Monday, May 23, 2016

A Potential New Area for PTSD Research

Post-traumatic stress disorder (PTSD) is a common form of fear memory, in which a pervasive emotional stress is created by remembering experiences that evoked fear. If our brains could forget the fear memory, PTSD would decay away. Why can't we forget fear memories? In part, it is because they keep getting rehearsed, and much of this rehearsal occurs during our dreams. One major normal function of sleep is to help the brain to strengthen memory of things, good and bad, that happened during wakefulness.

Recent animal research suggests how the brain accomplishes this memory strengthening (called consolidation). More importantly, consolidation is manipulable. The study began with the established understanding that memories are of two kinds: explicit (episodic) and implicit (procedural). Fear memories are episodic; that is, we remember the episodes in our life that were traumatic. Episodic memories are laid down by a structure in the brain known as the hippocampus, a part of the cerebral cortex that is folded underneath the main cortex and has different internal structure and connections with other parts of brain. Moreover, the hippocampal consolidation effect is exerted when it generates a voltage rhythm of roughly 6-10 waves per second that also contains nested higher frequencies (gamma) of about 30-90.

With this background of information, researchers at McGill University in Canada* decided to see how fear memory might be affected by disrupting hippocampal theta rhythm, which in sleep occurs during the REM (dream) stage of sleep. The study was conducted in mice, monitored during their sleep, soon after they were trained to remember certain objects and also after they had learned a conditioned fear memory. The object-learning task was to remember where a novel object had been placed (the hippocampus is also known to provide the brain with spatial location information). The other learning task, and the one relevant to PTSD, involved exposing awake mice to a sound warning followed by electrical shock to their feet. They manifested the associated fear learning by freezing all movement as soon as the sound cue was heard, before the foot-shock was actually delivered.

The key part of the experiment was the ability to shut down theta activity. Other workers had shown that neurons can be made hypersensitive to laser light by injecting their environment with a virus that is fused to a fluorescent protein. The location of neurons that drive theta rhythm is known, and so the researchers injected such a virus into that area and also implanted a fiber optic that could deliver laser light on those neurons. Neuronal activity in this area could be stopped whenever laser light activated the protein.

With both memories of object location and conditioned fear, testing for recall on the next day revealed that memory formation was prevented by blocking theta activity during the preceding REM sleep when the blocking occurred during a critical four-hour period immediately after initial learning. Similar activity disruption during the non-dream, non-theta, stage of sleeping did not prevent either form of memory.

Even if you could use this laser-light technique in humans (and theoretically you can), you might say this approach could not work because it is usually not practical to institute formal therapy within four hours after an initial emotionally traumatic experience. But, a common current PTSD therapy is based on the established phenomenon of re-consolidation of memory. Every time you recall a memory, it has to be re-stored, and thus it is susceptible to modification (by talk therapy, for example). The revised memory can replace the original fear memory. A therapist could have a patient recall the bad experience, go to sleep right away, and receive light blocking of theta to disrupt the re-storage of the bad memory. Perhaps a simpler approach would be to get good dream sleep soon after talk therapy, which might help cement the revised, less traumatic memory.

*It was at McGill, about a half-century ago, that the role of the hippocampus in memory formation was first discovered.


Source:

Boyce, Richard, et al. (2016) Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science. 352, 812-815.


For more information about learning and memory, consult Memory Medic’s recent book, Memory Power 101.

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