Barbara J. Strupp

Developmental potential in the first 5 years for children in developing countries

Summary Many children younger than 5 years in developing countries are exposed to multiple risks, including poverty, malnutrition, poor health, and unstimulating home environments, which detrimentally affect their cognitive, motor, and social-emotional development. There are few national statistics on the development of young children in developing countries. We therefore identified two factors with available worldwide data—the prevalence of early childhood stunting and the number of people living in absolute poverty—to use as indicators of poor development. We show that both indicators are closely associated with poor cognitive and educational performance in children and use them to estimate that over 200 million children under 5 years are not fulfilling their developmental potential. Most of these children live in south Asia and sub-Saharan Africa. These disadvantaged children are likely to do poorly in school and subsequently have low incomes, high fertility, and provide poor care for their children, thus contributing to the intergenerational transmission of poverty.

Malnutrition and the Brain: Changing Concepts, Changing Concerns

Our conceptions of how malnutrition endured early in life affects brain development have evolved considerably since the mid-1960s. At that time, it was feared that malnutrition endured during certain sensitive periods in early development would produce irreversible brain damage possibly resulting in mental retardation and an impairment in brain function. We now know that most of the alterations in the growth of various brain structures eventually recover (to some extent), although permanent alterations in the hippocampus and cerebellum remain. However, recent neuropharmacological research has revealed long-lasting, if not permanent, changes in brain neural receptor function resulting from an early episode of malnutrition. These more recent findings indicate that the kinds of behaviors and cognitive functions impaired by malnutrition may be more related to emotional responses to stressful events than to cognitive deficits per se, the age range of vulnerability to these long-term effects of malnutrition may be much greater than we had suspected and the minimal amount of malnutrition (hunger) necessary to produce these long-term alterations is unknown.

Enduring Cognitive Effects of Early Malnutrition: A Theoretical Reappraisal

This article presents a reappraisal of the literature on the enduring cognitive effects of early malnutrition. In addition to summarizing the existing empirical literature, we present a theoretical framework for determining whether the processes likely to be most vulnerable to early malnutrition were adequately assessed. The two types of information used to make this determination are clinical and experimental behavioral data as well as reported neural changes. One point of clear consensus is that animals exposed to early malnutrition exhibit lasting changes in the realm of emotionality, motivation, and/or anxiety. Because these alterations profoundly affect all aspects of behavioral functioning, including cognition, it is suggested that future research focus on these changes, rather than control for them as many past studies have done. The functional integrity of specific cognitive processes is less clear. The only cognitive processes for which enduring cognitive changes were demonstrated in rehabilitated animals--outside of effects mediated by these affective changes--are cognitive flexibility and, possibly, susceptibility to proactive interference. However, the inference that these are the only processes affected does not appear to be warranted on the basis of the evidence that several cognitive processes likely to be affected have not been fully assessed. Examples include executive functions linked to the prefrontal cortex (for example, attention), transfer of learning, procedural learning and long-term memory. Future research focusing on these specific cognitive functions as well as on these unequivocal affective changes should allow a more definitive conclusion regarding the enduring functional consequences of early malnutrition.

Prenatal cocaine exposure impairs selective attention: Evidence from serial reversal and extradimensional shift tasks

This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment.

Tolerance to anorectic drugs: Pharmacological or artifactual ☆

Abstract The results of three studies are presented which demonstrate that the anorexia produced by amphetamine and fenfluramine is secondary to a direct weight suppressing effect of these drugs. Furthermore, these data strongly suggest that the decreasing weight loss and the return to normal appetite that occurs with repeated drug usage is not due to pharmacological tolerance, but rather reflects a successful physiological and behavioral adjustment to a lowered level of body weight.

Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome

In addition to mental retardation, individuals with Down syndrome (DS) also develop the neuropathological changes typical of Alzheimers disease (AD) and the majority of these individuals exhibit dementia. The Ts65Dn mouse model of DS exhibits key features of these disorders, including early degeneration of cholinergic basal forebrain (CBF) neurons and impairments in functions dependent on the two CBF projection systems; namely, attention and explicit memory. Herein, we demonstrate that supplementing the maternal diet with excess choline during pregnancy and lactation dramatically improved attentional function of the adult trisomic offspring. Specifically, the adult offspring of choline-supplemented Ts65Dn dams performed significantly better than unsupplemented Ts65Dn mice on a series of 5 visual attention tasks, and in fact, on some tasks did not differ from the normosomic (2N) controls. A second area of dysfunction in the trisomic animals, heightened reactivity to committing an error, was partially normalized by the early choline supplementation. The 2N littermates also benefited from increased maternal choline intake on 1 attention task. These findings collectively suggest that perinatal choline supplementation might significantly lessen cognitive dysfunction in DS and reduce cognitive decline in related neurodegenerative disorders such as AD.

Attentional Dysfunction, Impulsivity, and Resistance to Change in a Mouse Model of Fragile X Syndrome

On a series of attention tasks, male mice with a mutation targeted to the fragile X mental retardation 1 (Fmrl) gene (Fmrl knockout [KO] mice) committed a higher rate of premature responses than wild-type littermates, with the largest differences seen when task contingencies changed. This finding indicates impaired inhibitory control, particularly during times of stress or arousal. The KO mice also committed a higher rate of inaccurate responses than controls, particularly during the final third of each daily test session, indicating impaired sustained attention. In the selective attention task, the unpredictable presentation of potent olfactory distractors produced a generalized disruption in the performance of the KO mice, whereas for controls, the disruption produced by the distractors was temporally limited. Finally, the attentional disruption seen following an error was more pronounced for the KO mice than for controls, further implicating impaired regulation of arousal and/or negative affect. The present study provides the first evidence that the Fmrl KO mouse is impaired in inhibitory control, attention, and arousal regulation, hallmark areas of dysfunction in fragile X syndrome. The resistance to change also seen in these mice provides a behavioral index for studying the autistic features of this disorder.

A mnemonic role for vasopressin: The evidence for and against☆

This review critically evaluates the animal and human research concerning vasopressins putative mnemonic role. Weaknesses in the interpretations of the early animal experiments as well as the implications of the later inconsistent findings are discussed. It is concluded that both the initial enthusiasm and the subsequent skepticism concerning this hypothesized role were premature. This conclusion applies equally to the human research. A review of these studies reveals that almost all of the negative reports involved cognitively-impaired individuals. The relatively few studies that have been conducted concerning vasopressins effects in unimpaired human subjects are consistent with the hypothesis that vasopressin does affect cognition, though both the mechanism of action and the specific cognitive processes which are altered have yet to be elucidated.

Imprecise control of energy intake: Absence of a reduction in food intake following overfeeding in young adults

The objective was to examine the extent to which overfeeding reduces spontaneous food intake in humans. Twelve normal-weight adults participated in the three stage study. During the 14 day baseline period and 21 day recovery period, food intake was consumed ad libitum, beyond a minimum 5 MJ (1200 kcal) basal diet. During the 13 day period of overfeeding, each subject consumed 35% more energy than they consumed at baseline. Overfeeding resulted in a weight gain of 2.3+/-0.37 kg, (p<0.0001), approximately half the weight gain was determined to be fat (1.2+/-0.19 kg, p<0.0001) by underwater densitometry. Following overfeeding, mean daily caloric intake was not significantly suppressed returning immediately to baseline values. Despite normal energy intake, participants lost 1.3+/-0.24 kg of body weight (p<0.0001), of which 0.75+/-0.15 kg (p<0.0001) was fat. These results indicated that (1) the physiological control of eating behavior in humans is not the major mechanism responsible for the recovery of body weight following a period of overfeeding and (2) an increase in energy expenditure of 1.28 MJ (307 kcal)/day or about 14% was required to account for the weight loss following overfeeding.

Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that has been shown to alter spatial and visual learning following developmental exposure. The current study examined the effects of gestational and lactational exposure to TCDD on spatial and visual discrimination/reversal learning (spatial and visual RL) in rats using two-lever operant testing chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1 microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One male and one female from each litter were tested beginning at 100 days of age. For spatial RL, animals were reinforced for pressing the lever associated with the correct spatial location (either left or right). For visual RL, the animals were reinforced for pressing the lever associated with the correct visual stimulus (either the illuminated or nonilluminated cuelight). After reaching 85% correct for two consecutive days, the opposite spatial location or visual cue was reinforced. Five reversals were conducted for spatial RL, and two reversals for visual RL. For spatial RL, there were no differences between the TCDD-exposed and control rats in total number of errors committed. However, an in-depth analysis of errors in four different phases of the learning process revealed that TCDD-exposed rats made more errors early in learning when they were just beginning to learn the new reinforcement contingencies. The importance of this increase in errors during the initial stage of learning is unclear, given that there was no increase in overall errors to criterion. For visual RL, there was a reduction in errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed females exhibited a reduction in errors on the second reversal. Subsequent response pattern analyses revealed that the facilitation in performance was due to a more rapid transition through the early phase of learning. Why males were improved on OL and females were not until the second reversal is unknown, but the different patterns could reflect differences in learning style in male and female rats. In keeping with previous research, the results of the current study underscore the fact that (1) alterations in cognitive function observed following early TCDD exposure are very subtle and (2) under some conditions, learning is actually facilitated, rather than impaired, in TCDD-exposed animals.