Neuroscience and Neurobiology Commons^™

Frontoparietal Circuitry Underlying Saccade Control In The Common Marmoset, Janahan Selvanayagam

Electronic Thesis and Dissertation Repository

Our visual world is full of far more stimuli than can be processed simultaneously. Yet we are able to efficiently extract behaviourally relevant information from a scene, primarily by performing rapid saccadic eye movements. These processes are under the control the frontoparietal network, two critical nodes of which are: the lateral intraparietal area (LIP) and the frontal eye fields (FEF). Extensive research in the macaque has causally implicated these areas in visual attention and oculomotor control. However, the organization of the activity of single neurons in these areas across cortical layers remains poorly understood as these regions are deep within …

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

Electronic Thesis and Dissertation Repository

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

The Sensory Properties Of The Fast Visuomotor System, Rebecca Kozak

Electronic Thesis and Dissertation Repository

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

Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy

Electronic Thesis and Dissertation Repository

Neural activity in the primate lateral prefrontal cortex (LPFC) has been causally linked to working memory (WM) ⁠— the brief maintenance and mental manipulation of information. Primates use WM to perform tasks in complex contexts; however, neural mechanisms of WM and the pathophysiology related to WM deficits have traditionally been studied using simple tasks that deviate from naturalistic conditions. This raises the question, how is WM processed in naturalistic conditions? To explore this, I trained two macaque monkeys on a spatial WM task set in a naturalistic virtual environment. During the task, a target was presented in 1 of 9 …

Myeloarchitectonic Maps Of Cat Auditory Cortex, Austin Robertson

Electronic Thesis and Dissertation Repository

The cerebral cortex contains myriad cortical areas that differ in structure, function, and connectivity. Current methods of delineating cortical structures and their subregions are insufficient for in vivo applications, either being highly invasive or requiring a detailed knowledge of a region’s tuning properties. To address this, we seek to establish a structural biomarker capable of delineating the cortex that possesses a non-invasive correlate. We explore myelin as a potential candidate by evaluating its efficacy in parcellating the feline auditory cortex through the generation of depthwise myelin density profiles for each of the 13 auditory cortical subregions. Our analyses revealed significant …

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 …

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 …

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, …

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, …

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, …

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 …

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 …

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 …

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 …

Functional And Structural Brain Reorganization After Unilateral Prefrontal Cortex Lesions In Macaques, Ramina Adam

Electronic Thesis and Dissertation Repository

Visually exploring the surrounding environment relies on attentional selection of behaviourally relevant stimuli for further processing. The prefrontal cortex contributes to target selection as part of a frontoparietal network that controls shifts of gaze and attention towards relevant stimuli. Evidence from stroke patients and nonhuman primate lesion studies have shown that unilateral damage to the prefrontal cortex commonly impairs the ability to allocate attention toward stimuli in the contralesional visual hemifield. Although these impairments often exhibit a gradual improvement over time, the neural plasticity that underlies recovery of function remains poorly understood. The main objective of this dissertation was to …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …

Multisensory Responses In Primary Auditory Cortex Of The Cat, Catherine Boucher

Electronic Thesis and Dissertation Repository

Core auditory cortex of the cat is comprised of primary auditory cortex (A1) and the anterior auditory field (AAF). Neurons in both fields respond strongly to acoustic stimuli and are tonotopically organized. In hearing animals, a small number of cells in AAF respond to tactile stimulation. However, it is unclear if multisensory input influences responses in A1. In this study, multisensory stimuli were developed by pairing a pure tone stimulus with a flash stimulus at various stimulus onset asynchronies. A linear multielectrode array recorded multi-unit activity in A1 across cortical layers. We identified unisensory auditory, unisensory visual, bimodal, and subthreshold …

Differential Thickening And Thinning Of Auditory Cortex In Deaf Cats Revealed With Ultra-High-Field Mri, Stephen G. Gordon

Electronic Thesis and Dissertation Repository

In the absence of hearing, the brain must adapt and repurpose the former auditory cortex. In this study we scanned normal hearing (n=29) and deaf (n=26) cats to identify cortical areas of differing thickness using the auditory regions from a 3D cortical atlas. Compared to hearing controls, differential thickening and thinning was observed in specific regions of the deaf auditory cortex. More dorsal auditory regions tended to be bilaterally thicker in the deaf group, while more ventral regions in the left hemisphere were thinner. The location and nature of these changes creates a gradient along the dorsoventral axis wherein dorsal …

Ultra-High Field Magnetic Resonance Imaging For Stereotactic Neurosurgery, Jonathan Lau

Electronic Thesis and Dissertation Repository

Stereotactic neurosurgery is a subspecialty within neurosurgery concerned with accurate targeting of brain structures. Deep brain stimulation (DBS) is a specific type of stereotaxy in which electrodes are implanted in deep brain structures. It has proven therapeutic efficacy in Parkinson’s disease and Essential Tremor, but with an expanding number of indications under evaluation including Alzheimer’s disease, depression, epilepsy, and obesity, many more Canadians with chronic health conditions may benefit. Accurate surgical targeting is crucial with millimeter deviations resulting in unwanted side effects including muscle contractions, or worse, vessel injury. Lack of adequate visualization of surgical targets with conventional lower field …

Cortical Plasticity Following Adult-Onset Hearing Loss, Ashley L. Schormans

Electronic Thesis and Dissertation Repository

The consequences of hearing loss are not confined to how the central auditory system processes sound; crossmodal plasticity also occurs, which is characterized by an increased responsiveness of neurons in auditory areas to visual and/or tactile stimuli. In the primary auditory cortex, partial hearing loss causes a decrease in the number of auditory-responsive neurons, as well as an increase in multisensory neurons. However, it was relatively unknown how adult-onset hearing loss affected cortical areas that are already capable of integrating multisensory information, such as the lateral extrastriate visual cortex (V2L). Using a combination of in vivo electrophysiology, neuropharmacology and behavioural …

Learning Expands The Preplanning Horizon In Finger Sequence Tasks, Neda Kordjazi

Electronic Thesis and Dissertation Repository

Many everyday skills involve the production of complex sequences of movements. However, the dynamics of the interplay between action selection and execution processes in sequential movements is poorly understood.Here, we set out to investigate the extent to which information regarding upcoming actions is utilized by the motor system to preplan into the future and furthermore, how this ability is influenced by learning. We designed a finger sequence taskwhere participants were shown only a fixed number of upcoming cues regarding future presses in every trial (viewing window, W). W varied between 1 (next digit revealed with pressing the current digit – …

Characterizing The Sensorimotor Properties Of A Rapid Visuomotor Reach Movement On Human Upper Limb Muscles, Chao Gu

Electronic Thesis and Dissertation Repository

Humans and other primates rely heavily on vision as a primary sensory input to drive our upcoming volitional motor actions. Our motor system makes so many of these visual-to-motor transformations that they become ubiquitous in our daily lives. However, a central question in systems neuroscience is how does the brain perform these transformations?

Reaching movements have been an ideal model for studying volitional motor control in primates. Broadly, these visually-guided reach movements contain three inherent sensorimotor components: an action selection component, a motor execution component, and a motor learning component. A core assumption is that as reach movements become more …

Characterizing The Cortical Contributions To Working Memory-Guided Obstacle Locomotion, Carmen Wong

Electronic Thesis and Dissertation Repository

While walking in complex environments, the ability to acquire information about objects in our surroundings is essential for successful obstacle negotiation. Furthermore, the ease with which most animals can traverse cluttered terrain while grazing, exploring, or hunting is facilitated by the capacity to store obstacle information in working memory (WM). However, the underlying neural substrates supporting such complex behaviours are poorly understood. Therefore, the goal of this thesis is to examine the neural underpinnings of WM-guided obstacle negotiation in the walking cat.

Obstacle locomotion was studied in two main paradigms, characterized by whether obstacle presence was detected via vision or …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …

Prefrontal Cortex Dopamine Transmission Regulates Emotional Memory Processing And Morphine Reward Salience: Implications For Post-Traumatic Stress Disorder And Addiction Comorbidity, Jing Jing Li

Electronic Thesis and Dissertation Repository

Post-Traumatic Stress Disorder (PTSD) and addiction are strongly comorbid. However, the underlying neural mechanisms by which traumatic memory recall may increase addiction liability are poorly understood. The inability to suppress memory recall related to either stressful or rewarding, drug-related experiences may be an underlying neuropsychological feature capable of triggering both PTSD or addiction-related behaviours. Our previous research has shown that transmission through dopamine (DA) D₄ and D₁ receptor subtypes (D₄R, D₁R) within the prefrontal cortex (PFC) strongly modulates emotional memory acquisition and recall (Lauzon et al., 2009). Using olfactory fear conditioning and morphine conditioned …

Navigating The "Little Brain": Comprehensive Mapping Of Functional Organisation, Maedbh King

Electronic Thesis and Dissertation Repository

Two decades of neuroimaging research suggests that the cerebellum is functionally involved in a range of cognitive and motor processes. However, missing from the literature is a comprehensive map detailing a clear functional organisation of the cerebellum. Previous studies have used a restricted task-mapping approach to localise task-specific functional activation to cerebellar lobules. However, this approach, which is often limited to one or two functional domains within individual subjects, fails to characterise the full breadth of functional specialisation within the cerebellum. To overcome this restricted task-mapping problem, we tested 17 subjects on a condition-rich task battery (61 task conditions) across …

Altered Cortical Oscillations: Investigations Into A Putative Neural Correlate Of Tinnitus, Gregory G P Sigel

Electronic Thesis and Dissertation Repository

Abnormal cortical oscillations have been implicated in tinnitus generation. To gain further insight into this relationship, we performed two Experimental Series, both employing behavioural, pharmacological, and in vivo electrophysiological techniques in an animal model. To that end, we revealed three novel findings: (1) While exposure to 250 mg/kg sodium salicylate or transient loud noise induced behavioural evidence of tinnitus, these insults caused dissimilar effects on spontaneous cortical oscillations; (2) Despite these dissimilar effects, sodium salicylate and loud noise exposure caused similar deficits in the evoked oscillatory activity elicited by the auditory steady state response; and (3) Manipulation of medial geniculate …

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 …

Origins Of Thalamic And Cortical Projections To The Posterior Auditory Field In Congenitally Deaf Cats., Blake E Butler, Nicole Chabot, Andrej Kral, Stephen G Lomber

Psychology Publications

Crossmodal plasticity takes place following sensory loss, such that areas that normally process the missing modality are reorganized to provide compensatory function in the remaining sensory systems. For example, congenitally deaf cats outperform normal hearing animals on localization of visual stimuli presented in the periphery, and this advantage has been shown to be mediated by the posterior auditory field (PAF). In order to determine the nature of the anatomical differences that underlie this phenomenon, we injected a retrograde tracer into PAF of congenitally deaf animals and quantified the thalamic and cortical projections to this field. The pattern of projections from …