Title from title page of PDF (University of Missouri--St. Louis, viewed March 3, 2010). Includes bibliographical reference (p. 53-71).

Title from title page of PDF (University of Missouri--St. Louis, viewed February 23, 2010). Includes bibliographical references (p. 61-71).

<p>The ability to monitor, learn from, and respond to social information is essential for many highly social animals, including humans. Deficits to this capacity are associated with numerous psychopathologies, including autism spectrum disorders, social anxiety disorder, and schizophrenia. To understand the neural mechanisms supporting social information seeking behavior requires understanding this behavior in its natural context, and presenting animals with species-appropriate stimuli that will elicit the behavior in the laboratory. In this dissertation, I describe a novel behavioral paradigm I developed for investigating social information seeking behavior in rhesus macaques in a laboratory setting, with the use of naturalistic videos of freely-behaving conspecifics as stimuli. I recorded neural activity in the orbitofrontal and lateral prefrontal cortex of monkeys as they engaged in this task, and found evidence for a rich but sparse representation of natural behaviors in both areas, particularly in the orbitofrontal cortex. This sparse encoding of conspecifics' behaviors represents the raw material for social information foraging decisions.</p> / Dissertation

Source memory is defined as memory for not only the core aspect of some event, but additional contextual detail about that core aspect, or item. Source memory tasks are marked by their engagement of prefrontal cortex in addition to the brain circuits required by other episodic memory tasks. The dissertation examines the relationships among source memory accuracy, concurrent brain activity, and general cognitive principles derived from the study of episodic memory more generally. Electrical measures of brain activity (event-related potentials, ERPs) were recorded while manipulating factors hypothesized to improve or worsen source memory accuracy.The first experiment manipulated the task assigned during the encoding phase and its match to the retrieval demands of remembering objects (depicted in drawings) and their colors. As predicted by the principle of transfer-appropriate processing, source accuracy was higher when the encoding task fostered integration of the item (object) and source (color) attributes. Prefrontal activity during the retrieval phase was greatly reduced when retrieval could benefit from transfer-appropriate processing.In associative memory tasks, poor memory performance is observed when the to-be-retained stimuli share elements with other studied stimuli, as in a variety of interference paradigms. The second experiment thus examined the impact of feature overlap on source recognition by varying the quantitative mapping between the shape and color of an object depicted in a drawing. The results showed two frontal processes supporting source retrieval: an early differentiation between stimuli identical to those encoded and those that switch colors from study to test, and a later effect reflecting prolonged memory search that was truncated by reinstating unique object-color pairings at test.The final experiment compared conjunctions of "intra-item" versus "extra-item" features, by placing the features within a single visual object or distributing them across two visual objects. Source accuracy was worse when shape and color were spatially separated, but prefrontal activity did not vary. The insensitivity of prefrontal ERPs to this perceptual manipulation of difficulty stands in contrast to their sensitivity to encoding task. Individual variability in parietal ERPs was strongly correlated with source accuracy, and likely reflects a contribution of visual working memory to long-term memory.

The feasibility of using real-time functional magnetic resonance imaging (fMRI) feedback regarding the level of activation in rostromedial prefrontal cortex (rMPFC) to learn improved regulation of this brain area was examined in a group of 5 young adults. Subjects received real-time feedback from the target brain region while engaging in a blocked-design task involving alternating blocks of attempted up-regulation and down-regulation of the target brain region. A transient negative emotional state was induced prior to each scanning session. Subjects completed 6 scanning sessions (a pre-training session, 4 feedback sessions and a post-training session - no feedback was provided for pre and post-training sessions). The guideline strategy provided to subjects of engaging in emotional awareness during up-regulation and bodily awareness during down-regulation was found to consistently regulate the region in the pre-training session prior to the fMRI feedback sessions. This finding is in line with the previously proposed role of the rMPFC in emotional awareness. In contrast to previous real-time fMRI findings, greater recruitment of the region was observed in the pre-training session compared to the post-training session, with a non-significant negative trend observed across feedback sessions. These results suggest that there may be limitations to which the feedback techniques successfully employed for other brain regions extend to yet unexplored brain regions.

Many studies of ‘executive control’ have focused on the prefrontal cortex (PFC), which contains the neuronal functional properties, modulatory neurotransmitters, and network connections with sensory and motor regions to make this large brain area a candidate region to provide all the necessary elements to voluntarily control behavior. However, like the motor and premotor cortex, the PFC is integrated with the basal ganglia (BG) in such a similar fashion, that it is impossible not to consider that the PFC might depend on the BG to implement executive control effectively. This thesis draws on knowledge of PFC and BG function, and combines studies that require the instantaneous top-down control over motor behavior with a neurological patient group with primarily BG dysfunction (Parkinson’s disease), to provide for a new understanding of prefrontal-BG networks sub-serving executive control. The tasks performed by subjects consist of antisaccades (generate a voluntary eye-movement away from a visual stimulus) and those dealing with task switching (change behavior after an alternate was previously required). Numerous neural and functional imaging studies have identified key areas of the prefrontal cortex and BG that are critical to antisaccade generation, and studies in task switching have implicated similar neural mechanisms that are involved in overriding one behavior with another. By combining task switching with antisaccades, this thesis specifically examines the neural mechanisms related to suddenly changing behavior, under conditions where one behavior is easier to perform than the other. The methods utilize on-line eye-tracking in healthy young adults and older adults with, and without, Parkinson’s disease, to develop theories of a role of the BG in executive control, and to search for specific neural correlates of executive control signals in the PFC, premotor cortex and BG using functional magnetic resonance imaging (fMRI). Together, the conclusions drawn from this thesis point to an important role of the BG in overriding more automatic behavior with behavior that is more difficult to perform. This thesis also suggests that this overriding mechanism occurs through the boosting of cortical executive control signals via net excitatory feedback from the BG. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2010-09-09 12:17:46.904

L-glutamate (Glu) is the predominant excitatory neurotransmitter inthe mammalian central nervous system (CNS) and is associated with a widevariety of functions including motor behavior and sensory perception. Whilemicrodialysis methods have been used to record tonic levels of Glu, little isknown about the more rapid changes in Glu signals that may occur in awakeanimals. We have previously reported acute recording methods using anenzyme-based microelectrode array (MEA) with fast temporal resolution (800msec), that is minimally invasive and is capable of detecting low levels of Glu (andlt;0.2 ??M) in anesthetized animals with little interference from other analytes. Wehave made a series of modifications to the MEA design to allow for reliablemeasures in the brain of awake behaving rats. In these studies, wecharacterized the effects of chronic implantation of the MEA into the striatum andprefrontal cortex (PFC) of Fischer 344 and Long Evans rats. We measuredresting levels of Glu and local application of Glu for 7 days without a significantloss of sensitivity and determined that Glu measures due to exogenous Gluvaried between rat strain and brain region. In addition, we determined theviability of the recordings in the brains of awake animals. We performed studiesof tail-pinch induced stress which caused an increase in Glu in the striatum andPFC of Long Evans and Fischer 344 rats. Histological data show that chronicimplantation of our MEAs caused minimal injury to the CNS. Taken together, ourdata support that chronic recordings of tonic and phasic Glu can be carried out inawake rats reliably for 7 days in vivo allowing for longer term studies of Gluregulation in behaving rats.

No description available.

Behavioral evidence has shown that older adults are less able to overcome proactive interference in memory than young adults. However, it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require post-retrieval selection, a process thought to be mediated by the left mid-ventrolateral prefrontal cortex (VLPFC). Further, selection may resolve interference by enhancing or suppressing perceptual processing. The present fMRI study investigated whether age-related changes in VLPFC-mediated post-retrieval selection underlie older adults' deficits in overcoming interference in associative memory. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that as interference increased, memory performance decreased similarly across groups. Across groups, activity in the left mid-VLPFC also increased with interference. However, right PFC post-retrieval monitoring effects, but not left mid-VLPFC, distinguished successful vs. unsuccessful resolution of interference for both young and older adults, suggesting selection alone may be insufficient for successful resolution of interference. Age-related memory deficits may be related to reduced recruitment of relational processing effects in the dorsolateral and anterior PFC, as well as reduced memory retrieval effects in the hippocampus. Lastly, results showed evidence that selection may modulate perceptual processing of retrieved memory representations. Namely, activity in the parahippocampal place area (PPA) was greater when participants selected scene, versus face, regardless of accuracy. Further, older adults showed reduced effects in the PPA, possibly reflecting reduced differentiation of perceptual processing. Taken together, these results suggest age-related deficits in overcoming proactive interference are not related to post-retrieval selection, but reduced recruitment of PFC-mediated relational processes, coupled with reduced associative memory retrieval.

There is a large sex difference in the prevalence of attention deficit disorder; yet, little is known about sex differences in prefrontal attention circuitry. We investigated sex differences in the developmental nicotinic excitation of corticothalamic layer VI neurons, which play an important role in attention. Using whole cell recording in prefrontal brain slices, we examined the inward currents elicited by nicotinic stimulation in rodents. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater α4β2* nicotinic currents. Immunohistochemical analysis of α4YFP mice revealed no sex difference in the pattern or proportion of YFP-positive neurons in layer VI. Further electrophysiological experiments revealed that progesterone is able to rapidly and significantly suppress nicotinic currents in layer VI neurons. This is the first illustration at a cellular level that prefrontal attention circuitry is differently excited by nicotinic stimulation in males and females during development.