Dr. William Scoville
Dr. William Scoville

Dr. William Scoville didn’t know he’d make medical history on August 25th, 1953.

Dr. Scoville, a neurosurgeon at Hartford Hospital in Connecticut, had been experimenting with new surgical techniques for the treatment of psychiatric disorders such as schizophrenia and depression.  This was the first time he would use a similar technique to treat a patient suffering from severe epileptic seizures.

Jump forward 56 years to December 4th, 2009.  Dr. Jacopo Annese sits in front of a frozen brain at the University of California, San Diego, ready to cut it into thousands of tiny slices.  2,401, to be precise, each one of them .07 millimeters thick.

The brain Dr. Annese was about to slice that day belonged to the recently deceased Henry Molaison, also known as H.M., arguably one of the the most important subjects in medical history and the patient that William Scoville operated on so many years ago.

Dr. Scoville removed H.M.’s hippocampus and some of the surrounding tissue of the medial temporal lobe of his brain.  The operation achieved its primary goal:  H.M.’s seizures went away, but there was an odd side effect.  He was unable to form new memories.

In other words, Henry Molaison lived his life eternally in the present.  Even the researchers that worked with him had to re-introduce themselves every time they came into contact.

Over the course of his lifetime Molaison made immense contributions to science:  according to Dr. Annese, almost everything we now know about memory and the human brain has been thanks to H.M.’s unique case.

Jacopo Annese And The Brain Observatory

Dr. Jacopo Annese, The Brain Observatory
Dr. Jacopo Annese, The Brain Observatory

UCSD computational neuroanatomist Dr. Jacopo Annese founded the Brain Observatory in 2005.  A member of the scientific team convened by lead investigator Dr. Suzanne Corkin of MIT to determine the future of H.M.’s brain after his death, Annese was placed in charge of the project to minutely document the brain and preserve it for future researchers.

Before Dr. Annese established the Brain Observatory, traditional methods of study were destructive, in that brain slices were made and distributed piece by piece to individual researchers.  With the Brain Observatory and Project H.M., Annese created a new standardized methodology for documenting and archiving the brain, resulting in 3-D models and digitized maps available on the Web to all researchers.

During a period of 53 hours, Dr. Annese and his team used a microtome and specially designed neuroimaging equipment to create the slices that were later used to construct an extremely detailed digital model of H.M.’s brain.  The procedure was broadcast live on the Internet and nearly a half-million people tuned in.

Click here for more information on the Web atlas of H.M’s brain.

New Findings

Dr. Suzanne Corkin
Dr. Suzanne Corkin

Now, five years after the initial dissection took place, Annese, Corkin and the research team have published an article in Nature Communications with their first set of findings.  Published on January 28, 2014, the article reveals that Dr. Scoville had removed less of Henry Molaison’s brain than was previously thought.

Before the nearly 50 years of research into H.M.’s condition, it was believed that memory resided in many different areas of the brain.  H.M.’s case showed that the hippocampus, a seahorse-shaped structure in the medial temporal lobe, is crucial to the ability to retain learned facts.

Although a 1992 MRI showed that parts of H.M.’s hippocampus were still present, scientists believed that the remaining tissue had atrophied.  The dissection and subsequent 3-D model revealed that Scoville had missed the posterior hippocampus, and that the tissue had not in fact deteriorated.

Another region of the brain, the entorhinal cortex, through which all connections to the hippocampus pass, was removed entirely.  The researchers concluded that the entorhinal cortex may have been more important to H.M.’s condition than the removal of parts of his hippocampus.

According to Annese, the entorhinal cortex is also the region of the brain that is most heavily impacted in the early stages of Alzheimer’s disease.

In a press release issued in conjunction with the new article, Annese states that, while today’s MRI technology is powerful, there is still no substitute for “the meticulous examination of the actual brain tissue post-mortem.”  The methodology he created “provides a level of resolution and detail that dwarfs what even most high-powered MRI scanners can produce.” (Click here to read the release.)

Henry Molaison, Patient H.M.
Henry Molaison, Patient H.M.

While Henry Molaison’s unique form of amnesia prevented him from ever completely understanding his contributions to modern neuroscience, he was aware that he was participating in something that would benefit the greater good.

When asked about his work with the researchers he had this to say:

“Well, the way I figure it is, what they find out about me helps them to help other people.”

Five years after his death H.M. is still making major contributions to science and the understanding of the human brain.

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