A Brief Comparative Look at Experimental Memory Editing Techniques for Cognitive Dysfunction

: Neuroscience has long sought to develop methods that can “edit” or even “erase” mem- ories, with the aim to provide treatments for memory-related neurological and psychiatric diseases such as anxiety and addiction. Current efforts are heavily focused on modifying cognitive behavio- ral therapy protocols or pharmacological treatments, but the efficacy and safety of these methods have been called into question by several studies. Advances in modern technology and the rapid emergence of techniques that can directly stimulate/alter neuronal activity, such as neuromodula- tion, have great potential in achieving the goal of memory modification for treating dementia such as Alzheimer’s disease. However, more research and validation studies are required before these memory editing technologies can be applied clinically. In this mini-review, we compare and high- light the advantages and disadvantages of cognitive behavioral therapy, pharmacological methods, and neuromodulation techniques. We believe that neuromodulation techniques will play a key role in overcoming the challenges of translating memory-manipulating techniques to clinical applications.

Is Reconsolidation a General Property of Memory?

Memory reconsolidation holds great hope for memory modification approaches and clinical treatments of mental disorders associated with maladaptive memories. However, it remains controversial as to whether reconsolidation is a general property of all types of memory. Especially, discrepancies have been reported in research focusing on whether declarative memory undergoes reconsolidation, and whether old memories can be reorganized after retrieval. Here, we discuss how these inconsistent results can be reconciled and what information we need to uncover for the general use of reconsolidation.

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

Optogenetics is an invasive neuromodulation technology involving the use of light to control the activity of individual neurons. Even though optogenetics is a relatively new neuromodulation tool whose various implications have not yet been scrutinized, it has already been approved for its first clinical trials in humans. As optogenetics is being intensively investigated in animal models with the aim of developing novel brain stimulation treatments for various neurological and psychiatric disorders, it appears crucial to consider both the opportunities and dangers such therapies may offer. In this review, we focus on the memory-modifying potential of optogenetics, investigating what it is capable of and how it differs from other memory modification technologies (MMTs). We then outline the safety challenges that need to be addressed before optogenetics can be used in humans. Finally, we re-examine crucial neuroethical concerns expressed in regard to other MMTs in the light of optogenetics and address those that appear to be unique to the memory-modifying potential of optogenetic technology.

A practical approach to the ethical use of memory modulating technologies

Background Recent advancements in neuroscientific techniques have allowed us to make huge progress in our understanding of memories, and in turn has paved the way for new memory modification technologies (MMTs) that can modulate memories with a degree of precision, which was not previously possible. With advancements in such techniques, new and critical ethical questions have emerged. Understanding and framing these ethical questions within the current philosophical theories is crucial in order to systematically examine them as we translate these techniques to the clinic. Main body In this paper, we discuss the ethical implications of modern neuroscience techniques that aim to disrupt or enhance memories. We attempt to frame the MMTs in the context of existing ethical philosophical theories to provide a cohesive analysis of the myriad of ethical quagmires that might emerge from such technologies. We argue the application of Aristotle’s Golden Mean and multiple accounts of authenticity are useful in approaching the ethical questions surrounding MMTs. We then propose a framework in which ethical considerations can be systematically examined. Lastly, we provide caveats and considerations for the use of this framework. Overall, we provide a practical approach for the ethical use of MMTs depending on the situation. Conclusion While at face value, our model appears to put severe limitations on the application of MMTs, we are not completely opposed to their use, but rather our framework guides the agent to consider the implications before making any decisions. Most importantly, we argue that the use of MMTs does not reduce the responsibility of the initial decision, and the agent must accept the post-MMT self as the new “true self” regardless of the outcome. As the developmental trajectory of MMTs suggests we are getting closer to practical clinical applications, ethical concerns across a wide range of disciplines need to be addressed to develop best strategies and policies when dealing with MMTs. If this can be achieved, we believe the ethical use of MMTs is not only possible but would also be of tremendous benefit to many people suffering from memory-related mental disorders.

Emotional Memory in the Human Brain

Across a lifetime, people tend to remember some experiences better than others, and often these biases in memory are fueled by the emotions felt when initially encoding an event. The neuroscientific study of emotional memory has advanced considerably since researchers first detailed a critical role for the amygdala in enhancing memory consolidation for arousing experiences. It is now known that the influence of emotion on memory is both a more selective and multifaceted process than initially thought. Consequently, the neural mechanisms that govern emotional memory involve an expansive set of distributed connections between the amygdala and other medial temporal lobe structures, along with prefrontal and sensory regions, that interact with noradrenergic, dopaminergic, and glucocorticoid neuromodulatory systems to both enhance and impair items in memory. Recent neurocognitive models have detailed specific mechanisms to explain how and why the influence of emotion on memory is so varied, including arousal-based accounts for the selective consolidation of information based on stimulus priority, as well as top-down cognitive factors that moderate these effects. Still other lines of research consider the time-dependent influence of stress on memory, valence-based differences in neural recapitulation at retrieval, and the mechanisms of emotional memory modification over time. While appreciating these many known ways in which emotions influence different stages of memory processing, here we also identify gaps in the literature and present future directions to improve a neurobiological understanding of emotional memory processes.