[Source: Wikipedia]
[Source: Wikipedia]
In the pages of my graduate school neuroscience textbook he was known only as H.M., the mysterious man (we inexplicably assumed) whose misfortune led to a breakthrough in our understanding of the brain and provided both an elegant and gruesome illustration of the brain’s modular nature. In 2008, the year I defended my thesis, H.M. died at the age of 82 and his full name was revealed. At the AAAS Annual Meeting last month a panel of researchers who had personally studied the most famous patient in neurological history gathered to discuss Henry Gustav Molaison and how his case has impacted what we know about how the brain forms memories.

Molaison suffered from severe epileptic seizures. They forced him to drop out of high school, not because they were so incapacitating he couldn’t function, but because they evoked a different kind of torment – from fellow schoolboys. He went on to graduate high school, but years later, while working on the assembly line at a typewriter company Molaison’s seizures became so frequent he had to quit his job. When anti-epileptic drugs failed, the Molaison family sought the help of William Beecher Scoville, a neurosurgeon at Hartford Hospital in Connecticut.

The year was 1953 and, anatomical neuroscience still in its infancy (Egas Moniz had been awarded the Nobel Prize for inventing lobotomy just four years earlier), the treatment decided upon was to remove large parts of Molaison’s brain where the seizures occurred. Dr. Scoville ended up removing most of the anterior temporal lobe which included the hippocampus, the brain’s memory center, from both sides of Molaison’s brain. The procedure that Dr. Scoville called a “frankly experimental operation” worked – the seizures all but stopped. Molaison, however, would never be the same.

The hippocampus, located in the medial temporal lobe, is the brain's center for memory formation and storage. [Source: Wikipedia]
The hippocampus, located in the medial temporal lobe, is the brain's center for memory formation and storage. [Source: Wikipedia]
In the first hours after waking from surgery he appeared normal. He was cordial to the hospital staff and seemed to have no major cognitive deficits as a result of the surgery. But upon meeting someone new he could only converse normally as long as the person never left the room. If they left the room for just a few minutes, however, it was as if Molaison had never met them. They would come back into the room and have to reintroduce themselves. Brenda Milner, a neurophysiologist at McGill University, worked with Molaison for 30 years and it is primarily through her work that “H.M.” became famous. Over those three decades Molaison never managed to remember her name, only thinking, perhaps, that they had met in high school.

“I used to tell my students that this operation helped his epilepsy, but at an intolerable price,” Milner said in an interview with PBS.

Upon closer analysis the doctors realized that he could still recall facts that he’d known prior to the surgery – about the 1929 stock market crash, World War II, or his family – but he could no longer form new memories. He could, at most, hold information for only several minutes before it was lost to him forever.

Wrapped up in the sorrowful plight of a man who would never again form a new, longterm relationship was a scientific breakthrough.

Wilder Penfield was a Canadian neurosurgeon who cured people of epilepsy. He was also a neurophysiologist with a longing to know how different types of information was processed by the brain. After exposing the brains of his patients, he would take the time to electrically stimulate different brain areas. Because the brain has no pain receptors only local anesthesia was used. This enabled Penfield to determine the effect of the electrical shocks simply by asking his patients how the shocks made them feel. In this way he mapped the motor, sensory and language areas of the cerebral cortex. But once in a while, when stimulating the temporal lobes, the patient reported what Penfield called an “experiential response” – lucid recollections of a previous experience. It was the 1940s and for the first time the idea that memories were stored in a specific brain location had some experimental validation.

The hippocampus as drawn by the father of neuroscience, Santiago Ramon y Cajal, in 1911 [Source: Wikipedia]
The hippocampus as drawn by the father of neuroscience, Santiago Ramon y Cajal, in 1911 [Source: Wikipedia]
But it wasn’t until the bizarre case of patient H.M. that the seat of memory would be pinpointed to the tiny areas of the temporal lobes that Dr. Scoville had excised from both left and right hemispheres – and with it the patient’s ability to form new memories. Arguably more important than localizing memory was the clear demonstration that a person can, in fact, lose their ability to form new memories yet still retain their intellect, personality, and carry on with a normal life. It solidified the contested notion that memory was a discrete brain function independent of language, movement and perception. Molaison had an above-average IQ and was considered intelligent (he completed crossword puzzles every day) for his entire life. He didn’t have perceptual, language or psychiatric deficits. Above all, he was happy.

That Molaison could keep information for several minutes meant he had proper working memory, the type of memory that allows you to keep the doctor’s office number in your head long enough to dial it. His long-term memory was intact too, as he could remember things he’d learned prior to the surgery. The fact that he still retained both short- and long-term memories but could form no new long-term memories, meant the hippocampus – the tiny region whose removal scientists soon discovered caused Molaison’s memory loss – was crucial to converting working memory ruminations into lifelong recollections.

It was chiefly through Brenda Milner's work that patient H.M. became the most studied in neuroscience history [Source: McGill University]
It was chiefly through Brenda Milner's work that patient H.M. became the most studied in neuroscience history [Source: McGill University]
But not all memories are alike. Perhaps Milner’s most significant discovery involved a test in which Molaison was asked to trace a star on a piece of paper reflected in a mirror. It’s a moderately difficult task, but one that people normally improve upon with practice. Even though he couldn’t remember the name of someone he’d worked with for decades, over time Molaison – unexpectedly – got better at tracing the star. It seemed that what’s called ‘declarative memory,’ the conscious recollection of facts and events, and ‘non-declarative memory,’ a kind of “motor memory” in which you learn to perform tasks better with practice, were stored in the brain differently. Declarative memory requires the hippocampus. Non-declarative memory does not.

Later research showed that other types of non-declarative memory (also called implicit memory while declarative is called explicit) could be retained and used to learn without a hippocampus. Learning to ignore a bell that rings incessantly, for instance, or learning to salivate when a bell rings in anticipation of a food reward rely on non-declarative memory. As long as there's no need to consciously recall facts, the hippocampus was not necessary.

Behavior arises from the interaction between genes and the environment, and, at least for humans, the most important means by which the environment impacts behavior is through learning and memory. We acquire knowledge about the world through learning, and that knowledge is encoded and stored in the form of memories from which it can later be retrieved. Who we are is largely dependent on what we learn and what we remember. Perhaps Molaison’s legacy could be reasonably summed up by the enthusiasm that ensued following his case. In search of memory, the hippocampus has become one of the most studied – if not the most studied – areas of the brain.

For Molaison, he was never able to live independently after the surgery. He lived with his parents, tending to simple chores like going to the grocery store and spending hours with his crossword puzzles which, because it forced him to recall words, he thought were helping him. Having been 27 at the time of the surgery, he never got used to the graying person that greeted him in the mirror every morning decades later. But even though his condition left him incapable of remembering new facts and new people, including his own aged self, the AAAS session that gathered in Boston last month entitled “Understanding Memory: The Legacy of Case H.M.” affirms that he will always be remembered by a field on which he left a lasting mark.

Peter Murray was born in Boston in 1973. He earned a PhD in neuroscience at the University of Maryland, Baltimore studying gene expression in the neocortex. Following his dissertation work he spent three years as a post-doctoral fellow at the same university studying brain mechanisms of pain and motor control. He completed a collection of short stories in 2010 and has been writing for Singularity Hub since March 2011.