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The developmental trajectory of contour integration in autism spectrum disorders
Year of Dissertation:
Sensory input is inherently ambiguous and complex, so perception is believed to be achieved by combining incoming sensory information with prior knowledge. One model envisions the grouping of sensory features (the local dimensions of stimuli) to be the outcome of a predictive process relying on prior experience (the global dimension of stimuli) to disambiguate possible configurations those elements could take. Contour integration, the linking of aligned but separate visual elements, is one example of perceptual grouping. Kanizsa-type illusory contour (IC) stimuli have been widely used to explore contour integration processing. Consisting of two conditions which differ only in the alignment of their inducing elements, one induces the experience of a shape apparently defined by a contour and the second does not. This contour has no counterpart in actual visual space - it is the visual system that fills-in the gap between inducing elements. A well-tested electrophysiological index associated with this process (the IC-effect) provided us with a metric of the visual system's contribution to contour integration. Using visually evoked potentials (VEP), we began by probing the limits of this metric to three manipulations of contour parameters previously shown to impact subjective experience of illusion strength. Next we detailed the developmental trajectory of contour integration processes over childhood and adolescence. Finally, because persons with autism spectrum disorders (ASDs) have demonstrated an altered balance of global and local processing, we hypothesized that contour integration may be atypical. We compared typical development to development in persons with ASDs to reveal possible mechanisms underlying this processing difference. Our manipulations resulted in no differences in the strength of the IC-effect in adults or children in either group. However, timing of the IC-effect was delayed in two instances: 1) peak latency was delayed by increasing the extent of contour to be filled-in relative to overall IC size and 2) onset latency was delayed in participants with ASDs relative to their neurotypical counterparts.
Influences of the Female Reproductive Cycle on Inflammatory Induced Pain Resonses
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Abstract Influences of the Female Reproductive Cycle on Inflammatory Induced Pain Responses by Nicole J. Amador Advisor: Professor Vanya Quiñones-Jenab Clinical and preclinical studies have demonstrated significant sex differences in the perception of inflammatory pain; females display higher nociceptive responses to inflammatory stimuli than male rats. Additionally, the complex endocrinological profile of females has been shown to impact their nociceptive responses. For example, estradiol reduces Phase II behavioral-nociceptive responses after formalin administration. However, little is known about the specific biological pathway(s) and/or mechanisms in which cycling endogenous female sex hormones affect inflammatory pain responses. Current literature has established that cyclooxygenases and prostanoids are major pro-inflammatory mediators directly linked to inflammatory responses. Additionally, glucocorticoids, (i.e. corticosterone) negatively regulate inflammatory induced COX-2, resulting in attenuation of inflammatory responses. The objective of this study was to further understand how fluctuations of endogenous female sex hormones alter inflammatory-induced responses by examining two physiological pathways (i.e. NO/COX-2 regulation of the prostanoid biosynthetic pathway and corticosterone regulation of the NO/COX pathway) which may in part be responsible for these effects. Endogenous peaks of estrogen and progesterone during proestrus, were shown to significantly attenuate behavioral responses after formalin administration. This attenuation of behavioral responding was accompanied by a significant increase in PGD2 serum levels. Cortiscosterone serum levels were unaffected after formalin administration suggesting that regulation of behavioral responses by endogenous hormones may be occurring through a pathway independent of the corticosterone biosynthetic pathway. COX-2 and nNOS levels in the spinal cord were not significantly affected by the estrous cycle, suggesting that regulation of behavioral responses by endogenous hormonal fluctuations may be occurring through a pathway independent of the NO/COX biosynthetic pathway. Furthermore, although no estrous cycle effects were seen in paw withdrawal latency after carrageenan administration, we observed estrous cycle effects in the contralateral paw at baseline and one hour post-injection. Rats in proestrus showed a significant reduction in thermal- induced hyperalgesia as measured by increased paw withdrawal latency. Although no significant differences were seen in PGD2 serum levels, rats in estrus had significantly higher PGE2 serum levels after carrageenan administration. A significant decrease in PWL was observed in rats during estrus, a time of the lowest levels of fluctuating hormones. These results suggest that hormonal troughs during the cycle may affect inflammation through the PG biosynthetic pathway. Finally, during ages when animals are considered "middle aged" attenuation in inflammatory induced behavior was observed. This finding was accompanied by significant decreases in PGE2 and PGD2 levels and a significant increase in corticosterone serum levels. Taken together these results suggest a relationship between endogenous hormonal fluctuations, corticosterone release and PG activity. In summary, our results suggest that endogenous hormonal peaks and troughs effects on inflammation may be mediated through the regulation of the NO/COX-2/prostanoid biosynthetic pathway.
Object Relations, Internal Resources, and HIV/AIDS Risk: A Rorschach Study
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Abstract The purpose of this study was to explore the quality of Rorschach scores of a population who self-reported sexual risk-taking behaviors that place them at increased risk for contracting HIV. It was hypothesized that this group would produce scores indicative of fewer internal resources available for impulse inhibition, specifically capacity for affect regulation and stress tolerance. It was further predicted that a measure of object relations would indicate that study participants would generally experience interpersonal interactions as imbalanced and possibly threatening. This group produced significantly lower scores with regard to affect regulation, but did not differ from the normed, non-clinical sample with regard to stress tolerance. Further, study participants produced scores in the healthy range on the measure of object relational development. The potential theoretical and clinical implications of this finding are discussed.
Electrophysiological markers of short-term visual adaptation: an examination across the schizophrenia spectrum
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Abstract ELECTROPHYSIOLOGICAL MARKERS OF SHORT-TERM VISUAL ADAPTATION: AN EXAMINATION ACROSS THE SCHIZOPHRENIA SPECTRUM by Gizely N. Andrade Adviser: Professor John J. Foxe The experiments comprising this dissertation sought to contribute to the understanding of basic sensory processing in schizophrenia-spectrum disorders and risk-liability. We leveraged the sensitivity of visual processing deficits along with widely reported sensory-gating deficits (in other modalities) to develop a new paradigm assaying short-term visual adaptation to repetitive stimuli. In the first experiment, adaptation properties of the visual system were characterized in neurotypical adults using a classic "paired adaptation paradigm" and a more taxing "block adaptation paradigm," using high-density EEG. In the second experiment, we deployed our new visual adaptation assay in a clinical population. We replicated classic early VEP amplitude attenuation and uncovered novel visual adaptation deficits in participants diagnosed with a schizophrenia-spectrum disorder. We further tested the specificity of these findings by employing a somatosensory analog to the block adaptation paradigm utilizing vibrotactile stimulation of the median nerve. Differences in basic somatosensory function and adaptation were present in the clinical group although less apparent than in the visual system. In the third experiment, we examined whether altered visual adaptation could serve as a schizophrenia endophenotype. We utilized a shortened version of our visual adaptation paradigm (15mins, 32-channel electrode array) to characterize a larger sample of neurotypical adults who were also assessed using the Schizotypal Personality Questionnaire (SPQ). Multiple regression analysis revealed a significant relationship between high SPQ and less sensitive VEP adaptation. Overall the findings across these studies provide strong support for atypical visual adaptation in schizophrenia and suggest a potential role for altered visual adaptation as an electrophysiological schizophrenia endophenotype. Future studies employing pharmacological manipulations (e.g. administering nicotinic treatment or dopamine/glutamate/GABA agonists) and examining first degree relatives of patients may offer greater mechanistic insight into the processes underlying these observed phenomena.
DISSOCIATION AND POTENTIAL SPACE ON THE RORSCHACH AS PREDICTORS OF CONCURRENT PTSD AND SUBSTANCE DEPENDENCE TREATMENT OUTCOMES
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Both posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are ongoing public health crises. Dissociative experiences are considered core processes within both of these conditions (van der Kolk & van der Hart, 1989; Briere & Runtz, 1987; Schafer et al., 2010). Dissociation, which involves the compartmentalization of psychic experience, also exerts a significant influence over psychotherapies that aim to address both PTSD and SUD (Davidson & Foa, 1991; Spitzer, Barnow, Freyberger, & Grabe, 2007). However, dissociation is a wide concept that encompasses several perceptual, cognitive, affective, memory, and self-state processes (Bernstein & Putnam, 1986; Briere, Weathers, & Runtz, 2005). Through separate self-reports and projective measures that operationalize dissociation in distinct ways, this study investigated the quality and intensity of dissociative experiences in a sample of treatment-seeking individuals with comorbid PTSD and SUD. Additionally, this dissertation explored whether these measures of dissociation had significant relationships with treatment outcome. Results: Cross-sectional correlation analysis identified convergence between certain measures of dissociation, but not others. Within hierarchical regression analysis, specific subscales of dissociation demonstrated discrepant relationships with response-to-treatment variables. Altogether, this study further evidenced the multidimensional nature of dissociative processes and, subsequently, the value of multi-method assessment. In addition, separate types of dissociation appeared to differentially influence treatment, indicating a pathway through which to improve customization of treatment planning.
GUILTY STEREOTYPES: THE SOCIAL PSYCHOLOGY OF RACE AND SUSPICION IN POLICE INTERVIEWS AND INTERROGATIONS
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Over 300 people have been exonerated by post conviction DNA testing, unequivocally proving their innocence. Nearly 70% of these post conviction DNA exonerees are members of minority groups, and approximately 69% of those convicted as a result of false confessions are racial/ethnic minorities (www.innocenceproject.org). To date, there is little research on the role of race in police interviews and interrogations. The present research had two goals. First, we examined Black and White participants' experiences during a mock crime interview. Second, using the interviews from Study 1, we evaluated the role suspect race plays in police officers' veracity judgments. Using a sample of community members, Black and White suspects in Study 1 reported similar levels of anxiety and exhibited similar rates of nonverbal behaviors commonly believed to be cues to deception. Similarly, Black and White suspects cooperated with the investigation at similar rates. Police officers in Study 2 exhibited chance levels of accuracy in their culpability decisions. However, police officers were significantly more likely to misjudge innocent Black suspects as guilty than innocent White suspects, while showing no difference in their accuracy rates for guilty suspects. Additionally, police officers judged Black suspects to be less cooperative and less forthcoming than White suspects. These results suggest that being questioned about a crime is stressful regardless of a suspect's race or ethnicity. They also suggest that innocent Black suspects are at a greater risk of being erroneously judged as guilty during police interviews and interrogations. Implications and directions for future research are discussed.
Increasing the Variability of Verbal Responding in Children and Adolescents with Autism Using a Conjunctive-Differential Reinforcement Schedule
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A procedure intended to teach variation in appropriate verbal responding to an antecedent stimulus was systematically manipulated for 5 individuals with autism. Four antecedent stimuli that include the clause, "else do you like to do" were presented in a varying order. Five responses that were appropriate to any of the antecedent stimuli were taught using a script-fading procedure. Percentage of varied verbal responses was studied under a conjunctive-differential reinforcement procedure using a multiple-baseline-across-subjects experimental design. Under a modified percentile requirement of the conjunctive schedule, responses were ranked according to their frequency of emission after every session and reinforcement was omitted for the 2 most frequent responses on the subsequent session. Under a lag-1 schedule requirement, reinforcement was omitted for consecutive occurrences of a given response within a given session. Data showed that the percentage of responses meeting the conjunctive schedule requirement increased with the systematic implementation of the schedule. A variability measure showed that responses were more stereotyped during baseline sessions in comparison to treatment sessions. Comparisons between the numbers of different statements emitted by individuals with autism versus those of their typically developing peers suggest that further research is necessary to increase responding to a typical level. Nevertheless, responses by teachers and parents to a social validity questionnaire suggest that the procedure could be applied in clinical and home settings and used to increase varied verbal responding.
Construction of a Forced-Choice Task for the Assessment of Factual Understanding and Feigning in Competency to Stand Trial Evaluations
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Psychologists are commonly called upon to conduct evaluations of a defendant's competency to stand trial. Under Dusky v. United States (1960) the legal criteria for competency to stand trial were enumerated and since then, a number of standardized assessment instruments that aim to assess those criteria have been developed, each with its own noted strengths and weaknesses. Although there are several instruments available to aid clinicians in these types of evaluations, only three include screens for feigning, and only one assesses for feigned cognitive impairment. In the current research an instrument was constructed to assess for competence related knowledge, while also incorporating several logical and statistical methods to assess for a feigned lack of knowledge of the legal system, including forced-choice testing, floor effect strategies, and completion time methodologies. The Factual Understanding Instrument (FUI) was constructed over five studies. Studies 1-3 involved instrument construction and included a review of the literature, a critical incidents phase with experts in the field, and item construction. Studies 4-5 focused on item evaluation and included an expert review of the constructed items and the pilot testing of the FUI in a simulation study with unimpaired college students. In study 5, multiple statistical analyses were conducted to evaluate the FUI items and the various feigning detection strategies. In this sample reliability of the FUI was high. Items were relatively easy for honest responding participants, with many scoring near perfect. Feigning participants did not score as low as would be predicted by symptom validity testing, as responses varied from less than 50% correct to values seen in honest responders. Intelligence level, item difficulty, and response condition were found to be significant predictors in responses to FUI items. Completion time was not supported as a feigning detection method as hypothesized, however, alternative interpretations of the theory are offered. Further research on the FUI with a known-groups sample in forensic settings is needed to establish a floor value, to further evaluate item performance, and to improve the external validity of the current research. Research methodologies and future directions are offered.
SUPRASPINAL AND SPINAL MECHANISMS OF MORPHINE-INDUCED HYPERALGESIA
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Morphine is the most prominent pharmacological treatment for moderate to severe pain in both acute and chronic paradigms. However, morphine notoriously elicits a paradoxical state of increased pain sensitivity known as hyperalgesia that complicates its use in clinical application. Research over the past three decades has reported that morphine-induced hyperalgesia is dose- and sex-dependent, and likely involves the synchronous activity of several neural networks beyond the opioid system. Whereas systemic, supraspinal, and spinal administration of morphine all cause hyperalgesia that is differentially reversible by N-methyl-D-aspartate receptor (NMDAR) antagonists or melanocortin-1 receptor (MC1R) antagonists, it is unknown as to whether or not these non-opioid systems that contribute to this state are located supraspinally or spinally. The current studies were performed with the goal of elucidating the precise location of regulatory action of this sex- and dose- dependent state of morphine hyperalgesia. In all studies, outbred CD-1 male and female mice were pretreated with the general opioid receptor antagonist, naltrexone (NTX) 24 hours prior to morphine treatment. All mice were subsequently implanted with osmotic pumps, continuously dispensing a low (1.6mg/kg/24h) or high dose of morphine (40mg/kg/24h). As noted previously, mice of both sexes were hyperalgesic by Day 4 of continuous infusion of either morphine dose, a state that persisted through Day 6 of infusion. The first series demonstrated that NMDAR and MC1R systems that mediate this morphine-induced hyperalgesic state are located supraspinally, as intracerebroventricular injections of MK-801 and MSG606, respectively successfully reversed hyperalgesia during a one-hour testing period. A second series of studies investigated possible involvement of spinal systems. Whereas intrathecal MK-801 significantly reversed hyperalgesia in males at both doses, and females at the low morphine infusion dose, spinal administration of MSG606 significantly reduced hyperalgesia in females following continuous high dose morphine infusion. This indicates that the sex-dependent mechanism involved in morphine-induced hyperalgesia is located supraspinally and spinally, and either locus can independently modulate female-typical hyperalgesia. A third series of studies investigated hormonally-regulated mechanisms involved in morphine-induced hyperalgesia. Ovariectomized females displayed male-typical patterns of hyperalgesia after i.c.v. and i.t. antagonist injection paradigms following continuous infusion of either dose of morphine on Day 4. On Day 6, NMDAR and MC1R antagonist injections were preceded by an acute systemic progesterone injection in ovariectomized female mice, and intact male mice. Following continuous morphine infusion, ovariectomized females displayed male-typical patterns of hyperalgesic reversal. However, following progesterone administration, hyperalgesia elicited by high doses of morphine was reversed by i.c.v. injection of MK-801 and MSG606 in both males and ovariectomized females. Conversely, following i.t. injections the data show that ovariectomized females are able to recruit the NMDAR or MC1R system, while males exclusively used the NMDAR system to mediate hyperalgesia. The current studies indicate that in terms of modulating morphine-induced hyperalgesia, there are both supraspinally- and spinally-regulated sex-dependent effects that mediate morphine-induced hyperalgesia.
Cerebrospinal Fluid Biomarkers for the Differential Diagnosis of Normal Pressure Hydrocephalus and Alzheimers Disease
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Differential diagnosis of Idiopathic Normal Pressure Hydrocephalus (NPH) is complicated by symptomatic overlap with neurodegenerative conditions such as Alzheimers Disease (AD). Efforts to improve diagnosis through the use of cerebrospinal fluid (CSF) biomarkers have led to the identification of more than a dozen potential diagnostic markers for NPH. However, no single biomarker has proven sufficient for differential diagnosis in clinical practice. The current study uses proteomic analysis of CSF to identify sets of protein markers that are expressed differentially in NPH and AD. Two-dimensional gel electrophoresis was used to analyze the CSF of 8 probable NPH and 8 probable AD patients. Gels were stained with SYPRO Ruby and the percentage volume of over 1339 spots was determined. The Random Forest statistical method was used to identify proteins that optimally segregated NPH cases from AD. Protein identification was achieved by the use of a previously published CSF map and mass spectrometry. Eleven protein spots were found to optimally distinguish the groups, correctly classifying 100% of all NPH and AD samples. Of the 11 proteins of interest, six were identified and include the following: beta-trace, serum albumin A, serum albumin B, apolipoprotein A-IV precursor, pigment epithelium-derived factor, and complement component 3 precursor. The current study identifies CSF biomarkers that differentiate between NPH and AD cases. The highly successful separation of cases obtained in this study suggests that multiplexed CSF markers have the potential to improve the differential diagnosis of NPH from one of its most common competing diagnoses.