Consolidation of associative memories may depend on communication between the lateral entorhinal cortex (LEC) and hippocampus (HPC) for recently learned memories and the LEC and medial prefrontal cortex (mPFC) for remote memories. To determine whether direct connections between these regions are necessary for the retrieval of a recently or remotely learned memory, rats acquired an associative memory through trace eyeblink conditioning and were tested for memory retention after inactivating the regions of interest with the GABAA agonist, muscimol. Inactivating the LEC-HPC connection did not impair memory retrieval. However, inactivating the LEC-mPFC connection impaired remote, but not recent, memory retrieval. Thus, the LEC and mPFC connection is necessary for the retrieval of a remotely, but not recently learned associative memory. Increased reliance on the entorhinal-prefrontal connection indicates the strengthening of functional connectivity between the two regions, which may be a biological correlate for the proposed reorganization during systems consolidation.

Cognitive dissonance has traditionally been defined as the negative affective state which accompanies inconsistent cognitions and motivates one to make the cognitions consistent. This thesis critically evaluates two theories about cognitive dissonance. The action-based model of dissonance argues that inconsistent cognitions have the potential to interfere with effective and unconflicted action. The new look model of dissonance, contradicting the traditional definition of dissonance, argues that it is aversive consequences rather than inconsistent cognitions that cause dissonance. Recent studies investigating the neural correlates of dissonance show that parts of anterior cingulate cortex and prefrontal cortex seem to be involved in the dissonance process. One of the major predictions of the new look model of dissonance has been undermined by recent evidence. In contrast, the action-based model of dissonance is supported by recent studies.

Probability learning is the ability to establish a relationship between stimulus and outcomes based on occurrence probabilities using repetitive feedbacks. Participants learn the task according to the cue-outcome relationship, and try to gain in depth understanding of this relationship throughout the experiment. While learning is at the highest level, people rely on their working memory. In this study 20 participants were presented a probability learning task, and their prefrontal cortex activity was measured with functional Near-Infrared Spectroscopy. It was hypothesized that as participants gain more knowledge of the probabilities they will learn cue-outcome relationships and therefore rely less on their working memory. Therefore as learning precedes a drop in the fNIRS signal is expected. We obtained results confirming our hypothesis: Significant negative correlation between dorsolateral prefrontal cortex activity and learning was found. Similarly, response time also decreased through the task, indicating that as learning precedes participants made decisions faster. Participants used either the frequency matching or the maximization strategy in order to solve the task in which they had to decide whether the blue or the red color was winning. When they use the frequency matching strategy they chose blue at the rate of winning for the blue choice. When they use the maximization strategy they chosed blue almost always. Our task was designed such that the frequency for blue to win was 80%. We had hypothesized that the people in frequency matching and maximization groups would show working memory differences which could be observed from the fNIRS signal. However, we were unable to detect this type of behavioral difference in the fNIRS signal. Overall, our study showed the relationship between probability learning and working memory as depicted by brain activity in the dorsolateral prefrontal cortex which widely known as the central executive component of working memory.

Abnormal connectivity of the intrinsic anticorrelated networks, the task-negative network (TNN) and task-positive network (TPN), is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings offer an opportunity to further understand illness susceptibility and pathophysiology. We hypothesized that schizophrenic patients would demonstrate hyperconnectivity in the intrinsic networks and that similar, but less pronounced, hyperconnectivity would be evident in the networks of the unaffected siblings. Resting-state functional magnetic resonance images were obtained from schizophrenic patients (n=25), their unaffected siblings (n=25), and healthy controls (n=25). The posterior cingulate cortex/precuneus (PCC/PCu) and right dorsolateral prefrontal cortex (DLPFC) were used as seed regions to identify the TNN and TPN. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to the intrinsic networks of the three subject groups. In the TNN, schizophrenic patients alone demonstrated hyperconnectivity between the PCC/PCu and left inferior temporal gyrus and between the ventral medial prefrontal cortex and the right lateral parietal cortex. Both schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. In the TPN, schizophrenic patients showed hyperconnectivity between the left DLPFC and right inferior frontal gyrus relative to unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls. Resting-state hyperconnectivity of the intrinsic networks may underlie the pathophysiology of schizophrenia by disrupting network coordination. Similar, though milder, hyperconnectivity in unaffected siblings of schizophrenic patients may contribute to their cognitive deficits and increased risk to develop schizophrenia.

Decades of research have demonstrated that people sometimes provide self-evaluations that emphasize their most flattering qualities. Different theoretical accounts have been offered to explain the mechanisms underlying positively-biased self-evaluation. Some researchers theorize that positively-biased self-evaluations arise from a self-protection motivation because positivity biases increase in situations of heightened self-esteem threat. Alternative views question whether self-protection motivation is a necessary or even dominant source of positivity bias by demonstrating that positively-biased self-evaluations occur even when threat is not heightened, and that a general judgment approach leads to positivity biases in some domains but also to negativity biases in other domains. One reason for this gap in knowledge is that behavioral measures are limited in their ability to resolve whether the processes underlying positively-biased self-evaluation are the same or different depending on contextual motivators. Neuroimaging methods are well suited to examine whether different mechanisms underlie similar behaviors, specifically similar positively-biased responses in different contexts. The four studies presented here explore the neural mechanisms of positively-biased self-evaluation by first identifying a core set of neural regions associated with positivity bias (Study 1A and 1sB), examining whether a heightened self-protection motivation changes the engagement of those neural systems (Study 2), and specifying the precise mechanisms supported by those regions (Study 3). Studies 1A and 1B revealed evidence for a neural system comprised of medial and lateral orbitofrontal cortex (OFC) and, to a lesser extent dorsal anterior cingulate (dACC) that was modulated by positivity bias. Study 2 found that a heightened self-protection motivation changes the engagement of medial OFC in positively-biased self-evaluation. Finally, Study 3 found evidence that medial OFC may support a common mechanism in positively-biased judgment that is implemented differently as a function of the motivational context. Taken together, these studies represent a first step toward developing a neural model of positively-biased self-evaluation. The findings provide some preliminary evidence that positivity biases may represent distinct processes in different motivational contexts. This dissertation sets the stage for future work to examine how specific positively-biased cognitive mechanisms may be supported by specific neural systems and computations as a function of motivational contexts. / text

Behavioral studies have documented impaired working memory in childhood brain tumor survivors; however, neural mechanisms have yet to be identified using fMRI. The current study investigated BOLD response differences between twenty survivors (Mean age=23.1(4.14), 55% female) and twenty age- and gender-matched controls from the start to the end of a twenty minute 3-back task. There were no differences in task performance between groups or over time. Effects of practice were present in left prefrontal regions, with both groups showing decreases in activation as the task progressed. There were qualitative and quantitative differences in the brain regions that survivors recruited relative to controls in bilateral prefrontal (including the dorsolateral prefrontal cortex) and parietal cortices. Findings suggest that areas under top-down control of the dorsolateral prefrontal cortex become less activated with practice, and that survivors may require more top-down processing and attentional control to perform at similar levels to healthy controls.

Prior work has shown important effects of the early life environment on development of adult stress response systems in both rats and humans. The present thesis is based on experiments that attempt to explore: 1) adolescent stress responding at hormonal and behavioural levels, and 2) the effects of repeated adolescent stressor exposure on adult stress responding (hormonal and behavioural) and levels of dopamine receptors expressed in prefrontal cortex, using both male and female rats. Defensive behaviours exhibited during stressor exposure and post-stress levels of circulating corticosterone were quantified as behavioural and hormonal measures of stress responding, respectively. In the first study, responses were compared among groups of adolescent rats exposed repeatedly to one of two different types of cat odour stressor stimuli (J-cloth coated in hair/dander or cat collar previously worn by a cat) or control stimuli, and long-term outcomes were examined in adulthood. Adolescent rats showed behavioural responses to both stressor stimuli, but behavioural inhibition was more consistent using repeated cat collar exposure, and this treatment resulted in long-term increases in anxiety-like behaviour in adulthood, whereas a stress-induced adolescent corticosterone elevation was observed only in the group that received exposure to the J-cloth stimuli. In the second study, adolescent and adult rats were compared directly using repeated exposure to the cat collar stressor or control stimuli. Adolescents were found to be more sensitive to the effects of the stressor stimuli, relative to adults. Finally, in the third study, repeated exposure to the J-cloth stressor or control stimuli was used, and stressor-exposed females showed elevated baseline corticosterone levels prior to the final exposure. Furthermore, stressor-exposed males and females showed lower levels of the D2 dopamine receptor in infralimbic and dorsopeduncular cortices of the prefrontal cortex in adulthood. In addition, these studies together provide evidence that sex differences in corticosterone levels emerge during the adolescent period. It may be concluded that adolescence should be considered a sensitive developmental timeframe for stress response programming.

Neural changes in the forelimb cortex were studied at Postnatal (P) 10, 15, 20, 25, 30, and 100 days. Six biological markers of brain development, cortical thickness, Layer III pyramidal cell morphology, glial fibrillary acidic protein (GFAP), myelination, c-fos activity and Acetylcholinesterase (AChE) were correlated with the behavioural development of reaching, bimanual coordination, postural adjustment, and defensive feeding behaviours. The behaviours were filmed from P15 until P30 and then also in adulthood. For the behaviours there was a gradual development of the skilled patterns of paw and digit use seen in adults as well as in the patterns of movements in postural adjustment, carry behaviours and dodging and robbing type behaviours. The development of the adult patterns of movement were correlated to the morphological and biochemical changes in the cortex. The results suggest that the maturation of skilled movements depends upon anatomical and neurochemical maturation of the neocortex as well as upon learning. / x, 132 leaves : ill. ; 28 cm.

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