Given that our ability to remember is inherently limited, one “solution” is to artificially
enhance memory. Here I discuss four general approaches that have been developed to
augment human long-term memory: nootropics agents, brain stimulation, mnemonic strategies,
and external aids. The former two have only been recently developed in the field of
systems neuroscience, and have become the focus of ethical debate. For example, some
ethicists question the propriety of artificial memory enhancement in healthy individuals.
As I demonstrate here, all four methods have been considered ethically suspect at
one time or another. In medieval times, the use of mnemonics was considered immoral
by many, and even the use of written texts as memory aids has been suggested as producing
the appearance of knowledge, void of actual knowledge. Here I present a summary of
each approach, beginning with those that fall within the scope of systems neuroscience,
and discuss considerations critical to each of their respective ethical debates.
Nootropics
Nootropics are pharmacological agents consumed solely for the purpose of cognitive
enhancement, sometimes referred to as “cosmetic use.” Most nootropics are prescription
drugs developed to treat a disorder, but are instead taken off-label for cognitive
enhancement. However, nootropics by the broadest definition can also include well-accepted
psychoactive compounds including caffeinated drinks and energy drinks. Currently there
is some evidence that caffeine can enhance memory (Jarvis, 1993; Hameleers et al.,
2000; Borota et al., 2014), however, results are not conclusive (Nehlig, 2010). Active
ingredients used in energy drinks, such as taurine and guaraná, can also enhance memory
(Alford et al., 2001; Haskell et al., 2007). There is also evidence that nicotine
and sage have beneficial effects on memory (Tildsley et al., 2005; Heishman et al.,
2010). In general, nootropics can enhance memory encoding, but also may influence
retrieval processes.
Numerous drugs are taken off-label for their nootropic properties (see Lannii et al.,
2008, for a review). Piracetam is credited as the first nootropic (Winblad, 2005;
Winnicka et al., 2005; Margineau, 2011) and has demonstrated memory enhancing effects
(Dimond and Brouwers, 1976). Unlike most drugs, piracetam has a very weak affinity
to receptors (Winblad, 2005; Margineau, 2011) and its mechanism of action is unclear.
Since the initial report of piracetam's memory facilitation in 1976, pharmacology
research has attempted to identify other compounds with memory enhancing abilities.
Modafinil, marketed as a treatment for sleep disorders, has been found to enhance
memory (see Repantis et al., 2010, for a review). Of particular interest, Kohli et
al. (2009) found modafinil to enhance both quality and speed of memory. Additionally,
memory enhancements were sustained after continued administration. Recent research
with ampakines in non-human primates have also yielded promising results (e.g., Porrino
et al., 2005). While many other nootropics also exist, such as adderall and ritalin,
these drugs do not enhance memory directly, but can effect other cognitive abilities
(de Jongh et al., 2008; Lannii et al., 2008).
Recent studies have shown that university students around the world are taking nootropics
to improve academic performance (e.g., Eickenhorst et al., 2012; Dietz et al., 2013;
Kudlow et al., 2013; Mazanov et al., 2013; Partridge et al., 2013; Sattler and Wiegel,
2013), though prevalence rates vary greatly between studies. Eickenhorst et al. (2012)
surveyed students to determine the motivations for using nootropics and found that
improving concentration, vigilance, and cognitive potential ranked the highest, though
enhancing memory was also a major motive. However, it can be argued that nootropics
lead to an uneven playing field, where wealthier individuals, who have access to nootropics,
can perform better academically. While the ethics of nootropics is an emerging topic,
the consumption of drugs to enhance performance is a time-worn topic within the field
of athletics, where such drugs are considered cheating. Additionally, it is unclear
what would constitute enhancement versus therapy—consider an older adult with gradually
decreasing memory, is it “fair” to use nootropics to perform at the same level as
a young adult, or would this be cheating?
Brain stimulation
Brain regions can be non-invasively stimulated using transcranial magnetic stimulation
(TMS) or transcranial direct current stimulation (tDCS). Briefly, both of these techniques
modulate the excitability of neurons in the targeted regions. See Sparing and Mottaghy
(2008) for a technical review of TMS and tDCS methodology. As both of these methods
have limited depth of penetration, the main memory-related regions (i.e., the medial
temporal lobe) cannot be targeted. However, the dorsolateral prefrontal cortex (DLPFC)
has been shown to be important to memory encoding and is often the target of TMS or
tDCS in memory studies (e.g., Marshall et al., 2004; Gagnon et al., 2011; Javadi and
Walsh, 2012; Javadi et al., 2012). As both of these methods are unlikely to globally
enhance cognitive function, but instead increase activity in one region while decreasing
activity in another (net zero-sum model; Brem et al., 2014), it is important to consider
the role of DLPFC in memory. The DLPFC is often associated with attention and working-memory
(e.g., Lebedev et al., 2004). Though the aforementioned studies focused on DLPFC stimulation,
other regions of the PFC have also been related to memory function (Blumenfeld and
Ranganath, 2007). The PFC in general has been associated with several facets of higher-level
cognition (see Wood and Grafman, 2003, for a review), with an emphasis on goal planning
(Passingham and Wise, 2012). One view of the relation between attention and episodic
memory is that information must first be attended to before it can be successfully
encoded into memory. Along with this, working memory can serve as an intermediate
process between attending to the information and the encoding of it.
To stimulate a brain region using TMS, pulses need to be applied concurrent with the
memory task (also see Walsh and Cowey, 2000). As a result, TMS can only be effectively
used within a controlled (i.e., laboratory) setting and cannot be readily used as
a memory enhancement technique by one's self. In contrast, though not done in conjunction
with a memory task, changes in cortical excitability due to tDCS stimulation have
been shown to persist 90 minutes after stimulation (Nitsche et al., 2003, 2005), and
in some cases can have persisting after-effects even 30 days later (Boggio et al.,
2008). Additionally, tDCS devices are becoming available to the public (Nature Editorial,
2013), targeted at improving attention and reaction time in gamers. Of particular
concern, this also allows parents to use tDCS in-home with their children to hasten
learning (Kadosh et al., 2012), despite the effects of tDCS on development being unclear.
Kadosh et al. (2012) suggest that using tDCS to enhance learning may be viewed as
cheating as it can confer an “unearned,” and thus unfair, advantage to the user. However,
hiring a tutor could be similarly unfair as the tutor's guidance would make learning
easier.
Memory can also be enhanced through invasive stimulation. Of course, invasive methods
cannot be ethically conducted on the same scale and with the same control measures
as with non-invasive methods. Hamani et al. (2008) describe a case where a patient
was implanted with a deep brain stimulation (DBS) device targeted at the hypothalamus
to treat morbid obesity. Through post-operative CT scans, the researchers estimated
that the electrodes were located in the hypothalamus, but two were notably proximal
to the fornix. Initial stimulation of one electrode evoked an autobiographical memory
from decades prior. Of particular relevance, the patient developed enhanced memory
function. Hamani et al. found that DBS led to greater activation in the patient's
hippocampus and parahippocampal gyrus. Suthana et al. (2012) implanted DBS electrodes
in the entorhinal cortex of epilepsy patients and found enhanced spatial memory. Generally,
such DBS studies are only conducted with patients that have already been implanted
with electrodes for non-memory reasons (e.g., localizing epilepsy foci), but recent
successes may soon lead DBS to be used as a treatment for patients with memory impairments.
Laxton et al. (2010) implanted DBS electrodes in the fornix in Alzheimer's patients.
Stimulation drove activity in entorhinal and hippocampal regions and improved memory.
Recent research in non-human primates has also lead to the development of a neuroprosthetic
device that enhances memory through task-specific activity (Hampson et al., 2013).
In contrast to DBS, where fixed frequency stimulation is used to activate regions,
this neuroprosthetic device is built using a nonlinear systems approach that computes
multiple-input-multiple-output (MIMO) associations with CA3 spike trains as inputs
and CA1 spike trains as outputs (see Figure 1; Berger et al., 2011, 2013). More recent
developments with this model have allowed for the transference of memories between
individuals (Deadwyler et al., 2013). Converging with non-invasive methods, the MIMO
device has also been implanted in the PFC and shown to enhance memory (Hampson et
al., 2012).
Figure 1
Graphical representation of the mathematical model developed by Berger et al. (2011)
to simulate connectivity between CA3 and CA1 of the hippocampus. Figure adapted from
Berger et al. (2013).
Invasive stimulation techniques involve a myriad of additional ethical issues that
are not present with non-invasive methods. For instance, it is unethical to implant
stimulation devices purely for research, an upcoming ethical issue will be the option
to opt for elective brain implants. As people are already able to opt for cosmetic
surgery in the absence of any medical issues, it seems reasonable that one should
also be able to elect for cognitive enhancements without a medical need. Along these
lines, individuals who get cosmetic surgery can still compete in a beauty pageant
without being considered “cheaters.” Simply put, assuming no significant risks, should
an operation to improve attractiveness be more ethical than improving cognition? That
being said, further research is needed before one can ask their family physician for
a referral to get a “memory implant.”
Mnemonics
The least controversial approach to enhancing one's memory is to use a strategy (i.e.,
mnemonics), sometimes referred to as internal aids. Countless strategies exist to
improve memory encoding, several of which can be used spontaneously, such as rote
repetition, making a sentence or story, imagining the to-be-remembered words, and
forming a mnemonic using the first letters of the words (Harris, 1980; Intons-Peterson
and Fournier, 1986). Additionally, everyday memory experts such as waiters (Ericsson
and Polson, 1988; Bekinschtein et al., 2008), taxi drivers (Maguire et al., 2000),
and chess masters (Chase and Simon, 1973; Gobet and Simon, 1996) use more specialized
strategies.
For more generalizable strategies it is most useful to focus on individuals who have
trained themselves to have superior memory. Maguire et al. (2003) compared superior
memorizers, those who placed highly in the World Memory Championships, to controls.
Most superior memorizers reported using the method of loci, a strategy first developed
by ancient Greeks, and sometimes referred to as a “memory palace.” In this strategy,
one imagines a familiar environment (usually their home) and walks through this imagined
environment, placing the to-be-remembered items at various locations (loci). To recall
the items, the individual imagines walking through the environment and sees the items
once again (also see Yates, 1966; Raz et al., 2009; Legge et al., 2012; Madan and
Singhal, 2012). Importantly, superior memorizers have been found to exhibit differences
in functional activations in the hippocampus and retrosplenial cortex (Maguire et
al., 2003). Other techniques can also be used to achieve extraordinary memory, such
as chunking, where information is hierarchically grouped (e.g., Chase and Simon, 1973).
The primary flaw of mnemonics is that effective use often requires extensive practice.
Considering the ethics of mnemonic use, some Christians in the middle ages viewed
mnemonics as immoral, considering them to be magic, in part due to their pagan roots
(Yates, 1964, 1966). However, others embraced it and used it as a tool for the remembrance
of Biblical text.
External aids
External aids such as written lists can artificially improve memory (see Harris, 1980,
and Intons-Peterson and Fournier, 1986, for a comprehensive list of aids), and are
primarily used as retrieval cues. Modern technology has vastly increased the capacity
and convenience of external aids, particularly due to the advent of cell phones (Wilson
et al., 1999; Wade and Troy, 2001; Svoboda et al., 2012). While the use of external
aids is relatively innocuous, it is not free of debate. In Phaedrus, Plato (360 BC,
275a) recounts a conversation where Socrates cautions Phaedrus against being too dependent
on written texts:
Trust in writing will make them remember things by relying on marks made by others,
from outside themselves, not on their own inner resources, and so writing will make
the things they have learnt disappear from their minds. [Writing] is a potion for
jogging the memory, not for remembering. You provide your students with the appearance
of intelligence, not real intelligence. Because your students will be widely read,
though without any contact with a teacher, they will seem to be men of wide knowledge,
when they will usually be ignorant.
This passage still rings true and may even be more relevant today. With ready access
to the Internet, people have even less reason to remember information directly, instead
remembering where to find the information, but not the information itself (Sparrow
et al., 2011). However, information stored using external aids is less susceptible
to memory biases (e.g., false memories, primacy and recency effects). Future neuroimaging
research comparing cued versus uncued memories using external aids may provide additional
insight into the neuronal mechanisms of memory.
Conclusion
Recent advances in systems neuroscience have provided new approaches to artificially
enhancing memory; however, these have not come without controversy. While it is not
possible to resolve these debates without further discussion, it is important to acknowledge
that although other approaches to artificially enhancing memory appear innocuous now,
this has not always been the case. One direction forward is to draw parallels with
other fields that have observed similar debates in the past, such as in the case of
performance-enhancing drugs for athletes and cosmetic surgery for beauty competitions,
and benefit from the discourse that has already surrounded their own ethical disputes.
Memory augmentation as an intervention
While the focus of this article is the use of augmentation to enhance memory in healthy
individuals, it is important to acknowledge that these methods should be equally,
if not more, beneficial to individuals with diminished memory function (e.g., older
adults and Alzheimer's patients). Additionally, it is possible that diminished function
can be a form of enhancement (Earp et al., 2014). With respect to impaired memory
as an intervention, one such case would be patients with post-traumatic stress disorder.