Executive function refers to a collection of abilities that allows an individual to organize their behavior to respond to the current environment and plan for future situations. These skills, including attention, impulse control, decision making, and working memory, allow an organism to attend to relevant variables, compare these variables to past experiences, evaluate which responses would be most effective, and inhibit inappropriate responses. Well-developed executive functioning will contribute to an individual’s success, socially, academically, and professionally. However, disruption of executive function is associated with adverse outcomes and is a component of numerous mental health disorders, including attention deficit hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder.

However, it is well-known that the above named neuropsychiatric conditions are not typically matched between genders in diagnosis rates, onset, severity, and/or prognosis. For example, ADHD is more likely to be diagnosed in boys [1]. A meta-analysis revealed that impulsivity was significantly more prevalent in boys with ADHD versus girls, while no gender differences in attention were indicated [2]. Moreover, the presentation of ADHD may differ between the sexes, with impulsivity more often diagnosed in boys [3]; however, other studies have reported similar presentation of ADHD symptoms between the sexes [4,5,6]. Further, adult women with ADHD have more severe symptoms if they were diagnosed with ADHD as a child, while this relationship is not present in boys [7]. The incidence of schizophrenia is higher in males [8], and may be slightly more prevalent in men [9], and the initial presentation is different by sex, with onset typically seen later in females [10, 11]. Bipolar disorder equally affects men and women, but again the onset and presentation differs, with onset occurring later in women, and women showing more rapid cycling between mania and depression than men [12]. These differences extend to work in animal models of these disorders as well [13, 14]. One question that emerges is whether fundamental sex and gender differences in the different executive functions exist as a possible mechanism contributing to the sex- and gender-disparate risk for neuropsychiatric conditions. In this review, we examine the evidence for baseline sex and gender differences in four essential executive functions in both the human and animal literatures.

Executive function can be impacted by deleterious events throughout the life span, including gestational and early life insults, stress, drug abuse, and aging [15,16,17,18,19,20]. These adverse environmental events are also linked to an increased risk for the development of many, if not most, neuropsychiatric conditions including mood disorders, dementias, psychosis, and neurodevelopmental disorders such as autism and attention deficit/hyperactivity disorder. Therefore, the present review will approach the topic of sex differences in executive function with a particular focus on differences related to developmental programming. We conclude that (1) individual components of executive functions may be enhanced in one sex or gender over another, but that there is no systematic advantage, (2) that these effects depend greatly on the modality of testing and the parameters tested, suggesting that apparent differences in the abilities in executive functions may in fact reflect different strategies employed by each sex and gender when confronted with a challenge or ambiguous situation and (3) early life adversity can disrupt executive function, with important influences of both gender/sex and age/timing on the severity and expression of these effects.

Human gender differences in attention

Attention and impulsive action are often measured concurrently, within the same tests, and will therefore be discussed collectively here. A wide variety of neuropsychological tests are available, including the widely used continuous performance task (CPT). While the specifics of the task can vary (type of stimulus presentation (visual vs. auditory) or the required response), the basic strategy of the CPT remains the same. In the CPT, individuals must respond correctly to target stimuli, and inhibit responding to incorrect stimuli (e.g., presentation of the letters A and B, in which responding should occur only on the presentation of A (target) and never to B (foil)). If the target is presented repeatedly, in rapid succession, followed by a single presentation of the foil, it can be difficult to inhibit responding to the foil, which is a measure of impulsive action. Similarly, if the target is only presented very infrequently, the subject is required to pay close attention, and errors of omission are a measure of inattention.

Age of testing, as well as the specific testing modality, impact the findings of gender differences in attention. In a normative sample of 8- and 10-year-old children tested with a standard neuropsychological battery, girls were found to have better scores on attention as compared to boys [21]. However, testing later, during adolescence, using the CPT, revealed no gender differences in attention [22].

Another study that examined the full life span (ages 17–90) failed to find any gender differences in attention; however, women were found to have slower reaction times [23], consistent with another report using adults that reported slower reaction times in females, but no gender differences in attentional performance [24]. Another study that used responses in an online format of the CPT from a very large number of respondents (n = 9–11,000/gender) also indicated a slower reaction time in women, as well as gender differences, such that females made more omission errors, while males made more commission errors (responding inaccurately to the foil); however, it was noted that the effect size of these differences was quite small [25].

Human gender differences in impulsive action

Analysis of typically developing 8- and 10-year-old children found that girls were less impulsive than boys [21]; however, by adolescence, girls scored higher in impulsive action in the CPT compared to boys [22]. Similar to the findings in adults, 9–10-year-old boys were found to have faster reaction time in a go-no/go task as compared to girls, a finding that was also seen in 9–17-year-old population [26, 27]. In that population, boys were also found to be more impulsive [26]. The fact that boys may have faster reaction times may underlie or contribute to the noted increase in impulsive action, particularly when tested in CPT, as premature responses are more likely with a faster reaction time and are coded as impulsive behavior.

Sex differences in animals in attention and impulsive action

The five-choice serial reaction time task (5CSRTT) has been used to assess attention and impulsivity in mice [28], and is considered the gold standard for evaluating executive function deficits in rodents. This task is analogous to the CPT used to assess sustained and selective attention in humans [29], and screen for ADHD [30]. This operant task requires localization of brief visual stimuli presented randomly in one of five locations. A large number of correct target detections indicates good attentional performance as reflected by high response accuracy accompanied by few errors. The intertrial interval (ITI) can be manipulated to make the task more challenging. A longer ITI can increase premature responding, while a variable length ITI can challenge attentional systems, as an animal can no longer rely on timing strategies to indicate the presence of the cue. Assessment of higher executive function in rodents is relatively time and resource intensive, limiting the broad adoption of these assays in research. Consequently, there are limited studies overall, and of those, only very few that include females.

Attention

In one of the earliest studies to assess both male and female mice in the 5CSRTT, no sex differences were identified in acquisition of the task, or performance metrics (accuracy, omissions, premature responses); however, female mice were reported to have faster reaction times [31]. Importantly, this paper also reported how changes in task difficulty impacted performance. When the intertrial interval (ITI) was lengthened, impulsive errors increased acutely in both males and females, but males rapidly habituated, while female premature responding persisted. Similarly, in adult rats, females appear to be more adversely affected by increasing task difficulty. Females, more so than males, showed a greater decrement in attention under challenging 5C parameters, either a shorter stimulus and variable intertrial interval (ITI; [32] or when the ITI was long [33]). Environmental changes have also been shown to impact performance in a sex-dependent manner, with males showing an increase in susceptibility to performance decrements. Exposure to a mild stressor was found to decrease attention and increase impulsive responding in male mice, while female accuracy was not affected [31]. This group also tested animals that were ad lib fed (rodents are typically food restricted for the 5CSRTT to increase motivation to perform) to remove the stress and motivation factors. In this context, females outperformed males, and were more accurate and had fewer premature responses. Vitamin D deficiency has also been examined in adult mice. Similar findings were observed here, as it was shown that males were the only sex affected, with vitamin D-deficient males showing an increase in reaction time, less accurate performance, and more inattentive errors in the 5CSRTT, while there were no adverse effects of vitamin D deficiency in females [34].

Impulsive action

To examine impulsive action in rodents, the 5CSRTT is used. In our work, we did not observe any sex differences in attention, but did note a higher rate of impulsive errors in adult females versus male mice under baseline task conditions [35]. Similarly, using a modified version of the 5CSRTT to allow for testing in younger animals, adolescent female mice were found to make more impulsive errors [36]. Reaction time has also been examined, and no sex differences have been reported [33, 35, 37]. When parameters are changed to make the task more difficult (shorter stimulus and variable intertrial interval), males have shown increased impulsive action [32]. Similarly, in another study, males made more premature responses (impulsive action) when the ITI was long [33]. Additionally, male rats were found to be more impacted by a variable ITI, leading to more impulsive errors in 5CSRTT, while female performance remained robust, even in the face of increasing task difficulty [38]. However, another study using a two-choice task found that with increasing difficulty (long ITI), in adolescence, males were more impulsive than females, while as adults, females made more premature responses as compared to males [37]. Clearly, there are important developmental differences with regard to impulsive behavior, as it has also been reported that male rats showed greater preference for novelty and increased activity earlier in life, whereas these behaviors emerged later, during adolescence, in females [39].

Overall, considering both human and animal studies, one can conclude that large gender or sex differences in attention and impulsive action are absent. Baseline differences in attentional performance are not described; however, the extent to which subjects are adversely affected by task difficulty or environmental stressors differs by gender/sex, such that females appear to be more adversely affected by task difficulty and males by environmental perturbations. There may be support for an increase in impulsive action in males, potentially related to a faster reaction time seen in human studies. In animals, a few studies support increased impulsive action (at baseline) in female animals; however, males appear to be more impacted by increases in task difficulty or changes in the testing environment.

Decision making and impulsive choice

Aberrant decision-making processes are seen in a variety of neuropsychiatric conditions, including autism, psychosis, mood disorders, and addictions, reflecting both vulnerabilities in the ability to use this executive function, and in many cases contributing to worsening outcomes.

The process of decision making involves two key components: the ability to determine the most likely outcomes from a given choice, and the ability to weigh different choices according to probable outcomes and select an optimal choice. We can think of these processes as first, establishing the rewards and risks of various choices through learning when making decisions in unfamiliar circumstances, often measured in the early phases of decision-making tasks, and second, making selections when substantial evidence has been collected about relative rewards and risks among various options, often measured later in decision-making tasks.

Therefore, the potential role for sex and gender differences to influence decision-making processes could occur during the early stages of evidence collection and learning, or later, through differential weighting of risk and reward between sexes and genders. However, evidence collection processes are likely to be heavily influenced by rates of risk and reward. In fact, as discussed below, a differential sensitivity to risk versus reward, and the balance of risk versus reward in a given task, shifts the influence of sex and gender in decision-making tasks. While there is an apparent gender/sex effect in decision making, this appears to be driven by sex differences in the assessment of risk, not rewards, causing females to avoid frequent loss even if this is covertly advantageous, especially during learning in unfamiliar circumstances [40, 41]. When a task is run where loss frequency is controlled, or once sufficient evidence has been collected about risks and rewards, males and females are equally adept at making optimal decisions.

Human gender differences in decision making and impulsive choice

The most frequently employed decision-making task in humans is the Iowa Gambling Task (IGT), which was originally developed several decades ago as a method to examine the ability of losses to drive shifts in decision making in neuropsychological patients through long-term estimations of value. The ubiquity of this task means that there is quite a bit of data on the role of gender and sex, but confounds in the design [42, 43] mean that the interpretation of these data becomes challenging. At first glance, there appear to be differences in performance between genders on this task. However, careful analyses have shown that these are driven by gender differences in tolerance for frequency of loss rather than magnitude of gains, which are confounded.

Briefly, the IGT involves four decks of cards, each of which has cards that gain money, and cards that lose money. Over the long term, two of these decks (A and B) have a net loss of $250 over every ten cards, and two of these decks (C and D) have a net gain of $250 over ten cards. However, the decks differ not only in their “final outcome”, but in the probability of choosing a losing card on any turn; decks A and C have a rate of five losses and five gains over every ten cards, while B and D have a rate of one loss and nine gains over every ten cards. Finally, decks C and D have cards that have smaller individual gains ($50 per card) versus decks A and B ($100 per card); thus, there is no deck with both large individual gains and a beneficial final outcome. Thus, for ideal performance, participants have to make a counterintuitive decision to forgo large gains (which are frequent in deck B) in favor of smaller gains (deck C) and often to select more frequent losses (as in deck D). Participants in these experiments usually have 100 chances to pick a card from any of the decks.

A number of studies have shown that men tend to outperform women at the IGT, specifically by choosing from decks C and D more frequently [42, 44,45,46,47]. However, many studies have failed to find any gender difference in this task [42, 48, 49], suggesting this effect is modulated by environmental factors to which men and women may be differentially susceptible and that are not typically controlled for between genders, such as stress and anxiety [46, 50,51,52,53]. Performance on this task is often rated by the number of “gain” cards from the C and D decks a participant collected at the end of 100 trials. Critically, both men and women prefer deck D with a net gain over time and only one loss per ten cards, over the other three decks. However, men tend to develop a preference for a deck (C) with frequent losses of smaller magnitude, while women maintain a preference for a deck with rare losses, although of large magnitude (B) [42]. Given additional trials past 100, women develop a preference for deck C [42, 44], suggesting that women weight the frequency of loss more highly than men, while men rate the magnitude of loss more highly, when these options are put into conflict.

Because the IGT varies both frequency of loss and magnitude of loss, avoiding frequent loss can mean enduring losses of higher magnitude. However, it is possible to vary the frequency of loss while holding the magnitude of loss constant. In scenarios such as this, we would expect that this would lead to no sex differences in learning to make optimal choices, or even show enhanced performance in women by avoiding frequent loss. There is support for both of these possibilities in tasks where only loss frequency or loss magnitude are varied and the other option is controlled. In a modified version of the IGT, when men and women are given a choice only between decks A and C, which both have frequent losses, people of both sexes prefer deck C, with a net gain. However, when the task is modified to contain only decks B and D, which both have rare losses, people fail to distinguish that B leads to a greater magnitude of loss than D and choose them at equivalent rates [54, 55]. This suggests that observed gender differences in decision making as measured by the IGT are driven by wishing to avoid frequent loss, not by a gender difference in the ability to detect loss magnitude.

Another kind of decision-making task that varies only the frequency of loss/reward while keeping the magnitude of these outcomes constant is probabilistic decision making, sometimes called a multiarmed bandit task. These kinds of tasks provide two or more items which vary in the probability of reward, but provide the same size of reward across options. These kinds of tasks have been recently used to examine decision-making strategies, particularly whether a participant chooses to explore unknown options versus choosing to exploit options with which they have prior experience. Studies in humans have largely found no gender difference in bandit task performance [56,57,58], suggesting that the ability to identify items with a high probability of reward does not vary as a function of gender. When the learning phase of this kind of task was specifically examined, one study found that women were quicker to learn to choose an option associated with a high probability of reward [57]. A different probabilistic repeated gambling task where there was no learning component (deciding whether a number was likely to be higher or lower than a provided number) found no differences in choices as a function of gender [59]. This suggests that observations that women avoid frequent losses in the IGT may be the other side of the coin wherein men are willing to make choices associated with a higher probability of loss, even when loss is highly probable.

A final form of decision-making task varies the magnitude of outcomes and varies the cost of the high-magnitude option, either as temporal delay (delay discounting) or in probability of occurrence (probability discounting, also called a risky decision-making task). These kinds of tasks typically ask whether a person would prefer an immediate and guaranteed small reward, versus a larger reward at some delay, or with some chance of occurring. These kinds of discounting tasks have generally failed to show baseline gender differences in the tendency to prefer an immediate reward [60,61,62], though gender can interact with other conditions such as alcoholism to result in gender-specific effects [60]. Fewer studies have been conducted with probability discounting in humans with gender-specific analysis, but these have generally not seen evidence for gender differences in healthy controls [62, 63].

Overall, these findings support the idea that there is little gender difference in decision making in general. However, this is dependent on a task design that controls for the frequency of gains and losses, compared to the magnitude of these events, as the avoidance of frequent losses would lead to the observation of decreased performance in the IGT and increased performance in bandit tasks, as described above. These findings are consistent with a broader literature indicating greater sensitivity of women and female animals to both rewarding and punishing outcomes, indicating that while decision making itself is not consistently different between genders, the information used to influence decisions may be processed differently by men and women.

Animal sex differences in decision making

The subject of sex differences in animal models of decision making was recently beautifully reviewed by Orsini and Setlow [41]. Here, we will discuss this literature with an emphasis on drawing connections to the human findings. Briefly, several different gambling-type tasks have been developed for testing in animal models in operant chambers, and again, the relationship between the magnitude of negative outcomes versus the frequency of negative outcomes [64] appear to determine whether there is a female advantage or a male advantage. A clear finding across animal tasks tested so far is that females will avoid making choices associated with frequent negative outcomes, such as shock or unpalatable food, even if these options are also associated with higher magnitude positive outcomes (more palatable food) [41]. However, in tasks where options differ only in the cost or probability of a positive outcome, without punishment, there is either no sex difference or a female advantage.

As in human tasks, animal tasks can include an overt negative outcome, and as in human literature, these tasks lead to females avoiding frequent negative outcomes. A rodent version of the IGT compared choices in an operant chamber for a long-term advantageous option (with small amounts of palatable pellets and occasional highly unpalatable pellets), and a disadvantageous option (with large amounts of palatable pellets but more frequent punishment by delivery of highly unpalatable pellets). Performance at the end of this task did not differ between sexes, but males learned to stay with the advantageous option more quickly, despite punishment. Females, in contrast, were more likely to shift to the other option following punishment, suggesting that the avoidance of deleterious outcomes was more motivating [65]. Paralleling this, Orsini and colleagues recently employed a rodent risky decision-making task where animals were asked to choose between an option that resulted in a small food reward, and an option that resulted in a larger food reward paired with some probability of footshock. Females showed a strong preference for the safe option, although smaller, than the risk of footshock [66]. These findings are consistent with those from the human literature indicating that females weight deleterious outcomes more highly in decision making.

The vast majority of tasks evaluating decision making in rodent models at this time involve active punishment to make a high-magnitude reward less attractive. As noted above, the human literature indicates that tasks which set up a conflict between the ability to detect profitable options with the desire to avoid frequent negative outcomes lead to an apparent deficit in female decision making. Because of this, it is helpful to compare the findings from the rodent version of the IGT to a task that changes the probability of negative outcomes while holding these at the same magnitude. The “rat Gambling Task”, in contrast to the tasks described above, is more similar to a “bandit-style” task, in that losses involve the omission of a food reward, rather than an actively deleterious outcome such as unpalatable food or a shock. In addition, it involves forced choices, where females and males are obligated to pick each of the options in isolation, before being allowed to choose. Here, females learn more quickly than males to choose the advantageous option [67].

In delay discounting tasks, where animals choose between a small immediate food reward, and a larger food reward that occurs on a variable delay, there have largely been no significant sex differences reported [68,69,70], suggesting again that without active aversive outcomes, intact females and males assess reward outcomes similarly or with a slight tendency in females towards the detection of positive outcomes. Further, developmental time is a critical lens through which sex differences should be viewed. In a study that tested animals at early adolescence, late adolescence, and adulthood, an interesting pattern of sex differences was noted, and this related more to the developmental pattern of impulsive choice, as opposed to a simple sex main effect. In females, an inverted U-shaped curve was identified with impulsive choice peaking at late adolescence; however, in males the curve was quite different, remaining relatively high throughout adolescence, and decreasing only in adulthood [39].

Overall, as in the human data, animal decision-making research suggests that there is not a clear-cut sex difference or advantage, but a difference in outcome sensitivity that, critically, benefits males when punishments are severe and benefits females when punishments are minimal. Thus, again, while decision making itself does not appear to differ between animals of different sexes, the information processing that supports decision making does.