Change Detection Memory in Rhesus Monkeys and Humans

Visual short-term memory (VSTM) is the storage of visual information over a brief time period (usually a few seconds or less). Over the past decade, the most popular task for studying VSTM in humans has been the change detection task. In this task, subjects must remember several visual items per trial in order to identify a change following a brief delay interval. Results from change detection tasks have shown that VSTM is limited; humans are only able to accurately hold a few visual items in mind over a brief delay. However, there has been much debate in regard to the structure or cause of these limitations. The two most popular conceptualizations of VSTM limitations in recent years have been the fixed-capacity model and the continuous-resource model. The fixed-capacity model proposes a discrete limit on the total number of visual items that can be stored in VSTM. The continuous-resource model proposes a continuous-resource that can be allocated among many visual items in VSTM, with noise in item memory increasing as the number of items to be remembered increases. While VSTM is far from being completely understood in humans, even less is known about VSTM in non-human animals, including the rhesus monkey (Macaca mulatta). Given that rhesus monkeys are the premier medical model for humans, it is important to understand their VSTM if they are to contribute to understanding human memory. The primary goals of this study were to train and test rhesus monkeys and humans in change detection in order to directly compare VSTM between the two species and explore the possibility that direct species comparison might shed light on the fixed-capacity vs. continuous-resource models of VSTM. The comparative results suggest qualitatively similar VSTM for the two species through converging evidence supporting the continuous-resource model and thereby establish rhesus monkeys as a good system for exploring neurophysiological correlates of VSTM.

Psychiatric severity and behavior change in alcoholism

Individuals who are diagnosed with a chronic mental illness and an alcohol use disorder comprise a high risk population that challenges the mental health care system. Effective treatment for the dually diagnosed, who are characterized by heterogeneity in their psychiatric diagnoses, their substance use patterns, and their current degree of dysfunction, presents a challenge. Several integrated treatment models have been developed that attempt to concurrently treat patients' psychiatric and substance abuse problems. At this point in the development of these "dual diagnosis" programs, treatment planning is hindered by a lack of knowledge about the relation of psychiatric severity to the process of recovery from alcohol abuse and dependence.^ The present study sought to advance the field's understanding of the relation between psychiatric severity and the process of behavior change through an examination of the relation between dimensions of psychiatric severity and Prochaska and DiClemente's Transtheoretical Model (TTM) constructs. The TTM, which focuses on identifying the processes of change that appear to underlie the modification of addictive behaviors, provides a way of conceptualizing and measuring specific elements relevant to the desired behavior change. Knowledge of the relation between these constructs and psychiatric severity will enable treatment planners to develop dual diagnosis programs which target clients' needs with a much higher level of specificity.^ One hundred-thirty two alcohol dependent patients in a dual diagnosis treatment program were assessed on psychiatric severity (defined as number of symptoms and level of distress resulting from symptoms) and the Transtheoretical Model constructs. The constructs include stages and processes of change for alcohol use, alcohol decisional balance, and alcohol abstinence self-efficacy. Results indicate that the TTM variable of "temptation to drink" is most strongly related to psychiatric severity: the more psychiatric distress a person is experiencing, the more he or she is tempted to drink. The "cons" of drinking were also related to psychiatric severity, indicating that participants who were experiencing more psychiatric distress also endorsed as important a higher number of the negative aspects of drinking.^ Additional aims of this investigation were to determine whether participants' scores on the Transtheoretical Model variables were associated with their: (a) severity of drinking, defined as frequency, quantity and consequences of use, (b) previous psychiatric and substance abuse treatment episodes, and (c) functional impairment. Associations were found among these variables and each of the key constructs of the Transtheoretical Model. Each association is explored in detail and implications for treatment programming are discussed. ^

Changes in serum lipids with change and fluctuation in body mass index and body fat distribution in Mexican Americans with type 2 diabetes

This dissertation was written in the format of three journal articles. Paper 1 examined the influence of change and fluctuation in body mass index (BMI) over an eleven-year period, on changes in serum lipid levels (total, HDL, and LDL cholesterol, triglyceride) in a population of Mexican Americans with type 2 diabetes. Linear regression models containing initial lipid value, BMI and age, BMI change (slope of BMI), and BMI fluctuation (root mean square error) were used to investigate associations of these variables with change in lipids over time. Increasing BMI over time was associated with gains in total and LDL cholesterol and triglyceride levels in women. Fluctuation of BMI was not associated with detrimental lipid profiles. These effects were independent of age and were not statistically significant in men. In Mexican-American women with type 2 diabetes, weight reduction is likely to result in more favorable levels of total and LDL cholesterol and triglyceride, without concern for possible detrimental effects of weight fluctuation. Weight reduction may not be as effective in men, but does not appear to be harmful either. ^ Paper 2 examined the associations of upper and total body fat with total cholesterol, HDL and LDL cholesterol, and triglyceride levels in the same population. Multilevel analysis was used to predict serum lipid levels from total body fat (BMI and triceps skinfold) and upper body fat (subscapular skinfold), while controlling for the effects of sex, age and self-correlations across time. Body fat was not strikingly associated with trends in serum lipid levels. However, upper body fat was strongly associated with triglyceride levels. This suggests that loss of upper body fat may be more important than weight loss in management of the hypertriglyceridemia commonly seen in type 2 diabetes. ^ Paper 3 was a review of the literature reporting associations between weight fluctuation and lipid levels. Few studies have reported associations between weight fluctuation and total, LDL, and HDL cholesterol and triglyceride levels. The body of evidence to date suggests that weight fluctuation does not strongly influence levels of total, LDL and HDL cholesterol and triglyceride. ^

Adherence to a lifestyle physical activity program: Trends over time and associations with processes of change and physical activity

Research on lifestyle physical activity interventions suggests that they help individuals meet the new recommendations for physical activity made by the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM). The purpose of this research was to describe the rates of adherence to two lifestyle physical activity intervention arms and to examine the association between adherence and outcome variables, using data from Project PRIME, a lifestyle physical activity intervention based on the transtheoretical model and conducted by the Cooper Institute of Aerobics Research, Dallas, Texas. Participants were 250 sedentary healthy adults, aged 35 to 70 years, primarily non-Hispanic White, and in the contemplation and preparation stages of readiness to change. They were randomized to a group (PRIME G) or a mail- and telephone-delivered condition (PRIME C). Adherence measures included attending class (PRIME G), completing a monthly telephone call with a health educator (PRIME C), and completing homework assignments and self-monitoring minutes of moderate- to vigorous physical activity (both groups). In the first results paper, adherence over time and between conditions was examined: Attendance in group, completing the monthly telephone call, and homework completion decreased over time, and participants in PRIME G were more likely to complete homework than those in PRIME C. Paper 2 aimed to determine whether the adherence measures predicted achievement of the CDC/ACSM physical activity guideline. In separate models for the two conditions, a latent variable measuring adherence was found to predict achievement of the guideline. Paper 3 examined the association between adherence measures and the transtheoretical model's processes of change within each condition. For both, participants who completed at least two thirds of the homework assignments improved their use of the processes of change more than those who completed less than that amount. These results suggest that encouraging adherence to a lifestyle physical activity intervention, at least among already motivated volunteers, may increase the likelihood of beneficial changes in the outcomes. ^

Analysis of life expectancy using linear and nonlinear models

Life expectancy has consistently increased over the last 150 years due to improvements in nutrition, medicine, and public health. Several studies found that in many developed countries, life expectancy continued to rise following a nearly linear trend, which was contrary to a common belief that the rate of improvement in life expectancy would decelerate and was fit with an S-shaped curve. Using samples of countries that exhibited a wide range of economic development levels, we explored the change in life expectancy over time by employing both nonlinear and linear models. We then observed if there were any significant differences in estimates between linear models, assuming an auto-correlated error structure. When data did not have a sigmoidal shape, nonlinear growth models sometimes failed to provide meaningful parameter estimates. The existence of an inflection point and asymptotes in the growth models made them inflexible with life expectancy data. In linear models, there was no significant difference in the life expectancy growth rate and future estimates between ordinary least squares (OLS) and generalized least squares (GLS). However, the generalized least squares model was more robust because the data involved time-series variables and residuals were positively correlated. ^

Experimental models for p53, hepatitis B and aflatoxin hepatocarcinogenesis

The major risk factors for liver cancer in Southeast Asia: HBV infection, aflatoxin exposure and p53 expression/mutation, were examined in experimental models. Four groups were examined for development of hepatocellular carcinoma (HCC) with and without neonatal exposure to aflatoxin (AFB$\sb1)$: (Group I.) Transgenic HBsAg mice with one p53 allele. (Group II) Transgenic HBsAg mice with two p53 alleles. (Group III) Non-transgenic litter mates with one p53 allele. (Group IV) Non-transgenic litter mates with two p53 alleles. HCC developed in Group I animals exposed to aflatoxin at an earlier time and were of a higher grade than those seen later in other groups. These results provide an explanation for as to why p53 is a target for deletion and/or mutation in human HCC especially when found in high risk areas where HBV infection and Aflatoxin B1 food contamination is high, and nicely illustrates a synergistic interaction among these three factors. None of the tumors analyzed had loss or mutation in the p53 gene.^ To determine the significance of the specific p53ser249 mutation found in HBV/aflatoxin associated human hepatomas in an in-vivo experimental model using transgenic mice, a two-nucleotide change in the mouse p53 gene at amino acid position 246, which is equivalent to that of 249 in human p53, was introduced. Transgenic mice with mutant p53 controlled by the albumin promoter were generated and shown to express the p53ser246 mutant RNA and protein specifically in liver. Three groups were examined for development of HCC with and without neonatal exposure to aflatoxin: (Group V) Transgenic p53ser246 mice with two p53 alleles. (Group VI) Transgenic p53ser246 mice with one p53 allele. (Group VII) Double transgenic for p53ser246 and HBsAg with two p53 alleles. One hundred percent of male mice with the three risk factors injected with aflatoxin developed high grade liver tumors, compared to 66.6% from group VI and only 14.2% of group V suggesting synergistic interaction between HBsAg and this particular ser246 p53 mutation.^ In order to examine the growth properties of hepatocytes and correlation with p53 loss and/or mutation, cell proliferation and ploidy analysis of liver from normal heterozyous, homozygous null mice and from transgenic mutant p53ser246, mice were studied. Loss of wild-type p53 increased G1/G0 ratios of cells as well as proliferation and decreased cell ploidy. The mutant p53ser246 did not show a significant effect on cell ploidy or proliferation. However a striking 5-10X increase in G1/G0 ratio suggests that this specific mutation specifically induces G0 to G1 transition, which in turn further predisposes hepatocytes to the damaging effect of Aflatoxin. (Abstract shortened by UMI.) ^