April 05, 2025	PSY 340 Brain and Behavior Class 34: The Hippocampus and Striatum

The Hippocampus and Medial Temporal Lobe/System

Amnesia => memory loss

Memory Loss: Patient "H.M." & Damage to the Hippocampus (and nearby tissue)

Patient "H.M." was born in 1929 in Connecticut. He was knocked down by a bike when he was 7 and was unconscious for several minutes. He soon began having minor seizures. When we was 16-years-old (1942), he had his first major seizure. By the time he was 27 (1953), H.M. was suffering 10 minor seizures every day and a major seizure weekly. He could not hold a job or live any kind of a peaceful life.

So, in 1953 he met with Hartford, CT neurosurgeon, Dr. William Beecher Scoville who advocated a form of major surgery to treat his seizures.  H.M.  underwent a major brain operation by Dr. Scoville involving a bilateral medial temporal lobe resection (= removal of the hippocampus and nearby tissue structures including the perirhinal, entorhinal, and parahippocampal cortices as well as the amygdala).

The surgery was "successful" in significantly reducing H.M.'s seizures. However, by age 28 (1955), it became clear that H.M. had a pervasive problem with his memory. He was referred to Dr. Brenda Milner, a Canadian neuropsychologist, in Montreal. Beginning in 1955, H.M. has been the subject of many studies for the rest of his life.  BTW, on July 24, 2024, Dr. Milner turned 106 years old and, as of April 4, 2025, she is still alive. Here is a short video of her from her 106th birthday.

H.M., whose real name we now know was Henry Gustav Molaison, died in Windsor Locks, CT on December 2, 2008 (Carey, 2008).

What kind of brain functioning did H.M. show after his operation?

• No effect on intellect & language functions. I.Q. slightly higher in the years immediately after operation.
  

• Personality was relatively the same except for "emotional placidity" (= no complaints; no requests even for food)  

• Good short-term memory, i.e., for new items up to about 5-10 minutes after the experience.

• Massive anterograde amnesia (loss of memories of new events since brain damage) and moderate retrograde amnesia (loss of memories of events before brain damage).

• Little new learning of declarative memories, i.e., facts, and no new memories of events, e.g., what happened in the world since 1955. He did not learn new words which came into English since his operation. However he did respond with some new learning


• Prompt: "Elvis" • HM's response: "Presley"
• Prompt: "Fidel" • HM's response: "Castro"
• Prompt: "Martin Luther" • HM's response: "King"

• Also, when he examined pictures of past events including those of his family, he recognized names & some places, but could not recall the events pictures showed, thus, severe impairment in episodic (personal) memories. In fact, he had he had very little memory of any specific events of his earlier life (exception: he remembered that he once flew in a two-seater airplane as a child which was true).
  

• Intact procedural memory, i.e., learning how to do something new.

Explicit memory: recall of information which one knows is in memory

Implicit memory: influence of recent experience on behavior even though one doesn't recognize memory is being used.

• H.M. showed poor new explicit memory, but nearly normal implicit memory.

What does the Hippocampus Do? Theories of Hippocampal Functioning (= Medial Temporal Lobe/System)

For decades I've known that the word "hippocampus" is a Greek word for "seahorse".
But only in the last year did I find an image which shows why physiologists decided on the name hippocampus.

teRecall that the surgery on Patient H.M. involved more than just the hippocampus. Dr. Scoville removed various nearby tissue including the entorhinal, perirhinal, and parahippocampal cortices as well as the amygdala. These parts of the temporal lobe are now generally referred to as the Medial Temporal Lobe and the various functions described below as work of the Medial Temporal System.

1. Declarative Explicit Memory: As demonstrated by Patient H.M., bilateral damage in humans leads to impairment in storing any new memories for facts (declarative memories) and events (episodic memories). The basal ganglia (see below) seem to be more important for storing new procedural memories.

2. Spatial Memory

• "What is "The Knowledge" for London, England taxi drivers?  It's a demanding test that assesses a candidate's in-depth knowledge of London's streets, landmarks, and routes.
  

• Candidates must memorize over 25,000 streets and numerous landmarks within a six-mile radius of Charing Cross.
  They also need to learn and memorize 320 routes, or "runs," that criss-cross the city.
  
  Mastering "The Knowledge" typically takes three to four years of dedicated study. Some students who study full-time have been known to pass in as little as two years.
  
  Candidates undergo seven rigorous stages of examination. The examinations involve one-on-one oral examinations, or "appearances," throughout the qualification process.
  
  It's a requirement for obtaining a license to operate a black cab in London. "The Knowledge" is still a requirement for becoming a licensed London black cab driver." (Google AI)
  
  The ability of these drivers to know such a vast amount of spatial knowledge was originally studied by the late cognitive neuroscientist, Dr. Eleanor Maguire, (who died Jan 4, 2025 of cancer at age 54; see photo on right) and first reported in Maguire et al., (2000). Her studies and those of others show high levels of activation via PET scans for spatial related questions (e.g., What is the shortest route from the Tate Museum to Buckingham Palace?). Further, drivers have larger posterior hippocampi (plural of hippocampus) than normal.
  

• Humans with damage to the hippocampus do poorly on tests of spatial memory

• Bird species with good spatial memory (e.g., Clark's nutcracker which finds hidden seeds during winter) have larger hippocampi relative to rest of brain than birds who have poor spatial memory.

Brain's "navigational grid & place cell" system was  discovered by 2014 Nobel Laureates John O'Keefe (USA/UK) and May-Britt Moser & Edvard Moser (Norway)

"Place Cells" •  John O'Keefe discovered in the brain of rats a spatial map reference system associated with the hippocampus. When rats in an enclosed space moved to different places in that space, specific cells in the hippocampus fired. These creates a mental map of the space. These cells appear to have a memory function as well and allow an animal to navigate environments later on in which they had previously found themselves.

"Grid Cells" • In 2005 May-Britt & Edvard Moser found that the entorhinal cortex (the area just behind the hippocampus) is highly connected to the hippocampus. They discovered in the entorhinal cortex a special type of cell called a "grid cell" which (1) fires as rat moves around a spacial environment and (2) are arranged in a hexagonal patterns. These cells not only provide a knowledge of place but also of the direction of the animal's head as well. This brain area appears to allow an animal to calculate distance between itself and different places within the environment.

"Internal Continuous GPS System"?  Recent research reported by the Mosers and their colleagues (Vollan et al., 2025) found that as a rat moves about the world its place and grid cells constantly process the space/environment ahead: "“Here we show in freely moving rats that in individual theta cycles, ensembles of grid cells and place cells encode a position signal that sweeps linearly outwards from the animal’s location into the ambient environment, with sweep direction alternating stereotypically between left and right across successive theta cycles" (Abstract). Fundamentally it appears that the entorhinal and hippocampal cells of a rat (and presumably ourselves) are creating a kind of ever updated GPS understanding of what surrounds the animal, that is, an ever updated positioning signal to allow the animal to know where it is and where it is going.

3. Context: Configural Learning & Binding

• Recent work suggests a major role for the hippocampus in binding together all the elements of declarative memory, complex spatial memories, and single-event configurational memories.

• Memory is a collection of different pieces of experience: sights, sounds, smells, tastes, etc. These are probably stored in diverse parts of the brain and require some sort of map to bring them back together again. The hippocampus may provide that map via connections to the rest of the forebrain

V. Striatum: Implicit or Habit Learning (Where Skills and Habits Meet)
(Graybiel & Grafton, 2015)

Over many years we have learned that the "striatum" described below is involved in modulating the movement of our muscles. But, we have now come to understand that this are of the brain is also involved in a major way in learning.

We learn many memories of experiences after only a single event. But, consider how you tend to learn gradually what to expect of another person's behavioral tendencies, for example:

• how other members of your basketball player will move offensively
• how your mother will unpack the weekend's shopping from Wegman's, or
  
• the various cues your teacher might give about what he or she expects in class.
  

All of these relate to the notion of implicit or habit learning. 

Gradual implicit or habit learning appears to depend upon a diverse set of nuclei in the subsurface of the brain called the basal ganglia. These include the striatum (i.e., putamen and caudate nucleus) in particular as well as the globus pallidus, substantia nigra, and subthalamic nuclei. These bodies use dopamine as a neurotransmitter and have previously been shown to be centrally involved in movement.

The striatum appears to be mostly involved in what can be termed "reinforcement-level learning" - that is,

• Gradual learning over multiple trials
• Learning habits and skills
  
• Learning requires prompt feedback (= reward or punishment is clear)
  
• Learning is implicit, that is, what is learned is not put into words, but into actions
• If the striatum is damaged, the ability to learn new skills or habits is impaired and previously learned skills/habits are often impaired as well

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References

Carey, B. (2008, December 4). H.M., an unforgettable amnesiac, dies at 82. New York Times. [Obituary]

Graybiel, A. M., & Grafton, S. T. (2015) The striatum: Where skills and habits meet. Cold Spring Harbor Perspectives in Biology, 7, a021691. https://doi.org/10.1101/cshperspect.a021691

Maguire, E. A., Gadian, D. G., Johnsrude, I. S. … Frith, C. D. (2000). Navigation-related structural change in the hippocampi of taxi drivers. PNAS, 97(8), 4398-4403. https://doi.org/10.1073/pnas.070039597

Raslau, F. D., Mark, I. T., Klein, A. P., Ulmer, J. L., Matthews, V., & Mark, L. P. (2015). Memory part 2: The role of the medial temporal lobe. American Journal of Neuroradiology, 36(5), 846-849. https://doi.org/10.3174/ajnr.A4169

Vollan, A. Z., Gardner, R. J., Moser, M.-B., & Moser, E. I. (2025). Left-right alternating theta sweeps in entrorhinal-hippocampal maps of space. Nature, 639, 995-1005. https://doi.org/10.1038/s41586-024-08527-1

The first version of this page was posted on April 17, 2005