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Evaluation Of The Utility Of Decomposition-Enhanced Spike-Triggered Averaging Motor Unit Number Estimation As An Outcome Measure For The Study Of Amyotrophic Lateral Sclerosis, Colleen T. Ives

Electronic Thesis and Dissertation Repository

OBJECTIVES: The objectives of this thesis were to review the use of outcome measures systematically across amyotrophic lateral sclerosis (ALS) clinical trials, and evaluate the utility of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) as an outcome measure, with a particular focus on its application to the upper trapezius (UT).

METHODS: First, a systematic review quantified the frequency of use of outcome measures in ALS randomized controlled trials (Chapter 2). Next, the intra- and inter-rater reliability of DE-STA MUNE was evaluated in the UT of control subjects (Chapter 3), followed by the intra-rater reliability of the technique in …

Sexual Reward And Depression, Andrea R. Di Sebastiano

Electronic Thesis and Dissertation Repository

Sexual behavior in male rats is a complex rewarding behavior and many neurotransmitters and neuropeptides play an important role in mediation of sexual performance, motivation and reward. The hypothalamic neuropeptide orexin has been shown play a key role in reward associated with food and drugs of abuse, but the role of this neuropeptide in control of sexual performance, motivation and reward is currently unclear. First, it was shown that orexin neurons in the hypothalamus are activated during sexual performance and reward. Next, using cell specific lesions of orexin neurons it was demonstrated that orexin is involved in arousal and anxiety, …

Algorithmic Decomposition Of Shuffle On Words, Franziska Biegler, Mark Daley, Ian Mcquillan

Brain and Mind Institute Researchers' Publications

We investigate shuffle-decomposability into two words. We give an algorithm which takes as input a DFA M (under certain conditions) and determines the unique candidate decomposition into words u and v such that L(M) = u v ifM is shuffle decomposable, in time O(|u| + |v|). Even though this algorithm does not determine whether or not the DFA is shuffle decomposable, the sublinear time complexity of only determining the two words under the assumption of decomposability is surprising given the complexity of shuffle, and demonstrates an interesting property of the operation. We also show that for given words u and …

Expanding The Basic Science Debate: The Role Of Physics Knowledge In Interpreting Clinical Findings., Mark Goldszmidt, John Paul Minda, Sarah L Devantier, Aimee L Skye, Nicole N Woods

Brain and Mind Institute Researchers' Publications

Current research suggests a role for biomedical knowledge in learning and retaining concepts related to medical diagnosis. However, learning may be influenced by other, non-biomedical knowledge. We explored this idea using an experimental design and examined the effects of causal knowledge on the learning, retention, and interpretation of medical information. Participants studied a handout about several respiratory disorders and how to interpret respiratory exam findings. The control group received the information in standard "textbook" format and the experimental group was presented with the same information as well as a causal explanation about how sound travels through lungs in both the …

Frequency-Dependent Conduction Block In Demyelinating Focal Neuropathies, Brad V. Watson

Electronic Thesis and Dissertation Repository

It is the objective of this thesis to demonstrate conduction block across regions of focal demyelination by utilizing a conventional electrophysiological technique used frequently in the diagnosis of peripheral nerve disease. Specifically, patients with moderate to severe carpal tunnel syndrome (CTS), but, with no evidence of conduction block via conventional motor nerve conduction study techniques, were assessed in the initial studies of this thesis for evidence of frequency-dependent conduction block (FDB) by way of high-frequency nerve stimulation (HFNS) applied across the region of entrapment. The final studies examined whether FDB could be demonstrated along the median motor fibers in mild …

Psychophysical And Neural Evidence For Emotion-Enhanced Perceptual Vividness, Rebecca M. Todd, Deborah Talmi, Taylor W. Schmitz, Josh Susskind, Adam K. Anderson

Brain and Mind Institute Researchers' Publications

Highly emotional events are associated with vivid "flashbulb" memories. Here we examine whether the flashbulb metaphor characterizes a previously unknown emotion-enhanced vividness (EEV) during initial perceptual experience. Using a magnitude estimation procedure, human observers estimated the relative magnitude of visual noise overlaid on scenes. After controlling for computational metrics of objective visual salience, emotional salience was associated with decreased noise, or heightened perceptual vividness, demonstrating EEV, which predicted later memory vividness. Event-related potentials revealed a posterior P2 component at ~200 ms that was associated with both increased emotional salience and decreased objective noise levels, consistent with EEV. Blood oxygenation level-dependent …

Gonadotropin-Releasing Hormone Plasticity: A Comparative Perspective., T J Stevenson, T P Hahn, S A Macdougall-Shackleton, G F Ball

Brain and Mind Institute Researchers' Publications

Gonadotropin-releasing hormone 1 (GnRH1) is a key regulator of the reproductive neuroendocrine system in vertebrates. Recent developments have suggested that GnRH1 neurons exhibit far greater plasticity at the cellular and molecular levels than previously thought. Furthermore, there is growing evidence that sub-populations of GnRH1 neurons in the preoptic area are highly responsive to specific environmental and hormonal conditions. In this paper we discuss findings that reveal large variation in GnRH1 mRNA and protein expression that are regulated by social cues, photoperiod, and hormonal feedback. We draw upon studies using histochemistry and immediate early genes (e.g., c-FOS/ZENK) to illustrate that specific …

Perceptual Fluency Can Be Used As A Cue For Categorization Decisions., Sarah J Miles, John Paul Minda

Brain and Mind Institute Researchers' Publications

Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge …

Differential Effects Of Macaque Dorsolateral Prefrontal Deactivations During Uncued And Cued Role Conditions, Sabeeha Hussein

Electronic Thesis and Dissertation Repository

Cognitive control enables us to guide our behaviour in an appropriate, context-dependent manner. This behavioral flexibility is probed by task-switching paradigms, which require working memory to maintain relevant rules and flexibility to switch between rules. The dorsolateral prefrontal cortex (DLPFC) has been implicated in rule maintenance by neuroimaging and electrophysiological studies. While these studies have identified a correlation between DLPFC activity and rule maintenance, deactivation studies allow us to establish a causal relationship. Here we have examined the effect of bilateral deactivation of areas 46 and 9/46d on rule maintenance, while a monkey (Macacca mulatta) performed blocks of …

Calclium-Calmodulin Regulation Of Trpm2 Currents, Brian M. W. Lockhart

Electronic Thesis and Dissertation Repository

TRPM2 (1507 amino acids), a non-selective cation channel with substantial permeability for Ca²⁺, is responsive to oxidative stress, and is a mediator of cell death in several cell types. Ca²⁺-calmodulin has been shown to promote channel activation and inactivation, however the mechanisms are not fully understood. Identifying candidate CaM binding sites using in silico screening, I hypothesized that Ca²⁺-dependent inactivation (CDI) of TRPM2 is mediated by an intracellular CaM binding domain unique from that of activation (406-415AA). I systematically determined the minimum binding domains for three CaM candidate sites on TRPM2’s intracellular domains using …

The Role Of Amino-Terminal In Determining Transjunctional Voltage-Dependent Gating And Unitary Conductance Of Cx36 And Cx50 Gap Junction Channels, Li Xin

Electronic Thesis and Dissertation Repository

Gap junction (GJ) channels directly connect the cytoplasm of neighboring cells, and allow for the transfer of ions and small molecules between two cells. GJ channels are known to be gated by the transjunctional voltage (V_j, the voltage difference between the interiors of adjoining cells), which is referred to as V_j-dependent gating. GJ channels show varying degrees of sensitivity to V_j, depending on the type of connexin(s) comprising the GJ channel. GJ channels formed by different connexins also show unique unitary conductance ranging from ~ 10 pS to ~300 pS. However, the molecular structures …

Greater Benefits Of Multisensory Integration During Complex Sensorimotor Transformations., Verena N Buchholz, Samanthi C Goonetilleke, W Pieter Medendorp, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Multisensory integration enables rapid and accurate behavior. To orient in space, sensory information registered initially in different reference frames has to be integrated with the current postural information to produce an appropriate motor response. In some postures, multisensory integration requires convergence of sensory evidence across hemispheres, which would presumably lessen or hinder integration. Here, we examined orienting gaze shifts in humans to visual, tactile, or visuotactile stimuli when the hands were either in a default uncrossed posture or a crossed posture requiring convergence across hemispheres. Surprisingly, we observed the greatest benefits of multisensory integration in the crossed posture, as indexed …

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Brain and Mind Institute Researchers' Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Encoding Of Sensory Prediction Errors In The Human Cerebellum., John Schlerf, Richard B Ivry, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which …

Dna Damage And Oxidative Stress Induced-P53 Activity In Astrocytes Causes Growth Arrest, Sarah A. Humphrey

Electronic Thesis and Dissertation Repository

An increasing body of evidence suggests that astrocytes play a key role in modulating neuronal fate during acute and chronic neurodegenerative conditions. Following CNS injury, an upregulation of p53 has been noted in both neurons and reactive astrocytes. p53 is an extremely important protein in determining cell fate decisions and its activation can result in the transcriptional induction of target genes that regulate apoptosis, autophagy, senescence and cell-cycle arrest. We found that p53 is upregulated in primary cortical astrocytes following oxidative stress and DNA damage and that this upregulation results in the p53-dependent transcriptional induction of several target genes involved …

Distinct Patterns Of Functional And Effective Connectivity Between Perirhinal Cortex And Other Cortical Regions In Recognition Memory And Perceptual Discrimination., Edward B O'Neil, Andrea B Protzner, Cornelia Mccormick, D Adam Mclean, Jordan Poppenk, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched …

Discriminating Famous From Fictional Names Based On Lifetime Experience: Evidence In Support Of A Signal-Detection Model Based On Finite Mixture Distributions., Ben Bowles, Iain M Harlow, Melissa M Meeking, Stefan Köhler

Brain and Mind Institute Researchers' Publications

It is widely accepted that signal-detection mechanisms contribute to item-recognition memory decisions that involve discriminations between targets and lures based on a controlled laboratory study episode. Here, the authors employed mathematical modeling of receiver operating characteristics (ROC) to determine whether and how a signal-detection mechanism contributes to discriminations between moderately famous and fictional names based on lifetime experience. Unique to fame judgments is a lack of control over participants' previous exposure to the stimuli deemed "targets" by the experimenter; specifically, if they pertain to moderately famous individuals, participants may have had no prior exposure to a substantial proportion of the …