotopically veridical position. Specifically, we collect functional MRI data while participants experience motion-induced position shifts and use a multivariate pattern analysis approach …

Hearing On The Fly: The Effects Of Wing Position On Noctuid Moth Hearing, Shira D. Gordon, Elizabeth Klenschi, James F. C. Windmill

Dartmouth Scholarship

The ear of the noctuid moth has only two auditory neurons, A1 and A2, which function in detecting predatory bats. However, the noctuid's ears are located on the thorax behind the wings. Therefore, as these moths need to hear during flight, it was hypothesized that wing position may affect their hearing. The wing was fixed in three different positions: up, flat and down. An additional subset of animals was measured with freely moving wings. In order to negate any possible acoustic shadowing or diffractive effects, all wings were snipped, leaving the proximal-most portion and the wing hinge intact. Results revealed …

Effectiveness Of A Novel Qigong Meditative Movement Practice For Impaired Health In Flight Attendants Exposed To Second-Hand Cigarette Smoke, Peter Payne, Steven Fiering, James C. Leiter, David T. Zava, Mardi A. Crane-Godreau

Dartmouth Scholarship

This single-arm non-randomized pilot study explores an in ervention to improve the health of flight attendants (FA) exposed to second-hand cigarette smoke prior to the smoking ban on commercial airlines. This group exhibits an unusual pattern of long-term pulmonary dysfunction. We report on Phase I of a two-phase clinical trial; the second Phase will be a randomized controlled trial testing digital delivery of the intervention. Subjects were recruited in the Northeastern US; testing and intervention were administered in 4 major cities. The intervention involved 12h of training in Meditative Movement practices. Based on recent research on the effects of nicotine …

Adaptor Protein 2 (Ap-2) Complex Is Essential For Functional Axogenesis In Hippocampal Neurons, Jae Won Kyung, In Ha Cho, Sukmook Lee, Woo Keun Song, Timothy A. Ryan, Michael B. Hoppa, Sung Hyun Kim

Dartmouth Scholarship

The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in

concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a …

Variations In Crowding, Saccadic Precision, And Spatial Localization Reveal The Shared Topology Of Spatial Vision, John A. Greenwood, Martin Szinte, Bilge Sayim, Patrick Cavanagh

Dartmouth Scholarship

Visual sensitivity varies across the visual field in several characteristic ways. For example, sensitivity declines sharply in peripheral (vs. foveal) vision and is typically worse in the upper (vs. lower) visual field. These variations can affect processes ranging from acuity and crowding (the deleterious effect of clutter on object recognition) to the precision of saccadic eye movements. Here we examine whether these variations can be attributed to a common source within the visual system. We first compared the size of crowding zones with the precision of saccades using an oriented clock target and two adjacent flanker elements. We report that …

Individual Differences In Response Of Dorsomedial Prefrontal Cortex Predict Daily Social Behavior, Katherine E. Powers, Robert S. Chavez, Todd F. Heatherton

Dartmouth Scholarship

The capacity to accurately infer the thoughts and intentions of other people is critical for effective social interaction, and neural activity in dorsomedial prefrontal cortex (dmPFC) has long been linked with the extent to which people engage in mental state attribution. In this study, we combined functional neuroimaging and experience sampling methodologies to test the predictive value of this neural response for daily social behaviors. We found that individuals who displayed greater activity in dmPFC when viewing social scenes spent more time around other people on a daily basis. These findings suggest a specific role for the neural mechanisms that …

A Face Versus Non-Face Context Influences Amygdala Responses To Masked Fearful Eye Whites, M. Justin Kim, Kimberly M. Solomon, Maital Neta, F. Caroline Davis, Jonathan A. Oler, Emily C. Mazzulla, Paul J. Whalen

Dartmouth Scholarship

The structure of the mask stimulus is crucial in backward masking studies and we recently demonstrated such an effect when masking faces. Specifically, we showed that activity of the amygdala is increased to fearful facial expressions masked with neutral faces and decreased to fearful expressions masked with a pattern mask—but critically both masked conditions discriminated fearful expressions from happy expressions. Given this finding, we sought to test whether masked fearful eye whites would produce a similar profile of amygdala response in a face vs non-face context. During functional magnetic resonance imaging scanning sessions, 30 participants viewed fearful or happy eye …

The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko

Dartmouth Scholarship

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Cosmomvpa: Multi-Modal Multivariate Pattern Analysis Of Neuroimaging Data In Matlab/Gnu Octave, Nikolaas N. Oosterhof, Andrew C. Connolly, James V. Haxby

Dartmouth Scholarship

Recent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and …