The ability to control one’s behaviour is a fundamental cognitive function subserved by the prefrontal cortex (PFC). Whereas the neural basis of inhibitory control is reasonably well-established, the possible influence of individual differences in personality on cortical activity associated with this ability remains largely unexplored. The present study obtained self-report ratings of Five-Factor Model personality traits from 42 healthy adults while hemodynamic oxygenation in the PFC was recorded during a Go/No-Go task. Results indicated that Neuroticism, Agreeableness and Openness to Experience were associated with attenuated activity in the lateral PFC, a region critical for emotion regulation and behavioural control, whereas Extraversion and Conscientiousness were associated with greater activation in these regions. Activity within the medial PFC, an area linked to task engagement and self-monitoring, shared a positive association with Agreeableness. These findings provide important insights into how neural systems supporting inhibitory control may be affected by individual differences in personality.

Impulse control, an executive process that restrains inappropriate actions, is impaired in numerous psychiatric conditions. This thesis reports three experiments that utilized a novel animal model of impulse control, the response inhibition (RI) task, to examine the substrates that underlie learning this task. In the first experiment, rats were trained to withhold responding on the RI task, and then euthanized for electrophysiological testing. Training in the RI task increased the AMPA/NMDA ratio at the synapses of pyramidal neurons in the prelimbic, but not infralimbic, region of the medial prefrontal cortex. This enhancement paralleled performance as subjects underwent acquisition and extinction of the inhibitory response. AMPA/NMDA was elevated only in neurons that project to the ventral striatum. Thus, this experiment identified a synaptic correlate of impulse control. In the second experiment, a separate group of rats were trained in the RI task prior to electrophysiological testing. Training in the RI task produced a decrease in membrane excitability in prelimbic, but not infralimbic, neurons as measured by maximal spiking evoked in response to increasing current injection. Importantly, this decrease was strongly correlated with successful inhibition in the task. Fortuitously, subjects trained in an operant control condition showed elevated infralimbic, but not prelimbic, excitability, which was produced by learning an anticipatory signal that predicted imminent reward availability. These experiments revealed two cellular correlates of performance, corresponding to learning two different associations under distinct task conditions. In the final experiment, rats were trained on the RI task under three conditions: Short (4-s), long (60-s), or unpredictable (1-s to 60-s) premature phases. These conditions produced distinct errors on the RI task. Interestingly, amphetamine increased premature responding in the short and long conditions, but decreased premature responding in the unpredictable condition. This dissociation may arise from interactions between amphetamine and underlying cognitive processes, such as attention, timing, and conditioned avoidance. In summary, this thesis showed that learning to inhibit a response produces distinct synaptic, cellular, and pharmacological changes. It is hoped that these advances will provide a starting point for future therapeutic interventions of disorders of impulse control. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2011-07-11 09:44:54.815

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The ability to control one’s behaviour is a fundamental cognitive function subserved by the prefrontal cortex (PFC). Whereas the neural basis of inhibitory control is reasonably well-established, the possible influence of individual differences in personality on cortical activity associated with this ability remains largely unexplored. The present study obtained self-report ratings of Five-Factor Model personality traits from 42 healthy adults while hemodynamic oxygenation in the PFC was recorded during a Go/No-Go task. Results indicated that Neuroticism, Agreeableness and Openness to Experience were associated with attenuated activity in the lateral PFC, a region critical for emotion regulation and behavioural control, whereas Extraversion and Conscientiousness were associated with greater activation in these regions. Activity within the medial PFC, an area linked to task engagement and self-monitoring, shared a positive association with Agreeableness. These findings provide important insights into how neural systems supporting inhibitory control may be affected by individual differences in personality.

The concept of age has undergone a shift from a non-specific measure of chronological age, to an identification of underlying biological, psychological and functional factors leading to age-related changes over time. Loss of neurons (atrophy) and cognitive decline in healthy aging fit well in to this age paradigm. The aging brain is thought to undergo functional shifts in information processing in response to atrophy, which is conceptualised as a “Compensation Hypothesis” of cognitive aging. Using behavioural (reaction time, variability measures, and accuracy on the n-back task of working memory), structural (stereological cortical volume estimates) and functional (functional Magnetic Resonance Imaging) approaches, this study documents decreased whole brain, prefrontal and dorsolateral prefrontal cortex volumes in older individuals. Further, slower, less accurate, and more variable performance on the n-back task in older participants was accompanied by a posterior-to-anterior shift in processing, confirming the Compensation Hypothesis of cognitive aging. The behavioural data combined with structural and functional findings, suggest an aging brain that neuropsychologically compensates over time by paradoxically placing further processing demands on a structurally compromised dorsolateral prefrontal cortex. This produces adequate but slower, more variable, and less accurate performance compared to younger brains; compensation occurs in age, but is not complete. Decision making research has pointed to the important role of emotion in judgement, and has implicated the orbitofrontal cortex as critical for this processing modality. The structural data in this study showed preferentially less volume in the dorsolateral prefrontal cortex, but maintained cortical volume in the orbitofrontal cortex with age. Younger individuals took longer and maintained their accuracy with increasing complexity during the n-back task, with older participants decreasing their accuracy but not to the level of chance with increasing task complexity. As such, decision making on the n-back task may have shifted with age from the pure processing power of the structurally compromised dorsolateral prefrontal cortex to increasing reliance on emotionally-guided decision making inputs mediated by the intact orbitofrontal cortex resulting in adequate but not fully compensated performance in older people. These findings are discussed in relation to evolutionary pressures on the human working memory system, Hume’s concepts of reason and the passions, and to the emerging field of neuroeconomics. / Graduate

Near-infrared spectroscopy (NIRS) in an imaging technique that has gained much attention in brain-computer interfaces (BCIs). Previous NIRS-BCI studies have primarily employed temporal features, derived from the time course of hemodynamic activity, despite potential value contained in the spatial attributes of a response. In an initial offline study, we investigated the value of using joint spatial-temporal pattern classification with dynamic NIR topograms to differentiate intentional cortical activation from rest. With the inclusion of spatiotemporal features, we demonstrated a significant increase in achievable classification accuracies from those obtained using temporal features alone (p < 10-4). In a second study, we evaluated the feasibility of implementing joint spatial-temporal pattern classification in an online system. We developed an online system-paced NIRS-BCI, and were able to differentiate two cortical states with high accuracy (77.4±10.5%). Collectively, these findings demonstrate the value of including spatiotemporal features in the classification of functional NIRS data for BCI applications.

The placebo effect, a beneficial effect attributable to a treatment containing no specific properties for the condition being treated, has been demonstrated in a variety of medical conditions. This thesis includes four studies aimed at increasing our knowledge on the neurobiology of placebo. Study I, a review of the placebo neuroimaging literature, suggested that the anterior cingulate cortex (ACC) may be a common site of action for placebo responses. However, because placebo neuroimaging studies in clinical disorders are largely lacking, the clinical relevance of this needs further clarification. The subsequent three empirical studies were thus designed from a clinical perspective. Using positron emission tomography (PET) these studies investigated the underlying neurobiology of sustained placebo responses in patients with social anxiety disorder (SAD), a disabling psychiatric condition that nonetheless may be mitigated by placebo interventions. Study II demonstrated that serotonergic gene polymorphisms affect anxiety-induced neural activity and the resultant placebo phenotype. In particular, anxiety reduction resulting from placebo treatment was tied to the attenuating effects of the TPH2 G-703T polymorphism on amygdala activity. Study III further compared the neural response profile of placebo with selective serotonin reuptake inhibitors (SSRIs), i.e the first-line pharmacological treatment for SAD. A similar anxiety reduction was noted in responders of both treatments. PET-data further revealed that placebo and SSRI responders had similar decreases of the neural response in amygdala subregions including the left basomedial/basolateral (BM/BLA) and the right ventrolateral (VLA) sections. To clarify whether successful placebo and SSRI treatments operate via similar or distinct neuromodulatory pathways, study IV focused on the connectivity patterns between the amygdala and prefrontal cortex that may be crucial for normal emotion regulation. In responders of both treatment modalities, the left amygdala (BM/BLA) exhibited negative coupling with the dorsolateral prefrontal cortex and the rostral ACC as well as a shared positive coupling with the dorsal ACC. This may represent shared treatment mechanisms involving improved emotion regulation and decreased rumination. This thesis constitutes a first step towards better understanding of the neurobiology of placebo in the treatment of anxiety, including the neural mechanisms that unite and segregate placebo and SSRI treatment.

This study investigated executive function and sustained attention in preterm and full-term infants at 8 months after expected date of delivery and at 10-11 months chronological age. Executive function and sustained attention emerge in infancy and continues to develop throughout childhood. Executive function and sustained attention is believed to underlie some learning problems in children at school age. Although numerous studies have reported that the overall development of preterm infants is comparable to that of full-term infants at the same corrected age, it is unclear to what extent the development of specific cognitive abilities is affected by prematurity and/or other factors such as medical complications. As preterm infants have a high rate of learning difficulties, it is possible that factors associated with prematurity specifically affect the development of some regions of the brain associated with the regulation of executive function and sustained attention. Thirty-seven preterm infants without identified disabilities, and 74 due date and gender matched healthy bull-term infants, participated in the present study. The preterm infants were all less that 32 weeks gestation and less that 1500 grams birth weight. The current study aimed to examine the effects of maturation and length of exposure to extrauterine environmental stimuli on the development of executive function and sustained attention, by comparing the development of preterm infants with that of full-term infants at both the same corrected age and the same chronological age. All infants were therefore assessed on executive function and sustained attention tasks at 8 months after the expected date of delivery (when preterm infants were actually 10-11 months chronological age). The full-term infants in the study were then reassessed at an age equivalent to the chronological age of their matched preterm infants at the time of the first assessment. The findings of the study showed that preterm infants performed significantly more poorly than full-term infants at both 8 months after the expected date of delivery and 10-11 months chronological age on all measures of executive function and sustained attention. However the difference between preterm and full-term infants at 8 months after expected date of delivery was much less that at 10-11 months chronological age. The results suggested that the effects of maturation are greater that the effects of exposure to extrauterine environmental stimuli on the development of executive function and sustained attention. However, as the performance of the preterm infants was below that of the term infants at the same corrected age, it was necessary to consider whether other factors associated with preterm birth were contributing to this difference. Confounding factors including cognitive abilities and psychomotor skills on the Bayley Scales of Infant Development, infant temperament, maternal education, family socioeconomic status and maternal psychological wellbeing were examined. Statistical analysis of the effects of these factors on the difference between preterm ad full-term infants found that only psychomotor sills significantly affected the differences between preterm and full-term infants of the same corrected age on executive function measures, although not on sustained attention measures. The differences between preterm and full-term infants of the same corrected age remained even when psychomotor skills were taken into consideration; therefore psychomotor skills were not sufficient to fully explain the differences between preterm and full-term infants in the performance of executive function. Consequently, the preterm infants were divided into two subgroups on the basis of (a) low or high medical risk factors, (b) birth weight of less that 1000g versus 1000-1500g, and (c) gestation age of less that 28 weeks versus 28-32 weeks, in order to assess the effects of these variables on the performance of executive function and sustained attention. Medical risk, lower birth weight and lower gestation age were all found to adversely affect performance on executive function, but did not affect the performance on sustained attention tasks. It is argued that these factors may influence the development of specific areas of the brain which govern executive function, and that as the prefrontal regions are particularly immature they may be especially vulnerable to damage or disruption. The fact that these perinatal factors did not contribute to the difference between preterm and full-term infants' performance on sustained attention tasks. This suggests that the deficits of sustained attention in preterm infants may be associated with birth prematurity per se, and that additional complications may not have any further detrimental effect. The three components of executive function (i.e., working memory, inhibition, and planning) did not correlate with each other when only infants with Bayley psychomotor ability scores greater that 85 were included, suggesting that the components of executive function may be discrete abilities which are governed by different parts of the prefrontal cortex. Sustained attention correlated with planning, supporting the suggestion that it may be a cognitive dimension which overlaps with executive function, depending upon the task requirement. Neither executive functio nor sustained attention correlated with the Bayley mental ability and Bayley psychomotor ability scores when infants with scores of less than 85 were excluded. This suggests that executive function and sustained attention measures are independent of general development.

Thesis (Ph. D.)--University of Oregon, 2008. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 188-219). Also available online in ProQuest, free to University of Oregon users.

Thesis (M.Sc.). / Written for the Dept. of Neurology & Neurosurgery. Title from title page of PDF (viewed 2009/06/23). Includes bibliographical references.