A New Study Suggests the Hippocampus Is Not Crucial for Memory

The hippocampus is a tiny area of the brain, and in humans it is about  twice the size of a peanut. Neuroscientists have often made the claim that the hippocampus is necessary for the formation of new memories. Typically they offer as their main evidence for this claim the assertion that a patient H.M. suffered damage to his hippocampus and could no longer form new memories. Although often made, the claim about patient H.M. is incorrect, as I discuss in my post here, and in the Appendix at the end of this post. Although he had memory difficulties, patient H.M. clearly could form new memories, according to several papers that studied him. 

In my 2023 post here ("Studies Debunk Hippocampus Memory Myths") I discuss a wide body of evidence that debunks claims that the hippocampus is crucial for memory. Now let us look at a new paper discussing new experimental evidence  discrediting the idea that the hippocampus is crucial for memory. The paper (entitled "Is Memory Spared in Monkeys With Selective Lesions of the Hippocampus?") documents experiments done on monkeys that had been given drugs causing the destruction of most of the hippocampus. 

One of the drugs was ibotonic acid, and the group of monkeys that was given this drug is referred to in the paper as "the IBO lesion group." We read this:

"Stereological quantification of histological material in the IBO lesion group revealed an overall reduction of 53% in the volume of the hippocampus relative to intact brains. The average hippocampal volume was 732 mm³ for controls and 346 mm³ for monkeys with lesions, with volume in the experimental animals ranging from 270 to 414 mm³ (Figures 1 and 2). It should be noted, however, that these values significantly underestimate the extent of the lesions, since 24% of the remaining hippocampal tissue in IBO lesion monkeys appeared grossly atrophied and dystrophic. Summing this damaged tissue together with the estimated frank loss yields an overall 63% reduction in hippocampus volume in the IBO group."

Another group of monkeys got a drug called NMDA. We are told that for this group, "The volume of the hippocampus was reduced 72% in lesion monkeys relative to intact controls (see Supplemental Figure 1, J.)." 

Roughly speaking, we may say that the hippocampus-tested monkeys had about two-thirds of their hippocampus destroyed by the drugs given them. The brain has a left hippocampus and a right hippocampus. Figures 2 and 3 of the paper make clear that this roughly two-thirds destruction occurred for both the left and right hippocampus of the monkeys tested. 

Figure 3 shows the results of one series of tests involving six IBO-group monkeys with these hippocampus lesions, and four normal controls. We see no significant difference in performance. 

Below is part of Figure 4 of the paper, showing performance on something called  "Delayed Nonmatching-to-Sample Performance Averaged Across Test Episodes." Again, the difference in performance between the monkeys without most of their hippocampus and normal undamaged controls was insignificant. 

Below is part of Figure 5 of the paper, showing performance on something called  " Trial-Unique and Repeated Objects Versions of Delayed Nonmatching-to-Sample." We have a group of six normal control monkeys and six "NMDA-group" monkeys (with about 72% of the hippocampus destroyed) performing without any significant difference. (B) graphs "recognition accuracy across increasing retention intervals" while (D) graphs "recognition accuracy across delays (D) on the delayed nonmatching-to-sample retest with a single, repeated object set." 

Figure 6 is very similar, showing no significant difference between the hippocampus-damaged monkeys and controls. 

Figure 7 gives us the data below comparing memory performance in normal control monkeys and monkeys with very severe hippocampus damage. The (A) and (C) portions of the graph are remarkably similar. In the (B) part of the graph the control monkeys (having no damage) perform slightly better than the heavily hippocampus-damaged monkeys; but in the (D) part of the graph the opposite is true (with the heavily hippocampus-damaged monkeys performing better than the undamaged control monkeys). And the damaged monkeys in the (D) part of the graph were significantly more damaged than the damaged monkeys in the (B) part of the graph. The paper says the NMDA group had 72% destruction of the hippocampus compared to roughly two-thirds destruction of the hippocampus in the IBO group. 

The authors conclude that "the specific operating characteristics of memory supported by the primate hippocampus—and that might serve as proxies for hippocampus integrity in clinical disorders that feature memory impairment as an early symptom— remain enigmatic." This is a very understated conclusion. 

A more blunt conclusion would say something like this: we have been told a huge myth by those claiming that the hippocampus is some "memory center" of the brain; and when monkeys lose 62% to 72% of their hippocampus, this produces no major difference in the performance of the monkeys on memory tests. 

Appendix

The claim is commonly made that following a 1953  operation damaging his hippocampus, patient H.M. (Henry Molaison) was unable to form new memories. But a 14-year follow-up study of patient H.M. actually tells us that H.M. was able to form some new memories. The study says this on page 217, referring to the assassination of Kennedy in 1963:

"In February 1968, when shown the head on a Kennedy half-dollar, he said, correctly, that the person portrayed on the coin was President Kennedy. When asked him whether President Kennedy was dead or alive, and he answered, without hesitation, that Kennedy had been assassinated...In a similar way, he recalled various other public events, such as the death of Pope John (soon after the event), and recognized the name of one of the astronauts, but his performance in these respects was quite variable."

Another paper tells us that patient H.M. was able to learn new motor skills., stating this: "H.M. could successfully acquire, and subsequently retain, new motor skills in the context of several other experimental tasks (e.g., rotary pursuit, bimanual tracking, tapping)."  Another paper ("Evidence for Semantic Learning in Profound Amnesia: An Investigation With Patient H.M.") states this:

"We used cued recall and forced-choice recognition tasks to investigate whether the patient H.M. had acquired knowledge of people who became famous after the onset of his amnesia. Results revealed that, with first names provided as cues, he was able to recall the corresponding famous last name for 12 of 35 postoperatively famous personalities. This number nearly doubled when semantic cues were added, suggesting that his knowledge of the names was not limited to perceptual information, but was incorporated in a semantic network capable of supporting explicit recall. In forced-choice recognition, H.M. discriminated 87% of postmorbid famous names from foils. Critically, he was able to provide uniquely identifying semantic facts for one-third of these recognized names, describing John Glenn, for example, as 'the first rocketeer' and Lee Harvey Oswald as a man who 'assassinated the president.' Although H.M.’s semantic learning was clearly impaired, the results provide robust, unambiguous evidence that some new semantic learning can be supported by structures beyond the hippocampus proper."

Another paper tells us on page 15 to 16 that patient H. M. was able to draw an accurate map of a bungalow he had moved to after his hippocampus damage, and that he was also able to correctly state the address of that bungalow. On page 20 that paper tells us that patient H.M. had close-to-normal skills in being able to remember visual information:

"In  a  picture  recognition  experiment,  H.M.  was  asked  to  look  at  complex colorful  pictures,  for  20  seconds  each,  and  to  try  to  remember  them  (Freed & Corkin, 1988 et al.,  1987). H.M.'s performance revealed a normal recognition of the  pictures  after 10,  24  hours,  72  hours,  and  one  week  after  encoding (Augustinack et al., 2014; Corkin, 2020; Freed & Corkin, 1988). Surprisingly, six months later, H.M. could score within one standard deviation from the controls’ average (Freed & Corkin, 1988)."

The myth that patient H.M. lost the ability to form new memories after hippocampus damage is therefore an "old wives' tale" of neuroscience literature, a claim not justified by the facts.