One reason for the often polarized debates has been the lack of hard evidence. Without empirical findings, it is easy to maintain any position, as well as regard opponents as having unfounded views. A further essential source of disagreement and theoretical confusion is a tendency to view enhancement as a unitary phenomenon to be judged as a whole, rather than as a broad set of techniques with important differences and diverging implications. Only on the basis of a clear picture on how a particular enhancement strategy might affect specific cognitive processes in specific populations, along with side effects and costs to be expected, an informed theoretical debate can evolve and a promising empirical research designs to test the strategy can be proposed. In the following, we aim to elucidate seven essential dimension of cognitive enhancement, namely, (a) its mode of action, (b) the cognitive domain targeted, (c) personal factors, (d) its time scale, (e) side effects, (f) availability, and (g) social acceptance (see Figure 1 ). Further, we will review empirical data of prominent examples of cognitive enhancers that differ across these dimensions and thereby illustrate some of their nuanced implications. The aim of our Review is to sketch a general framework that will foster both theoretical discussions and empirical research.

An increasingly complex world exerts increasing demands on cognitive functions—functions that evolved for a fundamentally different environment. Daily life in an information society and a postindustrial economy require cognitive skills that have to be acquired through slow, effortful, and expensive processes of education and training. Likewise, these skills can become obsolete as the world changes ever faster or be lost by the processes of aging. People also vary in their mental abilities, allowing them to acquire certain skills more quickly or slower, which may have significant effects on life outcomes. Strategies to improve the acquisition and maintenance of cognitive skills are thus increasingly important on both an individual and societal level. These challenges of our times have fostered the exploration of strategies to enhance human brain function. While people have since time immemorial sought to improve their performance, the present era is unique in that not only the challenges are growing rapidly but so are technologies that promise to meet them. Just like the hacking culture in the realm of computer software and hardware, an increasing number of individuals experiment with strategies to creatively overcome the natural limitations of human cognitive capacity—in other words, to hack brain function. This development has led to both enthusiasm and dread, as observers have sharply differing intuitions about the feasibility, utility, risks, and eventual impact of enhancement technologies on the world.

In addition to these natural and cultural standard activities, several behavioral strategies have been developed to enhance certain brain functions intentionally. Two strategies that reach back to ancient times are mnemonic techniques to enhance learning and memory (101,102) and meditation training to enhance attention processes and mindfulness. (103,104) In contrast, commercial video games (105,106) and customized computer trainings (107) represent historically very recent developments that are targeted to enhance specific cognitive capacities and skills. In contrast to several years of enthusiasm and widespread commercial application, however, more recent controlled studies and meta-analyses have shed some doubt on the efficacy of computerized brain training programs, (108) particularly criticizing claims of “far transfer” of training gains to cognitive domains considerably different from the specifically trained skills. (109,110)

Although not commonly recognized as such by the public, cognitive enhancers with the most wide use and longest history are probably behavioral strategies: a rapidly growing body of evidence shows that everyday activities such as sleep (93) or physical exercise (94−96) improve cognitive functioning. Also well-established cultural activities such as musical training, (97,98) dancing, (99) or learning a second language (100) have been demonstrated to enhance cognition beyond the specifically trained skills.

Finally, humans have always deployed physical tools to assist cognitive functioning. In current developments that converge minds and machines, these tools become more closely integrated with the person. (86) Crowdfunding or biohacking communities have developed numerous novel technical devices to increase cognitive functions transiently with, e.g., wearable electronic memory aids or augmented reality gadgets, (87,88) or more permanently as in the case of cognition enhancing or extending bodily implants. (88,89) Neural implants or prosthetics have progressed; in controlled laboratory settings, implants could facilitate human memory. (90) In addition, Brain–Computer Interfaces connect the central nervous system with computers through wearable or implanted electrodes and may afford a range of applications that enhance cognitive functions or joint outputs of minds coupled with machines. (91,92)

Physical enhancement methods that target brain processes more indirectly include whole body vibrations, (76) stochastic resonance motor control improvement, (77,78) and several forms of neurofeedback, (79) with, e.g., EEG neurofeedback in the upper alpha band enhancing memory, (80) working memory, (81) and visuospatial skills. (82) Besides classical neurofeedback training that involves unspecific but active effort of the subject, also neurofeedback interventions that automatically feedback low energy currents in response to EEG activity have been developed, thereby allowing the subject to receive the training procedure passively. (83) Recently, the use of fMRI neurofeedback, utilizing multivariate pattern analysis, has shown the potential to increase sustained attention (84) or visuospatial memory. (85)

The current most widely discussed physical strategies for cognitive enhancement include a number of brain stimulation technologies. Whereas the cognition enhancing effects of invasive methods such as deep brain stimulation (53,54) are restricted to subjects with pathological conditions, several forms of allegedly noninvasive stimulation strategies are increasingly used on healthy subjects, among them electrical stimulation methods such transcranial direct current stimulation (tDCS (55) ), transcranial alternating current stimulation (tACS (56) ), transcranial random noise stimulation (tRNS (57) ), transcranial pulsed current stimulation (tPCS (58,59) ), transcutaneous vagus nerve stimulation (tVNS (60) ), or median nerve stimulation (MNS (61) ). Details of the stimulation procedures appear to be crucial: commercial do-it-yourself electrical brain stimulators might impair rather than enhance cognition, (62) and systematic reviews have shed doubt on a clear and simple enhancing effect of electrical brain stimulation on different cognitive domains also under controlled laboratory conditions. (63,64) Recent studies have even questioned if some of the most commonly used setups for electrical brain stimulation have neurophysiologically meaningful effects at all. (65−68) On this background, the development of noninvasive deep brain stimulation via temporally interfering electric fields might provide a more systematic and targeted mechanism compared to the currently used approaches. (68)

A further biochemical strategy for cognitive enhancement consists of genetic modifications, which have been demonstrated to augment several learning and memory processes in animal models. (46−51) Although progress has also been made in elucidating the genetic basis of cognitive traits in humans, (52) genetic modifications in humans still have to be considered as future strategies rather than currently available enhancement options.

Pharmaceuticals are in particular by the public regarded as prototypical cognitive enhancers: synthetic stimulants such as amphetamine, methylphenidate, or modafinil, or antidementia drugs such as acetylcholinesterase inhibitors and memantine are at the core of public debate on cognitive enhancement. However, evidence for their efficacy for augmenting brain function and cognition in healthy subjects is often markedly lower than assumed in theoretical discussions. (32−37) Importantly, the lack of an objective effect on cognition can be accompanied by a considerable placebo effect: for example, users who believed to have received mixed-amphetamine salts subjectively rated themselves as performing better and even show minor objective performance increases, independent of actual medication state. (38)

A further biochemical intervention with a long history concerns drugs that are being used recreationally and that have demonstrated the potential to enhance certain cognitive functions. For example, nicotine improves attention and memory, (26−28) and even alcohol, despite impairing many cognitive functions, might enhance others such as creative processes (29,30) or, retroactively, memory. (31)

Also certain traditional natural remedies have been discussed as cognitive enhancers: besides herbs that also grow in Western regions such as salvia, (21) particularly traditional Chinese and Indian herbal medicines such ashave been ascribed with cognitive enhancing effects. (22,23) However, with ginseng and ginkgo biloba, the most prominent examples of such traditional Asian herbal remedies so far have failed to consistently show positive effects on cognitive functions in healthy individuals. (24,25)

Biochemical enhancers with the longest tradition in human history are strategies to make use of certain nutritional components. Most widely used are probably glucose (7) and caffeine, (8,9) which both have demonstrated cognition-enhancing effects in numerous studies. In addition to coffee, other beverages from caffeine-bearing plants such as guarana have shown to enhance cognition. (10) While the noncaffeine components in caffeine-bearing plants might exert independent effects on cognition, (11) it has been doubted that industrially designed drinks contain cognitive enhancing components that go beyond caffeine, glucose, or guarana extract. (12) Further nutritional components with some evidence for cognitive enhancing effects are flavonoids, e.g., in cocoa, (13,14) curry powder (most likely due to the curcumin that it contains, (15,16) folic acid, (17) or omega-3 fatty acids. (18) Besides specific dietary supplements, also the absence of food might enhance cognition: some evidence has been reported that fasting and general caloric restriction might improve memory in elderly individuals. (19,20)

A widely cited definition characterizes enhancement as interventions in humans that aim to improve mental functioning beyond what is necessary to sustain or restore good health. (1) While the current bioethical debate on cognitive enhancement is strongly focused on pharmacological ways of enhancement, improving mental capabilities also by nonpharmacological means has to be considered as cognitive enhancement proper according to the given characterization. We have reviewed elsewhere the efficacy of a number of nonpharmacological enhancers. (2,3) To systematize the vast variety of different approaches of cognitive enhancement, we suggest clustering enhancement strategies into three major areas according to their main mode of action. Even though boundaries are not strict, most cognitive enhancement strategies can be considered to work as either biochemical, physical, or behavioral interventions ( Figure 2 ). In the following, we will give an overview on the different cognitive enhancement strategies within these clusters.

The costs and benefits of a single cognitive enhancer might even change through slight changes in the application process: for example, electrical stimulation of posterior brain regions was found to facilitate numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation on frontal brain regions impaired the learning process, whereas automaticity for the learned material was enhanced. (121) Brain stimulation has thus been suggested to be a zero-sum game, with costs in some cognitive functions always being paid for gains in others. (122) This implies that enhancement may have to be tuned to the task at hand, in order to focus on the currently most important cognitive demands.

Some interventions might even enhance one but impair another cognitive domain: Intranasal application of oxytocin has been shown to enhance social cognition and cognitive flexibility but impairs long-term memory. (116,117) Methylphenidate improves the ability to resist distraction but impairs cognitive flexibility. (118) Computerized working memory training has been reported to enhance working memory, reasoning, and arithmetic abilities; however, it might deteriorate creativity. (119) Also for amphetamines and modafinil, potential impairments on creativity are discussed besides their enhancing effects on other domains. (120,34) In contrast, alcohol might enhance creative processes while impairing most other cognitive functions. (29)

The human mind is not a monolithic entity, but consists of a broad variety of cognitive functions. Not surprisingly, no single cognitive enhancer augments every cognitive function. Instead, most cognitive enhancers have specific profiles regarding their efficacy for different cognitive domains. Memory is, e.g., strongly enhanced by mnemonic strategies, but not by meditation; attention, in turn, is strongly enhanced by meditation training, but not training in mnemonic strategies. (101,103,104) Sleep, in contrast, enhances both cognitive capacities. (111,112) Some computerized cognitive trainings have been found to enhance memory, processing speed and visuospatial skills, but not executive functions or attention. (107) It is currently highly debated in how far specific training strategies exert transfer effects also to nontrained cognitive domains. (113)

Cognitive enhancers can also affect individuals differently depending on basic biological, psychological, or social factors. For example, effects of training interventions on selective attention can depend on the genotype of the trainee; (142) effects of methylphenidate on creativity can depend on personality characteristics; (143) the cognition enhancing effects of sleep (144) or video games (145) are modulated by gender. In turn, such modulations of enhancement effects might reduce existing differences in cognitive profiles, as seen, e.g., in action video game training, that have the potential to eliminate gender differences in spatial attention and decrease the gender disparity in mental rotation ability. (146) Also the hormonal status of subjects affects how strongly they profit, e.g., from sleep (144−148) or brain stimulation. (149) Caffeine enhances working memory particularly in extraverted individuals, (150) and memory enhancement through sleep (151) or mnemonic training (140) has been reported to depend on the age of subjects. Health status affects how much users benefit from different kinds of cognitive enhancers, including pharmaceuticals, (3) mnemonics, (152) or sleep. (153−156) Finally, also socioenvironmental factors such as social resources, parental occupation, or family composition can modulate cognitive enhancement interventions, e.g., with cognitive training programs. (157)

The baseline-dependency of cognitive enhancement is not restricted to pharmaceuticals: also in the case of video games, (133) cognitive training, (134) or brain stimulation, (135,136) individuals starting at a lower baseline performance benefit more than those with an already high performance at baseline. In contrast, sleep appears to improve memory particularly in subjects with a higher baseline performance of memory, (137) working memory (138) or intelligence. (139) Also mnemonic training appears to work particularly well in individuals with a higher cognitive baseline performance. (140) This has been interpreted in terms of an amplification model, in which high baseline performance and cognitive enhancement interventions show synergistic effects. (141)

The efficacy of cognitive enhancers does not only differ for different cognitive domains, but also for different users. An important factor in this regard are the cognitive skills of the individual prior to the enhancement intervention. Many pharmaceuticals, including amphetamine, (123) modafinil, and methylphenidate, (124) work mainly in individuals with low baseline performance. In some cases, even impairments in individuals with higher performance at baseline have been reported, e.g., in the case of amphetamine, (125) methylphenidate, (124) nicotine, (27) or acute choline supplementation. (126) The phenomenon of enhanced cognition in individuals with low baseline performance and impairments in those with high baseline performance can be explained by the classical inverted U-model, (127,128) where performance is optimal at intermediate levels of the targeted neurochemicals and impaired at levels that are either too low or too high. (129−131) For some drugs such as methylphenidate, enhancement dependency on the baseline might even differ between cognitive functions, with performance in specific tasks being improved in low, while impaired in high, performers, (124) but showing the opposite pattern for other tasks. (132)

Interventions can also differ regarding the time point of application relative to the situation when enhanced cognitive performance is needed. For example, application of stress hormones such as cortisol or adrenaline before or after memory encoding enhances memory, whereas application before retrieval impairs memory; (41) benzodiazepines impair memory when given before and enhance memory when given after encoding; (164) in contrast, caffeine before learning enhances memory under certain conditions but might impair memory when consumed afterward. (165,9) Mnemonic strategies on the other hand work solely when taught/applied before/during encoding, but can hardly be applied afterward.

Enhancing effects of most quickly acting pharmacological or nutritional cognitive enhancers also wear off rather rapidly. In contrast to such transient effects, interventions such as brain stimulation, (160,161,57) sleep, (162) mnemonic strategies (163) or genetic modifications (46) have the potential for long-term up to chronic enhancement. However, in the latter case, the reversibility of the effects (and side effects) of an enhancement intervention might be a further aspect to be considered.

Most pharmacological enhancers can be applied quickly and without further preparation; however, some drugs such as acetylcholinesterase inhibitors or memantine are thought to require longer periods of intake to be effective. (33) Also some nutritional enhancers such as glucose and caffeine exert their effects rather quickly, whereas other nutritional supplements have to be taken over extended periods to show an impact on cognition. (158,18) Obviously, behavioral strategies like sleep, exercise, video games or mnemonic training need hours or weeks to robustly enhance cognition. Some effects of meditation might even take years of training. (159) For brain stimulation methods, both immediate effects of acute stimulation, but also more delayed effects after repeated stimulation haven been observed. (55,69) Technological gadgets or implants need some preparation to be installed and accommodated to, however then exert their cognition augmenting effects on demand.

Interventions for cognitive enhancement differ in the specific time scale they require to achieve their aims. The prototypical “smart pill” discussed in popular accounts of cognitive enhancement needs practically no preparation time, exerts its effects within seconds or minutes, and lasts for several hours. While this is close to reality in the case of some pharmacological enhancers, the temporal pattern of most other enhancement strategies differs strongly from these time scales. In particular, the time needed for application and the duration of their effects markedly varies between enhancement interventions.

A somewhat nonobvious negative effect of some cognitive enhancers is their illusional efficacy: users sometimes believe their performance to be enhanced by amphetamine in absence of any verified and objectively visible enhancing effects, even if administered in a double blind manner. (183,184,38) This is particularly counterproductive in cases of already high-functioning individuals whose cognitive capabilities might be impaired rather than enhanced by amphetamine. (125,184) Also for caffeine, under certain conditions higher subjectively perceived mental energy in the absence of objectively enhancing effects have been observed. (185) The often subtle effects of enhancers can be hidden or amplified by placebo effects.

Related to the time scale dimension, side effects of short- vs long-term use of cognitive enhancers can be differentiated. For example, while side effects for the acute use of methylphenidate include increased heart rate, headache, anxiety, nervousness, dizziness, drowsiness, and insomnia, in the case of long-term use side effects such as abnormal prefrontal brain function and impaired plasticity have been reported. (179,180) Also addiction is a well-known side effect for the long-term use of pharmacological enhancers, which is particularly detrimental to the aim of enhancement if combined with tolerance effects such that larger doses are needed to achieve the same effect (or prevent impairing withdrawal effects). Also behavioral addictions have been observed, e.g., physical exercise (181) or the use of technological gadgets. (182)

It has been suggested to differentiate enhancement strategies according to their level of invasiveness. (172,173) However, while invasiveness has a more or less definite meaning in its original medical context, physically breaching the skin or entering the body deeply through an external orifice, (174) it is difficult to determine the level of invasiveness in the context of cognitive enhancement. Both nutritional supplements and pharmaceuticals enter the body, and thus could be considered invasive in a narrow medical sense, as might be certain forms of physical exercise due to the risk of bruises or scratches as common, e.g., in martial arts or a hike through the woods. Brain stimulation that does not break the skin would, by contrast, be classified as noninvasive. This taxonomy can be disputed for good reasons. (175) Besides known risks of these stimulation methods such as scalp burns from tDCS or seizures from TMS, the “known unknowns” have been suggested to pose potentially even greater risks: potential build-up effects across multiple sessions or in sensitive nontarget areas. (176) Of note, only few neuroscientists use brain stimulation on themselves for cognitive enhancement. (176) Given the still unclear risks and side effects of do-it-yourself brain stimulation use, it has been proposed to extend existing medical device legislation to cover also nonpharmacological and in particular physically acting cognitive enhancement devices. (177,178) In contrast to strict medical definitions, the more intuitively assessed level of invasiveness of an intervention often seems to depend on familiarity and cultural traditions. This leads to the Western attitude according to which changing one’s diet or performing exercise appears less invasive than taking pharmaceuticals or applying brain stimulation, independent of their actual effects on health.

The pharmaceutical platitude that there is no effect without side effects holds true also for many nonpharmacological enhancement interventions. It appears obvious that cognitive enhancers differ in the severity and form of side effects: prima facie, deep brain stimulation or implants have higher risks for side effects than sleep or cognitive training. However, also more indirect enhancement strategies such as neurofeedback potentially bear the risk of side effects up to inducing epileptiform activity, (167) and even gentle intervention such as meditation training might exert negative effects on specific cognitive domains: a negative relationship between mindfulness and implicit learning (168,169) and an increased susceptibility to false memory formation after mindfulness meditation (170) have been observed. Here, the intended training goal of nonjudgemental mindfulness opposes tasks where either a more critical or automatic mindset was needed. Further examples of side effects intrinsically associated with the enhancement goal are trade-offs between stability vs flexible updating of memory systems: (129) memories can also become “too stable” due to a memory enhancement intervention, as observed, e.g., for the anti-obesity drug rimonabant. (171)

A common ethical argument in the enhancement debate concerns distributive justice: also legally available enhancers come with cost barriers, restricting individuals of low socioeconomic status from access. (187) A main factor in the costs of cognitive enhancers is their patentability, which is not restricted to pharmaceuticals. (188) However, in particular, behavioral enhancement strategies are typically not subject to patentability or other cost-driving factors: sleep, exercise, meditation, or training in mnemonic strategies are largely free of cost and, thus, in contrast to pharmaceuticals or technological strategies, are available independent from the financial background of the user. On the other hand, these behavioral strategies require some time and effort: the 24/7 working manager as the cliché user of cognitive enhancement drugs might have the financial means to afford quickly taking his expensive smart pill between two meetings, but might be unable or unwilling to spend extended periods of time with sleep, meditation, or mnemonic training.

Cognitive enhancers differ in at least three aspects of availability: legal status, cost, and application time. In terms of legal regulation, different enhancement methods are regulated by sometimes drastically varying frameworks. Pharmaceuticals, for instance, are regulated by strict international control regimes that effectively prohibit nontherapeutic uses or by more lenient domestic drug laws. Brain-stimulation methods, by contrast, fall under medical device regulations, pertaining to basic safety standards in terms but not proscribing the uses to which they might be put. (177,178) Behavioral strategies are usually not regulated at all. The regulatory landscape is thus vast and possibly incoherent (for a review, see ref (186) ). Besides practical hurdles to the acquisition of illicit drugs for cognitive enhancement, the legal status appears to affect the motivation of users to decide which cognitive enhancers to take. (166)

8. Social Acceptance ARTICLE SECTIONS Jump To

Largely independent from their specific enhancing effects on different cognitive capacities, social acceptance of cognitive enhancement interventions differs strongly depending on traditions, their perceived naturalness, and the perceived directness of their mode of action. Enhancement interventions with a tradition of thousands of years such as meditation and nutrition are typically much better accepted than many currently debated enhancement strategies such as brain stimulation and pharmaceuticals. (189) Also more “natural” interventions such as sleep or exercise are seen in a more positive light compared to technological innovations. (190) Moreover, in how far the mode of action is perceived as psychologically mediated or more biologically direct, affecting the brain indirectly through the senses or more directly through the cranium or metabolism, often plays a role for their social acceptance: if an enhancement intervention such as intense cognitive or physical training requires extended efforts or is seen as a quick and effortless shortcut to the same goal as in the case of smart pills or brain stimulation touches different intuitions about human virtues and is thus valuated differently. Even though views based on such purely intuitive aspects of tradition, naturalness, or directness often rely on cognitive biases rather than rational argument, (191) a negative social perception for whatever reason might generate indirect psychological costs for users, which in turn might influence also rational evaluations of the respective enhancement intervention. (192)

Accordingly, one of the central points in the ethical controversy revolves around the question of whether enhancement strategies only relevantly differ with respect to their outcomes, i.e., their benefits and side effects, (193) or also with respect to their mode of operation. (194) Some argue that the relevant ethical distinction runs along the lines of enhancements that are active, in the sense of requiring participation, and those that work on persons more passively. (195)

Not surprisingly, different views on cognitive enhancement prevail in different (sub)cultures, with, e.g., a more positive view on enhancement interventions in Asia (196) or in younger populations. (197) Empirical studies on attitudes toward cognitive enhancement interventions found medical safety, coercion, and fairness the most common concerns, with nonusers displaying more concerns regarding medical safety and fairness than users. (198) Sometimes readily available substances for cognitive enhancement such as caffeine, energy drinks, or herbal drugs are dubbed “soft enhancers”; (199) however, considering that prohibition of substances is not only based on their potential harm, but also on historical circumstances, this differentiation between soft and hard enhancers appears questionable.

cognitive enhancement denotes any action or intervention that improves cognitive capacities, independent from the specific aim of this improvement. The use of the term in the empirical, philosophical, and sociopolitical literature, however, varies with regard of the specific aim of enhancement interventions: people appear to be more tolerant toward enhancement of traits considered less fundamental to self-identity, A further aspect that determines the social acceptance of cognitive enhancement is the aim of the given intervention. Taken by face value, the termdenotes any action or intervention that improves cognitive capacities, independent from the specific aim of this improvement. The use of the term in the empirical, philosophical, and sociopolitical literature, however, varies with regard of the specific aim of enhancement interventions: people appear to be more tolerant toward enhancement of traits considered less fundamental to self-identity, (200) and also more tolerant toward enhancement in individuals with cognitive impairments or low performance baselines compared to enhancement of normal or high achievers. (201,202) At least four different aims can be identified, each leading to different research strategies and different ethical evaluations of existing or potential enhancement strategies. (203) The least problematic concept of cognitive enhancement targets those everyday medical or psychological interventions that are meant to treat pathological deficiencies. Closely related are those cognitive enhancement interventions that aim to prevent or attenuate cognitive decline that is associated also with healthy aging. (204) Slightly less accepted appear to be those enhancement strategies that aim to improve cognition in completely healthy individuals, but still clearly stay within the normal limits of cognition. The probably most widely used and ethically most controversial concept of cognitive enhancement aims at the augmentation of cognitive capacities beyond normal function, as is represented in the cliché of high-functioning students or managers trying to further improve their performance by taking smart pills.