Neuroscience and Neurobiology Commons^™

The Association Between Prenatal Maternal Stress, Infant Brain Volumes, And Temperament During The Covid-19 Pandemic, Amber L. Di Paolo

Electronic Thesis and Dissertation Repository

Prenatal maternal stress (PNMS) is associated with altered trajectories of infant socio-emotional and brain development, including brain structures such as the amygdala and prefrontal cortex (PFC). During the COVID-19 pandemic, which was a major global stressor, PNMS was significantly elevated, yet the impact on infant neurodevelopment remains uncertain. The objective of the present study was to determine whether PNMS during the pandemic was associated with infant amygdala and PFC volumes as well as temperament. In addition, we examined whether social support and resilience during pregnancy were protective factors.

Participants were enrolled in the Canadian ‘Pregnancy during the COVID-19 Pandemic’ cohort …

The Impact Of Traumatic Brain Injury On Noradrenergic Innervation Of The Prefrontal Cortex, Jil P. Modi, Christopher P. Knapp, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic Brain Injury (TBI) is a common cause of death and disability in the United States, and it can occur due to varied reasons including motor vehicle accidents, gunshot wounds, and falls. Following TBIs, patients are often left with lifelong disabilities and cognitive problems that can lead to increased risk-taking behaviors. The main goal of my research was to understand the neural mechanisms that drive increased risk-taking behaviors due to TBIs. The specific areas of the brain I was interested in looking at were the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and/or anterior cingulate cortex (ACC) of the prefrontal …

Cholinergic Activation Of Corticofugal Circuits In The Adult Mouse Prefrontal Cortex, Allan Gulledge

Dartmouth Scholarship

Acetylcholine (ACh) promotes neocortical output to the thalamus and brainstem by preferentially enhancing the postsynaptic excitability of layer 5 pyramidal tract (PT) neurons relative to neighboring intratelencephalic (IT) neurons. Less is known about how ACh regulates the excitatory synaptic drive of IT and PT neurons. To address this question, spontaneous excitatory postsynaptic potentials (sEPSPs) were recorded in dual recordings of IT and PT neurons in slices of prelimbic cortex from adult female and male mice. ACh (20 µM) enhanced sEPSP amplitudes, frequencies, rise-times, and half-widths preferentially in PT neurons. These effects were blocked by the muscarinic receptor antagonist atropine (1 …

Cortical Representation Of Learning Social Interactions In Freely Moving Non-Human Primates, Melissa Franch

Dissertations & Theses (Open Access)

The motivation and capacity to be social is necessary for human survival. Successful learning of complex, prosocial behavior stems from the ability to perceive and respond to visual cues, such as the body language and facial expressions, from others in our environment. This dependence on visual information to guide social interaction is especially true for humans and non-human primates. Although recent studies in primate neurophysiology discovered neurons that can encode socially relevant variables, like reward and social actions, the underlying neural mechanisms of learning advanced social concepts, such as cooperation, are not well understood. Further, previous work has identified …

Connectional Analysis Of Brain Regions Associated With Feeding, Kenichiro Negishi

Open Access Theses & Dissertations

Rodent models are invaluable for understanding the foundations of motivatedbehaviors. One major obstacle faced by these efforts is the lack of a 'wiring diagram' or a 'parts list' of structures that support motivated behaviors. Here, I present work that advances our knowledge of the structural organization of connections and chemoarchitecture of the diencephalon. Chapter 1 aims to clarify a wiring diagram of the medial prefrontal cortex (mPFC) following a recent demonstration of cortically-evoked feeding through this region. Chapter 2 clarifies the distributions of a subpopulation of tyrosine hydroxylase (TH) neurons in the hypothalamus. These disparate datasets were analyzed and interpreted …

Does Seclusion Alter Amygdala Activity And Amygdala-Medial Prefrontal Cortex Connectivity Leading To Emotional Dysregulation In Children? A Case For Ending Seclusion And Restraint In Public Schools, Crystal Anyanwu

CMC Senior Theses

The use of seclusion as a disciplinary practice in schools has been cited as an effective way to mitigate a child’s behavior if they pose a threat of imminent danger to others or themselves and an effective means of helping a child regulate their emotions. However, research has shown that this practice has resulted in psychological harm (e.g. traumatic stress responses), physical injuries, and death to both staff applying these techniques and the children experiencing them. The effects of seclusion on the neurodevelopment of children remain widely unknown. Traumatic stress has been shown to increase the volume of the amygdala …

The Role Of The Prefrontal Cortex And Stress In Huntington Disease-Mediated Aggression, Kadambari Vyas

Honors Undergraduate Theses

Huntington Disease (HD) is a fatal neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although HD onset is determined by motor symptoms, psychiatric symptoms, like depression and aggression, can develop earlier, have a larger impact on quality of life, and are understudied due to stigma. Our lab has observed hyper aggression in our humanized HD mouse model (Hu97/18) compared to our knock-in HD mouse model (Q175FDN). We characterized these differences and found that the Hu97/18 mice overreact in neutral situations, behaving as if they are in threatening situations. We are now using this novel model of HD-related …

Extended Functional Connectivity Of Convergent Structural Alterations Among Individuals With Ptsd: A Neuroimaging Meta-Analysis, Brianna S. Pankey, Michael C. Riedel, Isis Cowan, Jessica E. Bartley, Rosario Pintos Lobo, Lauren D. Hill-Bowen, Taylor Sato, Erica D. Musser, Matthew T. Sutherland, Angela R. Laird

Psychology Faculty Publications

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated.

Methods: Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional …

The Subplate And Its Role In The Gaba System In The Prefrontal Cortex, Gaeul Kyla Lee

Electronic Thesis and Dissertation Repository

During early brain development, the subplate relays thalamocortical afferents. Lesions to the subplate have been implicated in developmental abnormalities of cortical GABAergic circuits. This thesis examined the effects of subplate lesions in the prefrontal cortex of rats on the expression of GABA markers (parvalbumin and GAD67) and GABA synapse maturation [potassium-chloride cotransporter (KCC2) and sodium-potassium- chloride cotransporter (NKCC1)] with relevance to the characterization of a rat model for schizophrenia. Lesions were made on postnatal day 1 (P1). Lesioned and control rats were sacrificed between P5 and P90 and immunolabelled for parvalbumin, GAD67, KCC2, and NKCC1. We found decreased parvalbumin expression …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

Modeling Interactions Between Brain Function, Diet Adherence Behaviors, And Weight Loss Success, Amanda N. Szabo-Reed, Laura E. Martin, Jinxiang Hu, Hung-Wen Yeh, Joshua Powell, Rebecca J. Lepping, Trisha M. Patrician, Florance J. Breslin, Joseph E. Donnelly, Cary R. Savage

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Summary

Introduction: Obesity is linked to altered activation in reward and control brain cir-cuitry; however, the associated brain activity related to successful or unsuccessful weight loss (WL) is unclear.

Methods: Adults with obesity (N = 75) completed a baseline functional magnetic res-onance imaging (fMRI) scan before entering a WL intervention (ie,3-month diet and physical activity [PA] program). We conducted an exploratory analysis to identify the contributions of baseline brain activation, adherence behavior patterns, and the asso-ciated connections to WL at the conclusion of a 3-month WL intervention. Food cue-reactivity brain regions were functionally identified using fMRI to index brain activation …

Role Of Cholinergic Receptors In Prefrontal Activity Of Nonhuman Primates During An Oculomotor Rule-Based Working Memory Task, Alex J. Major

Electronic Thesis and Dissertation Repository

The ability to flexibly react to our dynamic environment is a cardinal component of cognition and our human identity. Millions across the globe are affected by disorders of cognition, affecting their ability to live independently. Prefrontal cortex is required for optimal cognitive functioning, but its circuitry is often disrupted in conditions of impaired cognition. In addition, the cholinergic system is vital to optimal executive function, but this is disrupted in a number of conditions, including Alzheimer’s disease and schizophrenia. The actions of cholinergic receptors were explored in this project with local application of cholinergic compounds onto prefrontal neurons as rhesus …

Acc Theta Improves Hippocampal Contextual Processing During Remote Recall, Ryan A. Wirt, James M. Hyman

Psychology Faculty Research

Consolidation studies show that, over time, memory recall becomes independent of the medial temporal lobes. Multiple lines of research show that the medial frontal cortex, including the anterior cingulate cortex (ACC), is involved with contextual information processing and remote recall. We hypothesize that interactions between the ACC and hippocampal area CA1 will change as memories became more remote. Animals are re-exposed to multiple environments at different retention intervals. During remote recall, ACC-CA1 theta coherence increases, with the ACC leading area CA1. ACC theta regulates unit spike timing, gamma oscillations, and ensemble and single-neuron information coding in CA1. Over the course …

The Role Of Progesterone Receptor In The Development Of The Mesocortical Serotonergic Pathway, Allyssa Phillips

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical serotonergic pathway, consisting of serotonergic fibers projecting from the dorsal raphe nucleus (DRN) to the prefrontal cortex (PFC), regulates higher order executive functions and complex cognitive behaviors. Disruptions in this pathway lead to dysfunction in behavior and have been linked to several clinical disorders, including anxiety and ADHD. While this pathway continues to change throughout the lifespan, it is during early development that this pathway undergoes a rapid period of maturation, with the greatest rate of fiber innervation and synaptogenesis occurring in the mesocortical serotonergic pathway at this time. The development of a properly functioning circuit is directed …

Does Transcranial Direct Current Stimulation To The Prefrontal Cortex Affect Social Behavior? A Meta-Analysis, Sarah Beth Bell, Nathan Dewall

Psychology Faculty Publications

This meta-analysis (k = 48, N = 2196) examined the effect of transcranial direct current brain stimulation (tDCS) applied to the prefrontal cortex on a variety of social behaviors, including aggression, overeating, impulsivity, bias, honesty, and risk-taking. tDCS showed an overall significant effect on reducing undesirable behaviors, with an average effect size of d = −0.20. tDCS was most effective at reducing risk-taking behavior, bias, and overeating. tDCS did not affect aggression, impulsivity, or dishonesty. We examined moderators such as brain region of interest, online vs offline stimulation, within- vs between-subjects designs, dose, and duration, but none showed significant …

Social Status Modulates Restraint- Induced Neural Activity In Brain Regions Controlling Stress Vulnerability , Sahba Seddighi, Matthew A. Cooper

Haslam Scholars Projects

Understanding the cellular mechanisms that control resistance and vulnerability to stress is an important step toward identifying novel targets for the prevention and treatment of stress-related mental illness. Dominant and subordinate animals have been shown to exhibit different behavioral and physiological responses to stress, with dominants often showing stress resistance and subordinates often showing stress vulnerability. We have previously found that dominant hamsters exhibit reduced social avoidance following social defeat stress compared to subordinate hamsters, although the extent to which stress resistance in dominants generalizes to non-social stressors is unknown. In this study, dominant, subordinate, and control male Syrian hamsters …

Mechanisms Underlying Executive Function Deficits, Sagar Jayawantrao Desai

Electronic Thesis and Dissertation Repository

In our daily life, we come across situations where we meet unanticipated challenges, we must take certain decisions, pay attention, be flexible and inhibit impulsive actions to achieve goal directed behaviour. During these processes, we unknowingly use sets of interdependent cognitive processes collectively called ‘executive function’. Executive function is mainly regulated by the frontal lobe. Impaired executive function is associated with disorders such as schizophrenia, Alzheimer’s disease, autism and attention deficit hyperactivity disorder (ADHD).

In this thesis, we investigated neurotransmitters and interactions among them regulating executive function. Further, we investigated mechanisms underlying those interactions mediating executive function in rats using …

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 …

Macro- And Mesoscale Analysis Of Connections Between The Cingulate Region And The Lateral Hypothalamic Area: Tracer Co-Injection And Chemoarchitectural Studies In The Adult Male Rat, Kenichiro Negishi

Open Access Theses & Dissertations

Hypothalamic research since the middle of the 20th century shaped the view that the lateral hypothalamic area (LHA) has a central role in controlling appetitive drives. The LHA is anatomically positioned to receive converging axonal inputs which relay information about the body's metabolic state as well as descending projections from the cerebral hemispheres, which encode cognitive and emotional states that influence feeding. Cerebral inputs are capable of initiating feeding despite the presence of competing satiety signals. Recent work has shown that medial prefrontal cortical areas can drive feeding in sated animals, possibly by engaging hypothalamic hypocretin/orexin (H/O)-expressing neurons, which are …

Exercise In Developing Rats Promotes Plasticity In The Prefrontal Cortex: Behavioral And Neurobiological Indications, Meghan Eddy

Graduate College Dissertations and Theses

Physical exercise has repeatedly been shown to trigger positive effects on brain function including improved learning, memory, and executive functions. In addition, corresponding physiological changes have been observed, such as increased neurotrophic factors, changes in neurotransmitter concentrations, and increased dendritic spines. However, these changes have not been well described outside of the hippocampus, including the medial prefrontal cortex (mPFC), and have not been directly compared at different points of development. Because the prefrontal cortex is one of the last brain areas to fully mature, considering the age at which intervention, such as exercise, takes place is particularly important. Additionally, in …

Evaluating Competition Between Verbal And Implicit Systems With Functional Near-Infrared Spectroscopy, Troy A. Schiebel

Honors Undergraduate Theses

In category learning, explicit processes function through the prefrontal cortex (PFC) and implicit processes function through the basal ganglia. Research suggested that these two systems compete with each other. The goal of this study was to shed light on this theory. 15 undergraduate subjects took part in an event-related experiment that required them to categorize computer-generated line-stimuli, which varied in length and/or angle depending on condition. Subjects participated in an explicit "rule-based" (RB) condition and an implicit "information-integration" (II) condition while connected to a functional near-infrared spectroscopy (fNIRS) apparatus, which measured the hemodynamic response (HR) in their PFC. Each condition …

Neural Responses To Maternal Praise And Criticism: Relationship To Depression And Anxiety Symptoms In High-Risk Adolescent Girls, Robin L. Aupperle, Amanda S. Morris, Jennifer S. Silk, Michael M. Criss, Matt R. Judah, Sally G. Eagleton, Namik Kirlic, Jennifer Byrd-Craven, Raquel Phillips, Ruben P. Alvarez

Psychology Faculty Publications

Background: The parent-child relationship may be an important factor in the development of adolescent depressive and anxious symptoms. In adults, depressive symptoms relate to increased amygdala and attenuated prefrontal activation to maternal criticism. The current pilot study examined how depressive and anxiety symptoms in a high-risk adolescent population relate to neural responses to maternal feedback. Given previous research relating oxytocin to maternal behavior, we conducted exploratory analyses using oxytocin receptor (OXTR) genotype.

Methods: Eighteen females (ages 12-16) listened to maternal praise, neutral, and critical statements during functional magnetic resonance imaging. Participants completed the Mood and Feelings Questionnaire and the Screen …

Muscarinic Attenuation Of Mnemonic Rule Representation In Macaque Dorsolateral Prefrontal Cortex During A Pro- And Anti-Saccade Task, Alex J. Major

Electronic Thesis and Dissertation Repository

Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules, and is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Muscarinic receptors’ effect on local primate DLPFC neural activity in vivo during cognitive tasks remains poorly understood. Here we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-unit recordings while monkeys performed a rule-guided …

Behavioral And Cognitive Changes After Early Postnatal Lesions Of The Rat Mediodorsal Thalamus, Zakaria Ouhaz, Saadua B-M'Hamed, Anna S. Mitchell, Abdeslem Elidrissi, Mohamed Bennis

Publications and Research

Early insults to the thalamus result in functional and/or structural abnormalities in the cerebral cortex. However, differences in behavioral and cognitive changes after early insult are not well characterized. The present study assessed whether early postnatal damage to mediodorsal nucleus of the thalamus (MD), reciprocally interconnected with the prefrontal cortex, causes behavioral and cognitive alterations in young adult rats. Rat pups at postnatal day 4 received bilateral electrolytic lesion of MD, or aMD Sham lesion or were anesthetized controls; on recovery they were returned to their mothers until weaning. Seven weeks later, all rats were tested with the following behavioral …

The Cognition-Enhancing Effects Of Psychostimulants Involve Direct Action In The Prefrontal Cortex, Robert C. Spencer, David M. Devilbiss, Craig Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. …

Disruption Of Columnar And Laminar Cognitive Processing In Primate Prefrontal Cortex Following Cocaine Exposure, Ioan Opris, Greg A. Gerhardt, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell …

Multimodal Frontostriatal Connectivity Underlies Individual Differences In Self-Esteem, Robert S. Chavez, Todd F. Heatherton

Dartmouth Scholarship

A heightened sense of self-esteem is associated with a reduced risk for several types of affective and psychiatric disorders, including depression, anxiety and eating disorders. However, little is known about how brain systems integrate self-referential processing and positive evaluation to give rise to these feelings. To address this, we combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to test how frontostriatal connectivity reflects long-term trait and short-term state aspects of self-esteem. Using DTI, we found individual variability in white matter structural integrity between the medial prefrontal cortex and the ventral striatum was related to trait measures of …

An Epigenetic Hypothesis For The Genomic Memory Of Pain, Sebastian Alvarado, Maral Tajerian, Matthew Suderman, Ziv Machnes, Stephanie Pierfelice, Magali Millecamps, Laura S. Stone, Moshe Szyf

Publications and Research

Chronic pain is accompanied with long-term sensory, affective and cognitive disturbances. What are the mechanisms that mediate the long-term consequences of painful experiences and embed them in the genome? We hypothesize that alterations in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA,serve as a “genomic” memory of pain in the adult cortex. DNA methylation is an epigenetic mechanism for long-term regulation of gene expression. Neuronal plasticity at the neuroanatomical, functional, morphological, physiological and molecular levels has been demonstrated throughout the neuroaxis in response to persistent pain, including in the adult prefrontal cortex (PFC). We have previously reported …

Focal Cortical Thickness Correlates Of Exceptional Memory Training In Vedic Priests, Giridhar P. Kalamangalam, Timothy M. Ellmore

Publications and Research

The capacity for semantic memory—the ability to acquire and store knowledge of the world—is highly developed in the human brain. In particular, semantic memory assimilated through an auditory route may be a uniquely human capacity. One method of obtaining neurobiological insight into memory mechanisms is through the study of experts. In this work, we study a group of Hindu Vedic priests, whose religious training requires the memorization of vast tracts of scriptural texts through an oral tradition, recalled spontaneously during a lifetime of subsequent spiritual practice. We demonstrate focal increases of cortical thickness in regions of the left prefrontal lobe …

Activity-Dependent Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Prefrontal Cortex, Emily K. Stephens, Daniel Avesar, Allan T. Gulledge

Dartmouth Scholarship

Layer 5 pyramidal neurons (L5PNs) in the mouse prefrontal cortex respond to serotonin (5-HT) according to their long-distance axonal projections; 5-HT_1A (1A) receptors mediate inhibitory responses in corticopontine (CPn) L5PNs, while 5-HT_2A (2A) receptors can enhance action potential (AP) output in callosal/commissural (COM) L5PNs, either directly (in “COM-excited” neurons), or following brief 1A-mediated inhibition (in “COM-biphasic” neurons). Here we compare the impact of 5-HT on the excitability of CPn and COM L5PNs experiencing variable excitatory drive produced by current injection (DC current or simulated synaptic current) or with exogenous glutamate. 5-HT delivered at resting membrane potentials, or paired …