In the Memory of Henry Molaison

Scientists have grappled with the question of how memories are stored for quite some time. Today many technologies exist that allow for a variety of approaches to answering this question, but one tactic that has withstood the test of time has been the study of amnesiacs [1]. Henry Molaison, referred to as patient H.M., was one such amnesiac who gained fame for his willingness to partake in scientific studies. Over 100 scientists and teams have studied H.M., making him one of the most heavily examined amnesiacs of all time [1]. Over the years, study of H.M.’s brain helped to reveal some of the structural components of memory [2].  

H.M. was not always an amnesiac. In 1953 at the age of 27, H.M. elected to undergo an experimental surgery called a bilateral medial temporal lobectomy to control his epilepsy [3][4]. This surgery removed part of the hippocampus, amygdala, and other pieces of the cortex nearby [3][4]. While this surgery drastically reduced the number of seizures that H.M. experienced, it came at a cost – H.M. developed both anterograde amnesia (the inability to create new memories after the event that causes amnesia) and partial retrograde amnesia (the inability to recall memories that occurred before the event that caused amnesia) [2][3][4].

By creating functional deficits in H.M. that were so specific to memory while leaving other intellectual abilities (such as personality and IQ) unaffected, the surgeon unknowingly created a way to study the brain structures involved in memory [1][2][3][4]. The thought emerged that if H.M. could not perform tasks that people without the lobectomy could, the brain structures removed from H.M. were in some way related to memory [1][2][3].

Research teams have revealed that H.M. does not suffer from deficits in working memory, classical conditioning, or motor skill learning [1][2][3]. For example, H.M. was given the task of tracing a star while only able to see his drawing hand in a mirror [2][3]. H.M. improved in his performance over time even though he had no recollection of ever completing the task, indicating a lack of declarative memory, but presence of some degree of procedural memory [2][3].

Additionally, H.M. was able to keep information in short term memory, but would forget it as soon as he redirected his attention [2][3]. This research revealed that different forms of memory are stored in different parts of the brain [2,3]. Because H.M. had his medial temporal lobes removed and he suffered from anterograde amnesia, researchers concluded that the medial temporal lobes are important for memory consolidation, which is the process by which a short term memory is able to be stably converted to a long term memory [2][3].

The majority of information about H.M.’s lesions came from sketches drawn by the surgeon [5]. MRI imagining in later studies further clarified these original sketches, and revealed that H.M.’s brain lesion was not as large as originally thought [6]. However, MRI images could not capture everything [6]. In order to fully understand the lesions in H.M.’s brain, a post-mortem dissection needed to occur [1]. Because H.M. agreed to donate his brain to scientific research, this dissection was possible after his passing in 2008 [1].

A research team at the Brain Observatory of San Diego, led by Jacopo Annese, completed a broadcasted dissection of H.M.’s brain following his death [1]. The purpose of this dissection was to clarify exactly which structures were removed in the original lobectomy. Histological slices of the brain were prepared under strict protocol and pictures of these stained slices were taken [1]. These pictures, along with previous measurements of H.M.’s brain structures, allowed Annese’s team to create a 3D model of H.M.’s brain [1].

New insight garnered from this work revealed that less of H.M.’s hippocampus was removed than was originally assumed [1]. However, it was noted that a part of the hippocampus known as the entorhinal cortex was removed, and since the entorhinal cortex controls how information flows through the hippocampus, this may have prevented the hippocampus from functioning normally [1]. Along with this, removal of H.M.’s amygdala was confirmed, which may explain some of H.M.’s emotional unresponsiveness observed in other studies[1].  The researchers also discovered a previously undocumented lesion from the surgery in his frontal lobe, the significance of which is currently unknown [1].

This 3D reconstruction will allow other scientists to analyze H.M.’s brain and will give the most accurate understanding of what specific brain structures were removed during his lobectomy in 1953. Despite H.M.’s death, his legacy will live on and expand for years to come as researchers continue to study the man we will always remember.

References

1. Annese, J. et al. Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction. Nature Communications. 5, 1-9 (2013).
2. Corkin, S. What’s new with patient HM. Nature Reviews. 3, 153-160 (2002).
3. Squire, L. Legacy of patient HM for neuroscience. Neuron. 61, 6-9 (2009).
4. Milner, B. & Scoville, W.B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiat. 20, 11-21 (1957).
5. Scoville, W. B., Dunsmore, R. H., Liberson, W. T., Henry, C. E. & Pepe, A. Observations on medial temporal lobotomy and uncotomy in the treatment of psychotic states. Res. Pub. Assoc. Res. Nerv. Ment. Dis. 31, 347–373 (1953).
6. Salat, D. H. et al. Neuroimaging H.M.: a 10-year follow-up examination. Hippocampus 16, 936–945 (2006).