NOTICE: Posting schedule is irregular. I hope to get back to a regular schedule as the day-job allows.

Saturday, March 26, 2011

It came to me in a flash...

Memory, “Flashbulb” memory and PTSD.

In general, memory is a weak process. Learning and remembering factual items requires repetition and retesting . In general, if you want to remember a phone number, you repeat it. Particularly if you can’t write it down – interrupt the repetition, and you forget the information. Skills and more complex facts require more repetition, and usually occur over days. The overnight period with REM and nonREM sleep is very important to shuttling memory from short-term temporary memory to long-term memory (this is called “Consolidation”).

Standard memories are hard to record and easy to erase (at at the very least easy to lose track of). There is a subset of memory and learning that is permanently stored after only a brief or even single exposure. What we as scientists know is that to strongly record memory requires the input of several brain areas. At the same time, memory is stronger when it incorporates associated information such as sensation (light/sound/smell) and emotion.

There are three main areas of the brain involved in memory. The “Frontal Lobe” area above and behind the eyes, “Medial Temporal Lobe” just inward from the ears, and the “Basal Ganglia” which are the deep structures in the middle, bottom of the brain. A key structure that I will mention a lot is the Hippocampus, which is a major portion of the Medial Temporal Lobe. The hippocampus is the main processing area for memory. Along those same lines, Frontal Lobes are commonly thought of as the brain region we “think” with, while the Basal Ganglia are involved in motivation and reward.

Repeating and rehearsing memory involves passing the information back and forth between Frontal and Medial Temporal Lobes. Frontal areas can retain information for about 10 seconds to a minute, Hippocampus can hold information for 10 minutes to an hour. Learning also requires an evaluation of *reward* or the relative value of the information to be stored, thus incorporating connections with the Basal Ganglia. We are finding that the greater the value of the “reward” reinforcement, the easier a memory is to store, and the harder it is to erase. Remembering usually invokes a repeated shuffle of information from Frontal to Hippocampus and back again, with the Basal Ganglia adjusting the strength and speed of the process. By the way, this process *is* tied to sleep and dreaming, but some parts we don’t really know, and the parts we do aren’t really relevant to this discussion.
Now, on to the unusually strong, single event memories. There are three main types of events that lead to strong memories: very strong emotion, stress/danger and drug abuse. The examples of remembering events associated with marriage proposals, birth of a child, the Moon Landing, etc. fall into the strong emotion category. They tend to be clear memories with a lot of associated sensory information – day/night, temperature, cooking smells, music on the radio. The emotions can be positive or negative, and the accuracy of this memories is usually around 80% correct (compared to a well rehearsed “learned” accuracy in the mid 90’s). They can be so accurate, but based on only a single event with no “repetition” because the emotional feedback strengthens the “reward value” inputs to Hippocampus and does not require repetition. The reason the accuracy is not 100% is because every time a person “relives” a memory, it is in fact “rewritten” and there is a chance for *current* information to be written along with the memory. More on this later.

Stress/danger memories include the category of “Flashbulb” memories. Strong negative emotion, fear of death, loss of a loved one, traumatic circumstances – all invoke extremely strong stimulation from the Basal Ganglia to the Hippocampus. It’s a survival mechanism: Touch the fire and feel pain – store the memory “Do Not Touch Fire!” and don’t require it to be repeated in order to be remembered. One of the features of these “pathological” memories is that replaying the memory invokes all of the emotional sensation again. Since strong emotion affects the ease of memory storage, these memories are in even greater danger that other similar circumstances will be conflated with the original memory.

Hence, my Flashbulb Memory of hearing about the Challenger Explosion in 1986: I was present at a lab meeting discussing the unfortunate accident of a fellow student when a professor burst in to tell us the Space Shuttle had exploded. The reality is that the two events were separate, but only a month or two apart. There was a lab meeting setting each time, and both were strong negative emotional events. Somehow, the retelling of the Challenger event invoked the similar memory of the student’s accident and became conflated. [Likewise Sarah remembers viewing the JFK assassination and funeral on a color TV when there was no TV, let alone color, in her house at the time. Seeing a JFK documentary at a later time likely caused her to recall the emotional memory of the Portuguese President’s funeral and the two became associated. ] Flashbulb memories are strong and easily recalled, but their accuracy is typically less than 50% because the same mechanism which makes them easy to recall – that is, the emotional content – is also replayed and makes the memory sensitive to contamination. Generally the only way to detect these errors is by some external event that causes us to check the facts – such as by being challenged by another person who was present at same events and then consulting a factual source to realize the inconsistencies in our memories. It is also noteworthy that strong emotion memories are *very* hard to erase.

This brings us to PTSD: the extreme end of stress and emotionally charged memories. An enhanced sense of personal danger or trauma is the strongest modulator of memory. Battlefield and trauma memories are particularly vivid, incredibly easy to recall, and charged with multiple associations – in fact, the associations are so strong that a PTSD sufferer can have flashbacks triggered by a sound or smell that might seem to have *no* relationship to the event, but have become indelibly linked with the trauma. PTSD memories are nearly impossible to erase, and the current treatment options involve finding a way to interrupt flashbacks and prevent the replay/rewrite consolidation cycle. Note they also are *not* limited to battlefield incidents! Although pathological memory does not *require* repetition in order to store the memory, it *does* get repeated every time the subject has a flashback. Thus two memory mechanisms are invoked, contributing to the difficulty in breaking the cycle. There are not many good indicators of how accurate PTSD memories are, but it is likely, given the ease with which flashbacks can be triggered by associative memory, that there is a considerable amount of contamination.

OK, I mentioned drug abuse at the beginning, and flashbacks in conjunction with PTSD. How do these tie in? Well, a lot of what we now know about pathological memory is now starting to tie in with drug withdrawal and relapse. We know that drugs such as cocaine, Meth, LSD, etc. all operate on neurotransmitters that are most prominent in the basal ganglia. Marijuana and narcotics are as well, but not as strongly (in fact, any euphoric sensation alters emotion and Basal Ganglia activity). Conditions underlying relapse and drug cravings turn out to have a strong component of pathological memory. The drugs actually *trigger* the neurotransmitters in Basal Ganglia to promote pathological memory associating the “high” with the surrounding conditions. Thus “pictures of drug paraphernalia” really *do* promote craving because they associate with a pathological memory. Cocaine and Meth are the worst offenders, and not coincidentally have the greatest effect on Basal Ganglia. Like PTSD, these are pathological memories, but now we are learning the actually physiological and pharmacological basis for the memory, and starting to look into ways to prevent or degrade the memories.

Current treatments for drug abuse to prevent relapse are using many of the same techniques as PTSD therapy, but now are beginning to look into ways to use the physiology and pharmacology to best advantage to truly *erase* these memories.

Both fields stand to benefit.

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