Life Sciences Commons^™

Exercise As A Treatment For Cognitive Decline In Older Adults: The Role Of Growth Factors And Inflammatory Cytokines, Joshua A. Titus

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to investigate the effects that exercise modalities have on neurotrophic and inflammatory blood markers and cognitive outcomes in older adults. A systematic review and meta-analysis were completed. The included studies illustrated that most of the literature evaluated the effect of aerobic exercise interventions on systemic concentrations of the blood marker brain-derived neurotrophic factor (BDNF). The review found that aerobic exercise increases BDNF and resistance training increases insulin-like growth factor 1 (IGF-1). Interventions with sex-specific cohorts presented advantages in males for blood marker and cognitive outcomes compared to females. One of three included interventions decreased …

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 …

Dopaminergic Modulation Of A Fast Visuomotor Pathway In Parkinson's Disease, Madeline C. Gilchrist

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is associated with reduced dopaminergic (DA) input to the dorsal striatum (DS). This study investigated the role of DA in modulating automatic, stimulus-driven reactions by assessing contextual control of stimulus-locked responses (SLRs) in 10 PD patients off and on DA medication. The SLR is the rapid recruitment of limb muscles that drives the arm towards suddenly appearing stimuli. Participants reached away from (anti-reach) or towards (pro-reach) a target on a screen, depending on instruction appearing 500 or 1000ms before target appearance. Modulation of SLRs was assessed by comparing SLR magnitude on anti- and pro-reach trials using surface …

Early Experience And The Functional Calibration Of The Stress-Response Systems, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Individuals exposed to adversities in childhood are at a greater risk of developing various diseases as adults, including cardiovascular disease and cancer (Felitti et al. 1998). These findings have sparked an interest in examining biological mechanisms that might explain the link between exposure to adversity and disease. To date, evidence has linked adversity to the function of the hypothalamic-pituitary-adrenal (HPA) axis. More recently, adversity has been associated with the function of the mesolimbic dopamine pathway as well.

This thesis uses a variety of techniques to explore the association between adversity and the function of the HPA axis and mesolimbic dopamine …

Neuroanatomical Characterization Of Fruitless P2 Neurons And Assessment Of Their Role In Female Mate Receptivity, William Yeung

Electronic Thesis and Dissertation Repository

In behaviourally isolated species, preferential mate choice for conspecifics over heterospecifics is a primary isolating barrier for reducing interspecific gene flow. Drosophila males court heterospecific females more frequently than females are sexually receptive to courting heterospecific males, emphasizing the importance of female mate preference in reproductive isolation. The neurogenetic bases of female mate preference have been elusive historically, but recent research identified the D. melanogaster fruitless (fru) P2 exon to influence both conspecific and heterospecific female receptivity. I have expanded on these findings by creating a transgenic line that expresses Gal4 under fru^P2 regulation. Driving a fluorescent …

A Behavioral Study On The Adult Marmoset Interference Control In Spatial Working Memory, Mohadese Khosravi Najafabadi

Electronic Thesis and Dissertation Repository

Interference control deficit in Working Memory (WM) is associated with neurodevelopmental disorders. The common marmoset (Callithrix jacchus) is an ideal non-human animal model for studying WM disorders. Previous studies of marmoset WM have used a touch-screen self-ordered sequencing task (SOST), which resembles an n-back paradigm and targets updating processes in internal interference control. However, the training time for the marmoset to reach proficiency on this paradigm is long given the short marmoset lifespan. In an attempt to accelerate marmoset learning of the task, we developed a new version of SOST that relied on foraging behaviour. The goal of …

Assessment Of Executive Function Using A Series Of Operant Conditioning Based Tasks In T1dm Rodents, Kevin T. Murphy

Electronic Thesis and Dissertation Repository

This study examined the impact of Type 1 Diabetes Mellitus (T1DM) on executive function using a series of operant conditioning based tasks in rats. Sprague Dawley rats were randomized to either non-diabetic (n = 12; 6 male) or diabetic (n = 14; 6 male) groups. Diabetes was induced using multiple low-dose streptozotocin injections. All diabetic rodents were insulin-treated using subcutaneous insulin pellet implants. At week 14 of the study, rats were placed on a food restricted diet to induce 5 - 10% weight loss. Rodents were familiarized and tested on a series of tasks that required continuous adjustments to novel …

Direct Electrical Stimulation Of Prefrontal Cortex Modulates The Transient Heart Rate Response To Exercise In Conscious Humans, Bartek Kulas

Electronic Thesis and Dissertation Repository

Prefrontal cortical regions play an essential role in generating appropriate cardiovascular adjustments, particularly in cardio-vagally mediated heart rate (HR) responses to active tasks. Functional imaging studies provide correlational evidence that this region coordinates HR responses to exercise, however, direct experimental evidence of prefrontal cortical HR regulation in humans is not available. Seven persons with epilepsy implanted with intracranial electroencephalography (iEEG) completed 2-second isometric handgrip (IHG) contractions at no-stimulation (NO-STIM) or sham-stimulation (SHAM) conditions, and during direct electrical stimulation (STIM) of the orbitofrontal and medial prefrontal cortex. HR responses to IHG during NO-STIM and SHAM increased HR by Δ4.9±2.7 bpm, compared …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Motor Unit Firing Rate Control Of Agonist Skeletal Muscle During Voluntary Isometric And Shortening Contractions With Limb Movement, Eric A. Kirk

Electronic Thesis and Dissertation Repository

Voluntary movements throughout mammalian lifespan require skeletal muscle contractions that are controlled by time- and recruitment-dependent firing rate patterns. Single motor unit (MU) activity reflects the final efferent neural drive to the muscle, yet the underlying neural control of movement at the MU level is not well understood. Using intramuscular electromyography single MU recordings, relationships between voluntary contraction kinematics and MU firing rates were evaluated in vivo, in groups of young and older adult participants.

The purpose of study one was to characterize how MU firing rates are differently scaled among muscles relative to voluntary contraction intensity. Across 12 …

The Expression Of Guilt, Chloe A. Stewart

Electronic Thesis and Dissertation Repository

Though aversive, the experience and expression of guilt is important to healthy social functioning. Guilt is often described as visceral, and nonverbal guilt expressions are anecdotally observed, yet much remains unknown about how guilt is expressed. The present work aimed to explore the visceral experience of guilt via the autonomic nervous system (ANS), and the nonverbal display of guilt via facial, gestural, and postural expressions. Using a novel film paradigm, we explored ANS activity during guilt in healthy adults and adults with neurodegenerative disorders (NDs). We further explored the nonverbal behaviours associated with guilt in healthy adults. We hypothesized that, …

Understanding Neural Signals Related To Speech Processing In Humans During Sleep, Ashwin Harimohan

Electronic Thesis and Dissertation Repository

Many cognitive processes are surprisingly preserved during sleep, including the processing of basic language stimuli. However, whether the sleeping brain can process complex, natural speech is not yet known. The present study used regularized linear regression to understand which features of narrative speech, ranging from low-level acoustic information to higher-level linguistic information, are processed during sleep. Participants were exposed to an intact and scrambled narrative story while they were napping or lying awake. Temporal response functions (TRFs) mapped the relationship between participants’ EEG neural responses and the (1) auditory envelope, (2) word onsets and (3) semantic dissimilarity of words. For …

Regional Lipid Expression Abnormalities Identified Using Maldi Ims Correspond To Mri-Defined White Matter Hyperintensities Within Post-Mortem Human Brain Tissue., William J. Pinsky

Electronic Thesis and Dissertation Repository

Periventricular white matter hyperintensities (pvWMHs) are a neurological feature detected with magnetic resonance imaging (MRI) and are clinically associated with an increased risk of stroke and dementia. pvWMHs are characterized by white matter lesions with myelin and axon rarefaction, and as such likely involve changes in lipid composition, however these alterations remain unknown. Lipids are critical in determining cell function and survival, although their detection within tissue, until recently has been challenging. Perturbations in lipid expression have previously been associated with neurological disorders. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an emerging technique for untargeted, high-throughput investigation of …

The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak

Electronic Thesis and Dissertation Repository

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [¹⁸F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [¹⁸F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show …

Microstructural Alterations In Grey And White Matter Following Early-Onset Deafness In The Cat, Alessandra Sacco

Electronic Thesis and Dissertation Repository

Following sensory deprivation such as deafness, compensatory plasticity underlies the reorganization of sensory-specific brain areas to process remaining intact modalities. Previous studies have explored microstructural consequences throughout the brain following auditory deprivation, including the effect of deafness on cerebral water diffusion. However, nearly all investigations have studied these neuronal changes in humans rather than animal models. The present study investigates microstructural differences between 19 hearing and 27 early-deaf cats via diffusion tensor imaging (DTI). Diffusivity scalars were compared within 155 grey and 21 white matter regions. Results indicate structural plasticity in various regions throughout the deaf brain in both tissues, …

A Generative-Discriminative Approach To Human Brain Mapping, Deepanshu Wadhwa

Electronic Thesis and Dissertation Repository

During everyday behaviours, the brain shows complex spatial patterns of activity. These activity maps are very replicable within an individual, but vary significantly across individuals, even though they are evoked by the same behaviour. It is unknown how differences in these spatial patterns relate to differences in behavior or function. More fundamentally, the structural, developmental, and genetic factors that determine the spatial organisation of these brain maps in each individual are unclear. Here we propose a new quantitative approach for uncovering the basic principles by which functional brain maps are organized. We propose to take an generative-discriminative approach to human …

Inter-Subject Correlation Using Movie-Driven Fmri In Drug-Resistant Epilepsy, Hana H. Abbas

Electronic Thesis and Dissertation Repository

Treating drug-resistant epilepsy with surgery requires the localization of the epileptic focus. We explored the potential for movie-driven functional magnetic resonance imaging (fMRI) to act as a sensitive, non-invasive, and cost-effective tool to identify functionally disturbed networks. We assessed neural synchronization (inter-subject correlation; ISC) between presurgical epilepsy patients (n = 18) and healthy controls (n = 24) as they watched a suspenseful movie clip in the scanner. To optimize denoising, we compared ISC values with and without an automated Independent Components Analysis-based denoising step (ICA-AROMA). We found that denoising with ICA-AROMA elicited augmented correlation values, supporting its use …

Potential Sex-Related Differences In Neurophysiology Post-Concussion, Alexandra N. Pauhl

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine potential sex-related differences in neurophysiology in concussed and healthy individuals. There was a total of 21(9 F) participants in each group. The concussion (CONC) group reported to the lab within 72 hours, 1- and 2-weeks post-injury. The control (CONT) group followed a similar measurement schedule once recruited. Motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration was measured in the first dorsal interosseous muscle using transcranial magnetic stimulation. There were no significant differences in MEP amplitude or CSP duration between the CONC and CONT group. As well, there was no …

Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern

Electronic Thesis and Dissertation Repository

The brain senses inflammatory signals and drives the release of glucocorticoids (GCs) — potent immunosuppressants — via the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This inflammation-induced HPA axis activation is largely mediated by prostaglandin E2 (PGE2), acting on two subtypes of the PGE2 receptor, EP1 and EP3. Recently, our group revealed EP3 signaling mechanisms that excite HPA axis regulatory neurons. This thesis sought to tease out the remaining EP1 signaling mechanisms. Considering that the excitability of HPA axis regulatory neurons is constrained by GABA_A receptor-mediated synaptic inhibition that relies on low-level intracellular Cl^-. We hypothesized that PGE2-EP1 …

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 …

Does Aberrant Connectivity Underlie The Experience Of Misophonia?, Kate Raymond

Electronic Thesis and Dissertation Repository

Misophonia is a condition characterized by an extreme aversion to certain ordinary sounds, such as chewing or breathing. These sounds are typically innocuous but elicit strong feelings of anger, anxiety, and disgust as well as physiological stress in people with misophonia. This misophonic reaction to “trigger” sounds is also marked by increased activity in regions of the brain that process sound, ascribe salience, and regulate emotion (Kumar et al., 2017; Schroder et al., 2019). It has therefore been theorized that aberrant connectivity between these brain regions (particularly the anterior insula, auditory cortex, amygdala, and hippocampus) may underlie the experience of …

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

Tracking The Mechanisms Of Short-Term Motor Adaptation Within The Framework Of A Two-State Model, Susan K. Coltman

Electronic Thesis and Dissertation Repository

The motor system is continuously monitoring our performance, ensuring that our actions are occurring as planned. Sensory prediction errors, which arise from a discrepancy between the expected and actual sensory consequence of a motor command (i.e., a planned action), are assumed to drive sensorimotor adaptation. Sensorimotor adaptation is thought to involve changes in motor output that allow the motor system to regain its former level of performance in perturbed circumstances. We employed experimental paradigms that involved both mechanical and visual perturbations to evoke sensory prediction errors while participants performed planar reaching movements. Movement error activates learning processes in the brain, …

Modifications In The Representation And Control Of Finger Movement Sequences With Learning, Nicola Popp

Electronic Thesis and Dissertation Repository

From typing to playing the piano, sequences of finger movements are essential in our everyday lives. To become skilled at any task, takes practice and determination. To remember and perform a sequence of movements, we form an abstract mental representation of it. To estimate our performance accuracy, we usually rely on sensory feedback from our environment. For instance, when playing piano, we pay close attention to the tone that is played. To improve performance, we adjust our mental representation by integrating this sensory feedback. The goal of this thesis was to elucidate how the mental representation and feedback control of …

Brain Representations Of Dexterous Hand Control: Investigating The Functional Organization Of Individuated Finger Movements And Somatosensory Integration, Spencer Arbuckle

Electronic Thesis and Dissertation Repository

Using our hands to manipulate objects in our daily life requires both dexterous movements and the integration of somatosensory information across fingers. Although the primary motor (M1) and somatosensory cortices (S1) are critical for these two complementary roles, it is unclear how neural populations in these regions functionally represent these processes. This thesis examined the functional organization of brain representations (the representational geometry) in M1 and S1 for dexterous hand control and somatosensory processing. To that end, representational geometries were estimated from fine-grained brain activity patterns measured with functional MRI (fMRI). Since fMRI measures a blood-based proxy of neural activity, …

Cholinergic Modulation Of Behaviour, Ornela Kljakic

Electronic Thesis and Dissertation Repository

The cholinergic system is one of the most influential and essential signalling systems in the body. In the brain, cholinergic neurons innervate many brain regions where they influence a wide variety of behaviours. However, the precise role of each cholinergic region on distinct types of behaviour is not well known. Furthermore, in recent years there has been evidence that many cholinergic neurons in the brain have a capacity for co-transmission. Yet the functional significance of secreting two classical neurotransmitters from the same neuron is still largely unidentified. In this thesis, we investigated how different cholinergic nuclei modulate behavioural functions. To …

Neural Substrates Of Reward, Error, And Effort Processing Underlying Adaptive Motor Behaviour, Dimitrios J. Palidis

Electronic Thesis and Dissertation Repository

Human motor control is highly adaptive to new tasks and changing environments. Motor adaptation relies on multiple dissociable processes that function to increase attainment of reward and to reduce sensory error and physical effort as costs. This thesis tests the hypothesis that fronto-striatal and dopaminergic neural systems contribute to specific aspects of motor adaptation that occur through reinforcement of rewarding actions.

Behavioral tasks were designed to isolate learning in response to feedback conveying information about reward, error, and physical effort. We also measured behavioral effects of savings and anterograde interference, by which memories from previous motor learning can facilitate or …

Brain Signatures Of Human Skill Learning: From Single Movements To Movement Sequences, Eva Berlot

Electronic Thesis and Dissertation Repository

Sequences of finger movements, such as making a cup of coffee or playing the piano, have a key role in our lives. An important neuroscientific question is how such movement sequences are represented in the brain. The central goal of this thesis was to investigate how different brain regions represent individual movements, and how these representations change when learning sequences of movements. To that end, we used 1) high-field functional magnetic resonance imaging (fMRI) to measure brain activation in humans while they produced finger movements on a keyboard-like device, and 2) advanced multivariate analyses to characterize the brain representations underlying …

Interplay Between Shift Work, Psychological Distress, Sleep Quality, And Cognitive Performance, Rea Therese Alonzo

Electronic Thesis and Dissertation Repository

Shift work schedules are designed to maintain a continuous operation of goods and services. However, engaging in shift work may impact cognitive functioning. This thesis assessed the relationship between shift work and cognitive performance. Using cross-sectional data from the Canadian Longitudinal Study on Aging, multiple linear regression models were used to investigate the association between shift work and cognitive performance, as well as the moderating effects of psychological distress and sleep quality. Differences by sex and retirement status were also investigated. Shift work was significantly associated with poor performance for executive functioning but not for declarative memory. Poorer cognitive performance …

Blocking Pirb Function Increases Dendritic Spine Density In The Prefrontal Cortex Of Adult Rats, Hannah J. Macneil

Electronic Thesis and Dissertation Repository

Schizophrenia is a psychotic disorder consisting of positive, negative, and cognitive symptoms. While patients currently have access to treatments for the positive and negative symptoms, no satisfactory treatment exists to alleviate the cognitive deficits, which cause severe impairments to the quality of life of patients and their families. Although the mechanisms underlying the cognitive deficits of schizophrenia are not clear, a decreased dendritic spine density on layer 3 pyramidal neurons in the dorsolateral prefrontal cortex has been strongly implicated. Generally, the adult brain is not permissive to the formation of new dendritic spines. Recently, an immune receptor called paired immunoglobulin-like …