Bruno Sauce

The causes of variation in learning and behavior: why individual differences matter

In a seminal paper written five decades ago, Cronbach discussed the two highly distinct approaches to scientific psychology: experimental and correlational. Today, although these two approaches are fruitfully implemented and embraced across some fields of psychology, this synergy is largely absent from other areas, such as in the study of learning and behavior. Both Tolman and Hull, in a rare case of agreement, stated that the correlational approach held little promise for the understanding of behavior. Interestingly, this dismissal of the study of individual differences was absent in the biologically oriented branches of behavior analysis, namely, behavioral genetics and ethology. Here we propose that the distinction between “causation” and “causes of variation” (with its origins in the field of genetics) reveals the potential value of the correlational approach in understanding the full complexity of learning and behavior. Although the experimental approach can illuminate the causal variables that modulate learning, the analysis of individual differences can elucidate how much and in which way variables interact to support variations in learning in complex natural environments. For example, understanding that a past experience with a stimulus influences its “associability” provides little insight into how individual predispositions interact to modulate this influence on associability. In this “new” light, we discuss examples from studies of individual differences in animals’ performance in the Morris water maze and from our own work on individual differences in general intelligence in mice. These studies illustrate that, opposed to what Underwood famously suggested, studies of individual differences can do much more to psychology than merely providing preliminary indications of cause-effect relationships.

The Architecture of Intelligence Converging Evidence From Studies of Humans and Animals

A person’s performance across multiple cognitive tests tends to covary. This ubiquitous observation suggests that various cognitive domains are regulated in common, and this covariance underlies the interpretation of many quantitative tests of “intelligence.” We find that, as in humans, differences in intelligence exist across genetically heterogeneous mice. Specifically, we have observed a covariance in the performance of mice across diverse tests of learning, reasoning, and attention. As in humans, the processing efficacy of working memory is both correlated with animals’ general cognitive abilities and may in some instances serve to regulate behaviors indicative of intelligence. Beyond its axiomatic significance in demonstrating the evolutionary conservation of a cognitive trait, studies of mice may provide unique opportunities to assess the molecular (e.g., brain-specific RNA expression; transgenics) and neuroanatomic substrates for intelligence. One such approach is briefly described here. Using this approach, we have determined that the signaling efficacy of the dopamine D1 receptor in the prefrontal cortex is one potential link between performance on both working-memory tasks and tests of intelligence. In combination, studies of both humans and nonhuman animals provide converging lines of evidence that might evade either approach in isolation.

Voluntary aerobic exercise increases the cognitive enhancing effects of working memory training.

Increases in performance on tests of attention and learning are often observed shortly after a period of aerobic exercise, and evidence suggests that humans who engage in regular exercise are partially protected from age-related cognitive decline. However, the cognitive benefits of exercise are typically short-lived, limiting the practical application of these observations. Here, we explored whether physical exercise might induce lasting changes in general cognitive ability if that exercise was combined with working memory training, which is purported to broadly impact cognitive performance. Mice received either exercise treatment (6 weeks of voluntary running wheel access), working memory training (in a dual radial-arm maze), both treatments, or various control treatments. After this period of exercise, working memory training was initiated (alternating with days of exercise), and continued for several weeks. Upon completion of these treatments, animals were assessed (2-4 weeks later) for performance on four diverse learning tasks, and the aggregate performance of individual animals across all four learning tasks was estimated. Working memory training alone promoted small increases in general cognitive performance, although any beneficial effects of exercise alone had dissipated by the time of learning assessments. However, the two treatments in combination more than doubled the improvement in general cognitive performance supported by working memory training alone. Unlike the transient effects that acute aerobic exercise can have on isolated learning tasks, these results indicate that an acute period of exercise combined with working memory training can have synergistic and lasting impact on general cognitive performance.

The paradox of intelligence: Heritability and malleability coexist in hidden gene-environment interplay.

Intelligence can have an extremely high heritability, but also be malleable; a paradox that has been the source of continuous controversy. Here we attempt to clarify the issue, and advance a frequently overlooked solution to the paradox: Intelligence is a trait with unusual properties that create a large reservoir of hidden gene–environment (GE) networks, allowing for the contribution of high genetic and environmental influences on individual differences in IQ. GE interplay is difficult to specify with current methods, and is underestimated in standard metrics of heritability (thus inflating estimates of “genetic” effects). We describe empirical evidence for GE interplay in intelligence, with malleability existing on top of heritability. The evidence covers cognitive gains consequent to adoption/immigration, changes in IQ’s heritability across life span and socioeconomic status, gains in IQ over time consequent to societal development (the Flynn effect), the slowdown of age-related cognitive decline, and the gains in intelligence from early education. The GE solution has novel implications for enduring problems, including our inability to identify intelligence-related genes (also known as IQ’s “missing heritability”), and the loss of initial benefits from early intervention programs (such as “Head Start”). The GE solution can be a powerful guide to future research, and may also aid policies to overcome barriers to the development of intelligence, particularly in impoverished and underprivileged populations.

A link between thrifty phenotype and maternal care across two generations of intercrossed mice

Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test) these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J–who differ dramatically in their maternal care–and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission.

Individual differences: Case studies of rodent and primate intelligence

Early in the 20th century, individual differences were a central focus of psychologists. By the end of that century, studies of individual differences had become far less common, and attention to these differences played little role in the development of contemporary theory. To illustrate the important role of individual differences, here we consider variations in intelligence as a compelling example. General intelligence (g) has now been demonstrated in at least 2 distinct genera: primates (including humans, chimpanzees, bonobos, and tamarins) and rodents (mice and rats). The expression of general intelligence varies widely across individuals within a species; these variations have tremendous functional consequence, and are attributable to interactions of genes and environment. Here we provide evidence for these assertions, describe the processes that contribute to variations in general intelligence, as well as the methods that underlie the analysis of individual differences. We conclude by describing why consideration of individual differences is critical to our understanding of learning, cognition, and behavior, and illustrate how attention to individual differences can contribute to more effective administration of therapeutic strategies for psychological disorders.

Heterozygous L1-deficient mice express an autism-like phenotype.

The L1CAM (L1) gene encodes a cell adhesion molecule that contributes to several important processes in the developing and adult nervous system, including neuronal migration, survival, and plasticity. In humans and mice, mutations in the X chromosome-linked gene L1 cause severe neurological defects in males. L1 heterozygous female mice with one functional copy of the L1 gene show complex morphological features that are different from L1 fully-deficient and wild-type littermate mice. However, almost no information is available on the behavior of L1 heterozygous mice and humans. Here, we investigated the behavior of heterozygous female mice in which the L1 gene is constitutively inactivated. These mice were compared to wild-type littermate females. Animals were assessed in five categories of behavioral tests: five tests for anxiety/stress/exploration, four tests for motor abilities, two tests for spatial learning, three tests for social behavior, and three tests for repetitive behavior. We found that L1 heterozygous mice express an autism-like phenotype, comprised of reduced social behaviors and excessive self-grooming (a repetitive behavior also typical in animal models of autism). L1 heterozygous mice also exhibited an increase in sensitivity to light, assessed by a reluctance to enter the lighted areas of novel environments. However, levels of anxiety, stress, motor abilities, and spatial learning in L1 heterozygous mice were similar to those of wild-type mice. These observations raise the possibility that using molecules known to trigger L1 functions may become valuable in the treatment of autism in humans.

Dopamine D1 receptor density in the mPFC responds to cognitive demands and receptor turnover contributes to general cognitive ability in mice

In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified. GCA was positively correlated with both the rate of D1 receptor recovery and levels of DRiP78. Additionally, the density of D1 receptors was observed to increase within 60 min (or less) in response to intense demands on working memory, suggesting that a pool of immature receptors was available to accommodate high cognitive loads. These results provide evidence that innate general cognitive abilities are related to D1 receptor turnover rates in the prefrontal cortex, and that an intracellular pool of immature D1 receptors are available to accommodate cognitive demands.

A broader phenotype of persistence emerges from individual differences in response to extinction

The typical practice of averaging group performance during extinction gives the impression that responding declines gradually and homogeneously. However, previous studies of extinction in human infants have shown that some individuals persist in responding, whereas others abruptly cease responding. As predicted by theories of control, the infants who quickly resign typically display signs of sadness and despair when the expected reward is omitted. Using genetically diverse mice, here we observed a similar pattern of individual differences and the associated phenotypes. After learning to approach a food reward, upon extinction, some animals rapidly abandoned approach to the goal box, whereas other animals persisted in entering and searching the goal box. Interestingly, the persistent mice were slower to “give up” when confined to an inescapable pool of water (a test asserted to be indicative of susceptibility to depression) and exhibited a more extensive pattern of search for omitted rewards. Thus, extinction reveals a continuum in persistence, in which low values might reflect a susceptibility to the negative effects of stress and might predispose individuals to depression.

Evolution, brain size, and variations in intelligence

Across taxonomic subfamilies, variations in intelligence (G) are sometimes related to brain size. However, within species, brain size plays a smaller role in explaining variations in general intelligence (g), and the cause-and-effect relationship may be opposite to what appears intuitive. Instead, individual differences in intelligence may reflect variations in domain-general processes that are only superficially related to brain size.