Check out the abstracts from all our oral and poster presenters for NURC 2021 below:
Oral Presentations
Recognizing Suicidal Intent in Depressed Population using NLP: A Pilot Study
Sumaiya Binte Hassan
Abstract:
Depression is a prevalent form of mental disorder that can affect productivity in daily activities and might lead to suicidal thoughts or attempts. Conventional diagnostic techniques performed by mental health professionals can help identify the level of depression present in a person. To facilitate such a diagnostic approach, in this paper, we present an automated conversational platform that was used as a preliminary method of identifying depression associated risks. The platform was developed to understand conversations using Natural Language Processing (NLP) via machine learning technique. In the proposed two-phased platform, the initial intent recognition phase would analyze conversation and identify associated sentiments into four categories of ‘happy’, ‘neutral’, ‘depressive’ and ‘suicidal’ states. In the final emotion nurturing phase, the platform continued with supportive conversations for the first three states while triggering a local call to a suicide prevention helpline for ‘suicidal’ state as a preventive measure. This multi-layer platform integrated Google Home mini, Google Dialogflow Machine Learning (ML) algorithm and Twilio API. Dialogflow ML obtained classification accuracy of 76% in recognizing user's mental state via NLP and was found efficient over the classic SVM classifier. As a pilot study, current focus of this paper was solely based on the usage of words and intent of the user and was found effective.
​
​
Motherhood and APOEε4 genotype are associated with inefficient search strategies in middle age: Implications for ageing and Alzheimer’s Disease
Effects of Motherhood and APOEε4 genotype on Spatial Memory: Implications for ageing and Alzheimer’s Disease
Mel Cevizci
Abstract:
Females with Alzheimer’s disease (AD) show greater neuropathology and cognitive decline compared to males. These differences are further exacerbated with possession of APOEε4 alleles, the greatest genetic risk factor for sporadic AD. Pregnancy and motherhood (parity) are further associated with a greater AD risk, greater neuropathology, and an earlier age of AD onset. Previous parity also influences cognition and brain ageing in both middle-aged humans and rodents. Increased parity is associated with increased neuroinflammation and reduced neurogenesis in the hippocampus in the late postpartum in rodents – both of which are also observed in AD. This study investigated whether APOEε4 and parity interact to influence spatial working memory and AD neuropathology in middle-aged female rats.
Age-matched wildtype rats and rats with the humanized (h) form of APOEε4 were either nulliparous (no previous reproductive experience) or primiparous (one previous reproductive experience). At middle-age, rats were tested on the delayed win-shift version of the radial arm maze, in which performance depends on the integrity of the hippocampus and frontal cortex. . hAPOEε4 rats made more errors and more arm entries in the maze than wildtype rats. Primiparous rats made more omission errors than nulliparous rats. hAPOEε4 primiparous rats employed the most inefficient search strategy compared to other groups by entering adjacent arms to find food rewards. Analyses of hippocampal neuroinflammation and neurogenesis from collected brain tissues and plasma samples are ongoing. This research has implications for the importance of the influence of the reproductive history and genotype of females at risk for AD.
The Neuroregenerative Effects of Intraspinal Microstimulation Following Spinal Cord Injury
Stimulating damaged spinal cord to create movement and rehabilitation
Andy Lee
Abstract:
Intraspinal microstimulation (ISMS) is a novel electrical stimulation technique that has restored mobility in animals with SCI. ISMS may also enhance neural regeneration, but this remains unknown. This project investigated: (1) the capacity of ISMS to restore functional walking in rats following SCI, and; (2) the degree of neural regeneration induced by ISMS. We hypothesized that, compared to SCI control rats, ISMS rats will have improved functional walking scores and elevated levels of neuroregeneration. Thirteen Sprague Dawley rats were divided into three groups: (1) rats with hemisection SCI (hSCI, control group); (2) rats with hSCI and passive ISMS implants (sham group), and; (3) rats with hSCI and implants with active electrical stimulation (ISMS group). All groups were trained to walk on a horizontal ladder and their performance was quantified pre-and post-surgery. The average preoperative functional walking score of control, sham and ISMS rats were 5.7±0.2, 5.5±0.3 and 5.7±0.1, respectively (6-point scale). Following hSCI and stimulation, the scores were 3.2±0.9, 2.6±0.6 and 3.3±0.8 for control, sham and ISMS, respectively. Active ISMS elevated functional walking scores in hSCI rats to levels above both sham and control rats, though the improvement was not statistically significant. These preliminary findings suggest that ISMS may augment neuroregeneration. The sham group demonstrated impaired functional walking compared to control. Future studies will employ a larger sample size to fully elucidate this trend, and utilize thinner microwires (25 instead of 30 μm).
Investigating the Impact of Motor Imagery Training on Proprioception
How visualizing movements affect your sense of body position
Devyani McLaren
Abstract:
Motor Imagery (MI) is a promising form of rehabilitation, in addition to physical practice, for neurological populations with sensorimotor deficits. Although the link between MI and proprioception has been established, no studies have examined the impact of MI on proprioception in healthy adults. Objectives: 1) To establish a link between visual imagery (VI) and kinesthetic imagery (KI) abilities and proprioception, through assessment of each MI ability in relation to error on proprioceptive tasks. 2) To determine if MI impacts proprioception in healthy adults by assessing error on proprioceptive tasks after providing MI-training to participants. Design: Between Group, single session, study still in progress. Subjects/Methods: 18 healthy adults were recruited. After completing the Motor Imagery Questionnaire-Revised Second version to assess KI and VI ability, subjects were randomized to a control (N = 9) or experimental (N = 9) group. The control group performed a control task for 25 minutes, the experimental group received 25 minutes of MI training. Both groups’ proprioceptive abilities were then assessed using two tasks on the KINARM robot manipulandum. Results/Conclusions: Preliminary results showed a trending correlation between KI ability and proprioception, indicating a specific link between KI and proprioception in healthy individuals. Based on a 2 (condition) x 2 (proprioceptive task) ANOVA and post-hoc t-tests, no group differences in proprioceptive tasks were observed, indicating that MI did not have an impact on proprioception. Although the impact of MI on proprioception remains unclear, the findings highlight that KI should be used in a neurorehabilitation setting.
Characterization of a Novel Brain Network Derived from Task-Based Functional Magnetic Resonance Imaging: Auditory Attention for Response
Human Brain Mapping from a Reverse Inference Perspective
Judy Cheng
Abstract:
Task-based functional magnetic resonance imaging (fMRI) techniques have provided further insight into the reverse inference challenge, which proposes conclusions about active cognitive processes inferred from observation of brain activity. Several prototype task-based functional brain networks have previously been identified by averaging over replicating studies that performed constrained principal component analysis for fMRI. However, the specific cognitive function associated with each network remains undefined. The current study aimed to characterize the specific functions of the Auditory Attention for Response (AAR) network by comparing hemodynamic response (HDR) patterns across studies where the AAR configuration emerged, including activation in the superior temporal gyrus, supplementary motor area and thalamus. Based on cognitive tasks that revealed engagement of the AAR network, it is hypothesized that the AAR shows activation when an individual attends to auditory sounds and a motor response to a specific auditory stimulus is expected, and that AAR suppression is associated with intensive monitoring of visual details. An example is when an individual that is visually monitoring their phone is less likely to hear what someone else is saying to them. AAR activation was compared across 6 studies for which its activation has already been identified, and interpretation of the network involved comparing anatomical patterns and HDR plots to determine an interpretation that fits all studies. While the results support the hypothesized function of the AAR, an overlap was revealed between the AAR and the Auditory Attention network, and future studies are needed to tease apart the exact differences between these two networks.
Investigating the effect of Baf53b mutations observed in Autism Spectrum Disorder using a mouse primary neuronal culture system.
Effects of chromatin remodeler mutations on neuronal growth.
Michelle Lu & Tess Osborne
Abstract:
Autism Spectrum Disorder (ASD) is one of the fastest-growing neurodevelopmental disorders characterized by impairments in social communication and cognitive function, such as the presence of restricted interests and repetitive behaviours. The BAF (Brg1 Associated Factor) chromatin remodelling complex, which is key for chromatin packaging, contributes to regulating gene expression by modifying DNA accessibility. The neuron-specific nBAF complex has been implicated in memory functions like long term potentiation (LTP) and consolidation. Previous research has demonstrated that Baf53b deletions alter dendritic spine morphology and dynamics, affecting LTP consolidation. Mutations in the Baf53b subunit of nBAF have been identified in various intellectual disorders including ASD. This project will investigate mutations in subdomain 2 of Baf53b, as this region provides functional specificity in neurons. As well, a dominant mutation of a key amino acid at the Baf53b binding interface. To investigate the effect of these Baf53b mutations on neuronal growth, mutant Baf53b plasmids will be introduced to mouse primary Baf53bfl/fl neurons using nucleofection. As synapse formation plays an important role in establishing neuronal circuits which are essential for functions like memory formation, cells will be analyzed to determine if Baf53b mutations cause abnormal synapse formation, dendritic branching or synapse morphology. Mutant neurons will be visualized through immunostaining and high resolution microscopy. Morphology will be further quantified by Sholl Analysis and compared to wild-type Baf53b neurons. This project will help elucidate how Baf53b mutations could impair and alter neuronal growth which may lead to ASD and open possibilities to future therapeutic targets.
Poster Presentations
Reward-Seeking Strategies and Depressive Symptoms: Reversal Learning Using a Go/No-Go Paradigm
How depressive symptoms affect reward-seeking strategies in young adults
Ian Daly
Abstract:
The promotion of action and action inhibition are behavioural strategies used by all species to maximize appetitive events or minimize aversive events. Although altered avoidance and reward-seeking patterns are associated with mood disorders, more in-depth investigations could help capture the heterogeneity of depressive symptoms. Additionally, clinical research to date has not discriminated between active and inhibitory avoidance or reward seeking, and current knowledge about these behaviours largely relies on rodent research. The present study investigates how components of active and inhibitory reward-seeking strategies are associated with symptoms of depression in young adult humans. We created a multi-stage appetitive go/no-go task using visual cues and monetary rewards, which was used in conjunction with depression and anxiety questionnaires. The experimental task examines participants’ acquisition of active reward seeking, discrimination between active and inhibitory reward-seeking strategies, and adaptation to a rule reversal. We hypothesize that people higher in symptoms of depression will generally engage in fewer behaviours aimed at obtaining a reward compared to those lower in depression. Further, if people higher in depressive symptoms show decreased reversal performance, it would indicate impairments in updating their expected action outcomes. We expect that people with higher depressive symptoms will display decreased active reward seeking during each experimental stage and that the learning slope immediately after the rule reversal will be lower when depression symptoms are higher. Results may allow us to better predict and understand symptoms of depression in relation to active and inhibitory response strategies in an appetitively-motivated context.
The Lasting Impact of Prenatal SRI Exposure on Language Development
How prenatal exposure to neurotransmitters cause a lasting impact on language development
Deea K Dev
Abstract:
Critical periods (CPs) in post-natal development represent time windows when the relevant neural circuits are maximally open to environmental input. While predominantly seen in basic sensory processes, CP input contributes to cognitive processes like language. Although gated by maturation, an alteration of expected environmental experience can shift the timing of the opening and closing of CP windows. Previous research testing fetuses and infants aged 6- and 12-months suggested accelerated CP timing for native phonetic category formation following prenatal exposure to serotonin-reuptake inhibitors (SRIs) (Weikum et al., 2012). The present study investigates this same cohort of children, but at 10 years of age to explore the downstream effects of shifts in CP timing in their language outcomes. We hypothesized that the early closure of CPs due to pharmacological exposure would lead to less precise native phoneme categories, which would have cascading effects on lexical access. The Visual Word Processing paradigm was used to measure phonological representation and lexical access using an eye-tracking device. The proportion of time fixation to each image was analysed to reveal interactions between target and competitor words. We found that average fixation to target words was lower for SRI-exposed children as they were distracted by competitor words, indicating poorer phonological and lexical representation. The results of this study reveal a long-lasting impact of early pharmacological exposure on CP timing that in turn affects language development.
Sex differences in rate of cognitive decline in Parkinson’s disease
A look at how sex may impact the speed at which Parkinson's patients experience non-motor changes in brain function (memory and learning).
Brie Dungate
Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative condition, with men being 1.5 times more likely to be diagnosed. Sex differences in age of onset, motor symptoms, presentation, and degeneration have been described. Male patients are known to have earlier onset, and more rapid motor progression. Additionally, documented sex differences exist in the domains of cognitive impairment in patients with PD. However, there exists a lack of evidence for sex differences with respect to rate of cognitive decline. Montreal Cognitive Assessment (MoCA) scores from patients over multiple evaluations (at least two time points per patient) were analyzed. Our results suggest that females (average yearly decrease of 0.361 points) show slightly faster cognitive decline than males (average yearly decrease of 0.038) with no significant difference detected (p = 0.07; n = 452, 153 females). When controlled for age, no significant differences were uncovered. In a subset of 54 patients with PD (female = 29), using feature importance from a Random Forest model, other factors associated with cognitive decline in our cohort were explored. This model suggested that an increase in body mass index, anxiety, and fatigue are correlated with faster cognitive decline. Further analysis is needed to determine the details of the relationships between these factors and cognitive functioning. These data suggest that contrary to the motor symptoms of PD, males demonstrate similar rates of decline in cognitive functioning when compared to females.
HPA Axis and Serotonin (5-HT) 1A Receptor Responses to Repeated Restraint Stress in Male and Female Rats
Sex differences in how the rat stress system and serotonin receptors respond to chronic stress
Maya Koblanksi
Abstract:
Most research on the neural consequences of stress has been conducted only in male subjects, despite sex differences in mood related disorders. Our previous findings demonstrate that stress habituation results in sexually dimorphic modulations of the serotonin (5-HT) system. Considering that presynaptically, the 5-HT 1A auto-receptor of the dorsal raphe nucleus (DRN) negatively regulates 5-HT levels to the rest of the brain and that agonists of the postsynaptic 5-HT 1A receptor stimulates hypothalamic-pituitary-adrenal (HPA) axis activity, we hypothesized that male and female rats would show differential changes in 5-HT 1A receptor levels, coupling to secondary messengers, and function following exposure to one (Single) or five (Repeat) daily episodes of 2h restraint compared to naïve control. Both males and females exhibited a decline in corticosterone levels between the first and last bout of restraint (45 and 40% respectively). Corticosterone responses to 8-OH DPAT were potentiated in both males and females exposed to restraint. However, an increase in 5-HT 1A receptor levels and coupling was only identified in the female hippocampus and a decrease in the female zona incerta (ZI). Only males showed an increase in 8-OH-DPAT induced hypothermia, associated with an increase in 5-HT 1A receptor levels and coupling in the DRN. These findings corroborate our previous data to suggest that male and female rats use different mechanisms to habituate to stress.
Modelling a Bioreactor System to Identify Flow Variables for Application to Alzheimer’s
Modelling a Computer System for Useful Information to apply to Alzheimer's disease
Sophia Gu
Abstract:
Alzheimer’s disease is a disease related to amyloid-beta plaque build up surrounding blood vessels (including arteries and capillaries), and neurofibrillary tangles within the brain. A major area of focus for studying Alzheimer’s Disease is to examine the brain blood vessels and identify if the health of the surrounding cells, such as endothelial cells, smooth muscle cells, and astrocytes (for arterioles) can indicate if Alzheimer’s Disease pathology is present. Dr. Cheryl Wellington’s lab has developed a bio-engineered artery model that includes endothelial cells, smooth muscle cells and astrocytes. To identify if the endothelial cells are experiencing a physiological flow environment (1-50 dyn/cm2), it is necessary to identify the shear stress within the bio-engineered vessel. We are modelling a blank scaffold and system (with no cells), using the COMSOL software. There is a slight pressure gradient throughout the bioreactor system and the velocity profile does not fully develop in the scaffold region. Shear stress is the greatest at the walls of the system.
The Effects of Early Life Stress on the Serotonin System
How early life stress affects serotonin circuitry in the mouse brain
Moriah Edge-Partington
Abstract:
Early life stress (ELS) is a prominent risk factor for the development of mood disorders during later life. Previous research has established that stress during a critical developmental window can have long-lasting behavioural consequences, yet the neurobiological mechanisms still need to be determined. Serotonin is a neurotransmitter that peaks during development and can modulate the activity of neural networks throughout the brain, thus playing a role in stress-related psychiatric conditions. Our lab has previously identified that mice exposed to ELS have decreased serotonin neuron activity and deficits in depression, anxiety-like and social behaviours in adulthood. Our current study sought to determine the effects of ELS on brain-wide serotonergic circuits using a mouse model of chronic developmental stress. We used transgenic mice that express tdTomato specifically in serotonin neurons (Pet1-tdTomato mice). A total of 22 mice pups were exposed to chronic stress using the limited bedding and nesting model throughout postnatal days 2-9. When they reached adulthood (>2 months old), mice were perfused after footshock and brains were collected. Subsequently, a histological analysis was performed on 40 µm sections collected throughout the brain. We then quantified serotonin fiber density and cFos-based neuronal activity in the downstream projection regions of serotonin neurons. Our preliminary results suggest that ELS decreases serotonin fiber density and cFos expression in a sex-dependent manner in regions involved in emotional regulation. These findings may have important implications for the discovery of novel treatment targets for mood disorders linked to childhood stress.
An Immunological Stressor Elevates Local Glucocorticoid Levels in the Developing Mouse Brain
How Bacterial Infections Affect Neurodevelopment
Michael Li & Hitasha Bajaj
Abstract:
Glucocorticoids (GCs) are steroid hormones and critical modulators of nervous system development and function. Upon perceiving a stressor, the hypothalamic-pituitary-adrenal (HPA) axis is stimulated, resulting in the release of GCs from the adrenal glands into the bloodstream. During early development from postnatal day (PND) 1 to 12, mice display low circulating GC levels at baseline and in response to stressors, termed the stress hyporesponsive period (SHRP). Recent evidence shows that GCs are also produced in the brain at baseline, perhaps compensating for the low circulating levels during the SHRP. However, local GC production in response to an immunological stressor within specific brain regions during the SHRP remains unknown. We assessed GC levels in the bloodstream and in various brain regions (prefrontal cortex, hippocampus, hypothalamus, and amygdala) of neonatal (PND5) C57BL/6J mice 4 hours after an immunological challenge with lipopolysaccharide (LPS) (50µg/kg i.p.) or saline. GC (corticosterone and dehydrocorticosterone) levels were measured via liquid chromatography tandem mass spectrometry (LC-MS/MS), and gene expression of key steroidogenic enzymes (Hsd11b1, Hsd11b2) were quantified via RT-qPCR. LPS administration elicited greater corticosterone levels in every brain region but the prefrontal cortex compared to blood, and the reverse was true for dehydrocorticosterone levels. LPS administration also elicited differing mRNA expression of key steroidogenic enzymes within some brain regions. These results demonstrate differentially-regulated GC levels across specific brain regions in response to an immunological stressor. This study provides novel insight on the effects of bacterial infections on neural development and function.
Behavioural Effects of Tau Pathology
Age and Sex-specific effects of Tau Pathology on Behaviour
Sarah Singh
Abstract:
The research examines the role of the Entorhinal Cortex (EC) and Dentate Gyrus (DG) pathway in Alzheimer’s disease (AD). Recent evidence suggests age-related early vulnerability of the EC, which is known to have primary inputs into the DG, leads to tau pathology. Studies have highlighted a localized dysfunction in Lateral EC, which is involved in memory-related to object identity and discrimination, in AD patients and a higher tau accumulation in the LEC region in mice studies, before it spreads cortically. There is also considerable evidence for tau accumulation and specific early deterioration of object-related memory, encoded by the LEC, in preclinical patients with mild cognitive impairment. Additionally, sex differences in Alzheimer’s disease have also been researched, with a greater prevalence observed in females. There are also differences observed in hippocampal plasticity and memory functions in males and females. However, there isn't much evidence regarding age-specific behavioral effects of tau pathology in males versus females. Using a novel viral vector-based tau model, we are investigating the behavioural effects of LEC tau pathology in middle-aged male and female mice. Complex novel object tasks - replacing one object out of multiple objects in test phase - and novel object-context tasks - testing object-context associative memory - are dependent on LEC in mice and rats and will be used to study the behavioural implications in tau mice versus control mice. We hypothesize that tau-infected mice would perform more poorly on the novel exploration tasks due to memory impairment.