A detailed post-mortem look at the brain of a famous amnesiac is revealing new clues to his memory.

Henry G. Molaison, known in the medical literature as H.M., had parts of the hippocampus in his brain removed in 1953 at the age of 27, following increasingly severe seizures from epilepsy that couldn't be treated effectively with medications.

Preparing H.M.'s frozen brain

H.M.'s frozen brain at the level of the frontal lobes during the post-mortem cutting procedure. (Courtesy Annese et al/Nature)

"During life, H.M. was the best-known and possibly the most studied patient in modern neuroscience," Jacopo Annese of the University of California, San Diego, and his co-authors conclude in Tuesday's issue of the journal Nature Communications.

After the surgery, the Connecticut-born man had difficulty forming long-term memories of facts, faces and experiences. His willingness to participate in testing led to a range of contributions to science during his life and after his death in 2008 at the age of 82 from respiratory failure.

The latest is a digital 3D reconstruction of his brain based on thin tissue slices of his brain that Annese and his team at the Brain Observatory in San Diego began preparing in 2009. The slicing was livestreamed.

Annese said the 3D model uses virtual dissection to examine the original surgery. In the study, the researchers say the reconstruction revealed several findings, including pathology in the deep white matter and a small lesion with clearly defined edges in a frontal lobe that hadn’t been described before.

Jacopo Annese and slices of H.M.'s brain

Jacopo Annese examines final brain tissue slides that were also digitized for study by researchers worldwide. (University of California, San Diego)

They say neurosurgeon William Beecher Scoville "reached beyond and below the posterior hippocampus." A circuit that acts as a gateway to the hippocampus from the brain's outer layer to support the consolidation of long-term memories was also likely severely compromised during treatment.

For years, Montreal-based McGill University neuroscientist Brenda Milner travelled to Hartford to visit Molaison and test his abilities to learn tasks.

For example, Milner found that Molaison improved his performance at a co-ordination task over three days, despite his inability to recall previous attempts. Annese said a detailed survey of three brain areas could validate Milner's observations and give clues about how Molaison's brain was wired to perform tasks.

Microscopic studies of his remaining tissue in the hippocampus raise questions about how well it functioned.

Pathology observations of his white matter suggest changes acquired from medical conditions, including hypertension.

The researchers said closer study is needed to learn more about aging-related abnormalities that happened independently of Molaison’s surgery.

Molaison also lacked the ability to report internal states such as pain, hunger or thirst, which was attributed to the removal of his amygdala.

The study was funded by the U.S. National Science Foundation, the Dana Foundation Brain and Immuno-Imaging Award, and by contributions from viewers of the web broadcast of the dissection.