Carol L. Cheatham

n−3 Fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations

Several randomized clinical studies in infants born preterm and at term have explored the effects on visual acuity development of postnatal supplementation with various sources of docosahexaenoic acid (DHA). Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula. Differences in the sensitivity of the test may also be relevant in discussions of whether the effects of DHA on visual acuity are transient or persistent. A smaller number of studies have attempted to study the effects of DHA on cognitive development. The major focus of this article is to review the types of methods that have been used to evaluate the effects of DHA on cognition and to provide the rationale for measures that are a better conceptual fit. Research is needed (1) to probe the effects of variable DHA exposure on infant and child development, (2) to measure outcomes that better relate to preschool and school-age cognitive function, and (3) to reinforce, and in some cases demonstrate, links between specific infant and preschool measures of cognitive development. We strongly encourage collaborations with developmental cognitive neuroscientists to facilitate these research goals.

The emergence and basis of endogenous attention in infancy and early childhood.

Publisher Summary Attention is a familiar and ubiquitous psychological construct that is widely alluded to in various scientific, clinical, and colloquial domains. Attention also remains as one of the least well-understood cognitive functions. The processes that represent the construct of attention are often said to share a common theme of “selection.” However, the process of selection is complex and depends on a number of subsidiary processes, such as detection, localization, and probably some form of recognition. Advances in the cognitive neuroscience of attention have elucidated the neural pathways by which these processes occur and have lent support to the notion of the existence of many “varieties” of attention. Selection may be accomplished by different, seemingly independent neural substrates and thus, the nature, character, and function of attention during development can be determined by the interaction of different systems at different levels of maturity.

Long-term effects of LCPUFA supplementation on childhood cognitive outcomes

BACKGROUND The effect of long-chain polyunsaturated fatty acid (LCPUFA) intake on cognitive development is controversial. Most randomized trials have assessed cognition at 18 mo, although significant development of cognitive abilities (early executive function) emerge later. OBJECTIVE The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid (0.32%, 0.64%, and 0.96% of total fatty acids) and arachidonic acid (ARA; 0.64%) compared with children who were not fed LCPUFA as infants. DESIGN Eighty-one children (19 placebo, 62 LCPUFA) who participated in a double-blind, randomized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate standardized and specific cognitive tests. RESULTS LCPUFA supplementation did not influence performance on standardized tests of language and performance at 18 mo; however, significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks, the Peabody Picture Vocabulary Test at 5 y, and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory, simple inhibition, or advanced problem solving. CONCLUSIONS The data from this relatively small trial suggest that, although the effects of LCPUFAs may not always be evident on standardized developmental tasks at 18 mo, significant effects may emerge later on more specific or fine-grained tasks. The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood. This parent trial was registered at clinicaltrials.gov as NCT00266825.

Long-Chain Polyunsaturated Fatty Acid Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention

A double-blind, randomized, controlled, parallel-group prospective trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid (DHA) supplementation on the cognitive performance of infants. A total of 122 term infants were fed one of four different formulas varying in their DHA composition (0.00, 0.32, 0.64, and 0.96% of total fatty acids as DHA) from birth to 12 mo. The three DHA-supplemented formulas also contained 0.64% of total fatty acids as arachidonic acid (ARA, 20:4n-6). Infants were tested at 4, 6, and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention. Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition; there was no dose-response for this effect. The distribution of time that infants spent in different phases of attention (a cognitive index derived from the convergence of behavioral and cardiac responses) varied as a function of dosage. Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula, whereas infants fed the highest dose were intermediate and did not differ from any other group.

Gendered Social Worlds in Preschool: Dominance, Peer Acceptance and Assertive Social Skills in Boys’ and Girls’ Peer Groups

How dominance in the competitive MovieViewer (MV) task relates to peer preference and assertive behavior, and whether these relations differ for boys and girls were explored. Ninety-one preschool children in same-sex quartets were videotaped interacting in the MV task and dominance ranks were assigned according to viewing time. Peer preference was explored by looking separately at the number of likes and dislikes a child received in sociometric interviews. Multivariate analyses revealed that sex interacted with rank to explain peer acceptance but not peer rejection. High ranked boys were accepted more by peers than low ranked boys, while low ranked girls were accepted more than high ranked girls. Further analyses revealed that girls, but not boys, accepted the low ranked girls. The difference in girls’ and boys’ acceptance of same-sex peers who act assertively in the MV task is consistent with the notion that gendered cultures develop in the preschool years.

Construction of a more coherent story: Prior verbal recall predicts later verbal accessibility of early memories

The question of whether early event memories are later accessible for verbal report is of major interest to those concerned with mnemonic processes. In a controlled laboratory study, we examined this question in children 16 and 20 months of age at the time of exposure to event sequences in the context of an elicited-imitation paradigm and who were subsequently tested for memory for the events at delays of 1, 3, 6, 9, or 12 months, and again at the age of 36 months. Stepwise regressions revealed that the number of mnemonic utterances elicited by direct interview at 36 months is predicted by the number of spontaneous mnemonic utterances at the first delayed recall session. Language abilities at exposure were not predictive of verbal report at 36 months of age. Thus, variables from the most recent exposure were of more import than were variables from the time of the initial experience of the events.

Omega-6 to omega-3 fatty acid ratio and higher-order cognitive functions in 7- to 9-y-olds: a cross-sectional study

BACKGROUND Biochemical and behavioral evidence has suggested that the ratio of n-6 (omega-6) to n-3 (omega-3) could be an important predictor of executive function abilities in children. OBJECTIVE We determined the relation between the ratio of n-6 to n-3 and cognitive function in children. We hypothesized that children with lower ratios of n-6 to n-3 fatty acids would perform better on tests of planning and working memory. DESIGN Seventy 7- to 9-y-old children completed three 24-h diet recalls and a subset of the Cambridge Neuropsychological Test Assessment Battery. Parents provided information on their demographics and childrens diet histories. RESULTS Mean n-3 and mean n-6 intakes were related to the mean time spent on each action taken in the planning problem. The ratio of n-6 to n-3 significantly predicted performance on the working memory and planning problems. There was a significant interaction between the ratio and fatty acid intake; when children had high ratios, a higher intake of n-3 fatty acids predicted a better performance on the planning task than when children had lower n-3 intakes. When children had low ratios, a lower intake of n-3 and lower intake of n-6 predicted better performance than when intakes were higher. CONCLUSIONS The relation between cognitive abilities and the ratio of n-6 to n-3 may be mediated by an enzymatic affinity for n-3 fatty acids. The ratio of n-6 to n-3 should be considered an important factor in the study of fatty acids and cognitive development. This trial was registered at clinicaltrials.gov as NCT01823419.

Synergistic Effects of Human Milk Nutrients in the Support of Infant Recognition Memory: An Observational Study.

The aim was to explore the relation of human milk lutein; choline; and docosahexaenoic acid (DHA) with recognition memory abilities of six-month-olds. Milk samples obtained three to four months postpartum were analyzed for fatty acids, lutein, and choline. At six months, participants were invited to an electrophysiology session. Recognition memory was tested with a 70–30 oddball paradigm in a high-density 128-lead event-related potential (ERP) paradigm. Complete data were available for 55 participants. Data were averaged at six groupings (Frontal Right; Frontal Central; Frontal Left; Central; Midline; and Parietal) for latency to peak, peak amplitude, and mean amplitude. Difference scores were calculated as familiar minus novel. Final regression models revealed the lutein X free choline interaction was significant for the difference in latency scores at frontal and central areas (p < 0.05 and p < 0.001; respectively). Higher choline levels with higher lutein levels were related to better recognition memory. The DHA X free choline interaction was also significant for the difference in latency scores at frontal, central, and midline areas (p < 0.01; p < 0.001; p < 0.05 respectively). Higher choline with higher DHA was related to better recognition memory. Interactions between human milk nutrients appear important in predicting infant cognition, and there may be a benefit to specific nutrient combinations.

Declarative memory in abused and neglected infants.

To summarize, all children interacted with the experimenter and actively participated in the imitation task. There was evidence of improvement in performance from baseline to recall as would be expected with attention to, and memory for, the actions that were modeled by the experimenter. All participants evidenced a decrease in performance as the difficulty of the task increased, as would be expected. When the maltreated children were compared to the nonmaltreated children in a 2-group design, there was no statistically significant difference in performance. However, when the maltreated group was divided into two subtypes of either neglected or abused, and performance was compared in a 3-group design, it was revealed that the neglected children experienced deficits in performance relative to abused children. For production of target actions, the neglected childrens performance trended toward significance when compared to the nonmaltreated childrens performance. However, there was no significant difference between the performance of the abused children and the nonmaltreated children for either production of target actions or productions of ordered pairs. The children in this longitudinal study were assessed previously at 12 months of age in a mother-child play situation (Valentino et al., 2006). Interactions during structured play between mother and child were evaluated for maternal directives and child responses. Interestingly, the difference in social interactions that was most reliable was the finding that the abused children imitated their mothers more often than did the nonmaltreated children. There was no difference between the imitative behaviors of the neglected children and the abused or nonmaltreated children. The researchers note that by imitating their mothers, the abused children might be attempting to prevent further abusive incidents. Limit setting behaviors of the mothers in response to child initiations were positively related to the childrens imitative behaviors. Thus, it would appear that maternal negative feedback to child-initiated behaviors is related to an increase in imitative behaviors that are most likely met with positive reinforcement. The continued pursuit of this positivity may impede the development of self-initiated behaviors; delayed development of self-initiated behavior has been linked to disorders of social competence (Landry, Smith, Miller-Loncar, & Swank, 1998). However, imitation has long been known to be a mechanism of learning (Piaget, 1962) and has become an accepted tool for assessment of declarative memory (Bauer, 2004). Whereas the adaptation to abuse posited by Valentino et al. (2006) may be detrimental to social development, our data for this same sample indicate that the reliance on imitative behavior exhibited by the abused children may afford them an advantage at 21 months of age in imitation paradigms. The neglected children are thus at a disadvantage relative to the abused children in the study reported here in that they were not reinforced by mothers for imitative behavior. It is important to note that all children in this sample were from low-income homes. Scores on these events for both target actions and ordered pairs are higher in samples of higher SES children (e.g., Bauer et al., 2000). Thus, the low SES of the families affected performance across the groups. It is possible that the factor responsible for the difference between the abused group and the neglected group is resilience in the face of poverty. Resilience is the ability to recover following a traumatic event or adversity (Masten, 2001), and has been related to child characteristics, such as general intelligence (Masten et al., 1988). It has been proposed that neural plasticity may be responsible for this recovery (Cicchetti & Curtis, 2006). Alternatively, as has been detailed earlier in this chapter, the advantage afforded abused children could arise from the strengthening of neural pathways. It would be adaptive to develop exceptional event memory so as to avoid the events that lead to abuse. Mechanisms of plasticity are responsible for the laying down of memories (Aimone, Wiles, & Gage, 2006). Thus, the higher performance seen in the abused group could be related to a preservation of brain plasticity that facilitates resilience in the face of poverty, stress, and/or trauma. Plasticity in the brains of the neglected children may be lost due to the lack of stimulation, leaving them more vulnerable to the stress of poverty and neglect. In conclusion, maltreated children have often been studied as a single group. However, it is becoming clear from research conducted by our group and others that the subtypes of maltreatment may have different developmental sequelae. It is important that we understand the differential pathways involved in the development of abused versus neglected children. As discussed in other chapters of this volume, the imitation paradigm has emerged as a valuable tool in the identification of at-risk infants and toddlers. With the data reported here, it is evident that data from the elicited imitation procedure utilized herein differentiates between the subtypes of maltreatment. Research must be conducted to further elucidate the correlates of resilience in toddlers who have been abused. A longitudinal investigation would enable investigation of the questions of continuity of the observed increase in imitative behavior and whether increased imitation has a detrimental social effect while exerting a bolstering cognitive effect.

The development of declarative memory in infants born preterm

Publisher Summary The ability to recall modeled actions can be enhanced by extra experience when risk factors are at a minimum; the greater the number of risk factors in an infants history, the smaller the positive effect of the additional experience. It was also evident that experience did more to enhance the ability to recall modeled actions immediately relative to after a short delay. Moreover, with shorter gestational periods, the ability to tolerate a delay of minutes decreases. This can be seen in a comparison of the results of the higher risk moderately preterm group and the lower risk very preterm group. Although precise risk assessment was not possible due to only having access to complete medical records for the very preterm group, the risk factors for these two groups are similar—both groups had minor respiratory problems, minor infections, and non-major neurological events.