13.2: Patient HM

One of the most influential case studies in the neuroscience of memory is the story of Patient HM. HM was born in 1926 in a small Connecticut town. He had a mostly regular childhood: taking family road trips, riding bicycles, and learning about American presidents in school.

In his childhood, HM began having severe seizures, possibly the result of a head injury. In his teenage years, he started having tonic-clonic seizures, the most severe form of seizures that produces a loss of consciousness and convulsions (extreme muscle contraction or extension). In his early adulthood, he was having a tonic-clonic seizure monthly and several minor seizures daily, preventing him from working a normal job or living a normal life - despite taking a cocktail of anti-epileptic medications.

Neurosurgeon William Scoville proposed a “frankly experimental operation” to treat HM. It was known that most epilepsy originates in patches of neurons of the medial temporal lobe (MTL), and HM’s epilepsy was typical in this respect. Scoville suggested to surgically resect the MTL. In 1953, Scoville removed about 8 cm of the MTL bilaterally, including part of the amygdala, and notably the hippocampus, the seahorse-shaped structure of the brain.

Figure 13.1 Patient HM at 27 years old.

The surgery succeeded at its primary goal: HM’s seizures were less frequent and less severe. However, HM was left with a highly unusual and life-altering side effect: He was unable to create new discrete memories, a memory deficit called anterograde amnesia. For example, he could not remember what he had eaten for lunch just minutes after finishing the last bite. Despite being an avid fan of watching the news, HM couldn’t remember the names or the faces of different celebrities or public figures. It was as if he was permanently living in the present. (In contrast, retrograde amnesia affects the ability to successfully retrieve memory from one’s past.)

However, despite his pervasive memory deficits, HM did not display any deficits in intelligence. His language and speech were unaffected, and word recall was excellent, as he loved completing crossword puzzles and often did so successfully late in life, with only the occasional spelling errors. He could learn to acquire new skills, such as keeping a pen still on a moving circular platform, or a tapping task (these skills are different form of memory called procedural memory; see below). He was also capable of recalling things from his early childhood, such as geography facts he had learned in elementary school.

Figure 13.2 The location of the hippocampus in the medial temporal lobe (top). A dissected hippocampus and fornix (bottom left) looks like a seahorse (bottom right).

Types of memories

The fact that HM’s MTL surgery disrupted some types of memories (e.g., memory for facts) while others were still intact (e.g., motor skills) inspired neuropsychiatrists to try to define the different forms of memory. Much of the research was led by Dr. Brenda Milner, who carried out several behavioral tests on HM to figure out what types of memories are dependent on the intact MTL and which ones can function without MTL.

The most profound deficit was HM’s inability to create new declarative memories. Declarative memories, also called explicit memories, are the pieces of information that can be consciously declared or stated explicitly. Declarative memories are thought of as a “knowing what”. Declarative memories can be further subdivided into semantic memory and episodic memory.

Semantic memories are pieces of factual information. Some examples include:

1. “Jupiter is the largest planet of our solar system.”
2. “Rosalind Franklin discovered the double-helix structure of a DNA molecule.”
3. “The actor Keanu Reeves played the protagonist of the movie The Matrix.”

An episodic memory, sometimes also called an autobiographical memory, is the recollection of a discrete moment in a person’s life. It can be thought of as “mental-time travel” - what was it like when. The following memories are examples of episodic memories:

• “When I got home, I put my wallet and phone on the table.”
• “I ordered pizza last night.”
• “In 2019, I went to see my favorite musicians perform live.”

Several tests concluded that HM had lost his ability to create new semantic memories. In one such study, HM was asked to determine if a word was made up or real. He was shown words with very old origins, such as “shepherd” or “butcher.” On these words, he performed as well as the control group. When he was shown words that are made up, such as “phlage” or “thweise”, he likewise performed as well as the controls. However, when shown words that were added into the dictionary after his 1953-surgery, such as “granola” or “jacuzzi,” he scored about 50% correct - consistent with guessing at random, as if he never acquired the knowledge that these words have a meaning.

HM was also unable to create autobiographical memories. When asked to recall one of his birthday celebrations as an adult, he wouldn’t be able to give any significant details about the event. Instead, his answers were often vague and generic.

One interesting observation was that HM’s memory about details from his childhood were still intact. The inability to recall memories from the past, in this case, from before HM's surgery, is called retrograde amnesia. Patient HM’s retrograde amnesia was temporally graded, meaning that the farther back you examine, the more complete his memories were. Many of his memories for the two years before his surgery were completely lost, but memories from his youth and teenage years were intact as much as healthy individuals (there is contention about this observation, because HM was taking several anti-epileptic drugs, which may have impacted memory formation.) From this observation, memory researchers concluded that the MTL functions as short-term storage site for memories, but after some years, those memories get relocated to other brain areas outside of the MTL. Currently, the scientific evidence suggests that memories are distributed across several networks of cortical and subcortical brain areas.

Figure 13.3 Summary diagram of some of the major subtypes of memory.

Figure 13.4 In anterograde amnesia, a person is unable to create new memories following a lesion (top). In temporally-graded retrograde amnesia, older memories are better retained while recent memories are more likely lost.

While HM lost the ability to create new declarative memories, he was still able to maintain a different class of memories, called procedural memories (or implicit memories). They are unconscious memories, and can’t be explicitly stated. These can be thought of as “knowing how”. Some examples of procedural memories include, for example, performance of a series of motor actions without conscious thought such as an experienced musician playing a simple scale (sometimes commonly called “muscle memory”, even though the muscles do not store any actual memory!), or a priming effect (such as when a person sees pictures of bananas, they are more likely to answer the fill-in-the-blank prompt “b _ _ _ _ _” with “banana”, whereas other people might guess “bubble” or “badger”).

The original test of procedural memory conducted by Dr. Brenda Milner was called the mirror tracing task. In this test, the patient is told to draw a third star in between the two stars as quickly as possible without making any mistakes. The challenge is that the tracing is to be done while watching their hand and the star in their reflection in a mirror. Because of these unusual circumstances, completing this task is difficult. But over multiple days of practice, people become better at this mirror tracing task, completing it faster with fewer errors. Improvement on this task indicates that a person is learning or gaining some memory about how to better perform the task.

Figure 13.5 Patient HM performed poorly on the mirror tracing task (top), but improved at the task over time despite having no memory of performing the task (bottom).

After practicing this mirror tracing task, HM was able to finish drawing the star about ten times faster than when he first began. He improved his performance within each day’s worth of training, and he also improved day-to-day. There is evidence that he maintained these skills up to one year later, despite not having regular training on this task. Surprisingly, each day Milner examined HM, she would need to reintroduce herself since he forgot who she was. She also had to re-explain what HM was supposed to do in the mirror tracing task. Hence, while HM was unable to form declarative memory about the experiment or the people involved, learning of the procedural memories and motor actions involved in this task remained intact.

Another type of procedural memory is an associative memory. Associative memories are the types of information that we learn through traditional Pavlovian conditioning. For example, recall the classic Nobel prize-winning experiment in physiology conducted by Ivan Pavlov in the late 1800s. Normally, the presentation of dog food, an unconditioned stimulus (US), causes a dog to salivate, a naturally happening behavior, called the unconditioned response (UR). Dogs are not particularly interested in the sound of a whistle: this neutral stimulus will produce a minor response, such as a head turn and attentional shift towards the origin of the sound, but not much more than that. However, when this stimulus is repeatedly paired with the presentation of food, dogs quickly learn to associate that the whistle signals food. After multiple pairings, upon hearing the whistle, a conditioned stimulus (CS), the dogs begin to salivate, a conditioned response (CR), independent of any food being presented.

Separate from declarative or procedural memories, a different form of memory called working memory was tested in HM. Working memory involves processes of storing information temporarily while simultaneously manipulating those pieces of information. This type of memory can be thought of as a “short-term memory on overdrive.” Although HM struggled with working memory immediately after his surgery, several years later HM performed as well as age-matched control patients on these tasks.

Figure 13.6 A CR after exposure to a CS, such as in classical Pavlovian conditioning, is an example of an associative memory, one type of procedural memory.

For example, a test of working memory is the digit span test, where a person is given a series of numbers to remember, then they are asked to repeat the numbers in reverse order. After successfully completing this task, a different series of numbers, this time one digit longer, is presented to the patient until they first start making errors in recall. A related task is called the Corsi block tapping test, where an experimenter sets up several blocks on a table. The experimenter then taps a series of blocks in a specific order, then the participant is asked to tap on the blocks in reverse order. As with the digit-span test, the experimenter then makes the series of blocks longer until the participant makes mistakes in the tapping.

Patient HM died in 2008 at age 82 of respiratory failure. His name was Henry Molaison.

Figure 13.7 The digit span test (top) and the Corsi block tapping test (bottom) are measures of working memory.