In our last article we talked about why we are curious about the hippocampus and its role: It sits right at the center of processing highly pre-processed sensory information and there's strong reasons to assume that it performs an essential computation that generalizes across species. In order to get closer to what this computation actually consists of, we now take a look at the cognitive functions that rely on a properly working hippocampus.

Determining brain function

Before we can get deeper into understanding the hippocampus we first need to talk about some of the limitations that you have to deal with when performing neuroscience. In order to understand an area of the brain we usually have two fundamental questions:

1. What function (i.e., computation) does the area perform?
2. How exactly does the area perform its computation?

Now, the only sources of the the information we seek is brains, which, unfortunately, usually come enclosed within some kind of organism, most of whom do not speak a human language. This means that we can either (a) perform invasive studies on an organism that can only deliver responses in the form of behavior that we will have to subsequently interpret, or (b) only perform non-invasive studies on an organism that we can communicate with directly.

To illustrate this problem, imagine you are being tasked to understand how a given computer program works. However, the only tools at your disposal are to either (a) tamper with certain parts of your system's memory while the algorithm is running and observing how this influences its runtime behavior, or (b) choose different input parameters and record the output of the algorithm. Also, the program is being run on about 100 billion processing units that you don't know the exact inner workings of either.

As you can imagine, this would be rather difficult: Causal links of the inner workings of the algorithm would be very difficult to establish convincingly and communicating any results would require thorough documentation and careful interpretation of any observation. This is essentially the problem we face when trying to determine what any part of the brain is responsible for and how that particular function is implemented within the neural substrate.

In order to solve this problem for the hippocampus we first look at the cognitive functions it is involved in to hopefully get an idea about the functionality the hippocampus provides our brains with - and please note how those are two different things!

[ Note: A question similar to the metaphor above was asked in a paper from 2017 where the authors tried to understand the inner workings of a microchip using neuroscience methods. Spoiler alert: it doesn't really work. ]

Hippocampal function

While the actual computation performed by the hippocampus - let alone its neural implementation - is not actually entirely clear yet, we do know of at least two essential roles the structure plays in human and rodent brains, respectively:

• In rodents the hippocampus is tightly linked to spatial navigation. This usually refers to the phenomenon of place cells in areas CA3 and CA1, as well as grid cells in the entorhinal cortex - essentially an encoding of place and a distance metric, respectively.
• In humans the hippocampus is critical to episodic memory. This refers to our ability to recall episodes, i.e., memories about the course of specific events.

Let's start with humans. Often we only become aware of how different brain areas are connected to a particular function if something breaks. In 1953 an American epilepsy patient by the name of Henry Gustave Molaison (1926 - 2008) underwent a surgical procedure that entailed the complete removal of the hippocampal formation, as well as large parts of the entorhinal cortex, and the amygdaloid complex.

Even though the operation was successful in the sense that his epileptic seizures were reduced, it quickly became apparent that the procedure also caused severe anterograde amnesia: Henry Molaison became unable to form new episodic memories, or recall memories less than about two years old - if you have seen the movie Memento, this is what it is based on. (If you have not seen Memento then you really should, it's terrific!)

"Patient HM" - as Henry Molaison would be known from then on - was still able to access his long term memories, however, and his ability to form new procedural memories  was seemingly left intact as well - as demonstrated by him learning to play the piano after his operation despite being unable to recall ever having taken any piano lessons. He worked with scientists in countless studies and in doing so made an invaluable contribution to our understanding of human memory. [ Note: After working with Henry Molaison for almost 50 years - and introducing herself to him every day anew - Dr. Suzanne Corkin recounted her the experience in her book "Permanent Present Tense" (2014). ]

While the case of Henry Molaison helped our understanding of the human hippocampus, it proves problematic to apply this knowledge to non-verbal animals. Because of the obvious difficulties of cross-species communication it is challenging to confirm human-like episodic memory in other mammals - and consequently just as difficult to confirm that the mammalian hippocampus fulfills the same (or even just a similar) role in animal brains as it does in the human brain.

In addition, note that the "true" episodic memory label hinges primarily on a single component that technically cannot be proven in humans either: In 1984 Endel Tulving coined the term "episodic memory" and presented his criteria for a "real" memory episode. According to him, a key element of episodic memory is "autonoetic consciousness", the ability of the (human) consciousness to place itself inside a recalled episode. Because of this definition the most scientists can hope for is to show "episodic-like" memory in animals and show that animals are able to recall different aspects (what, where, and when) of an episode, without claiming the animals consciously relive a previously experienced episode.

Despite this limited capacity to examine episodic memory in animals - and thus the main role the hippocampus seems to play in human brain processong - an enormous body of research has gone into the study of the animal hippocampus as well. The majortiy of this research does not target memory, however, but focuses on the issues of navigation and spatial encoding.

Continue reading in part III where we discuss the role of the hippocampus in navigation and gather more evidence for the hippocampus to perform the same universally useful function across different species.

References

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Disclaimer: This series of articles is heavily based on the introduction chapter of my PhD thesis.