Conceptual design is a series of complex cognitive processing tasks and research seeking to further understand design cognition will benefit by considering literature from the field of psychology. This thesis presents two research projects, which sought to understand and mitigate design biases in conceptual design through the application of theories from biological and cognitive psychology. The first of these puts forward a novel model of design creativity based on connectionist theory and a neurological phenomenon known as long-term potentiation. This model is applied to provide new insights into design fixation and develop interventions to assist designers overcome fixation. The second project seeks to establish that cognitive heuristics and biases predictably influence design cognition. Two studies are discussed that examined the role of confirmation bias in design. The first establishes that confirmation bias is present during concept generation; the second demonstrates that decision matrices can mitigate confirmation bias in concept evaluation.

Conceptual design is a series of complex cognitive processing tasks and research seeking to further understand design cognition will benefit by considering literature from the field of psychology. This thesis presents two research projects, which sought to understand and mitigate design biases in conceptual design through the application of theories from biological and cognitive psychology. The first of these puts forward a novel model of design creativity based on connectionist theory and a neurological phenomenon known as long-term potentiation. This model is applied to provide new insights into design fixation and develop interventions to assist designers overcome fixation. The second project seeks to establish that cognitive heuristics and biases predictably influence design cognition. Two studies are discussed that examined the role of confirmation bias in design. The first establishes that confirmation bias is present during concept generation; the second demonstrates that decision matrices can mitigate confirmation bias in concept evaluation.

Background: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). Methods: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. Results: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. Conclusions: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 67-80).

Short-term synaptic plasticity results from use-dependent activity, lasts on the timescale of milliseconds to minutes, and is thought to underlie working memory and neuronal information processing. Here, we focus on two forms of short-term plasticity: 1) post-tetanic potentiation (PTP), which is induced by high-frequency stimulation, and 2) presynaptic ionotropic receptor-activated synaptic enhancement, which can be produced by the activation of presynaptic glycine receptors. Potentiation of evoked and spontaneous responses is thought to arise from elevations in presynaptic residual Ca2+, which activates one or more molecular targets to increase neurotransmitter release. However, the Ca2+ sensor protein has not yet been identified. The overall goal of this work is to elucidate the Ca2+-dependent mechanisms of short-term plasticity.

Οι ιπποκάμπιες συνάψεις επιδεικνύουν σημαντική ικανότητα για μακρόχρονη πλαστικότητα, η οποία θεωρείται ότι είναι η βάση της μνήμης και της μάθησης. Υπάρχουν ολοένα και αυξανόμενες αποδείξεις ότι αυτή η ικανότητα διαφέρει κατά μήκος του ιπποκάμπου, με τις συνάψεις της CA1 περιοχής του κοιλιακού ιπποκάμπου να επιδεικνύουν σημαντικά μικρότερη ικανότητα για μακρόχρονη ενίσχυση (LTP) σε σύγκριση με τις αντίστοιχες συνάψεις του ραχιαίου ιπποκάμπου, όταν ενεργοποιούνται με υψηλόσυχνο ερεθισμό. Στην παρούσα εργασία, δείχνουμε ότι μία μικρή συχνότητα ερεθισμού, των 10 Hz, επάγει μακρόχρονη ενίσχυση πιο αξιόπιστα στην περιοχή CA1 του ραχιαίου απ' ό,τι του κοιλιακού ιπποκάμπου. Προτείνουμε ότι η δραστηριότητα που επάγεται από του υποδοχείς α5GABAA παίζει έναν σημαντικό ρόλο στην ρύθμιση του κατωφλίου επαγωγής του LTP ειδικά στις συνάψεις της περιοχής CA1 του κοιλιακού ιπποκάμπου. Αυτό το γεγονός μπορεί να έχει σημαντικές συνέπειες για την λειτουργική εξειδίκευση κατά μήκος του ιπποκάμπου. / The hippocampal synapses display conspicuous ability for long-term plasticity which is thought to underlie learning and memory. Growing evidence shows that this ability differs along the long axis of the hippocampus, with the ventral CA1 hippocampal synapses displaying remarkably lower ability for long-term potentiation(LTP) compared with their dorsal counterpart when activated with high-frequency stimulation. Here, we show that low frequency, 10Hz stimulation induced LTP more reliably in DH than in VH CA1 field. Blockade of alpha5 subunit-containing GABAA receptors eliminated the difference between DH and VH. We propose that α5GABAA receptor-mediated activity plays a crucial role in regulating the threshold for induction of LTP especially at the ventral CA1 hippocampal synapses. This might have important implications for the functional specialization along the hippocampus.

Recent evidence indicates that the mature neocortex retains a higher degree of plasticity than traditionally assumed. Up- and down-regulation of synaptic strength, long-term potentiation (LTP) and long-term depression (LTD), is thought to be the primary mechanism mediating experience-dependent plasticity of cortical networks. The present thesis investigate factors that regulate adult cortical plasticity, focusing on the role of neuromodulators, recent sensory experience, and different anatomical divisions of the cortex in influencing synaptic strength. First, I investigated the role of the neuromodulator histamine in gating plasticity in the primary visual cortex (V1) of urethane anesthetized adult rats. Histamine applied locally in V1 produced an enhancement of LTP elicited by theta burst stimulation (TBS) of dorsal lateral geniculate nucleus (dLGN) and allowed a sub-threshold TBS to produce stable LTP. Second, the impact of visual deprivation on LTP in V1 was assessed. Animals that received 2 and 5 hr dark exposure showed greater potentiation of field potentials when stimulated though retinal light flashes or weak TBS of the dLGN, which failed to induce LTP in control animals kept in continuous light. Third, I performed a detailed characterization of LTP induced by different TBS protocols, recording in either the monocular or binocular segment of both V1 hemispheres (i.e., ipsi- and contralateral to the stimulated dLGN). Stronger, NMDA receptor-independent LTP was found in the contralateral V1. Interestingly, weak TBS induced LTD that was NMDA receptor-dependent in the ipsilateral V1. Furthermore, a lower LTP induction threshold was observed in the binocular than the monocular segment of ipsilateral V1. Lastly, I investigated cholinergic modulation of sensory-induced activity in the barrel cortex. Basal forebrain stimulation enhanced multi-unit activity elicited by whisker deflection, an effect that was more pronounced for weaker response driven by a secondary whisker than principal whisker deflection. This thesis demonstrates that neocortical plasticity consists of multiple forms of synaptic modification. Adult cortical plasticity is greatly influenced by preceding activity of the synapse by various neuromodulator systems, and by anatomical subdivisions within primary sensory cortex fields. Together, these mechanisms may facilitate the detection, amplification, and storage of inputs to primary sensory fields of the neocortex. / Thesis (Ph.D, Psychology) -- Queen's University, 2010-04-29 14:02:30.742

Many molecules and the complex interactions between them underlie plasticity in the cerebellum. However, the exact relationship between cerebellar plasticity and the different signalling cascades remains unclear. Calcium-calmodulin dependent protein kinase II (CaMKII) regulates many forms of synaptic plasticity, but very little is known about its function during plasticity induction in the cerebellum. The aim of this thesis is to contribute to a better understanding of the molecular mechanisms that regulate the induction of synaptic plasticity in cerebellar Purkinje cells (PCs). The focus of the thesis is to investigate the role of CaMKII isoforms in the bidirectional modulation of plasticity induction at parallel fibre (PF)-PC synapses. For this investigation, computational models that represent the CaMKII activation and the signalling network that mediates plasticity induction at these synapses were constructed. The model of CaMKII activation by calcium-calmodulin developed by Dupont et al (2003) replicates the experiments by De Koninck and Schulman (1998). Both theoretical and experimental studies have argued that the phosphorylation and activation of CaMKII depends on the frequency of calcium oscillations. Using a simplified version of the Dupont model, it was demonstrated that the CaMKII phosphorylation is mostly determined by the average calcium-calmodulin concentration, and therefore depends only indirectly on the actual frequency of calcium oscillations. I have shown that a pulsed application of calcium-calmodulin is, in fact, not required at all. These findings strongly indicate that the activation of CaMKII depends on the average calcium-calmodulin concentration and not on the oscillation frequency per se as asserted in those studies. This thesis also presents the first model of AMPA receptor phosphorylation that simulates the induction of long-term depression (LTD) and potentiation (LTP) at the PF-PC synapse. The results of computer simulations of a simple mathematical model suggest that the balance of CaMKII-mediated phosphorylation and protein phosphatase 2B (PP2B)-mediated dephosphorylation of AMPA receptors determines whether LTD or LTP occurs in cerebellar PCs. This model replicates the experimental observations by Van Woerden et al (2009) that indicate that CaMKII controls the direction of plasticity at PF-PC synapses. My computer simulations support Van Woerden et al’s original suggestion that filamentous actin binding can enable CaMKII to regulate bidirectional plasticity at these synapses. The computational models of intracellular signalling constructed in this thesis advance the understanding of the mechanisms of synaptic plasticity induction in the cerebellum. These simple models are significant tools for future research by the scientific community.

Introduction: Les stratégies d’optimisation de la performance chez les athlètes sont de plus en plus exploitées par les entraîneurs et préparateurs physiques. La potentialisation de post- activation (PAP) est reconnue comme étant un phénomène pouvant mener à une augmentation des performances. L’objectif de la présente étude était de donc décrire les effets d’une pré-sollicitation à la hanche sur la coordination inter-musculaire et la performance au cours d’un exercice épuisant. Méthodes: Six athlètes de patins de vitesse de courte piste (3 de sexe masculin et 3 de sexe féminin; âge: 20.2 ± 2.8 ans; moyenne±écart-type) ont exécuté aléatoirement un exercice qui consistait en 2 séries de 9 blocs de squats sautés maximaux, entre-coupés d’un squat isométrique d’une durée de 5 secondes sans pré-sollicitation préalable (CON) et avec une tâche de pré-sollicitation unilatérale de squat isométrique (EXP) contre une barre fixe de 2x3 secondes. Le pic de puissance moyen, l’amplitude et la fréquence moyenne d’EMG, et la vitesse et l’accélération angulaires des premiers et derniers blocs étaient enregistrés. Résultats: La pré-sollicitation isométrique maximale des membres inférieurs n’a pas amélioré de manière significative la performance de sauts et la coordination des muscles stabilisateurs à la hanche. La fréquence spectrale moyenne a néanmoins témoigné de l’implication de stratégies compensatoires du membre inférieur gauche en réponse à la fatigue. Conclusion: La pré-sollicitation des stabilisateurs à la hanche n’augmenterait pas la performance de squats répétés. Par contre, la fréquence moyenne du grand fessier et du tibial antérieur gauche ont suggéré meilleure résistance à la fatigue des muscles du membre inférieur non-dominant avec une pré-sollicitation. Les résultats de la présente étude indiquent donc la pertinence de considérer la pré-sollicitation dans un objectif de performance et de réadaptation sachant que l’asymétrie est omniprésente chez les athlètes et qu’elle est impliquée dans le taux élevé de blessures enregistré chez cette population. / Introduction: Strategies in order to optimize athlete’s performances are commonly used by coaches and trainers. Post-activation potentiation (PAP), occurring after a pre-activation, is known to be a phenomenon that can lead to an increase in force and power production and thus, performance. The aim of the present study was to describe the effects of a hip stabilizers pre-activation on multi-segment coordination and performance during a fatiguing exercise. Method: Six short-track speed skating athletes (3 males and 3 females; age: 20.2 ± 2.8 years; data reported as mean ± SD) participate in the study were they had to execute 2 sets of 9 blocks of 6 maximal squat jumps with 5 s isometric squats between blocks and 5 min rest between sets without (CON) or with (EXP) a 2x3s unilateral isometric squats against a fixed bar potentiating exercise 5 min before to the first set of 9 blocks intending to target the lower body hip stabilizers, flexors and extensors. Jumping average peak power, EMG amplitude, median frequency, angular velocity and acceleration were measured. The first and last blocks of jumps were recorded for each set. Results: There were no significant difference between conditions, as results showed an overall fatigue state. However, mean frequency showed compensating strategies in left leg muscles in response to fatigue. Conclusion: Hip stabilizers isometric pre-activation did not improve overall performance and coordination on jump squats. However, gluteus maximus and anterior tibialis showed a an improved fatigue resistance in non-dominant leg with pre-activation. Results from this study suggest that pre-activation protocols, while they produce no significant impact on performance, could be relevant for reducing lower-limb movement asymmetry during athlete training and as such, contribute to injury prevention and rehabilitation.

Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 100-118).