Lecture 5: Amnesia

Lashley's Search for the Engram

In 1950 Karl Lashley published an article entitled "In search of the engram" where he summarized his interpretation of the results of many experiments on the localization of memory. His rather gruesome experiments involved training rats on a maze until it was a well established habit, then lesioning different parts of the rats cortex in an attempt to remove the site of the memory (the engram). The rats were given some time to recover from the operation, then retested on the maze. The number of errors was taken as a measure of the extent to which Lashley had damaged the site of memory storage. He found that it didn't matter where he damaged the rat cortex, the crucial factor was the extent of the damage. Tongue-in-cheek, he confessed:
"I sometimes feel in reviewing the evidence on the localization of the memory trace, that the necessary conclusion is that learning is just not possible."
In a more measured tone he concluded that:
"The psychological studies, like the more limited direct experiments on the brain, point to the conclusion that the memory trace is located in all parts of the functional area; that various parts are equipotential for its maintenance and activation."

It is difficult to fit this "equipotential brain" conclusion with the results from many neuropsychological cases of patients with quite specific amnesias; where specific refers to botht the psychological dysfunction and the area of brain damage. I'll return to it after reviewing some of the vast literature on human amnesia.

Case Studies

The most famous amnesic in the neuropsychological literature is H.M., a young man who had an operation for temporal lobe epilepsy in 1954. He was one of a group of 10 patients operated upon by William Scoville, 8 of whom suffered some memory loss; H.M.'s was the most severe. The crucial brain areas removed (bilaterally) were his hippocampus (seahorse), amgydala, and surrounding temporal cortex. He had retrograde amnesia spanning several years (the cut off is hard to determine) and severe anterograde amnesia: he could not acquire new memories. His most well known statement on the subjective experience of amnesia was quoted by Greenfield: "Every day is alone by itself, whatever enjoyment I have had, whatever sorrow I have had." In fact, there is good reason to believe that his memory spanned less than a day.

Another frequent type of amnesia is Korsakoff's syndrome which arises from alchoholism, through the mechnaism of thiamine deficiency. One vivid example of this state is provided in Oliver Sacks essay "The Lost Mariner". A person that proved particularly compelling information was P.Z., an academic who had written his autobiography a few years before the onset of Korsakoff's; this allowed neuropsychologists studying him to examine his loss of specific autobiographical and semantic memories. Korsakoff's involves damage to diencephalic areas, specifically the dorsal medial thalamus and the mammillary bodies.

The person known in the literature as N.A. is a "pure" case of diencephalic amnesia. He acquired his amnesia as a consequence of an accident with a minature fencing foil that was inserted into the diencephalic area of his brain through his nose. He has very little retrograde amnesia, but marked anterograde amnesia. The pattern of N.A.'s deficits is simlilar to those of R.B., the "pure" hippocampal amnesic (CA1 damage only) described by Zola-Morgan, Squire and Amaral.

Although there are some differences documented between Korsakoff's and medial temporal lobe amnesics, they generally show the same types of memory loss: severe anterograde amnesia for both episodic and semantic information, and retrograde amnesia for episodic or autobiographical memories. The remarkable similarities in memory difficulties evidenced by patients with damage to disparate structures is not so surprising given the connections between the areas. The fornix connects the diencephalon to medial temporal lobe structures, and they are all part of an identified functional grouping known as the limbic system.

Schacter details a case of DeRenzi's who shows a complementary pattern of loss to the medial temporal lobe and diencephalic amnesics. This patient had damage largely confined to the front portion of the temporal lobe. The consequences of this brain damage were an inability to remember the meanings of common words and little knowledge of the basic attributes of animate and inanimate objects. Yet, she maintained accurate recollections of her personal past.

This type of double dissociation between psychological function and area of brain damage is one of the pieces of evidence that leads to the divisions of long term memory into distinct subtypes: episodic, semantic and procedural.

What types of memory are preserved? (in medial temporal lobe amnesia)

H.M. and many other amnesics have been intensively studied with the aim of dissecting memory into finer components. There are a number of things that amnesics can learn quite well and abilities that are preserved:
  1. Mirror Drawing
  2. Mirror Reading
  3. Pursuit Rotor
  4. Skill Memory (e.g., music, driving)
  5. Language Comprehension and Production
  6. Perceptual Learning (Picture Puzzles and savings on Gollin Incomplete Pictures task)
  7. Savings on Shortened Mazes
  8. Clasical Conditioning
  9. Tower of Hanoi
  10. Wisconsin Card Sorting Task (not some Korsakoff's with frontal damage)
  11. Priming - Perceptual and Semantic (Implicit Memory)
  12. Occasional Semantic Items (e.g., Kennedy)
Moscovitch abstracts the condtions necessary for a task to be amenable to an amnesic:
  1. structured so that the patient can immediately understand what is required
  2. the response called for is part of the subject's existing repetoire
  3. the goal of the task is attainable without reference to a specific past event

What is the role of the frontal lobes?

Damage to the frontal lobes in addition to diencephalic damage is quite common in Korsakoff's. Patients with such damage are more prone to confabulation. They also have extreme difficulty with memory probing. Another of Moscovitch's distinctions is helpful here: associative retrieval versus effortful or strategic retrieval. In PET studies of memory function enhanced blood flow was observed in the frontal lobes during explicit retrieval, taken as a reflection of the mental effort involved in searching memory. In contrast, increased blood flow in the hippocampus seems to reflect some aspect of the subjective experience associated with remembering the event. It should also be noted that blood flow increases in specific parts of the occipital and parietal lobes during recall.

Back to Lashley

This last characterization of many areas being involved in different aspects of remembering a single event gives us the clue to solve the Lashley puzzle I posed at the beginning of the lectue: why does amnesia result from damage to restricted areas if memories are represented throughout the brain. The maze learning task utilized by Lashley was multimodal in sensory terms and many aspects of memory were involved.

Damasio's theory of memory - distributed with convergence zones

What is known about the biological basis of long term memory?

Kandel's studies of potentiation LTP in hippocampus

Sources: