Karim Nader has been contemplating memory for years, particularly how memories are acquired, stored and recalled. Can they be disrupted, and if so, how? The psychology professor's earlier work, on the malleability of memory, inspired the 2004 Kate Winslet-Jim Carrey flick Eternal Sunshine of the Spotless Mind. Now, with McGill psychologist Alain Brunet and Harvard psychiatrist Roger Pitman, his findings in rodents are being applied to people incapacitated by Post Traumatic Stress Disorder (PTSD). The study is near completion and the results are encouraging.
"We've known for a long time that memory is labile," Nader explained, "that after it's formed, it exists in this unstable state for a while until it's fixed into long-term memory," a process known as consolidation. His earlier work demonstrated that when a fixed, well-established memory is recalled, it re-enters this unstable state and can be disrupted, even to the point of functionally wiping the slate clean.
Through his research, it's become clear that memories can be restabilized every time they're activated, through a process called reconsolidation. In fact, the very act of recalling a stored memory puts it in a state that could, if you suffer a concussion for example, cause it to be lost. To preserve it, it must be stored again. Instead of simply recalling a memory, the brain forges it all over again in a new context. In a sense, when something is remembered, a new memory is created, one shaped by the changes that have happened to the brain since the memory was recalled the time before. This process is called reconsolidation.
Nader uses fear conditioning in rats as his experimental model. "Basically, we exposed them to a tone and then a mild shock to the feet, leading to a strong fear response displayed even when the animals heard the sound alone." With Glenn Schafe, a postdoc in Joseph LeDoux's lab at New York University, Nader rediscovered that rats could "forget" these deep-seated, fearful memories if treated with chemicals that stop the synthesis of proteins, but the memory had to be reactivated (by playing the tone) for chemical-induced amnesia to occur.
Nader found that recall and reconsolidation of memories depend on protein synthesis in the lateral and basal nuclei of a brain structure called the amygdala, the site where memories are stored in fear learning. These results were surprising. "For a hundred years, we thought that once a memory is fixed, it's fixed forever," he said. As an ironic aside, it seems similar findings were made in 1968 by Donald Lewis and others, and forgotten (or at least, not carried forward).
Nader's rodent work also established that "emotional memory is based in the amygdala, while consolidation and reconsolidation of conscious memory take place in the hippocampus;" memories attached to very strong emotions are much more likely to make the cut to long-term storage, due to the effect of stress hormones like adrenalin. It's as though these strong emotions highlight the experience in biological terms.
Beta adrenergic receptors on neurons are deeply involved in the consolidation of conscious memory in the amygdala, but they also affect blood pressure throughout the body, Nader noted. So could a blood pressure treatment affect painful memories, too? Harvard's Roger Pitman tried propanolol, a common blood pressure regulator, to treat trauma victims in the ER. The medication decreased his patients' risk of later developing PTSD.
Douglas trials promisingNow Alain Brunet, based at the Douglas Hospital, is trying propanolol in long- established PTSD. "Traumatic events can be human-made or natural accidents," he explained. "Events that are human-made really shatter people's expectations of others. The world becomes a very dangerous place. Rape and traumas related to [the actions of] others" are most likely to lead to PTSD, which affects up to 50 percent of those who experience trauma. Brunet, who assesses UN peacekeepers, said one million Canadians suffer from PTSD.
The study has treated 19 long-term PTSD sufferers with symptoms between one and 40 years of duration. They write about their experiences as vividly as possible and then receive a dose of propanolol significantly lower than usually prescribed for blood pressure problems. A week later, their trauma accounts are read back to them and psychophysiological indices are monitored. It's clear the reactions of those treated with propanolol are less severe.
"We're very excited," Brunet said. If the results hold" - another 10 subjects are required to be confident of the findings - "this could open the door to a new way of treating PTSD," because only about one-third of patients derive lasting benefit from current practices - cognitive behaviour therapy and anti-depressants.
"Hopefully, we can decrease the level of distress for these patients, so their memories of these events will be less overwhelming and more responsive to traditional treatments in psychiatry such as psychotherapy. You wouldn't want to erase them completely because they form a large part of a person's identity," Nader pointed out.
For more information about brain structure and function, please see The Brain from Top to Bottom.