Digital Commons Network^™

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 …

Rapid Microscopic Fractional Anisotropy Imaging Via An Optimized Linear Regression Formulation., N J J Arezza, D H Y Tse, C A Baron

Medical Biophysics Publications

Water diffusion anisotropy in the human brain is affected by disease, trauma, and development. Microscopic fractional anisotropy (μFA) is a diffusion MRI (dMRI) metric that can quantify water diffusion anisotropy independent of neuron fiber orientation dispersion. However, there are several different techniques to estimate μFA and few have demonstrated full brain imaging capabilities within clinically viable scan times and resolutions. Here, we present an optimized spherical tensor encoding (STE) technique to acquire μFA directly from the 2nd order cumulant expansion of the powder averaged dMRI signal obtained from direct linear regression (i.e. diffusion kurtosis) which requires fewer powder-averaged signals than …

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 …

The Role Of Neuronal Nitric Oxide Synthase In Regulating Cerebellar Network Formation Across Murine Development, Vasiliki Tellios

Electronic Thesis and Dissertation Repository

The cerebellum is a region of the central nervous system widely known for its role in motor learning and coordination. In the past, mutant mice have been critical in discerning key pathways associated with cerebellar dysfunction and motor deficits. Although a variety of mouse models exist that model the symptoms and pathogenesis of cerebellar ataxia, some have yet to be characterized at the molecular level. Nitric oxide (NO), specifically derived from neuronal nitric oxide synthase (nNOS), is a well-established regulator of synaptic transmission in Purkinje neurons (PNs), governing fundamental processes such as motor learning and coordination. Previous morphological analyses showed …

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 …

Developmental Neurogenesis And Myelination Of Songbird Brains: Sex Differences, Hormones And Social Effects, Adriana Diez

Electronic Thesis and Dissertation Repository

Song learning in songbirds typically happens during the first months after hatching, when the young bird is transitioning to sexual maturity and is more sensitive to extrinsic factors, such as acoustic experience, and intrinsic factors, such as changes in sex hormones. These factors influence the protracted song learning process that involves both behavioral changes at the song level and changes at the cellular level in the underlying neural structures of the vocal control system, the brain circuitry that allows song learning and production. However, the understanding of the neurogenic processes involved in the development of the vocal control system and …

Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box

Electronic Thesis and Dissertation Repository

Sensory electrical stimulation can be used to suppress tremor in Parkinson’s disease. This study investigated the central mechanism underlying this suppression in healthy participants. Reciprocal inhibition (RI) of the wrist flexors before and after a session of sensory electrical stimulation (SES) applied to the antagonistic extensor muscles was assessed using electromyography. It was hypothesized that a 15-minute session of SES, rated by participants as a 3 on a 0-10 pain scale, would produce an increase in RI. Seven of the 18 participants experienced an increase in RI at 0-5 minutes post stimulation, which returned to baseline at 10-15 minutes. The …

Expression And Subcellular Localization Of Circrnas Dysregulated Als That Are Encoded In Cytoskeletal Protein Genes, Asieh Alikhah

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder that causes the death of motor neurons. While alterations in the metabolism of RNA, including RNA-binding proteins have been linked to the pathogenesis of ALS, our understanding of the role of non-coding RNAs including circRNAs is less well developed. In this study, using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence (IF) with markers of RNP granules, I investigated the effect of osmotic stress on the localization and expression of a selection of circRNAs whose expression is dysregulated in ALS. Alteration in the number of granules for …

Development Of A Wearable Haptic Feedback Device For Upper Limb Prosthetics Through Sensory Substitution, Marco B.S. Gallone

Electronic Thesis and Dissertation Repository

Haptics can enable a direct communication pipeline between the artificial limb and the brain; adding haptic sensory feedback for prosthesis wearers is believed to improve operation without drawing too much of the user's attention. Through neuroplasticity, the brain can become more cognizant of the information delivered through the skin and may eventually interpret it as inherently as other natural senses. In this thesis, a wearable haptic feedback device (WHFD) is developed to communicate prosthesis sensory information. A 14-week, 6-stage, between subjects study was created to investigate the learning trajectory as participants were stimulated with haptic patterns conveying joint proprioception. 37 …

Modulation Of Gabaa Receptor By Neurosteroids And Protein Kinases In Health And Disease, Jaymin Jeong

Electronic Thesis and Dissertation Repository

γ-aminobutyric acid type A receptors (GABA_A receptors) underlie the majority of inhibitory synaptic transmission in the brain. Modulation of GABAergic activity occurs in development and normal physiological functioning of the brain, and changes to GABAergic function has been implicated in numerous neurological disorders including epilepsy. Neurosteroids, metabolites of steroid hormones, and kinases are known to modulate GABA_A receptor mediated currents in health and disease. This thesis aims to investigate the effects of kinases and neurosteroids on modulating GABA_A receptor-mediated currents in cortical pyramidal cells and their effects on the piriform cortex (PCtx) circuit in naïve rats and …

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

Functional Loss Of Cntnap2 In The Rat Leads To Autism-Related Alterations In Behaviour And Auditory Processing, Kaela Elizabeth Scott

Electronic Thesis and Dissertation Repository

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant gene thought to play a role in the genetic etiology of neurodevelopmental disorders such as autism spectrum disorder (ASD). Despite its link to ASD, the field lacks a complete understanding of the role CNTNAP2 plays in the hallmarks of ASD: repetitive behaviours and abnormalities in social interaction, language, and sensory processing. Therefore, this thesis first examines if a loss-of-function mutation in the CNTNAP2 gene in the rat (SD-Cntnap2^tm1Sage) is sufficient to cause alterations in social interactions, stereotypic behaviour, and sensory processing. Cntnap2 knockout rats showed deficits …

Imaging Of Neurotransmitters And Small Molecules In Brain Tissues Using Laser Desorption/Ionization Mass Spectrometry Assisted With Zinc Oxide Nanoparticles., Chaochao Chen, Steven R Laviolette, Shawn N Whitehead, Justin B Renaud, Ken K-C Yeung

Chemistry Publications

Inorganic nanostructured materials such as silicon, carbon, metals, and metal oxides have been explored as matrices of low-background signals to assist the laser desorption/ionization (LDI) mass spectrometric (MS) analysis of small molecules, but their applications for imaging of small molecules in biological tissues remain limited in the literature. Titanium dioxide is one of the known nanoparticles (NP) that can effectively assist LDI MS imaging of low molecular weight molecules (LMWM). TiO₂ NP is commercially available as dispersions, which can be applied using a chemical solution sprayer. However, aggregation of NP can occur in the dispersions and the aggregated NP …

Uncovering Deficits In Auditory Processing And Cognition Following Hearing Loss And Prefrontal Cortex Dysfunction, Krystyna B. Wieczerzak

Electronic Thesis and Dissertation Repository

How the auditory cortex and higher-order cortical regions, e.g., the prefrontal cortex, interact for accurate auditory processing and perception is not fully understood. Furthermore, although hearing loss is correlated with cognitive impairment, and animal studies have shown that loud noise exposure causes hippocampal neuropathology, the effects of noise-induced hearing loss on the medial prefrontal cortex (mPFC) and higher-level cognitive functions have not been well studied. Using electrophysiological and cognitive-behavioural testing in rats, Chapter 2 provides the first evidence of noise-induced plasticity in the mPFC (e.g., loss of functional connectivity with the auditory cortex) and deficits in stimulus-response habit learning. Although …

Evaluating Anesthetic Protocols For Non-Human Primate Functional Neuroimaging, Megha Verma

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to measure a proxy of neural activity in vivo with high spatial specificity. One subject can be followed for a long period of time to assess changes in functional brain organization. However, fMRI is extremely sensitive to motion. The challenges of training non-human primates to reduce motion in an MRI scanner motivate the study of anesthesia which is commonly used to substitute for this training. In this thesis, I compare three different commonly used anesthetic protocols: isoflurane, propofol-fentanyl in combination, and fentanyl alone, to test which of …

Is Motor Excitability Modulated By Isochronous Rhythms?, Syed Z. Raza

Electronic Thesis and Dissertation Repository

Humans perceive and synchronize to regularity in auditory temporal sequences. Auditory regularity activates motor areas, but how the timing of motor responses relates to the regularity is unclear. Thus, we examined whether motor excitability, an index of motor activity, fluctuated to an isochronous sequence and characterized the timing of these fluctuations. Participants heard isochronous tones followed by a short silence, during which they imagined the tones continuing. Using single pulse transcranial magnetic stimulation (TMS), we indexed excitability throughout the sequence. Cosine models were fit to constructed excitability timecourses to quantify periodicity of the excitability fluctuations. Motor excitability did not fluctuate …

Assessing Cognitive Function In A Mouse Model Of Synucleinopathy, Mei Peng Lim

Electronic Thesis and Dissertation Repository

A common hallmark of neurodegenerative diseases is the formation and spreading of misfolded protein. In synucleinopathies, the aggregation-prone alpha-synuclein (α-syn) is the pivotal player. At present, whether cognitive deficits in synucleinopathies arise due to increased protein misfolding is unclear. We utilized the Bussey-Saksida touchscreen system to study the impact of α-syn pathology on cognition. M83 homozygous mice, a model of synucleinopathy, were impaired in reversal learning in the Pairwise Visual Discrimination (PVD) reversal task, but do not show attentional impairments in the 5-Choice Serial Reaction Time task. In contrast, M83 hemizygous mice do not show deficits in the PVD reversal …