Life Sciences Commons^™

Characterizing The Spatial Distribution Of Inhibitory Interneurons Across Early Sensory And Association Areas In Callithrix Jacchus, Nika Khajehdehi

Electronic Thesis and Dissertation Repository

The prefrontal cortex (PFC) is one of the cortical areas responsible for complex cognitive abilities, a function that is believed to arise from increased persistent activity within its microcircuits. Activity within microcircuits is regulated by parvalbumin-containing (PV), calbindin-containing (CB), and calretinin-containing (CR) inhibitory interneurons (INs). It remains unclear how the distribution of activity-regulating INs differs across cortical areas such that persistent activity increases specifically within association areas, allowing for their complex functions. This thesis aims to address this gap by characterizing the spatial distributions and differences in relative proportions of INs across early sensory areas and association areas of the …

Investigating Task-Free Functional Connectivity Patterns In Newborns Using Functional Near-Infrared Spectroscopy, Homa Vahidi

Electronic Thesis and Dissertation Repository

Robust functional connectivity in sensorimotor resting-state network (RSN) has been linked to positive neurodevelopmental outcomes in neonates. In the current study, we aimed to map the developmental trajectory of sensorimotor RSN in awake neonates using functional near-infrared spectroscopy (fNIRS). We acquired fNIRS resting-state data from 41 healthy newborns (17 females, gestational age range=36+0 to 42+1 weeks) within the first 48 hours after birth. At the group level, we observed robust positive connectivity in numerous channel-pairs across the sensorimotor network, especially in the left hemisphere. Next, we examined the relationship between functional connectivity, gestational age and postnatal age, while controlling for …

Neural Responses To Magnetic Orientation Information In Songbirds, Madeleine Ir Brodbeck

Electronic Thesis and Dissertation Repository

Effective navigation and orientation is essential for animals to survive. The study of migratory birds provides insights into these processes, particularly through mechanisms like the geomagnetic compass, which uses Earth's magnetic field for directional information. A brain region in songbirds relevant to this is cluster N, known for its potential role in processing geomagnetic information. Notably, cluster N appears exclusive to nocturnally migratory birds, being active solely at night, and lesion studies reveal that an intact cluster N is necessary for geomagnetic compass orientation. However, given the scarcity of empirical data concerning cluster N, substantial questions persist regarding its function. …

Invariant Object Recognition In Deep Neural Networks And Humans, Haider Al-Tahan

Electronic Thesis and Dissertation Repository

Invariant object recognition, a cornerstone of human vision, enables recognizing objects despite variations in rotations, positions, and scales. To emulate human-like generalization across object transformations, computational models must perform well in this aspect. Deep neural networks (DNNs) are popular models for human ventral visual stream processing, though their alignment with human performance remains inconsistent. We examine object recognition across transformations in human adults and pretrained feedforward DNNs. DNNs are grouped in model families by architecture, visual diet, and learning goal. We focus on object rotation in depth, and observe that object recognition performance is better preserved in humans than in …

Cortical Activation During Mobility In An Indoor Real-World Environment: A Mobile Eeg Study, Sam Marshall

Electronic Thesis and Dissertation Repository

Human mobility requires neurocognitive inputs to safely navigate the environment. Previous research has examined neural processes that underly walking using mobile neuroimaging technologies, yet few studies have incorporated true real-world methods without a specific task imposed on participants (e.g., dual-task, motor demands). The present study utilized mobile electroencephalography to examine and compare theta, alpha, and beta frequency band power (μV2) in young adults during sitting and walking in laboratory and real-world environments. Our findings support that mobility and environment may modulate neural activity, as we observed increased brain activation for walking compared to sitting, and for real-world walking compared to …

Selective Recruitment Of Cerebellum In Cognition, Ladan Shahshahani

Electronic Thesis and Dissertation Repository

Previous studies of cerebellar function in humans have shown that it is activated by a myriad of tasks ranging from motor learning and language to working memory and more. These studies have prompted a deviation from the traditional view of the cerebellum as a purely motor structure. However, the precise contribution of the cerebellum to these tasks remains ambiguous.

A prevalent assumption in fMRI studies is interpreting BOLD activation as evidence of the cerebellum's involvement in specific tasks. However, this interpretation is potentially misleading, especially considering that the BOLD signal predominantly represents cerebellar input, with output activity largely absent. Consequently, …

Modelling Prenatal Hypoxia As A Risk Factor For Schizophrenia Vulnerability In Patient-Derived Cerebral Organoids, Dana M. Gummerson

Electronic Thesis and Dissertation Repository

Prenatal hypoxia during fetal development is a significant environmental risk factor linked to schizophrenia (SCZ) vulnerability. However, hypoxia’s impact on human brain development at the cellular level remains unclear. Our laboratory has developed human cerebral organoids using induced pluripotent stem cells (iPSCs) derived from healthy control or SCZ patient cell lines to address these questions. This creates a platform that allows for the investigation into the pathophysiology of SCZ and hypoxia in tandem. Organoids were exposed to hypoxic conditions at one month of development, mimicking the early stages of cortical growth in the human fetus. Results reveal innate differences in …

Visual Cortical Traveling Waves: From Spontaneous Spiking Populations To Stimulus-Evoked Models Of Short-Term Prediction, Gabriel B. Benigno

Electronic Thesis and Dissertation Repository

Thanks to recent advances in neurotechnology, waves of activity sweeping across entire cortical regions are now routinely observed. Moreover, these waves have been found to impact neural responses as well as perception, and the responses themselves are found to be structured as traveling waves. How exactly do these waves arise? Do they confer any computational advantages? These traveling waves represent an opportunity for an expanded theory of neural computation, in which their dynamic local network activity may complement the moment-to-moment variability of our sensory experience.

This thesis aims to help uncover the origin and role of traveling waves in the …

Neural Dynamics Of Visual Processes In Challenging Visibility Conditions, Saba Charmi Motlagh

Electronic Thesis and Dissertation Repository

In our daily visual experience, our brain effortlessly categorizes countless objects, enabling us to perceive and interpret the world around us. This core object recognition process is vital for our survival and adaptive behavior, allowing us to recognize objects despite variations in appearance. The incredible speed at which we accomplish this task is a testament to the efficiency of our visual system and the significance of visual processing is evident in the allocation of nearly half of the neocortex in primates to this function. Unraveling the intricacies of how the human visual system tackles this complex challenge has long been …

White Matter Connectome Associations With Reading Functions In Children, Chenglin Lou

Electronic Thesis and Dissertation Repository

This thesis investigated associations between the white matter connectome and reading in children with a wide range of reading abilities. It is well established that the connectome supports the interplay among brain regions and connections within an integrated system. In this dissertation, I examine the hypothesis that it could therefore represent multiple mapping processes among reading components and further explain variations in reading performance. Such associations between the organization of the connectome and reading skills have not been well explored. This thesis aimed to address this issue by considering both the relationship between connectome measures and standardized reading performance out …

Examining The Emergence Of Mood And Anxiety Molecular Phenotypes Resulting From Chronic Prenatal Nicotine Exposure In Cerebral Organoids, Emma K. Proud

Electronic Thesis and Dissertation Repository

Prenatal nicotine exposure (PNE) from maternal smoking disrupts regulatory processes vital to fetal development. These changes result in long-term behavioural impairments, including mood and anxiety disorders, that manifest later in life. However the relationship underlying PNE, and the underpinnings of mood/anxiety molecular phenotypes remains elusive. To model nicotine exposure during prenatal development, our study used human cerebral organoids that were chronically exposed to nicotine and collected for molecular analyses. Short-term, nicotine altered molecular markers of neural identity, mood/anxiety disorders and those involved in maintaining the excitatory/inhibitory (E/I) balance in the cortex. RNA sequencing further revealed transcriptomic changes in genes pertaining …

Neural Dynamics Of Target Processing In Attentional Blink, Mansoure Jahanian

Electronic Thesis and Dissertation Repository

The attentional blink (AB) phenomenon refers to the failure to report the second target (T2) if it appears 200-500 ms after the first target (T1) in a stream of rapidly presented images. The present study aimed to investigate the neural representations of target processing under conditions where AB does or does not occur. We recorded EEG and behavioral data while participants viewed a rapid sequence of natural object images embedded with two face targets presented at two lag conditions: lag 3 (targets were 252 ms apart) and lag 7 (targets were 588 ms apart). Consistent with AB, our behavioral results …

The Role Of Serotonin In The Estradiol-Dependent Selectivity Of Auditory Regions In Songbirds, Calista J. Henry

Electronic Thesis and Dissertation Repository

Breeding-typical levels of estradiol in songbirds has been shown to lead to selective auditory processing and induce a release of serotonin in auditory regions of the forebrain. These findings triggered the question of whether auditory discrimination is driven by estradiol directly, or by the associated release of serotonin. I treated non-breeding female white-throated sparrows (Zonotrichia albicollis) with either blank implants, 17β-estradiol, serotonin enhancer and blank implants, or serotonin antagonist and 17β-estradiol implants. Birds then heard male conspecific songs or control tones, and ZENK-immunoreactivity was quantified in the caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM). While I did not …

Fraction Magnitude Understanding Across Learning Formats: An Fmri Study, Chloe A. Henry

Electronic Thesis and Dissertation Repository

Knowledge of fraction magnitudes are an important, but notoriously difficult mathematical concept to master. Behavioural work has begun to explore and compare the instructional tools used for fraction learning. However, how fraction instructional tools are processed in the brain remains an underexplored question. Therefore, in the present thesis, we used functional brain MRI methodology to examine the neural activity of adult participants while completing a fraction verification task using the number line and area model, two common methods of fraction learning. We found that both models commonly recruited fronto-parietal activity, the neural regions typically implicated in number processing. However, we …

Investigating The Roles Of The Dorsal And Ventral Striatum In Humor Comprehension And Appreciation Throughout Health, Aging, And Parkinson’S Disease, Maggie Prenger

Electronic Thesis and Dissertation Repository

Humor processing is thought to involve two distinct components. The first, humor comprehension, involves detecting and resolving incongruities that are present within a humorous stimulus. This is related to cognitive processes such as ambiguity resolution, response inhibition, working memory, and cognitive flexibility, functions that are mediated in part by the dorsal portion of the striatum (DS). Humor appreciation, on the other hand, refers to the subjective amusement and mirth that one experiences in response to a joke. This is related to reward processing, which implicates the ventral portion of the striatum (VS). Across three separate studies, we investigated the involvement …

Temporal Dynamics Of Natural Sound Categorization, Ali Tafakkor

Electronic Thesis and Dissertation Repository

While extensive research has elucidated the brain’s processing of semantics from speech sound waves and their mapping onto the auditory cortex, the temporal dynamics of how meaningful non-speech sounds are processed remain less examined. Understanding these dynamics is key to resolving the debate between cascaded and parallel hierarchical processing models, both plausible given the anatomical evidence. This study investigates how semantic category information from environmental sounds is processed in the temporal domain, using electroencephalography (EEG) collected from 25 participants and representational similarity analysis (RSA) along with models of acoustic and semantic information. We examined information extracted by the brain from …

Machine Learning Techniques For Improved Functional Brain Parcellation, Da Zhi

Electronic Thesis and Dissertation Repository

Brain parcellation studies are fundamental for neuroscience as they serve as a bridge between anatomy and function, helping researchers interpret how functions are distributed across different brain regions. However, two substantial challenges exist in current imaging-based brain parcellation studies: large variations in the functional organization across individuals and the intrinsic spatial dependence which causes nearby brain locations to have a similar function. This thesis presents a series of projects aimed to tackle these challenges from different perspectives by using advanced machine learning techniques.

To handle the challenge of individual variability in building precise individual parcellations, Chapter 3 introduces a novel …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

The Modulation Of Lfp Characteristics In The Freely Moving Common Marmoset, William Jm Assis

Electronic Thesis and Dissertation Repository

The hippocampus is a neural structure critical for navigation. Neurons in this region, along with others, create a functional network which generates large-amplitude modulations known as local field potential (LFP) activity. Prior LFP research has predominantly used rodent animal models, however recent studies have shown that frequencies associated with navigation in other mammals do not correlate to those of the rodent. We hypothesized that LFP characteristics in the common marmoset are modulated by the speed and axis of travel of the animal. Two marmosets were placed in a free moving 3-dimensional environment where movement and neurological activity were recorded. Results …

Disentangling The Role Of Parvalbumin-Expressing Interneurons In Stimulus-Response Learning And Cognitive Flexibility, Harleen Rai

Electronic Thesis and Dissertation Repository

Habits enable animals to efficiently navigate their surroundings while tending to more cognitively demanding environmental factors. One mechanism underlying habit is known as stimulus-response (S-R) learning, which takes place in the dorsolateral striatum (DLS). However, there is limited knowledge regarding the complex striatal microcircuits involved in S-R learning and cognitive flexibility. Recently, attention has turned toward the GABAergic Parvalbumin-expressing (PV) interneurons that can modulate striatal outputs. Here, we utilized chemogenetic techniques and touchscreen cognitive assessments to analyze the influence of PV neurons on S-R learning in mice. When PV neurons were inhibited, during the acquisition of a S-R and cognitive …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Category Learning Dlpfc Single-Dissociation By Fnirs, Tim Qiu

Electronic Thesis and Dissertation Repository

It remains an open question whether modern neuroimaging clearly dissociates the Explicit system that learns by encoding rules, and the Implicit system that learns by encoding information-integration boundaries. Further, there are nearly no applications of fNIRS as a modality in studying category learning. We conduct two behavioural experiments to validate a carefully controlled categorization task intended to dissociate Explicit and Implicit systems. Then we apply fNIRS neuroimaging within-subjects to localize a neuroanatomical dissociation. We localized two effects to R DLPFC (1) a simple single-dissociation of higher activity in RB categorization, and (2) a negative relationship between overall task performance and …

Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost

Electronic Thesis and Dissertation Repository

Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …

Exploring Brain-Derived Progenitor Cells As A Therapeutic Delivery System To Glioblastoma, Andrew T. Olin

Electronic Thesis and Dissertation Repository

Glioblastoma (GBM) is a devastating incurable malignant brain cancer in need of new treatments. We have begun to investigate the feasibility of a primary adult cell type (Brain-Derived Progenitor Cells, BDPCs) as a novel therapeutic delivery system to GBM. Our objective was to track the viability of BDPCs after intratumoral infusion into syngeneic orthotopic rat GBM tumours using non-invasive bioluminescence imaging (BLI). We hypothesize rat BDPCs will survive greater than 1 week following infusion into orthotopic F98 GBM tumors. BDPCs harvested from the cortex of adult Fischer rats were expanded in culture then engineered to co-express firefly Luciferase for BLI …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Postexercise Executive Function And Cortical Hemodynamics During The Different Phases Of The Menstrual Cycle, Priyanka Persaud

Electronic Thesis and Dissertation Repository

Resting cerebral blood flow (CBF) is increased during the luteal (LUT) phase of the menstrual cycle; however, it is unclear whether this change impacts a postexercise executive function (EF) benefit. Female participants (N=16) performed three experimental sessions: a V̇O_2peak task and 20-min single bouts of moderate intensity aerobic exercise (i.e., 80% of lactate threshold) during their follicular (FOL) and luteal (LUT) menstrual cycle phases. A separate group of male participants (N=21) additionally completed a V̇O_2peak test and a 20-min exercise intervention. Middle cerebral artery velocity (MCAv) was measured during exercise via transcranial Doppler ultrasound to estimate CBF and …

Effects Of 11-Kt And Prolactin On Gene Expression, Parental Care Behaviour And Immune Response In Male Bluegill Sunfish., Adriano A P Da Cunha

Electronic Thesis and Dissertation Repository

Parental care is very critical for reproduction in species that provide it. Hormones such as prolactin and androgens play a crucial role in parenting and reproductive behaviours. In mammals and birds, prolactin’s role in parental care is well-established; it stimulates milk production and stimulates attachment to newborns by its release in the preoptic area of the hypothalamus (POA), among other functions. Androgens, on the other hand, are commonly associated with male secondary sex characteristics, territoriality, and aggressiveness in mammals and birds. There are similar reports of prolactin and androgen effects in fish, but there are fewer studies. I investigated if …

Elucidating The Neural Circuitry Underlying Social Spacing In Drosophila Melanogaster Through The Lens Of Neuroligin 3, Abigail T. Bechard

Electronic Thesis and Dissertation Repository

Social interactions among animals can be complex, and abnormal social behaviours may result in negative fitness consequences for both the individual displaying them, and the entire group. To understand the neural basis of complex social behaviour, we can study simpler behaviours that precede and mediate them. Social spacing, the typical distance between individuals in a group, is an easily quantifiable behaviour in Drosophila melanogaster. Here, I investigated the neural circuitry underlying social spacing through the lens of Autism-candidate gene neuroligin 3. Based on the Nlg3 enrichment pattern in adult fly brains, I hypothesized that nlg3-expressing neurons, along …

Maturation Of Default Mode Network Functional Connectivity Strength In Utero And The Association With Subcortical Macrostructure: Mapping Brain Ontogeny Supporting Early Cognitive Processing, Susana Correa

Electronic Thesis and Dissertation Repository

The third trimester of gestation is scarcely studied despite this being a key window for the development of learning and memory systems. In a prospective cohort study, 30 pregnant women participated in one or two fetal MR imaging sessions between 28- and 39 weeks of gestational age. Activation time courses were extracted from the default mode (DMN), medial temporal lobe (MTL), and thalamocortical (TCN) networks of the fetal brain. Generalized estimating equations were used to examine the association between the DMN-MTL, DMN-TCV connectivity strength, and subcortical volumes. Increased functional connectivity strength between the DMN-MTL networks was negatively associated with smaller …

The Sensory Properties Of The Fast Visuomotor System, Rebecca Kozak

Electronic Thesis and Dissertation Repository

The brain has a remarkable capacity to rapidly transform vision into action, which allows us to initiate reaches towards targets within fractions of a second. Despite being fundamental to our interaction with a dynamic environment, these fast visuomotor transformations and their underlying neural substrates are poorly understood. This gap in the literature is further exacerbated by the unreliable presence of rapid visuomotor responses on the upper limb, likely due to the use of less optimal stimuli and paradigms. My thesis explores the stimulus properties which best evoke short latency reaction times and electromyographic responses during visually guided reaching, their application …