Tuesday, October 6, 2009

Erase and rewind (on designer memory)

Few topics have received as much attention in the field of neuroscience as the erasure of memory. Recent advances in our understanding of fear memory and its vulnerability under certain conditions have raised the tantalizing possibility that we might, in the near future, be able to target emotionally-charged memories in the treatment of post-traumatic stress disorder (PTSD). PTSD results from a catastrophic event in a person's life. As a result, an excessively pervasive memory is formed that continues to torment the sufferer long after the trauma is over, leading to chronic anxiety. This debilitating condition may arise in victims of physical assault, survivors of car crashes or, notably, in soldiers returning from war. In addition to PTSD, inappropriate storage of traumatic memory may underlie the emergence of some phobias, such as a fear of heights, crowds or open spaces. How are neuroscience and medicine working together to treat these conditions?

Any attempt to erase traumatic memory is challenged by two major obstacles: First, it is essential that we do not erase all memories. Our memory provides not only a unique and cherished autobiography but also allows us to walk, to talk, to tell friend from foe and to know right from wrong. We would be entirely dysfunctional without it. Neuroscientists need to find ways to target only the unwanted memories without affecting anything else. Second, the molecular mechanisms that our brain uses to store information pass through phases of fragility and stability. They are relatively easy to disrupt early on after we learn something but become much less plastic over time, which is why, for example, concussion can lead to amnesia for events that occurred just before a blow to the head but not for earlier events. Unfortunately, phobics and sufferers of PTSD are usually only available for treatment a long time after the causal traumatic episode. A successful treatment for PTSD or phobias will, therefore, likely have to find ways to destabilize long-term memory.

Neuroscience is now beginning to identify ways in which we may circumnavigate these two obstacles. One approach attempts to return old, stable fear memories back to the fragile state that they exist in early on after learning, through a process of controlled recall. Thanks in large part to the work of Susan Sara, in Paris, and Karim Nader and co-workers, at New York University and now at McGill University in Montreal, it is known that certain emotional memories can re-enter a period of sensitivity through a process described as reconsolidation. During this period, memories are susceptible to erasure by drugs that block the molecular mechanisms of long-term memory storage in the brain. This finding presents us with the possibility that debilitating memories such as those causing PTSD could be treated long after the precipitating trauma by simply allowing the subject to recall the causal events, thereby entering the relevant memories into the labile state of reconsolidation. A dose of one of several drugs that are already known to disrupt memory storage mechanisms in humans may erase fear and anxiety if taken shortly after recall.

An alternative approach focuses on assisting the natural neural processes by which we normally lose unwanted emotional memories. Michael Davis, based at Emory University in Atlanta, is currently attempting to treat fear of heights in people by facilitating a mechanism of unlearning known as extinction. His research group uses virtual reality to induce feelings of fear in subjects evoked by being high above the ground. It is known that repeated exposure to a phobic stimulus without any accompanying punishing event can lead to a weakening of the phobia. This behavioural therapy is the basis of traditional methods for treating such conditions as performance anxiety in public speakers, musicians and sportsmen. It is thought that behavioural therapy taps into the natural process of extinction. Extinction shares some of the molecular mechanisms of learning itself. We now know enough about some of these mechanisms to not only use drugs to block them, as Nader’s group has done, but also to facilitate them. So far, Davis and colleagues have had some success in using drugs to enhance the molecular mechanisms of extinction and, in conjunction with virtual reality, treat the fear of heights.

It is worth considering that these advances in medical research may have long-term ramifications for society that extend beyond those afflicted by PTSD or phobia. Imagine a scenario in the future in which the treatments for disorders described above become reliable. Might people be able to selectively erase their own memories of a failed love affair, infidelity or some other similarly unwanted passage of their life? This scenario was engagingly portrayed in the 2004 motion picture ‘Eternal sunshine of the spotless mind’. Here Jim Carrey’s character, Joel, has his memory of a doomed relationship with Clementine, played by Kate Winslet, erased by the cosmetic memory company Lacuna.inc. The company website - http://www.lacunainc.com/ - will give you a flavour of how successful and popular this erasure technology is supposed to be in the film. How close is this movie to our real future? We might consider how smoothly other technologies, such as plastic surgery, have transitioned from a purely medical application, the reduction of disfigurement in victims of severe burns in this case, to a cosmetic application, the creation of perfect ski-jump noses and pneumatic breasts. Given how many technologies have followed this same path from medical treatment to lifestyle enhancement, it seems highly plausible that humans may soon be walking the streets not just with cosmetically-enhanced bodies but also with cosmetically-sanitized minds.

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