In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an advantage on spatial tasks, and females on verbal tasks, there is increasing evidence that sex differences are more widespread than previously supposed. Differing performance between the sexes have been observed on a number of common learning tasks in both the human and animal literature, many neither purely spatial nor verbal. We review sex differences reported in various areas to date, while attempting to identify common features of sexually dimorphic tasks, and to place these differences in a neurobiological context. This discussion focuses on studies of four classes of memory tasks for which sex differences have been frequently reported: spatial, verbal, autobiographical, and emotional memory. We conclude that the female verbal advantage extends into numerous tasks, including tests of spatial and autobiographical abilities, but that a small but significant advantage may exist for general episodic memory. We further suggest that for some tasks, stress evokes sex differences, which are not normally observed, and that these differences are mediated largely by interactions between stress and sex hormones.Sex influences on brain function are ubiquitous. Differences between the sexes have been documented at every level of neuroscience, from single neurons in cell culture to systems level processes as measured by neuroimaging. In some cases, consideration of sex may significantly alter, even reverse, conclusions about brain function drawn from the study of one sex alone (Cahill 2006). In some fields, such as the study of drug addiction, the evidence for sex differences is so strong that consideration of sex as a factor is becoming the norm, rather than the exception (Wetherington 2007).The claim that these neurobiological sex differences extend to the behavioral level has typically been more controversial. A recent review of the literature on this topic warns against the ''costs of overinflated claims of gender differences.'' The review holds that overall ''males and females are alike on most-but not all-psychological variables'' (Hyde 2005), but notes exceptions where sex does have an effect, including sexual and aggressive behaviors. Still, given how broadly sex differences are distributed on the neural level, it seems unlikely that their behavioral effects would be restricted solely to these domains.One area of behavior not considered in Hyde's review is the influence of sex on learning and memory. It is becoming increasingly clear, however, that an understanding of the neurobiological and cognitive consequences of sex is relevant across this field. In the review that follows, behavioral evidence indicating differences between men and women from numerous memory tasks will be co...

Glucocorticoid hormones have been shown to enhance memory consolidation when applied at low doses posttraining, but are ineffective or impair memory at high doses. In a test of whether this quadratic relationship also exists for endogenously released glucocorticoids, healthy men and women received cold-pressor stress (CPS) or a control procedure immediately after reading a relatively neutral story and were tested for retention 1 week later. Cortisol levels in response to the stressor were assayed from saliva. CPS significantly elevated salivary cortisol in both sexes, but enhanced memory only in male subjects. Among CPS-treated male subjects, there was a significant quadratic correlation between cortisol release posttraining and subsequent memory. Thus, these findings represent the first demonstration of an inverted-U relationship between activity of endogenous stress hormones and human memory.

Decline in cognitive skills, especially in memory, is often viewed as part of "normal" aging. Yet some individuals "age better" than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20 -30 years younger (i.e., "superagers"), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60 -80 years old) based on their performance compared to young adults (18 -32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function.