Eternal Sunshine of the Memory-Modulated Mind

Blessed are the forgetful, for they get the better even of their blunders.

In the film Eternal Sunshine of the Spotless Mind, Joel Barish strives to relieve the burden of a bad breakup by erasing the memories of his ex-girlfriend through a medical procedure. Though the film contains no dialogue with concrete neuroscience, it still demonstrates a remarkable understanding of how our brains form memories, particularly emotional ones, and provokes discussion about the ethics of changing such memories. While current technologies are not advanced enough to wholly erase memories of people or events, recent advances in memory modulation techniques (MMTs) have inched us closer to the reality set forth by Eternal Sunshine, where modification for traumatic memories is as commonplace as antidepressant prescriptions or cosmetic surgery. Of course, with these developments comes a host of bioethical considerations about the implementation of such a practice. In this post, I will examine several methods of memory modulation and discuss their ethical implications—namely, the interaction between autonomy and authenticity, identity, and other societal consequences.

Memory Modification

In a 2017 paper, Dr. Andrea Lavazza defines memory editing broadly as a psychological or neurobiological intervention to change the valence of autobiographical memories or remove the memory trace altogether. Memory editing can occur at two phases: consolidation and reconsolidation. Consolidation refers to the process by which information transfers from short-term memory (STM) to long-term memory (LTM) for storage. Consolidation results from protein synthesis by neurons to cause structural changes in neurons and the connections between them, creating a firm neural network that represents the memory. A labile process, this protein synthesis can be inhibited to block the expression of LTM but not STM.

Even once consolidated, memories, if recalled, can still undergo changes and require further protein synthesis to be restabilized. In an auditory fear conditioning experiment, rats were exposed to a tone followed by an electric shock. Because of the learned association, the rats developed a defensive freezing response to the tone, which the researchers used to quantify fear memory. They found that stopping protein synthesis in the amygdala after reactivation of the auditory fear conditioning memory blocked LTM in the rats, providing evidence for the presence of a reconsolidation process. The malleability of reconsolidated memories also explains why the memories of events that are recalled often end up changing over time.

Neuromodulatory Techniques

Numerous techniques, both neuromodulatory and pharmacological, exist to modify memories. Based on consolidation/reconsolidation and Hebbian theory, modern MMTs seek to augment synaptic plasticity to enhance neurogenesis or synaptogenesis. Changing memory processing can happen in one of two ways:

1. Increasing neuronal activity involved in the memory process
2. By altering the transmission of memory-related neurotransmitters and their receptors

Repetitive Transcranial Magnetic Stimulation (rTMS)

If performed on the dorsolateral prefrontal cortex (dlPFC), rTMS can disrupt the reconsolidation of fear memory and prevent its return. In one study, researchers stimulated the dlPFC using rTMS shortly after a cue that reactivated a fear memory acquired 1 day earlier. Twenty-four hours after treatment, “participants exhibited decreased physiological expression of fear, as shown by their skin conductance response.” However, this intervention was only effective within a reconsolidation time window.

Optogenetics

This technique, which involves the use of light to stimulate genetically modified neurons, has allowed for the improvement of the valence of memories, selective activation or inhibition of memories, and even the formation of new memories in the absence of experience. While optogenetics has the benefit of versatility, its invasiveness currently limits its use to transgenic animals and makes translation to humans difficult. Because animals lack declarative memory, researchers are unsure of whether there could be negative side effects in humans. Even more, ethical concerns regarding gene editing in humans persist (not discussed in this post).

Deep Brain Stimulation (DBS)

DBS has been shown to change memory in both rodent and human models. A review by Lee et al. suggests that DBS might improve memory by mimicking the neural oscillatory patterns in memory and that by the same principle, DBS could impair memory if applied at a frequency that interfered with memory encoding. Researchers are currently exploring the use of DBS to target the hippocampus to help treat Alzheimer’s disease (AD), and several clinical trials have already been done. As of now, DBS has the advantage of higher spatial and temporal specificity over non-invasive techniques like rTMS, but DBS comes with its own set of limitations. DBS for treating AD has had very limited success and only in patients 65 years old and above. Furthermore, DBS faces challenges in targeting specific memories; with heightened synaptic plasticity, long-term potentiation could result in increased “off-target memories” and an “overgeneralized increase in learning and memory functions, which could have severe implications for diseases such as addiction and anxiety disorders.”

Propranolol

The most promising avenue for memory modulation, in terms of both scope and efficacy, is the molecule propranolol, which can interfere with the consolidation or reconsolidation of traumatic memory. This molecule, ordinarily used as a β-blocker to treat hypertension, can reduce the emotional salience of a memory. In traumatic situations, an uptick in the production of the stress hormones adrenaline and cortisol causes an increase in the neurotransmitter norepinephrine. The norepinephrine in turn “connects the given memories to the fear circuit” and, upon binding to β-adrenergic receptors of the basolateral amygdala, “produces a stream of molecules signaling the codification of the memory,” writes Lavazza. This also explains why a highly emotional event will likely produce a stronger, more permanent memory. Propranolol blocks the activation of the receptors, thus interfering with the emotional consolidation or reconsolidation of a given memory.

Lavazza also notes that propranolol “acts best if taken during or shortly after the stressful event, but is inefficacious on emotionally ‘bland’ memories,” highlighting the drug’s ability to remove a memory’s negative emotional component and accompanying physiological symptoms of distress. Several studies have supported this observation.

In an experiment in which participants learn an association between stimuli and shocks, the administration of propranolol disrupted reconsolidation, returning participants’ startle responses to the level of a stimulus never paired with shock.

In another study, Brunet et al. asked patients with chronic PTSD to share their traumatic experiences, and then gave them propranolol. Patients returned a week later and listened to imagery scripts based on their traumas. Physiological responses to the scripts lowered significantly in the patients treated with propranolol compared with the placebo, and in some cases, had dropped below previously defined PTSD cutoffs.

Importantly, reactivation followed by placebo did not bring about changes in the memory, and neither did administration of propranolol without reactivation. Moreover, subjects did not lose episodic memory during reactivation. Because propranolol specifically binds to receptors in the amygdala, and episodic memory is stored in the hippocampus or neocortex, propranolol may suppress memories by disrupting the amygdala's influence on reconsolidation and curbing the emotions that make the memory particularly salient.

Ethical and Societial Issues with Memory Modification

Two Viewpoints

As we quickly approach a future that may make MMTs a conventional treatment, a number of ethical and societal issues rear their heads. To address these concerns, two rival paradigms have emerged in current bioethical literature.

1. The bio-liberal approach advocates for individual autonomy based on the harm principle, which maintains that people should be free to act however they wish unless their actions harm somebody else. People who endorse this view respect an individual’s right to self-govern according to their own motives without interference from insidious external forces or internal limitations. It follows that the bio-liberal approach supports the application of any therapy as long as the patient perceives a net benefit.
2. The bio-conservative view, conversely, appreciates the patient’s personal identity and thus holds authenticity in high esteem. Supporters are often skeptical about biotechnological advances, especially those that attempt to enhance the human condition, as this would undermine the core tenets of human identity, such as one’s values or characteristics. Because significant memory modulation might erode authenticity by altering identity, bio-conservatives do not approve of this practice.

The Case of Elizabeth and Sonya

Alexandre Erler puts forth the following thought-experiment:

Two friends, Elizabeth and Sonya, have both been bullied throughout high school. Despite this, they finish school and go on to live satisfactory lives. Years later, however, the girls’ former bullies invite them to parties; Sonya accepts the invitations with peace of mind, but Elizabeth differs. On one hand, she had been scarred deeply by the bullying and requires an apology. On the other, she wishes she could be as carefree as Sonya, letting the painful memories of her past go. Opting for the latter, Elizabeth decides to take propranolol, suppressing the negative emotions in her memories of high school. She remembers all the facts and events, but no longer with any contempt, and can see her former peers as if she had forgiven them.

In contexts like these, moral bioenhancement generally seems like a very positive route: a person modifies their neurobiology to quickly achieve a result that may not be solvable with other tools available right now, such as therapy. Memory editing could lead to an improvement of a person's condition, both psychologically and physiologically, as well as lead to better social integration. Elizabeth rid herself of the painful memories that plagued her and increased her wellbeing. But was Elizabeth’s choice authentic?

What Even is Authenticity?

In order to understand authenticity, we must first understand identity. Two conceptions of identity prevail within our current understanding of psychology and philosophy: that of rigid identity and that of the extended self. These notions are not mutually exclusive in ideology, and they even share characteristics, but are helpful in framing the debate of authenticity.

1. Philosophers characterize rigid identity as a “self-consciousness of a thinking self.” This identity may partially change over time, but always maintains a stable core that must be preserved because it makes us unique.
2. The extended self, on the other hand, manifests from interpersonal relationships because, unlike rigid identity, it is not innate and fixed but arises from interactions and other sociocultural elements. In this sense, one’s extended self reads more like an autobiographical narrative which can be rewritten as one ages.

The concept of authenticity seems to presuppose a rigid personality, for which there exists both empirical and philosophical evidence, albeit limited. In a case study of Patient D.B., who suffered from severe episodic amnesia, Dr. Stanley Klein observed the loss of this patient’s ability to remember any specific events, with no recollective or episodic memory. Nevertheless, D.B. could accurately ascribe traits to himself, when comparing self-attribution to traits described by close relatives. Klein also found that this ability to accurately self-assess endured despite total loss of episodic memory and change in one's personality.

In terms of philosophy, John Rawls suggested a thought experiment in which subjects are unaware of their personal characteristics and of the sociohistorical context. His implication is that even without a detailed autobiographical memory, people still understand their identity, which they can use to make meaningful decisions consistently.

So, rigid identity or extended self?

If our “core self” remains unwavering, the threat MMTs pose to authenticity appears self-evident. MMT-influenced choices that oppose actions or feelings that would naturally follow from one's identity “betray” the core self, to which one should be faithful to uphold personal authenticity. Society also encourages people to respect authenticity by expecting consistency in people’s interpersonal interactions. If a person violates authenticity they become unreliable, erratic, and perhaps even removed from reality. In the Elizabeth and Sonya scenario, Erler seems to subscribe to the rigid identity approach, arguing that Elizabeth’s choice is indeed inauthentic because by partially deleting her memories, she changes her natural response to the situation (as opposed to Sonya, whose forgiveness comes natural). For the character and convictions of her “core self,” Elizabeth would not forgive without hearing an apology first.

Modern cognitive sciences, however, are trying to dismantle the notion of a rigid identity. A growing number of experimental studies, especially in children, have shown the construction of self-consciousness that develops from the interplay between self-awareness, autobiographical memory, social communication, and culture. Children begin to rationalize their identity as an autobiography around ages 5–6 and begin to view their memories as a unified life story with purpose and meaning. Children construct their subjective identity upon absorbing how others see and define them. Studies have shown the development of a “self-reflective capacity that can grow or change… particularly from childhood to maturity. These studies challenge the understanding of our identities as inelastic, implying one may not need to keep a particular memory to preserve identity, which would be unstable anyway. The position of an extended identity welcomes positive changes to personality because they don’t infringe upon any moral obligation to sustain authenticity.

My Thoughts

Although I respect an individual’s autonomy and, to some extent, even concede to the notion of an extended self, I see too many legal and societal implications associated with the implementation of memory modulation to endorse its cosmetic use—that is, use in a non-rehabilitative manner. My concerns with MMTs as a widespread practice stem from two related ideas:

1. Use of MMTs in “cosmetic neurology” will gain popularity
2. Mainstream use of MMTs may actually detriment society, even if some choose not to use them.

A society based on a legal system requires a stable personal identity. Otherwise, in an admittedly extreme scenario, a person found guilty of a crime could request the blocking of key memories connected to their personal identity and then, claiming to have become another individual, request the annulment of the sentence and avoid legal and financial consequences.

A method to weaken the memory can create a clash between an individual’s right to control their own memories and society’s right to safeguard itself from criminals. A victim of aggression may hold the right to erase a traumatic event from their memory, but if in doing so, they lose the motivation to press charges or testify against their aggressor, they deprive society of the information and ability to apprehend the criminal and ensure others are protected from this individual. The physician who prescribed the MMT to the victim may even risk obstruction of justice charges.

It seems then that such behavior violates the harm principle that forms the basis of the bio-liberal perspective. While the victim may alleviate their own pain, their actions may inflict damage upon others by potentially letting a criminal run free. If everyone were inclined to use MMTs in this way, the security of society would collapse. Criminals would not only go unpunished, but also the gradual realization that many victims prefer to forget rather than pressing charges would decrease deterrence against crimes.

In another example, imagine that in a masculinist society, if subjugated women resort to MMTs to tolerate their circumstances, the potential for resistance against societal oppression would decline. Notably, this wouldn’t be limited to a situation where all women used MMTs. If enough women did, even if not all, they could significantly impede the ability of themselves and those who abstained to emancipate themselves. The supposition then becomes that for the general welfare of society, some people might have to keep a traumatic memory.

Even if there is no rigid identity to preserve, this doesn’t justify a practice of cosmetic neurology. Changing any aspect of one’s personality at whim, especially if done en masse by a population, has potentially devastating sociolegal effects. Major memory modification could decouple someone from their autonomous interactions with the external world, so it seems even the extended self connects on some level to authenticity, at least in a society that values personal continuity. A person can exercise their right to autonomy and act on their memory; however, if this were to alter their continuity of existence, they could actually threaten the very conditions for their own autonomy. In this regard, an exercise of autonomy (i.e. deciding to use MMTs) is morally justifiable if it acts in accordance with personal authenticity and continuity.

Conclusion

For lack of a better answer, use of MMTs must be reviewed on a case-by-case basis, but should be used sparingly and generally only as a rehabilitative technique rather than a self-enhancing one. In particular, individuals afflicted with PTSD often have a number of emotional burdens that do not necessarily point to their own moral transgressions, including guilt and unjustified self-blame due to their victimization. Though there may be repercussions if society were to encourage dulling of all negative emotional responses, cases like these may justify the use of MMTs to treat PTSD. An ever-changing field, the advent of new memory modulation innovations will surely warrant further bioethical discussion. But for now, I can firmly contend that Joel Barish should not have erased his memories of his ex-girlfriend.