The challenge of retrograde amnesia to theories of memory

I am reading Oliver Sacks' “The man who mistook his wife for a hat”. On chapter 2, he describes a case of retrograde amnesia. Around 1970, the patient went into an episode of alcoholism, which resulted in the loss of 25 years of his most recent memories (declarative memory). As a result, the patient thought he was 19 and lived in 1945, as if time had stopped. So not only could he not transfer short-term memory to long-term memory, but a large part of his previously stored memory got erased. In addition, it is not a random fraction of his memories that were erased: it was exactly the most recent ones. He seemed to perfectly remember old memories, and have absolutely no memory of the more recent events.

This is quite a challenge for current neural theories of memory. The main theoretical concept about memory is the notion of neural assembly supporting associative memory. Imagine a memory is made of a number of elements that are associated together, then the substrate of this memory is a connected network of neurons that “code” for those elements, in some structure in the brain, with connections to relevant parts of the brain (say, the visual cortex for visual features, etc). This conceptual framework can be extended with sequential activation of neurons. Now in this framework, how do you erase the most recent memories? Note that by “most recent”, I am talking of 25 years, not of short-term memory.

One trivial possibility would be that each memory has a timestamp, encoded as part of the neural assembly supporting that memory. Then some mechanism erases all memories that have a timestamp more recent than a particular date. Why and how this would happen is mysterious. In addition, “reading the timestamp” would entail activating those memories (all of them), which would then need to exist at that time, and then erasing them. It simply sounds absurd. A more plausible explanation is that, for some reason, recent memories are more fragile than old ones. But why is that?

This is a very interesting point, because in current neural theories of memory, it is the old memories that are more fragile than the recent ones. The reason is that memories are imprinted by modifications of synaptic connections according to a Hebbian mechanism (neurons that are co-activated strengthen their connections), and then these connections get degraded over time because of the activation of the same neurons in other contexts, by ongoing activity. So in current theories of memory, memory traces decay over time. But what retrograde amnesia implies is exactly the opposite: memory traces should strengthen over time. How is it possible that memories strengthen over time?

One possibility is that memories are replayed. If you recall a memory, the neurons supporting that memory activate and so the corresponding connections strengthen. But conscious recollection will probably not do the trick, because then there would not be a strict temporal cut-off: i.e., some recent memories might be recalled more often than some older ones. So what seems to be necessary is a continuous subconscious replay of memories, independent of emotional or attentional states. Clearly, this is quite a departure from current neural theories of memory.

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