The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics

As already mentioned, memory-modifying research is one area which can provide a glimpse of the capabilities of optogenetics. The first optogenetic study to gain widespread publicity⁵ was a study by Ramirez et al. [29] in which authors attempted to implant a false memory in a mouse by means of contextual fear conditioning. To this end, they tagged neurons of memory-engram regions of the hippocampus⁶ that were active when the mouse was placed in one context (context A), and then activated them with light when the mouse was placed in a different context (context B), in which it was given mild electric shocks. This procedure produced an association between the memory of the previously neutral context A and the aversive stimulation received in context B, which, when the mouse was reintroduced into context A, generated a fear response (despite the absence of any further light stimulation). To confirm that researchers did not create a generalized fearful memory response to any context, the mouse was placed in a completely new context, C, where it displayed no fear response, instead freely exploring the new environment. These results were replicated by another research group [30]. Although false memories had previously been planted using relatively simple misinformation techniques, i.e., providing misleading information about a past event either to distort the recollection of certain details of an existing memory or to implant a new, completely fabricated memory, this was the first study to implant a “false memory” by manipulating the brain activity of a non-speaking subject, bypassing the need of any form of communication, on which simpler psychological methods rely heavily (see [31]). This optogenetic procedure also has the unique advantage of not relying on human-derived factors that might moderate the rate of success in implanting false memories. For instance, in a classic study that used the “Lost in the Mall” technique,⁷ implantation of false memories of being lost in a shopping mall in childhood [31] was successful in only ~ 25% of participants (or even less, see [32]); further studies showed that this success rate might be greatly dependent on the convincingness of the story, the characteristics of those subjected to this procedure (e.g., age and level of suggestibility), and the characteristics of those conveying the story (such as age advantage and family relationship between the implanter of the false memory and the individual who had the memory implanted) (e.g., [33]).

Another impressive demonstration of the potential of optogenetics was provided by research on the recovery of “lost” memories. Autobiographical memories formed in early infancy in both humans and animals (including mice) are rapidly forgotten, a phenomenon known as childhood or infantile amnesia [34]. Until recently, it was unknown whether such memories were permanently erased, e.g., due to storage failure, or became increasingly inaccessible with time, e.g., due to retrieval failure. Initial resolution of this question was provided by Guskjolen et al. [35]. In this study, infant mice were subjected to contextual fear conditioning, creating a memory of having received an electric shock in a particular context (a specific chamber). Although such memories normally decay with time due to infantile amnesia, Guskjolen et al. [35] managed to retrieve these “lost” infant memories by first targeting the hippocampal neurons responsible for their original encoding during infancy and then reactivating them 3 months later when the mouse reached adulthood. This finding demonstrated for the first time that infant memories are probably not permanently erased, but rather become inaccessible with time due to retrieval failure. In a similar vein, another research group showed that memories retained under retrograde amnesia which resist retention based on the use of natural recall cues are not completely lost and can be recovered using optogenetic stimulation, once again providing evidence of a failure of retrieval rather than of storage [36, 37]. Both instances are pioneering, as the retrieval of “lost” or inaccessible memories has never been achieved by any other memory-manipulation technique and opens up completely new and exciting avenues for future research. For instance, its application to human subjects may at last verify some psychoanalytic claims which attribute a special role to bringing repressed memories to consciousness in order to integrate them with the subject’s representation of the self, with the aim of self-treatment.

Some evidence indicates that optogenetics can also erase and recover selected memories on demand—the capability so desperately sought after by the protagonists of the film Eternal Sunshine of the Spotless Mind (2004), who change their minds about consigning their love affair to oblivion. This extraordinary possibility was demonstrated by Nabavi et al. [38], who were able to repeatedly deactivate and reactivate a specific memory by modifying its synaptic strength. In this study, animals learned to associate optogenetic stimulation (applied to the lateral amygdala) with an aversive shock. Once this memory had been formed—as evidenced by a conditioned freezing response to optogenetic stimulation—researchers exposed the rats to an optical long-term depression (LTD) protocol which disturbed this associative memory—as evidenced by the absence of the freezing response to optogenetic stimulation applied on the following day. To test whether this suppressed memory could be restored, the animals were then exposed to a long-term potentiation (LTP) protocol, which succeeded in recovering the previously deactivated memory—as evidenced by re-establishment of the freezing response to optogenetic stimulation.

Remarkably, another line of research demonstrated that it may be possible to reversibly deactivate and reactivate not only relatively new [38] but even very remote, well-consolidated memories with the use of optogenetics [39]. This was achieved by first training a group of mice to associate an auditory cue with an electric shock (which resulted in the acquisition of an auditory-cued fear memory), and then exposing them to the cue 4 weeks later while inhibiting CA1 hippocampal neurons, which abolished recall of the remote fear memory. Importantly, this interference was shown to be temporary (i.e., reversible): when mice were re-tested on the next day without optogenetic intervention, the fear memory was still present and mice expressed the freezing response to the shock-predicting auditory cue. Heretofore, no other method has yet been able to switch selected memories on and off “at will.” Although the erasure of memories has been previously achieved using amnestic agents, which, administered after learning, can prevent the consolidation of newly-acquired memories, these compounds were shown not only to act non-selectively—i.e., impairing memory of all recently encoded events and producing a form of general retrograde amnesia—but also to be toxic for humans, which precludes their (clinical) use [40].

However, for both therapeutic and ethical reasons, erasing memories may not always be desirable.⁸ Thus, some researchers attempted to apply optogenetics to evoke memory valence changes (for instance, by turning a “bad” memory into a “happy” one) without affecting the content of memory (declarative memory of an event). This was achieved for the first time by researchers from the Tonegawa group [41], who demonstrated that upon reactivation of a memory engram (encoded by dentate gyrus cells of the hippocampus), the valence of an elicited conditioned response could be reversed by means of its reassociation with a new unconditioned stimulus of an opposite valence. Although influencing memory valence had been achieved earlier by means of memory-modifying drugs [42], these substances usually act through attenuating memory consolidation, which changes, to some extent, the degree to which the memories being consolidated are remembered.

Optogenetics was also demonstrated to modulate memory consolidation, i.e., the process of stabilization of a memory trace following its initial acquisition [43]. For instance, researchers showed that it was possible to facilitate or impair retention of selected new memories by stimulating or inhibiting selected groups of neurons of the amygdala [44]. As mentioned above, modification of consolidation processes can be carried out using memory-modifying drugs such as propranolol or mifepristone, which manipulate the release of stress hormones. Specifically, research shows that emotional events cause an increase in the production of stress hormones, such as adrenaline, norepinephrine, and glucocorticoids, which strengthens memories of such events by enhancing consolidation [45]. For this reason, drugs that mimic or block the release of stress hormones can non-selectively modulate memory for events that are currently being consolidated. These agents were proved to work especially well, reinforcing or impeding the consolidation of an emotional memory, when administered in the immediate aftermath of the emotional event [42, 46].

However, as victims typically seek help several weeks after the traumatic event, when memories are well-consolidated, researchers tried to determine whether propranolol could also affect memory reconsolidation, a process during which previously consolidated memories are made labile again via reactivation of the memory trace [47], in order to lessen the symptoms of post-traumatic stress disorder (PTSD).⁹ In a series of three experiments, Wood et al. [48] demonstrated that administration of propranolol (a β-adrenergic blocker) or mifepristone (a glucocorticoid antagonist) proved ineffective compared with a placebo treatment in blunting PTSD symptoms or affecting physiological response following reactivation of a traumatic memory. These findings were further supported by [49], who also failed to observe propranolol-induced suppression of a retrieved memory in humans. However, it is worth noting that propranolol was shown to be effective in reducing PTSD symptoms [50] or fear-related responses [51] when administered prior to memory reactivation. The initial 1-year follow-up study showed that propranolol could also be effective in treating anxiety disorders and phobias, as patients who received treatment for arachnophobia showed no relapse [52]. However, propranolol-based interventions may cause development of maladaptive dispositions in patients; e.g., some patients wanted to pick up a tarantula or let it crawl up their arm, thus doing things that many nonphobic individuals would refuse to do [53]. Furthermore, some researchers argue that the effectiveness of propranolol might be ascribed to disturbed memory retrieval or new facilitated learning [54].

Amnestic agents have also been used to interfere with memory reconsolidation. For instance, it was shown that infusion of a protein synthesis inhibitor [40] or application of electroconvulsive shocks [55] following memory retrieval might be successful in disrupting subsequent memory retention. However, as mentioned earlier, such treatments were shown not only to be too dangerous to be used in humans, but also to produce general retrograde amnesia (i.e., disruption of all encoded memories) rather than specific memory changes (ibidem).

In contrast to amnestic treatment, alteration of the content of specific memories upon their retrieval has been successfully and safely induced using much simpler behavioral methods, such as extinction training or memory updating [56]; for an extensive overview of different behavioral methods of inducing reconsolidation in humans, see [57]. Extinction training—a laboratory model for exposure therapy—is also used to treat patients suffering from anxiety disorder. This therapy is based on repeated exposure to cues or situations evoking fear in patients in order to reduce this emotion as well as to replace a fear-related memory with a new extinction memory. A major limitation of this approach is that its effects are not permanent; when a fear-related memory begins to dominate over the extinction memory, the fear may quickly return [58, 59]. Contrastingly, behavioral memory updating, which is a type of extinction paradigm, has the distinct advantage of updating a fear-related memory with non-fearful information introduced upon memory retrieval within the reconsolidation window. Thanks to this procedure, new information is incorporated into an old memory, which is thus updated. Although as of now this approach seems to be the most promising type of therapy for affective disorders, it is susceptible to spontaneous recovery/relapse, as shown by several independent attempts to translate laboratory findings into clinical practice [54]. The potential advantage of using optogenetics or optogenetic-like technology for this purpose would be its ability to instantaneously suppress the neural activity responsible for reactivating an unwanted memory at the moment it occurs.

Optogenetic modifications were also demonstrated to enhance well-consolidated memories of positive experiences, through reactivation of the dentate gyrus engram cells responsible for encoding them originally [60]; importantly, reactivating positive experiences reduced stress-induced behaviors, counteracting deficits in motivation, abnormal responses to behavioral challenges, and anhedonia (reduced ability to seek and experience pleasure) when investigated in an animal model of depression (ibidem). Memory enhancement is being sought today through a vast array of different methods aimed at offering such benefits, ranging from physical exercises and yoga to psychostimulants (e.g., methylphenidate) and invasive neuromodulation techniques (for an extensive review, see [61]). None of them, however, is capable of influencing memory processes in a manner as precise and selective as that of optogenetics. Moreover, even methods that bear the closest resemblance to optogenetics—such as DBS, which inhibits or exacerbates neural activity of selected brain regions via an implanted electrode—appear to possess certain inherent limitations. For instance, stimulation of the hippocampal neurons, although successful in inducing specific memory changes via optogenetics, caused the disruption of memory processes when less precise and selective electrical currents were applied via DBS [62].

Last but not least, optogenetic intervention has been recently tested as a potential treatment for various models of neurological disorders tested in animals. The latest evidence indicates that optogenetics, similar to DBS [63], shows potential for improving memory impairments observed in neurological conditions such as diencephalic amnesia and Alzheimer’s disease through stimulating small thalamic nuclei [7]. Optogenetics has also contributed significantly to an improved understanding of the dysfunctional neural circuits underlying PTSD [64] and Parkinson’s disease [65], inspiring novel circuit-inspired applications of DBS (ibidem). Here, again, the precision of optogenetics may prove to be crucial in obtaining the most desirable outcomes from applied treatment.

One basic ethical concern associated with medical interventions is the question of who should receive the treatment. As long as prognostic indicators of the development of psychological disorders such as PTSD in the immediate aftermath of trauma are not fully developed, MMTs that rely on intervention within the consolidation window take the risk that the patient will be deprived of the opportunity to attempt recovery from trauma on his or her own through an appeal to rational capacities, for example via the construction of a redemptive story to promote posttraumatic growth [95].¹¹ On the other hand, as some MMTs (e.g., propranolol, optogenetics) have the potential to modify even well-consolidated memories, this opportunity may reduce the above ethical concern through the introduction of legal regulations mandating that only memories contributing to the development of a particular trauma are to be treated (see also [53]).

One fundamental and inherent issue common to all of the interventions discussed above is that memories constituting the most plausible candidates for such modifications often involve some form of moral transgression, as experiences of this kind are especially disturbing and traumatic for humans. However, alteration of the valence of memories involving moral transgression (i.e., switching them from negative to positive) may be ambivalent even in cases where memories have proved to be maladaptive and have resulted in the development of a psychological disorder. Consider the potential usage of MMT to alter the valence of memories of war veterans who have developed PTSD. A government which pursues an imperialist policy may actually possess a vital interest in the modification of the valence of soldiers’ war memories not only in order to treat these soldiers but also to use their testimony to propagate more positive images of war in order to gain broader support for military campaigns as well as to gain new recruits attracted by military stories.

The discussed case, however, entails not only the potential malpractices of authoritarian governments but also the issue of appropriate moral reaction. As moral agents, we can respond to events in more or less appropriate ways [97, 98]. In the case discussed above, soldiers may have either harmed others or been harmed themselves. Some argue that it is appropriate to feel resentment and indignation in the case of experiencing harm and guilt and regret after harming others [97, 99, 100]. Arguably, if soldiers experienced harm and developed PTSD as the result of an event, the issue of appropriate moral reaction would be less problematic, provided the government did not use the soldiers as a propaganda tool.

However, cases in which soldiers harm others are particularly morally problematic. It may be argued that it would be at least morally ambivalent to modify memories of soldiers who had committed horrific acts, even if those memories resulted in PTSD. Consider the consequences of altering the valence of the dreadful memories of a soldier who had committed genocide, who would thus arguably be free from PTSD along with the guilty conscience that would normally have resulted from his deeds. Some would argue that murderers should express appropriate moral reactions to deeds they have every reason to feel guilty about.¹²

Even more morally alarming in this case is that the valence of the soldier’s memory of genocide would be changed from negative to positive—the opportunity provided by the novel potential of optogenetics. Thus, he might actually develop a disposition to take pleasure in recalling his inhuman acts. This situation seems entirely different, from a moral standpoint, from one in which the valence of a traumatic memory is merely blunted (as is already offered by MM drugs, such as propranolol). It might be argued that every human being—independently of his or her past—deserves to be free from psychological disorders or even from a guilty conscience; however, it is much more controversial to argue that humans have the right to alter the valence of memories of their own horrific acts so as to actively enjoy them.

Moreover, assuming that alteration of the valence of a particular memory could become generalized to other instances of this type of memory (e.g., from a memory of killing a particular person to memories of killing other people), it might introduce changes in an individual’s overall evaluative system of such acts as well as in his desires. For instance, a soldier, having changed the valence of his war memories, could develop “a taste for killing.” Thus, meddling with the valence of traumatic memories of war veterans could make them “sociopathic,” as they might become disposed to obtain satisfaction from harming others—the possibility that seems to be especially acute in case of optogenetic interventions involving the change of valence from negative to positive.

The possibility that blunting memories may change the evaluative system of a person is linked to the issue of authenticity. In many conceptions of authenticity, deriving from various lineages—essentialist (self-discovery) (e.g., [102]), existentialist (self-creation) (e.g., [103] [1943]), and dual-basis framework (e.g., [104])—being “truthful” to oneself is directly associated with living in alignment with one’s values. Thus, a person whose values have been changed as a result of alteration of the valence of her memories would commit either an act of “betrayal” of her true self, according to the essentialists, since, as a result of her evaluative change, she might begin to lead a life inconsistent with her given and fixed essence (for further considerations, see [105]), or an act of self-deception, according to the “Sartrean” existentialists, as the process of self-creation would stem not from the values that she had freely chosen, but from those constituting side effects of the memory-modifying intervention (for additional considerations see, [99, 106]). Either way, such an intervention may pose a threat to the patient’s authenticity.

Another problem with the kinds of memory-modifications common to various MMTs is that some memories, despite being unequivocally negative or disturbing, may be highly adaptive; accordingly, changing the valence of certain highly aversive and unpleasant memories may be undesirable or even dangerous in cases where the memory is indicative of a genuine threat. Let us recall the above-mentioned consequences of propranolol-based interventions in cases of arachnophobia, in which participants developed generalized and excessively positive responses to spiders—a disposition which could prove deadly in an encounter with a venomous spider in the wild [53]. As optogenetics potentially offers not only to blunt the emotionality of specific memories and associated emotional reactions—as in the case of propranolol—but also to switch the valence of specific memory, the issue of adaptiveness could become even more problematic when memory-modifying interventions are applied with the use of optogenetics.

Elsey and Kindt [53] also point out that interventions that resulted in “the development of an overly potent appetitive memory could be highly disruptive. This is evident in addiction, in which the rewarding properties of drug consumption gave so much control over behavior that the drug is pursued even to the detriment of the person’s health, relationships, and personal commitments.” Therefore, going “beyond the norm” regarding the emotional valence of a given memory may prove unfavorable, whether the change of valence is from positive to negative or vice versa.

The nature of the human mind is such that often the most plausible target of optogenetic erasure comprises traumatic yet self-defining memories, since traumas often play a critical role in forming personal identity [95, 107]. Furthermore, traumatic memories may also play a role in shaping the personality; for instance, those who experienced childhood trauma were shown to exhibit greater empathy than those who did not [108]. Finally, as demonstrated by the #MeToo movement or, recently, by the #BlackLivesMatter movement, some intersubjectively shared types of traumatic experiences and memories (such as of sexual abuse or racial discrimination) may, for instance, motivate people to organize in order to combat systemic forms of maltreatment that they and those close to them have experienced. Thus, removing traumatic memories may render systemic change in society impossible: people freed from traumatic experiences might lose the motivational component of their traumatic memories and cease to fight against the injustices they have experienced.

It can be argued, nonetheless, that people should not be forced to retain their traumatic memories, as a human being should be treated not as a means for other ends (here, the welfare of society), but rather as an end in itself. However, as Lavazza [109] points out, the combination of several individual choices can entail negative composition effects. In a nutshell, although each individual does what appears, prima facie, to be the best for herself—e.g., erase memories of maltreatment—and enjoy temporarily subjective relief from painful experience, in the absence of centralized coordination of these actions, individual choices may backfire on both the individual making them as well as, in the future, other members of society, as the objective conditions that led to the traumas in the first place remain unchanged; thus, the aggregate consequences of the choice to erase traumatic memories made by a sufficient number of individuals would actually help to preserve oppressive social relations and serve the interests of oppressors.

Negative composition effects need not appear at the level of society; they may also be revealed at the more “local” level of the life of an individual. A hypothetical case posed by Glannon [110] is a good exemplification of this: a young academic experiences a traumatic failure during a public event; devastated, she decides to erase the memory of this event. However, similar failures happen again and again. On every occasion, she uses optogenetics to erase the disturbing memory. Thus, as the opportunity to erase memories is always available to the young scholar, she avoids dealing with the structural weakness responsible for her failures. Consequently, she falls into a cycle of repeating mistakes and erasing her memories of them. Thus, although subjectively well, she will eventually be overwhelmed by external reality, ending up worse off than she would have been without optogenetic interventions.¹³

Not allowing for dampening traumatic memories on the above discussed grounds—due to concerns about negative composition effects—may breach not only the Kantian imperative, but also the liberal principle of individual autonomy understood as “self-rule” or “self-government” [113]. According to the latter principle, the very idea of self-rule relies on the right to control one’s own mind; thus memories—being a fundamental part of it—would certainly seem to be included (see [114]). However, given the nature of life in society, it is apparently beneficial for all parties to impose certain limitations on the potential choices and actions of its members; here, for example, Mill’s principle of liberty might be recalled.¹⁴ Moreover, in an apparent paradox, imposing restrictions on personal autonomy can be beneficial in terms of exercising autonomy: a Hobbesian society functioning according to the homo homini lupus rule would possibly exercise autonomy at the beginning (at least of some of the most powerful members of society), but over time “continuous conflict would repeatedly put at risk our ability to self-determination, since violent interferences with our choices would be the norm. It therefore seems that the “rule” of autonomy should be implemented so that, even if everyone took it to the highest degree, it would still be possible for everyone to exercise it” [109].

We are not arguing that an individual’s interest in avoiding pain from traumatic memories and potential development of PTSD should be always subordinate to society’s interest in changing oppressive structures. Potential middle-ground pragmatic solutions exist. Lavazza [109] proposed, for instance: “to allow the treatment to those who show the greatest signs of suffering.” At the same time, we may want to ask the most motivated individuals to be “volunteers” and to preserve their memories intact in order to continue the fight against experienced injustices. Moreover, it is worth noting that, as long as choices to erase memories arise only occasionally, the principle of autonomy appears to outweigh the principle of conformity regarding memory erasure mentioned above.

In our view, however, there will always be a tension between the interests of the individual and society, as it is unlikely that governments (or other decision-makers) will ever be able to reliably predict the aggregate consequences emerging from the decisions of individuals. Thus, assessment of the admissibility of optogenetic memory modifications is no simple matter, as it requires careful consideration of the aggregate societal consequences of these interventions.

Kolber [114] considers a situation in which a bystander is the only person to see the face of a serial rapist fleeing the home of his latest victim. Arguably, most would agree that even though this bystander might find this memory upsetting and might want to erase it, she should be legally obliged to retain it in the interests of preventing the serial rapist from committing future crimes. This case raises the issue of moral obligations regarding memory modifications. However, should we reach the same conclusion when the only person to see the serial rapist’s face is the victim of the rape? When Kolber posed this question in 2006, the only way to diminish a given memory was through interference with the process of its formation. Therefore, the decision whether to dampen a memory had to be made quickly, within several hours after the event in question, which would preclude the victim’s testimony in a subsequent court trial. Postponing memory erasure, on the other hand, would render the procedure ineffective. In an attempt to answer the above question, we may again consider negative composition effects: if every victim erased her traumatic memory, social safety would deteriorate greatly, since no victims would testify and criminals would remain free to commit additional crimes [109]. However, given the novel capacity of optogenetics to target and selectively erase well-consolidated memories, we may possess tools in the future to erase traumatic memories after their deposition within the context of a criminal prosecution; thus, this protocol could provide a solution to the discussed problem. Moreover, speculatively, in a case where such memories were desperately needed during other stages of the prosecution (as arguably might sometimes be the case), optogenetics could potentially reintroduce them into the victim’s memory system in order to gain additional necessary evidence. Our considerations here demonstrate that confronting existing arguments with empirical data is crucial as answers to neuroethical problems can differ given distinct capabilities of various technologies.

The moral obligation to remember can be discussed either when one experienced harm (one is the victim), or when one harms others (one is the offender). Liao and Sandberg [97] argue that in a case in which one is the offender, one has “a duty not to remove these kinds of memories until one has come to realize one’s errors.” Thus, Liao and Sandberg argue for “the duty to remember” on the grounds of the value of the appropriateness of moral reactions. On the other hand, they also emphasize that the moral obligation to remember is particularly relevant if deliberately forgetting might increase the likelihood of future crimes of this type. However, this solution might be questioned, as Liao and Sandberg acknowledge, citing Levy [116], who argues that “deliberate forgetting could decrease the likelihood of future crimes of this type, because remembering may make it easier to commit the crime in the future, since one has already done it before” [97].

Thus—from the perspective of the interests of society and for consequentialist reasons—which of these strategies would be more beneficial in terms of crime prevention is an empirical question. Obviously, however, one can argue in favor of the duty not to erase offenders’ memories of moral transgressions on the grounds of other moral values, such as autonomy. Let us recall the protagonist Alex in Stanley Kubrick’s A Clockwork Orange (1971), who was “rehabilitated” by means of the aversion therapy to the extent that, as Cabrera and Elger [117] point out, he ceased to be capable of any moral action.

Although it appears that the reversible erasure of a specific memory offers an ideal form of memory manipulation (as we can always bring the erased memory back), there is the risk that the restoration of an erased memory may not be accomplished without consequences. Studies show that some memories may exert enormous impacts on who we are and what we pursue in our lives. These are so-called self-defining memories [118]. Singer et al. [119] argue that such memories serve as the ingredients for an individual’s overall life story, and thus constitute that individual’s narrative identity. Schechtman [120] famously argues that the narrative is the answer to the “characterization question”—the question of “what makes a person who she is.” Schechtman also imposes normative constraints upon a narrative considered constitutive of the self. According to the articulation constraint, the narrative must be coherent and intelligible. According to the reality constraint, it must correspond to basic facts about the person’s life ([120], 83; 113–114). Thus, in the light of Schechtman’s theory of narrative identity and the above insights concerning self-defining memories, the concern regarding optogenetic erasure of a self-defining memory is that a given individual’s narrative—the very requirement of being oneself—might be disrupted.¹⁵

If this were the case, however, it could be argued that, given the capacity of optogenetics to reintroduce memories into the memory system, these potentially undesirable effects of memory erasure/deactivation could easily be reversed through reactivation of the memory trace. However, reactivation of self-defining memories may fail, as the individual’s narrative identity may have already changed. Therefore, the individual might feel alienated from the newly reactivated memory as a result of feeling that she is no longer the same person.¹⁶ Consequently, the re-integration of (previously) self-defining memories with a subject’s newly developed narrative identity might prove impossible.