An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat.

The goals of this research were to develop a within-subject test of spatial working memory and performance for the rat in a T-maze, based on a delayed alternation, or "win-shift" foraging strategy. Using this model, specific aims were to compare the effects of: (1) age, (2) basal forebrain, medial septal, and amygdala lesions, (3) four vessel occlusion (4-VO), forebrain ischemia, and (4) physostigmine, scopolamine, arecoline, piracetam, and clonidine on memory and performance of young middle-aged, and old rats. Aging significantly impaired working memory and performance of Long-Evans rats. Memory of septal and basal forebrain, but not of amygdala lesioned rats was significantly impaired without effects on performance. Transient, 4-VO forebrain ischemia produced significant memory impairment, without effects on performance, and highly selective CA1 cell loss in the hippocampus. Physostigmine enhanced working memory in middle-aged and old rats. Scopolamine impaired memory in young, middle-aged, and old rats. Physostigmine reversed the scopolamine impairments of working memory. Arecoline enhanced memory in old rats without effects on performance. Piracetam and clonidine had no direct effects on memory, but piracetam increased and clonidine decreased speed of performance. From the aging, lesion, ischemia, and drug studies it was concluded that there was a convergence of evidence from 4 different approaches for a critical role for the hippocampus, particularly the CA1 fields, in spatial working memory.

Effect of exercise on longevity, body weight, locomotor performance, and passive-avoidance memory of C57BL/6J mice.

Studies of human and animal subjects have suggested that exercise may retard aging, help prevent age-related diseases, and prolong life span. Earlier studies focused on the effects of exercise on the heart, skeletal muscles, lungs, metabolism, and longevity. Researchers recently have begun to direct their attention to possible benefits of exercise on the brain. The goals of this study were to examine the effects of voluntary wheel-running exercise on life span, body weight, food and water intake, locomotor performance, and one-trial passive-avoidance memory of mature (10-14 month), middle-aged (20-24 month), and old (28-30 month) C57BL/6J male mice. No significant differences in life span, expressed in months, were found between control and exercised mice when exercise was carried out during maturity, senescence, intermittently across both periods, or continuously throughout maturity and senescence. Exercised adult mice maintained body weight compared to adult controls, an effect not apparent in old mice. Locomotor performance was reduced in old mice, and exercise increased performance much more in adult than in old mice. In the passive avoidance test of recent memory, exercise significantly increased latency, that is, it improved retention, in adult, middle-aged, and old mice. The effect was greatest in middle-aged, next in old, and lowest in adult mice. The findings indicate that exercise may be an important modulator of the rate of aging.

Temporal order judgements in good and poor readers.

The amount of time required to make accurate (75% correct) temporal order judgements was measured in groups of 3rd and 4th grade children who were selected on the basis of reading ability. The stimuli, two words (Box and Fox), were tachistoscopically presented to the left and right or above and below a fixation point. Subjects were asked to say which word came first under one condition, or which position contained the stimulus that occurred first under another condition. The stimulus onset asynchrony (SOA) was varied in half octave steps until threshold was determined. The results indicate that good readers required significantly longer SOAs to achieve 75% correct than adults, but significantly shorter SOAs than poor readers. There was not a significant difference in thresholds for the word and position conditions for adults or good readers, but poor readers required significantly more time to achieve criterion for the word condition. The word thresholds were highly correlated (-0.77) with reading level, but the correlation between position threshold and reading level was not significant. The implications of a temporal order deficit are discussed.

Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxin lesions.

Rats were trained for 20 days in a modified T maze to perform an invariant, tactile discrimination and a variable, delayed spatial discrimination, and then were exposed either to 30 min of transient forebrain ischemia or to low- or high-dose ibotenic acid to damage the dorsal hippocampus bilaterally. Only rats exposed to ischemia or high-dose ibotenic acid demonstrated impaired performance during 30 postoperative test days on both aspects of the task (p less than .05). Volume of hippocampal damage did not predict performance. However, the extent of CA1 pyramidal neuron loss correlated significantly with performance on the delayed spatial discrimination (p less than .01). Damage to the dentate gyrus and CA2-3 did not correlate with performance. These results support the view that the hippocampus, in particular the CA1 region, is crucial for certain types of memory performance.

Gender differences in the learning status of diabetic children.

The learning status of 95 diabetic boys and girls and 97 matched controls was evaluated using the Wechsler Intelligence Scale for Children--Revised IQ factors and school histories. Of interest was whether diabetic boys would evidence more learning difficulties. Results indicated that diabetic boys had significantly lower Freedom From Distractibility scores compared with scores of diabetic girls and control Ss and lower Perceptual Organization scores compared with scores of control boys. Although group scores were still within the average range of functioning, a significantly high percentage of diabetic boys (40%) compared with diabetic girls (16%) had learning problems that warranted either special instructional services or grade retention. Diabetic children experienced more learning difficulties (24%) than controls (13%), supporting research findings that diabetes is associated with increased risk of learning problems.

Local brainstem glucose utilization in the squirrel monkey.

The 2-deoxy-D-[14C]-glucose method for the measurement of local cerebral glucose utilization (LCGU) in individual brain nuclei and regions has been applied to the squirrel monkey (Saimiri sciureus). The determinations were conducted in five conscious, lightly restrained adult, female, Colombian squirrel monkeys. Local glucose utilization in brainstem structures (LBGU) was highest in nuclei involved in auditory and vestibular functions and in some nuclei involved in general motor activity. The values for glucose utilization (mumoles/100 g/min) were generally lower than in comparable structures reported by other authors in the rat and slightly lower than those in the macaque monkey. In the Beagle dog the values for "medulla" are markedly lower than for most individual structures in the squirrel monkey medulla, about equal in the inferior colliculus and appreciably higher in the superior colliculus.

The shape of the high frequency flicker sensitivity curve.

For a light flickering with a modulation amplitude delta L, there is a single frequency f above which the light appears steady (fused). The relationship between delta L and f has been measured often under a variety of conditions, but its mathematical form is disputed. Three candidate functions have been proposed: (1) log delta L alpha f [Ferry-Porter law], (2) log delta L alpha f1/2 [diffusion model], and (3) log delta L alpha log f [cascaded integrator model]. Although all three functions roughly fit flicker fusion data (after appropriate linear transformation), they differ in curvature. We compared these functions using the general expression (4) log delta L alpha f lambda, where lambda denotes a curvature parameter. Functions (1)-(3) are special cases of (4) with lambda = 1, 0.5, and 0 respectively. When applied to 35 sets of flicker fusion data, the mean values of the best fitting lambda for each data-set was 0.919 (95% confidence interval 1.027 to 0.812). We conclude that the Ferry-Porter law describes most data better than a diffusion model, and that an integrator model deviates consistently in every case.

Hyperuricemia and locomotor activity in developing rats.

This research was motivated by the previous finding that serum uric acid levels correlate with symptoms of hyperactivity in normal children. We attempted, therefore, to investigate this relationship in an animal model. Dose and time relationships between allantoxanamide-induced heightened serum uric acid and locomotor activity were investigated. A dose- and time-dependent relationship was shown between serum uric acid levels and allantoxanamide. Those doses of allantoxanamide which elevated serum uric acid produced time-dependent changes in locomotor activity. In the first two hours following injection, activity increased relative to controls, in the next two-hour block activity decreased, only to rise again above control levels in the third two-hour period. The possible role of uric acid and allantoxanamide are discussed in relation to these complex changes in activity.

Effects of uric acid and caffeine on A1 adenosine receptor binding in developing rat brain.

Previous studies have demonstrated that elevated levels of serum uric acid or caffeine are associated with increased locomotor activity in rats and humans. Since uric acid and caffeine are structurally similar, it was hypothesized that these compounds alter locomotor activity through a common neural mechanism, specifically by acting as receptor antagonists at adenosine A1 binding sites. In vitro competition of caffeine and uric acid against the A1 agonist, [3H] cyclohexyladenosine ([3H]CHA), was conducted using homogenates of adult rat forebrain. Caffeine effectively competed for the A1 binding site as previously reported (IC50 = 107 microM), but uric acid failed to compete with [3H]CHA binding at concentrations within a relevant physiological range. Nevertheless, in vivo experiments indicated that chronic elevation of uric acid following allantoxanamide treatment of male rats on days 4-27 of life significantly decreased A1 receptor binding in the striatum, a region traditionally implicated in mammalian locomotion. In contrast, chronic caffeine treatment on days 4-27 of life caused an increase in A1 receptor binding in the cortex similar to increases reported previously in whole brain. These changes in A1 receptor binding following chronic elevation of uric acid or caffeine did not persist in rats that had been withdrawn from allantoxanamide or caffeine treatment for 14 days. Results from in vitro and in vivo experiments indicate that despite a similar molecular structure uric acid does not act by the same mechanism as caffeine to increase locomotor activity in rats.

The use of dose equivalency as a risk assessment index in behavioral neurotoxicology.

This article reports changes with graduated dosage of alcohol on a standardized set of cognitive and psychomotor performance tests and refers to the approach as dose equivalency. Subjects (N = 20) were tested until their performance was stable on 10 tests from a microcomputer test battery. After administration of sufficient alcohol to achieve .15 blood alcohol level (BAL), using breath as the independent variable, the descending branch of the BAL curve was followed by measuring performance at set levels of alcohol. A dose-response relationship was confirmed in all performance tests (p less than .01), and multiple regression was used to select performance subtests that maximally predicted alcohol level. Four subtests were combined into a linear composite that related well to alcohol levels above 0.05 BAL (shrunken R = .75), which was used in a power function to approximate the roughly linear relation above 0.05, as well as the clearly nonlinear function between 0.05 and zero. It is suggested that alcohol, a powerful central nervous system depressant, can be a useful metric in communicating risk in neurotoxicological research.

Eye movement indices of mental workload.

Four investigations were carried out to assess the feasibility of using eye movement measures as indices of mental workload. In the first experiment, saccadic extent was measured during free viewing while subjects performed low, moderate and high complexity, auditory tone counting as the workload tasks. The range of saccadic extent decreased significantly as tone counting complexity (workload) was increased. In the second experiment the range of spontaneous saccades was measured under three levels of counting complexity with a visual task that did not require fixation or tracking. The results indicated that the extent of saccadic eye movements was significantly restricted as counting complexity increased. In the third experiment, the effects of practice were examined and decreased saccadic range under high tone counting complexity was observed even when significant increases in performance occurred with practice. Finally, in experiment 4, the first experiment was repeated with additional optokinetic stimulation and the saccadic range was again observed to decrease with tone counting complexity. The results indicated that the extent of spontaneous and elicited eye movements was significantly restricted as counting complexity increased. We conclude that this measure may provide a valuable index of mental workload.

Indexing cognitive tests to alcohol dosage and comparison to standardized field sobriety tests.

Cognitive tests from a computerized battery of mental tests and standardized roadside field sobriety tests (FST) were administered in three experiments involving graded dosages of alcohol but different administration schedules. In the first experiment, subjects were raised to one of four levels of alcohol dosage in four sessions 1 week apart. In the second experiment, the descending branch of the blood alcohol concentration (BAC) curve was monitored from 150 mg/dl BAC in a single session. In the third experiment, the ascending and descending limbs of the alcohol dosage curve were followed over a single session. Dose response relationships were observed for all tests, and the changes were statistically significant (p < .001) in all three studies for all tests when evaluated singly, except for grammatical reasoning. When cognitive and FST tests were combined into a single multiple regression analysis, Gaze Nystagmus consistently accounted for the most variance in BAC, followed by code substitution. While multiple regression analyses reveal that tests from the two batteries can be combined to improve overall prediction of alcohol concentration, it is also true that the two batteries share considerable variance (i.e., > 30%). This suggests that, while the two batteries may not be substitutable, they are measuring different aspects of the same thing.

Psychophysical scaling of circular vection (CV) produced by optokinetic (OKN) motion: individual differences and effects of practice.

Vection (V) refers to the compelling visual illusion of self-motion experienced by stationary individuals when viewing moving visual surrounds. The phenomenon is of theoretical interest because of its relevance for understanding the neural basis of ordinary self-motion perception, and of practical importance because it is the experience that makes simulation, virtual reality displays, and entertainment devices more vicarious. This experiment was performed to address whether an optokinetically induced vection illusion exhibits monotonic and stable psychometric properties and whether individuals differ reliably in these (V) perceptions. Subjects were exposed to varying velocities of the circular vection (CV) display in an optokinetic (OKN) drum 2 meters in diameter in 5 one-hour daily sessions extending over a 1 week period. For grouped data, psychophysical scalings of velocity estimates showed that exponents in a Stevens' type power function were essentially linear (slope = 0.95) and largely stable over sessions. Latencies were slightly longer for the slowest and fastest induction stimuli, and the trend over sessions for average latency was longer as a function of practice implying time course adaptation effects. Test-retest reliabilities for individual slope and intercept measures were moderately strong (r = 0.45) and showed no evidence of superdiagonal form. This implies stability of the individual circularvection (CV) sensitivities. Because the individual CV scores were stable, reliabilities were improved by averaging 4 sessions in order to provide a stronger retest reliability (r = 0.80). Individual latency responses were highly reliable (r = 0.80). Mean CV latency and motion sickness symptoms were greater in males than in females. These individual differences in CV could be predictive of other outcomes, such as susceptibility to disorientation or motion sickness, and for CNS localization of visual-vestibular interactions in the experience of self-motion.

Influence of chroma on spatial balance of complementary hues.

In 1905, Munsell proposed that if the relative areas of two colors are adjusted so that they mix to produce a neutral gray on a spinning Maxwell disk, these colors should appear balanced when juxtaposed with the same relative areas in a composition. This law of "inverse ratios of area" indicates that hues of low chroma should require larger relative areas to balance complementary hues of higher chroma. Several experiments have compared colors of varying chroma in terms of apparent weight, but none have assessed the validity of Munsell's law directly. A group of artists and a group of nonartists with no prior training in the use of color adjusted a panel until the relative areas of two complementary colors appeared balanced. Within-subject correlations between actual settings and theoretical predictions were predominantly high and positive. This was especially true of subjects with formal color training.

Differential effects of scopolamine and amphetamine on microcomputer-based performance tests.

Scopolamine (1.0 mg) and d-amphetamine (10 mg) were administered alone and in combination to 16 subjects (medical students), randomly assigned to testing sessions in a fully crossed-over (Latin square) within-subjects design. After being practiced to stability, 9 performance tests from a menu of portable microcomputer-based tests were administered double-blind over 4 weekly treatments (including a placebo). Differential effects of drugs on performance were found. Motor and perceptual speed tests appeared enhanced by d-amphetamine and not degraded by scopolamine. Two of the five cognitive tests showed reductions with scopolamine. The findings are discussed in connection with using a menu of performance tests that can have diagnostic significance for assessment of drug treatments. The effects of scopolamine in this study and others are considered in terms of a model which implies that magnitude of performance deficit depends on performance type (cognitive, motor, self-report) and dosage level. Applying the model, we offer the following summary: below 0.15 mg scopolamine is without any effect; below 0.50 mg, the effect is limited, but can be revealed by some sensitive, complex performance tests and self-report; above 1.0 mg, the effect is likely to impact on operational efficiency.

Relating alcohol-induced performance deficits to mental capacity: a suggested methodology.

Performance tests are generally more reliable and more easily administered than on-the-job measures of performance, and in this way are preferable for studying the adverse consequences of environmental stressors. However, a linkage or context would be useful in interpretation of these laboratory measures. This paper reports findings with two indexing methods using multiple regression. In the first study, we illustrate "dose equivalency" where deficits on microcomputer performance tests were related to graded dosages of alcohol, and prediction equations of blood alcohol level were established. In the second experiment, "surrogate criteria" are demonstrated where cognitive mental tests of military aptitude, known to be predictive of operational performances, were administered to a sample who were tested repeatedly on the same microcomputer performance test. Multiple regression analyses of the computerized tests with the amplitude tests were significant (p < 0.01) and ranged from R = 0.50 to 0.94. Finally, the loss in performance owing to alcohol was indexed to loss on the microcomputer tests through the relationship of the tests to the Armed Services Vocational Aptitude Battery (ASVAB). Since the latter is strongly predictive of all forms of military operational performance, we suggest that alcohol-related losses in microcomputer performance test scores can serve as a useful intermediary, permitting meaningful linkage to these real-world performances.

Cognitive performance deficits in a simulated climb of Mount Everest: Operation Everest II.

Cognitive function at simulated altitude was investigated in a repeated-measures, within-subject study of performance by seven volunteers in a hypobaric chamber, in which atmospheric pressure was systematically lowered over a period of 40 d to finally reach a pressure equivalent to 8,845 m, the approximate height of Mount Everest. The portable cognitive test battery used, Automated Performance Test System (APTS), was specifically designed for field research under adverse environmental conditions as evidenced by compact computer design; automated test administrations, data storage, and retrieval; psychometric properties of stability and reliability; and factorial richness. Significant impairments of cognitive function were seen for three of the five tests in the battery; on two tests, grammatical reasoning and pattern comparison, every subject showed a substantial decrement. The results are discussed in terms of the impact of altitude on specific aspects of cognitive function and the importance of having sensitive and reliable instruments to monitor such effects.

Reduction of visually-induced motion sickness elicited by changes in illumination wavelength.

This experiment was undertaken to assess the degree of stimulus generalization in visually-induced motion sickness. Sixteen subjects participated in six sessions in which they were exposed to a rotating field of vertical stripes for five 4-min trials. This stimulus elicited the perception of self-vection. In the first three sessions, the stripes were illuminated by one monochromatic light (red or green) and in the last three sessions, the stripes were illuminated by the other monochromatic light. Magnitude estimates of motion sickness increased significantly within sessions, but the rate at which this measure increased was significantly diminished across trials in the last three-session block. Magnitude estimates of vection increased within sessions and decreased across sessions, but did not increase with color change. These results can be explained in terms of a model of stimulus generalization and have implications for the reduction of motion sickness in applied settings.

Canonical correlation and chi-square: relationships and interpretation.

A 2 x 2 chi-square can be computed from a phi coefficient, which is the Pearson correlation between two binomial variables. Similarly, chi-square for larger contingency tables can be computed from canonical correlation coefficients. The authors address the following series of issues involving this relationship: (a) how to represent a contingency table in terms of a correlation matrix involving r - 1 row and c - 1 column dummy predictors; (b) how to compute chi-square from canonical correlations solved from this matrix; (c) how to compute loadings for the omitted row and column variables; and (d) the possible interpretive advantage of describing canonical relationships that comprise chi-square, together with some examples. The proposed procedures integrate chi-square analysis of contingency tables with general correlational theory and serve as an introduction to some recent methods of analysis more widely known by sociologists.

Reaction time measures of backward masking.

We employed both simple and choice reaction time (RT) paradigms in which the subjects were required to respond to 3.0 cycles per degree (c/d) square-wave gratings presented to one eye, while checkerboard masks were presented at various stimulus-onset asynchronies to the other eye. No masking was evident using the simple RT paradigm, but with the choice RT task, checkerboard masks presented to the contralateral eye of three subjects resulted in substantial decreases in response speed when the test preceded the mask by stimulus-onset asynchronies of 25 to 75 ms. Masks that contained lower fundamental spatial frequencies (1.0 c/d) than the target were more effective than masks containing fundamental spatial frequencies (6.0 c/d) higher than the target, while masks that contained fundamental components identical to those in the target (3.0 c/d) produced maximum masking. The results offer support for the sustained-transient theory of visual processing and validate RT as a technique for examining spatio-temporal factors in masking.