Just a little bit of hippocampus, thanks.

Fifty-nine years ago, Henry Gustav Molaison—better known as H.M.—underwent a bilateral medial temporal lobe (MTL) resection that included the hippocampus. Ever since, and thanks also to several other studies in human and non-human animals, the hippocampus has been tightly associated with memory. You loose your hippocampus, you loose your capacity to consolidate new memories. End of the story. And if recent meta-analyses revising the role of the hippocampus and adjacent regions during episodic memory retrieval are correct (e.g., Nadel and Moscovitch, 1997), extensive damage in the MTL may also result in complete incapacity to recollect events from one’s past. You loose your MTL, you loose your capacity to remember the past. End of the history. So it is not surprising that, for the last half a century, the hippocampus was as closely tied to memory as Broca’s area was to language production.

Perhaps for this reason the recent observation that the MTL (especially the hippocampus) plays a critical role in future simulation constitutes such a surprising discovery. In 1985, Endel Tulving observed that patients with amnesia due to hippocampal damage had trouble coming up with vivid simulations of possible personal future events (Tulving, 1985). Is not that they were unable to give an answer to a question like “can you tell me how your next Christmas is going to be?” It is rather that their answers were formulaic, devoid of detail, kind of semantic: “I guess there will be a tree, and presents, and maybe family”, and not what one would expect from an individual that can run, as it were, a detailed episodic simulation of a possible future Christmas in her mind: “I guess I’ll see aunt Annie with her loud voice, drinking her gin and tonic, as always, and going about singing Christmas carols, because this year we have new nieces, you know? And she’s going to be all over them…” No such mental movie. When asked about specific details of their mental simulation of future events, individuals with amnesia are unable to articulate detailed descriptions of what they are imagining, limiting their answers to “that’s all I see” or “nothing else comes to mind”. The observation that the hippocampus plays a pivotal role in personal future thinking has been further corroborated by numerous behavioral and neuroimaging studies.

However, in 2010, Larry Squire and collaborators tested a handful of individuals with hippocampal damage on their ability to construct mental simulations of possible future events. Surprisingly, they found that their capacity to think abut possible personal futures did not differ from controls. What gives? In response to this report, Mcguire and Hassabis (2011) observed that the patients used by Squire and colleagues had some remnant hippocampal tissue that may have been sufficient to support the construction of future simulations. But this was merely a conjecture. Empirical evidence was needed.

In a recent paper, Mullally, Hassabis and Maguire (2012) report such evidence. As it turns out, one of the patients (P01) studied by Hassabis and collaborators in 2007, despite having extensive hippocampal damage, was nonetheless able to produce relatively detailed descriptions of mental future simulations. Compared with the other patients, though, P01 had some remnant hippocampal tissue. Could it be possible that this difference really made such a difference? To answer this question, Mullally et al (2012) asked P01 to visualize possible future scenes while undergoing fMRI. The results were astonishing: the little bit of preserved right hippocampal tissue was very much engaged during future scene construction. In addition, all other regions engaged in episodic future thinking overlapped with those that were engaged by the control group. Moreover, the activity of said regions coupled with that of the hippocampus when successful episodic future simulation was achieved. Again, you loose your hippocampus, you loose your capacity to vividly think about your personal future in a detailed manner. But if some hippocampal tissue is spared, maybe you won’t.

What I really like about Mullally et al’s (2012) study, besides the very interesting result, is the underlying structure of the argument with which the data is put forth as evidence for the hypothesis. Normally, in neuropsychology, it is assumed that the ultimate source of evidence for a particular brain region being necessary for a certain cognitive process is double dissociation. Initially introduced by Teuber in 1955, the notion of double dissociation was supposed to help elucidate whenever two processes were orthogonal to one another, provided the researcher could show that two experimental manipulations could differentially affect two independent variables. In cognitive neuroscience, this principle is implemented by way of showing that damage to brain region A impairs process X but not Y, whereas damage to brain region B impairs process Y but not X.  But double dissociation cannot show sufficiency. Usually, claims about sufficiency are much harder to come by, and when you do, they are usually questionable and pretty local. What I find so impressive about the Mullally et al (2012) study is that they conjectured that a specific brain region, in this case the very posterior tissue of the right hippocampus, was sufficient for engaging the brain network required for future simulation. Thus, unlike demonstrations of double dissociation, in which the relevant brain area is shown to be necessary but not sufficient for a particular cognitive process to occur, Mullally and collaborators (2012) managed to demonstrate that a portion of a certain brain region, which is normally functionally connected to other neural areas to support future thinking, is sufficient to engage such a network. A highly recommend paper, which orchestrates careful neuropsychological assessment and skillful neuroimaging analysis.

Maguire, E. A., Hassabis, D. (2011). Role of the hippocampus in imagination and future thinking. Proc Natl Acad Sci U S A 108(11), E39- doi:10.1073/pnas.1018876108.

Mullally, S. L., Hassabis, D., Maguire, E. A. (2012). Scene Construction in Amnesia: An fMRI Study. J Neurosci 32(16), 5646-5653

Nadel, L. and Moscovitch, M. (1997). Consolidation, retrograde amnesia and the hippocampal formation. Current Opinion in Neurobiology, 7: 217-227, 1997.

Squire, L.R., van der Horst, A., McDuff, S.G.R., Frascino, J.C., Hopkins, R.O., Mauldin, K.N. (2010). Role of the hippocampus in remembering the past and imagining the future. Proc. Natl. Acad. Sci. U.S.A. 107: 19044-19048

Tulving, E. (1985). Memory and consciousness. Canadian Psychologist 25, 1–12.

Let the blogging begin

Not that the world needs another neuro-psycho-philo-blog. But there is a surge of wonderful work in the philosophy, psychology and neuroscience of memory and imagination that may be of interest to some readers, who might be totally or partially unaware of such developments. So I’ve decided to overcome my fear of making grammatical and stylistic mistakes in the public arena of the bloggosphere in English, and I decided to start this blog. Mind you, though: I have an agenda. I believe research in the psychology and cognitive science of memory and imagination is lending strong credence to the view that these aren’t single faculties, that the cognitive processes that compose them are intertwined, multifarious and complex, and—more importantly—that the best way to understand the functional roles of specific brain regions requires moving away from the view that there is a clear correspondence between brain functions and psychological functions. In fact, I believe that trying to find neural correlates for X, where X is a folk psychological term is almost always the wrong way to go. The rules that govern the functional structure of the brain are not the same rules that dictate the meaning and uses of folk psychological terms. Sorry Professor Armstrong, but if you were to have all the platitudes of folk psychology pinned down, the job of understanding the mechanisms that fulfill the functional roles that correspond to such platitudes wouldn’t have even started. And maybe, only maybe, psychological readings of the massive modularity hypothesis will be jettisoned, and people would again pay more careful attention to Lashley. But I’m getting ahead of myself.