Neuroscience and Neurobiology Commons^™

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 …

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 …

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 …

Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice

Electronic Thesis and Dissertation Repository

The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …

Using Machine Learning To Identify Neural Mechanisms Underlying The Development Of Cognition In Children And Adolescents With Adhd, Brian Pho

Electronic Thesis and Dissertation Repository

Childhood and adolescence are marked by improvements to cognition and by the emergence of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). What neural mechanisms are associated with cognitive development in ADHD? In this study, I applied machine learning models to functional connectivity profiles to identify patterns of network connectivity that predict various cognitive abilities in a group of participants ages 6 to 16 with ADHD. The models successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not adolescents. Furthermore, the models identified connections with the default mode, memory retrieval, and …

The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong

Undergraduate Student Research Internships Conference

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), …

Examining The Relationships Between Socio-Cognitive Factors And Neural Synchrony During Movie Watching Across Development, Kathleen M. Lyons

Electronic Thesis and Dissertation Repository

While different cognitive abilities mature, the conscious experiences of children likely become richer and more elaborate. A challenge in investigating relationships between cognitive development and real-world experiences is having measures that assess naturalistic processing. Movie watching offers a solution, since following the plot of a film requires cognitive processes that are similar to real-world experiences. When different adults watch the same film, their brain activity begins to align (known as neural synchrony). The strength of this alignment has been shown to reflect the degree to which different individuals are having a similar experience of the movie. While this phenomenon has …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Modeling Fetal Brain Development: A Semi-Automated Platform For Localization, Reconstruction, And Segmentation Of The Fetal Brain On Mri, Jianan Wang

Electronic Thesis and Dissertation Repository

With advances in fetal magnetic resonance imaging (MRI), research in neonatal neuroscience has shifted to identify in utero brain-based biomarkers for outcome prediction in high-risk fetuses, particularly those impacted by growth restriction. Volumetric segmentation of the fetal brain can provide better understanding of the trajectories of brain development and may aid in predicting functional outcomes. The current thesis aimed to develop semi-automatic methods to target deep brain structures in the fetal brain identified on MR images in fetuses with and without growth restriction. In this study, pregnant women (35-39 weeks gestational age [n=9]) with growth appropriate (n=8) and growth restricted …

Intergenerational Transmission Of Functional Connectivity Profiles In Isolated Reading And Math Networks: A Scoping Review And Study Proposal, Ashini Peiris, Ira Gupta, Lien Peters, Eric D. Wilkey

Undergraduate Student Research Internships Conference

The scoping review surveyed the existing literature on the topic of resting-state functional connectivity (rsFC) and mathematical cognition. The review revealed that rsFC is indicative of distinct long-term developmental trends in mathematical processing, alluding to individual differences in math abilities. Though there have been multiple studies that investigate individual differences in functional connectivity patterns related to math development and math learning disorders, no study has directly investigated to what degree these neurobiological factors are heritable. To address this topic, the following intergenerational transmission (IT) study is proposed. IT is the transfer of personal values, abilities, behaviours, and traits, from parents …

Task-Based And Resting-State Functional Connectivity In Children With Dyscalculia, Ira Gupta

Undergraduate Student Research Internships Conference

Resting-state functional connectivity (RSFC) is a unique method in neuroimaging that measures the spontaneous neural activity as the brain is at rest, not actively undergoing any task. It is important in investigating brain patterns that result from brain regions working together throughout an individual’s development. The application of this technique has been limited in the mathematical cognition field, and thus, should be explored further. This preregistration poster focuses on the depth of the literature and studies available in regards to RSFC and math cognition through a scoping review, and then proposes a study in which task-based and resting-state functional connectivity …

Investigating The Effects Of Maternal Immune Activation On Sensory Processing: Timing, Immune Mechanisms, And Gene-Environment Interactions, Faraj Haddad

Electronic Thesis and Dissertation Repository

Maternal infection during the first or second trimester of pregnancy poses a risk factor for the child to have neurodevelopmental disorders like autism spectrum disorder (ASD) and schizophrenia. Various clinical and preclinical studies have shown that the maternal immune response to infection, also known as maternal immune activation (MIA), can disrupt fetal brain development.

Over the past two decades, MIA has been studied in rodents using the Polyinosinic Polycytidylic acid (Poly I:C) rodent model. Poly I:C has a molecular pattern resembling viruses that can induce a robust immune response. Following exposure to Poly I:C MIA, rodent offspring exhibit many brain …

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 …

The Role Of Histone Demethylases In Learning And Memory In The Mushroom Body Of Drosophila Melanogaster, Crystal Keung

Electronic Thesis and Dissertation Repository

Intellectual disability (ID) is a neurodevelopmental disorder associated with many epigenetic regulators and chromatin modifying enzymes like histone lysine methyltransferases (KMTs) and demethylases (KDMs). Here, I systematically investigate the role of 7 KDMs: Su(var)3-3, KDM2, Lid, CG2982, UTX, KDM4B, JHDM2, and 1 KMT: trr in the context of learning and memory using Drosophila melanogaster. Genetic knockdown of each gene in the mushroom body (MB) of flies are tested for short- and long-term memory impairment using courtship conditioning. Knockdown of 6 KDMs and trr resulted in memory loss. MB morphology was analyzed to determine potential cause of memory loss. …

Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland

Electronic Thesis and Dissertation Repository

ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in Atrx^Foxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …

Using An Internal Auditory Stimulus To Activate The Developing Primary Auditory Cortex: A Fetal Fmri Study, Estee Goldberg

Electronic Thesis and Dissertation Repository

Insight into the rapidly developing brain in utero is scarce. Fetal functional magnetic resonance imaging (fMRI) is a technique used to gain awareness into the developmental process. Previous auditory task-based fMRI studies employed an external sound stimulus directly on the maternal abdomen. However, there has since been recommendation to cease doing so. We sought to investigate a reliable paradigm to study the development of fetal brain networks and postulate that by using an internal stimulus, such as the mother singing, it would result in activation of the fetal primary auditory cortex. Volunteers carrying singleton fetuses with a gestational age of …

In Search Of Psychiatric Kinds: Natural Kinds And Natural Classification In Psychiatry, Nicholas Slothouber

Electronic Thesis and Dissertation Repository

In recent years both philosophers and scientists have asked whether or not our current kinds of mental disorder—e.g., schizophrenia, depression, bipolar disorder—are natural kinds; and, moreover, whether or not the search for natural kinds of mental disorder is a realistic desideratum for psychiatry. In this dissertation I clarify the sense in which a kind can be said to be “natural” or “real” and argue that, despite a few notable exceptions, kinds of mental disorder cannot be considered natural kinds. Furthermore, I contend that psychopathological phenomena do not cluster together into kinds in the way that paradigmatic natural kinds (e.g., chemical …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

The Origins And Development Of Visual Categorization, Laura Cabral

Electronic Thesis and Dissertation Repository

Forming categories is a core part of human cognition, allowing us to make quickly make inferences about our environment. This thesis investigated some of the major theoretical interpretations surrounding the neural basis of visual category development. In adults, there are category-selective regions (e.g. in ventral temporal cortex) and networks (which include regions outside traditional visual regions—e.g. the amygdala) that support visual categorization. While there has been extensive behavioural work investigating visual categorization in infants, the neural sequence of development remains poorly understood. Based on behavioral experiments, one view holds that infants are initially using subcortical structures to recognize faces. Indeed, …

Evaluating Devices For The Measurement Of Auditory-Evoked Fetal Movement, Patrick Gatutsi

Electronic Thesis and Dissertation Repository

Determining normal and abnormal fetal function in utero in order to better predict which fetuses are at risk for adverse outcome is critical. However, the medical imaging tools that could assist with diagnosis are very expensive and rarely available in the developing world. In this study, we developed a prototype audio-motio-tachograph (AMTG), which measures fetal movements through the recording of abdominal wall deformations and tested it in Rwanda. First, we showed that AMTG detected fetal signals and that fetuses respond to complex acoustic stimuli. In order to improve the sensitivity of the device, we then measured whole abdominal wall deformations …

Girls’ Internalizing Symptoms And White Matter Tracts In Cortico-Limbic Circuitry, Ola Mohamed Ali

Electronic Thesis and Dissertation Repository

Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders, but less is known about whether structural abnormalities precede disorder, thus potentially marking risk. I therefore examined associations between white matter tract integrity in cortico-limbic circuitry at age 7, obtained using Diffusion Tensor Imaging, and concurrent and longitudinal patterns of internalizing symptoms, over a 5-year period, in 42 typically developing girls. Using Automated Fiber Quantification, diffusion properties were examined at multiple points along tract length (cf., an average diffusion measure of the entire tract). Concurrent internalizing symptoms were associated with reduced fractional anisotropy in segments of the cingulum bundle and uncinate …

Immature Auditory Evoked Potentials In Children With Moderate-Severe Developmental Language Disorder., Elaine Yuen Ling Kwok, Marc F Joanisse, Lisa Archibald, Janis Oram Cardy

Health and Rehabilitation Sciences Publications

Purpose: Immature auditory processing has been proposed to underlie language impairments in children with developmental language disorder (DLD; also known as specific language impairment). Using newly available normative auditory evoked potential (AEP) waveforms, we estimated AEP maturity in individual children with DLD and explored whether this maturational index was related to their language abilities.

Method: AEPs were elicited by 225 trials of a 490-Hz pure tone. Using intraclass correlation and our previously established normative AEP waveforms of 7- to 10-year-old children with typical development, we estimated the age equivalent of the AEPs (AEP-age) from 21 children with DLD. The relation …

Chromatin Organizer Ctcf In Brain Development And Behaviour, Adrienne Elbert

Electronic Thesis and Dissertation Repository

Chromatin architecture is an important regulator of gene expression, which dictates development. Mutations in one copy of the CTCF chromatin organizer gene cause intellectual disability and autism. Polymorphisms in CTCF have also been associated with increased risk for schizophrenia, a condition that overlaps in biological etiology with autism and intellectual disability. In this thesis, we sought to understand the role of CTCF in neurodevelopment using brain-specific conditional knockout and heterozygote mouse models. Using the Ctcf-null animals, we identify a cell-autonomous role for CTCF in regulating cortical interneuron development in the medial ganglionic eminence (MGE) through the transcriptional control of …

Maturation In Auditory Event-Related Potentials Explains Variation In Language Ability In Children., Elaine Yuen Ling Kwok, Marc F Joanisse, Lisa Archibald, Margot E. Stothers, Heather M Brown, Janis Oram Cardy

Health and Rehabilitation Sciences Publications

Processing of auditory information in the cortex continues to develop into later childhood and adolescence. Recent research has indicated that intraclass correlation (ICC) is the best method for capturing maturation in auditory event-related potentials (AEPs) of school-age children. However, the sensitivity of the ICC approach in discerning AEP changes in children has not been consistently demonstrated and positive results have not been replicated. We attempted this replication and further explored whether AEP maturation estimated using the ICC approach predicts cognitive and linguistic abilities in addition to chronological age. We measured AEPs in response to simple tones in groups of 7-, …

Role Of The Swi/Snf Chromatin Remodelling Complex In The Axon Development Of The Drosophila Mushroom Body, Melissa C. Chubak

Electronic Thesis and Dissertation Repository

The SWI/SNF complex is an evolutionarily conserved ATP-dependent chromatin remodelling complex that has been implicated in the aetiology of intellectual disability (ID). Among the dominant ID genes, the SWI/SNF complex is the most highly enriched protein complex. However, its role in the nervous system is not yet understood. I systematically investigated the role of this complex in the development of the Drosophila mushroom body (MB), a complex brain structure required for learning and memory. Gross MB morphology was assessed using confocal microscopy to identify morphological defects following RNAi-mediated knockdown of the 15 individual SWI/SNF genes in the MB. Knockdown of …

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …

Early Life Immune And Physical Stress Directly Influences Anxiety-Like Behaviour In Adolescent Rats: Examining Sex Differences, Jordan M. Ward

Electronic Thesis and Dissertation Repository

This thesis examined the effects of neonatal acute immune activation with the endotoxin, lipopolysaccharide (LPS) on postnatal days 3 and 5 on adolescent anxiety-like behaviour in rats before and after a stress period. Previous research has shown that adults rats exposed to LPS during the neonatal stage show anxiety-like behaviour following a period of stress. This thesis investigated this effect in adolescence. The present results showed significantly higher anxiety-like behaviour in saline controls, and a potential neuroprotective effect of low dose LPS (15 µg/kg) contrary to what was reported in adult rats. As well, a phase of stressful, aversive conditioning …

Functional Connectivity In The Motor Network Largely Matures Before Motor Function, Jordynne L V Ropat

Electronic Thesis and Dissertation Repository

The brain changes in many ways in the first year. It is not known which of these changes are most critical for the development of cognitive functions. According to the Interactive Specialization Theory, developments in behaviour result from changes in brain connectivity. We tested this using functional connectivity magnetic resonance imaging (fcMRI) of the motor system. fcMRI was acquired at three and nine months – two time-points between which motor behaviour develops enormously. Infants were additionally compared with adults. Subjects were scanned with a 3T MRI scanner, yielding BOLD signal time-courses that were correlated with one another. Our results do …

P35. Investigating The Effect Of Maternal Immune Activation On Sensory Filtering, Social Behaviour And Attention, Faraj Haddad

Western Research Forum

Background

Altered brain development is associated with many neuropsychiatric disorders like Autism Spectrum Disorder (ASD) and schizophrenia. Environmental insults can interfere with neurodevelopment, and a prominent example is maternal infection during pregnancy. Epidemiological studies show that children born to mothers who were infected during pregnancy display a higher risk of developing ASD and schizophrenia, and this effect is mainly due to the maternal immune response. Polyinosinic-polycytidilic acid (Poly I:C) is a double stranded RNA molecule that mimics viral markers and elicits an immune response. When injected in pregnant rodents, this model produces offspring that exhibit core symptoms of ASD and …

Maternal Nutrient Restriction In Pregnant Guinea Pigs And The Impact On Fetal Growth And Brain Development, Andrew Ghaly

Electronic Thesis and Dissertation Repository

Maternal nutrient restriction (MNR) in guinea pigs results in placental structural abnormalities that reduce nutrient transport contributing to fetal growth restriction (FGR). However, whether brain weights are similarly reduced, or preserved by “brain sparing” mechanisms, and whether energy levels are depleted leading to membrane failure and overt injury remains unknown. Guinea pig sows were fed ad libitum (Controls) or 70% of the control diet pre-pregnant switching to 90% at mid-pregnancy (MNR). Animals were necropsied near term for fetal growth measures and fetal brains were assessed for markers of necrotic cell injury, apoptotic cell injury, endoplasmic reticulum stress, and altered development …