The present study was conducted to evaluate perceptions of the importance of various factors that may determine the wage or salary level in jobs. Items describing various job characteristics reflecting the factors of Skill, Effort, Responsibility, Working Conditions, and Organizational characteristics were rated by 510 subjects from a variety of organizations. Results indicated that the items did not cluster into the five categories noted above. Instead, three factors were identified and labeled Job Complexity, Accountability, and Work Context. There were few gender or occupational differences in the ratings of the items. The implications of the results for the development of equitable wage and salary systems are discussed.

<p>This thesis presents research documenting the effectiveness of computer-assisted cognitive remediation for patients with mood disorders. The first chapter provides an overview of cognitive impairment in patients with bipolar disorder (BD) and major depressive disorder (MDD), and a concise review of cognitive remediation in patients with schizophrenia, where the efficacy of these interventions has been reasonably well studied. The results of an analysis comparing neuropsychological test performance in patients with BD, MDD, and healthy controls is presented in Chapter 2, where we show a similar degree of deficit in both patient groups on processing speed, working memory, and mental flexibility tasks, and a greater degree of deficit in patients with BD on delayed recall and verbal fluency tasks. In Chapter 3 we present the results of our primary analysis examining the effectiveness of CACR for patients with BD and MDD; we show significant improvement on neuropsychological tests of working memory and delayed memory following remediation, and positive associations between improvement in neuropsychological test performance, and improvement in subjectively-rated cognitive and psychosocial functioning. Finally, in Chapter 4 we present functional neuroimaging evidence that shows increased activation following cognitive remediation in frontal control regions supporting working memory and in the right hippocampus supporting recollection memory. Although behavioural performance on the corresponding tasks was stable, the observation of increased activation in frontal and medial temporal brain regions following remediation is in line with our finding of improvement on neuropsychological tests of working memory and delayed recall post-training. Taken together, the results presented in this thesis provide convergent behavioural and neural evidence to demonstrate the efficacy of computer-assisted cognitive remediation for patients with mood disorders. These novel findings contribute to a growing body of literature that shows cognitive remediation to be an effective cognitive management strategy across a range of psychiatric and neurological disorders.</p> / Doctor of Philosophy (PhD)

<p>Autism Spectrum Disorder (ASD) is a heterogeneous disorder with a high burden of suffering and economic cost to society. The current Thesis represents a systematic attempt to investigate ASD heterogeneity, as it relates to the measurement and classification of the clinical phenotype. The Thesis integrates information from multiple constructs (symptoms, traits, behaviours), methods (factor analysis, cluster analysis, and factor mixture modeling), populations (clinical and high-risk samples) and time points (at diagnosis and at age 6) for the investigation of the underlying structure of the ASD phenotype in young children. The Thesis consists of four interrelated empirical studies and one Editorial. Results can be organized into three overarching themes: 1) in preschool children with ASD core diagnostic symptoms (social communication deficits and repetitive behaviours) appear to overlap with other emotional/behavioural problems (attention, withdrawal, anxiety, aggression, emotional reactivity); 2) along the heterogeneous autism spectrum there appear to be distinct, relatively homogeneous subgroups of children; on average, children across these subgroups differ in their levels of symptom severity, adaptive skills, and emotional/behavioural problems; 3) the underlying structure of the ASD symptom phenotype changes as children grow and develop. Thesis findings lend support to a much-needed shift in our conceptual and methodological approach to the study of measurement and classification of autism pathology: that is, instead of a set of categorical symptoms that present early in childhood and remain static over the life span, ASD might be better understood as a complex and dynamic disorder, structured on both categorical and dimensional constructs that vary not only across individuals at any given point, but also within individuals across time.</p> / Doctor of Philosophy (PhD)

Neonatal treatment of quinpirole in rats increases dopamine D2-like receptor sensitivity over the animal’s lifetime, a phenomenon referred to as D2 priming. Male and female Sprague-Dawley rats were given quinpirole (1mg/kg, i.p.) or saline on postnatal days (P)1-21. After habituation to a locomotor arena on P29-31, beginning P33, animals were administered nicotine (0.3 mg/kg, 0.5 mg/kg, or 0.7 mg/kg, i.p.) or saline and placed into a locomotor arena for behavioral testing every second day for a total of 9 treatments. The results showed that adolescents neonatally treated with quinpirole produced more enhanced sensitization to nicotine than controls. Brains tissues were analyzed for brain-derived neurotrophic factor (BDNF), a protein involved in neuron development and maintenance. The results showed that neonatal quinpirole treatment produced a significant increase in accumbal BDNF. Also, adolescent nicotine treatment produced a significant increase in BDNF in the nucleus accumbens and dorsal striatum. These findings help to broaden understanding of behavioral and chemical changes involved in schizophrenia and nicotine use and could have applications in aiding to alleviate this common comorbidity.

Nicotine use is very prevalent in the schizophrenic population, which is a 2.5 fold greater than the general population. In the present study, the drug quinpirole (dopamine D2/D3 agonist) or saline was given neonatally to 25 Sprague-Dawley male and female rats. Rats were randomly assigned to condition. Beginning postnatal day 33 animals were given twice daily administrations of nicotine (0.5 mg/kg free base). After the first of the daily injections they were placed in a locomotor arena every other day for behavioral testing. One day after behavioral testing, the dorsal striatum and nucleus accumbens were removed for brain-derived neurotrophic factor (BDNF) assay. BDNF is a neurotrophin that plays an important role in neuronal development, neuronal maintenance and plasticity, and synaptic activity. Results showed that nicotine produced locomotor sensitization but this was not enhanced by neonatal quinpirole, unlike past work. Regarding BDNF, there was a significant increase in the nucleus accumbens in rats treated with nicotine; neonatal quinpirole increased the BDNF response produced by nicotine. Nicotine produced an increase in dorsal striatum BDNF that was not affected by neonatal quinpirole treatment. Importantly, it appears that nicotine administrations, that occurred in two different contexts, may result in differential behavioral results relative to nicotine administrations given consistently in the same context.

Incremental improvements are continuously being made to P300-Speller BCI paradigms. Accurate classification depends on a high signal-to-noise ratio (SNR) between the target and nontarget items. Fixed presentation rates produce a large flash-evoked response that persists throughout the recording epoch, which can potentially undermine the classification of P300-responses. By introducing a random interstimulus interval (ISI) to a previously improved P300-Speller paradigm (i.e., Checkerboard Paradigm; CBP) we expect to reduce the deleterious flash-evoked responses and increase the P300 classification SNR. Data were recorded from 32 EEG locations (right mastoid referenced) from 13 subjects using the CBP with two conditions. In the Random ISI (RI) condition, ISI varied between 0 ms and 187.5 ms and averaged 93.75 ms. In the Fixed ISI (SI) condition, ISI remained static at 93.75 ms. In both conditions, participants were instructed to spell out 72 characters using an 8x9 matrix of alphanumeric characters by silently counting each target flash. The first 36 characters served as ‘calibration’ data for a stepwise linear discriminant analysis (SWLDA; 0 - 800 ms poststimulus epochs). This SWLDA classifier was then used to provide online feedback for an additional 36 character selections. Absolute amplitude of target and nontarget responses were summed across the recording epoch for each subject and averaged between Pz and Cz (maximum). Target averages were then divided by nontarget averages to create a SNR measure and compared between RI and FI conditions. The RI manipulation produced a significantly (p = .04) larger SNR (M = 5.85) than the FI condition (M =4.07).Further analysis of the averaged waveforms revealed a significantly (p = .05) greater positive peak at Cz (253 ms peak latency) for the RI condition. Classification performance measures for RI and FI conditions were high for accuracy (84 and 85%, respectively; NS) and bitrate (21 and 23 bits/min, respectively; NS). Together these results suggest that while randomizing ISI can yield higher SNR, response classification is not affected. It is possible that SWLDA is a useful classification method, in general; however, these data suggest that it does not capitalize on the additional information gained from the increase in SNR. Alternative classification techniques that can take advantage of specific subcomponents of the response may be able to utilize this additional information to improve BCI speed and accuracy.

The aim of this thesis is to examine the mechanisms of Methylphenidate (MPH) on Conditioned Place Preference (CPP), a behavioral test of reward. The psychostimulant MPH is therapeutically used in the treatment of ADHD, but has been implicated in many pharmacological actions related to drug addiction and is considered to have abuse potential. Past work in our lab and others have shown substantial sex-differences in the neuropharmacological profile of MPH. Here a discussion of the relevant mechanisms of action of MPH and its relationship to neurotrophins and CPP are reviewed. Furthermore, previous work is reviewed and a rationale for two experiments are presented. The study resulted in two experiments conducted earlier this year. Each experiment is presented, examining sex differences in CPP in two different methodological paradigms as well as the effects of MPH on levels of the dopamine transporter (DAT) in striatal and accumbal neurons.

Traumatic brain injury (TBI) causes life-debilitating conditions. While patient survival after a TBI has improved, the outlook for quality of life after TBI currently remains poor. In order to address this problem, there is a significant unmet need for new therapeutic options to prevent progression of deficits associated with TBI. To this end, we investigated two strategies to combat the deleterious affect of TBI. First, we targeted cerebral acidosis associated with TBI by testing whether disruption of acid sensing ion channel 1a (ASIC1a) in CNS, or buffering acidosis with sodium bicarbonate, could prevent neurological deficits after TBI. We next tested whether treatment with the neovel class of aminopropyl carbozoles, known as the P7C3 series, could also prevent TBI-associated neurological decline. Using the mouse fluid percussion injury model of TBI, we observed post-injury acidosis in the cortex, consistent with what has been shown in humans following brain injury. Administering HCO3- after fluid percussion injury prevented acidosis and reduced neurodegeneration. Because acidosis activates acid sensing ion channels (ASICs), we also studied AIC1a-/- mice and found reduced neurodegeneration after injury. Both HCO3-3 administration and loss of ASIC1a reduced functional deficits caused by fluid percussion injury. These results suggest that fluid percussion injury induces cerebral acidosis, which activates ASIC channels in the brain and contributes to neurodegeneration. Blocking ASIC1aactivity may thus offer a new therapeutic strategy to attenuate the adverse consequences of TBI. We next applied the blast injury model of TBI to test whether the P7C3 class of neuroprotective aminopropyl carbazoles would be of therapeutic benefit. In addition to preventing neuronal cell death, P7C3 molecules also preserved axonal integrity before neuronal cell loss in this model. The mechanism of P7C3 neuroprotection may be linked to its ability to activate the enzyme, nicotinamide phosphoribosyltransferase, which catalyzed the rate limiting step of nicotinamide adenine dinucleotide salvage pathway. Administration of the lead compound in the series, P7C3-S243, 1 day after blast-mediated TBI blocked axonal degeneration and preserved normal synaptic activity. P7C3-S243 administration also reduced neuronal functional deficits, including impaired learning, memory, and motor coordination in mice. We additionally reported persistent neurologic deficits and acquisition of anxiety-like phenotype in untreated animals 8-months after blast-mediated TBI. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both. Together, the results of this body of work identify novel therapeutic interventions that may attenuate deficits associated with TBI, and thus improve the quality of life in people after TBI.

This study addresses the use of attitude and personality variables as predictors of compensation and award in a personal injury suit. Safety seeking behavior and attitudes toward tort reform are introduced as case-specific factors that may predict this verdict decision. Two hundred registered voters were surveyed on scales measuring attitudes toward safety, tort reform, and psychiatrists. Subjects also indicated their demographic characteristics and the degree of compensation and amount of award they would render the plaintiff in a civil suit. Results indicated attitudinal variables were more predictive of compensation and award than were demographic variables. The implications of these findings are discussed.

No description available.