HOW does the brain encode the spatial representations which enable us to successfully navigate our environment? Four decades of research has identified four cell types in the brains of mice and rats which are known to be involved in these processes: place cells, grid cells, head direction cells and, most recently, border cells. Although the functions of most of these cell types are well characterized in rodents, it remains unclear whether they are also found in humans. A new functional neuroimaging study, by researchers from University College London, published online in the journal Nature, now provides the first evidence for the existence of grid cells in the human brain.
Grid cells were discovered in 2005 by Edvard and May-Britt Moser of the Kavli Institute for Systems Neuroscience in Trondheim, Norway, using multi-electrode arrays chronically implanted into the hippocampus and surrounding regions of freely moving mice. Whereas place cells fire when the animal is in a unique, specified position in its environment, grid cells – which are located in the entorhinal cortex – increase their activity in multiple locations, firing periodically as the mouse traverses a space. When a grid cell’s activity is correlated with the animal’s position and trajectory, and then superimposed onto a map of the environment, it is found to define a repeating pattern of equilateral triangles which ’tiles’ the space (panel b, below). Each cell is activated whenever the animal’s position coincides with any vertex in this grid, but each has its own periodicity, and so ’tiles’ the environment using a unique scale.
Christian Doeller of UCL’s Institute of Cognitive Neuroscience and his colleagues first carried out a series of experiments in which grid cell activity was recorded from the brains of mice. This revealed several previously unknown properties of the cells. First, they found that grid cell activity is modulated by the direction in which the animals are moving, so that the increase in grid cell activity is greater when the animals move along the main axes of the grids. Further, they found that the activity of the cells is also modulated by running speed – the faster the animals moved, the more the quickly they crossed the virtual triangle boundaries encoded by the grid cells and, as a result, the shorter was the interval between each burst of activity.
The researchers reasoned that if grid cells exist in the human brain, the activity of the population as a whole should produce a signal that is large enough to be detected by functional neuroimaging. And, because the orientations of the triangular grids encoded by the cells in the population are all aligned to each other, the activation pattern should exhibit six-fold rotational symmetry. They therefore recruited 42 male participants, and scanned their brains while they explored a circular virtual reality environment consisting of a grassy plain bounded by a cliff and surrounded by mountains (panel a, below).
When they analyzed the fMRI data, the researchers found that the signal was modulated by direction and running speed, just as they had predicted. The grid orientation appeared to vary randomly between the participants, suggesting that the activity of grid cells is independent of landmarks in the surroundings. In each participant, however, the increase in entorhinal cortex activity was greatest when their movements through the virtual environment were aligned with the three main grid axes. That is, the signal exhibited 6-fold rotational symmetry; no activity with 4-, 5-, 7- or 8-fold symmetry was observed. The signal obtained during high speed movements was also stronger than the one recorded during slower movements (panels c and d, above).
While navigating the virtual environment, the participants were required to collect various objects and then return them to the same location. In their analyses, the researchers also found that the signal obtained was related to performance on this memory task – the more coherent the signal, the better was the participant’s performance. The regions from which neuronal activity was recorded overlaps extensively with brain areas known to be involved in encoding and retrieval of autobiographical memory. This provides some insight into the neural basis of this type of memory; it suggests that the brain may use information about both time and space when encoding life events.
Unlike most functional neuroimaging studies, which simply correlate behaviours with patterns of brain activation, this one is driven is hypothesis. The researchers made predictions about the signal they would expect to see, based on known properties of grid cell activity. They only provide indirect evidence that grid cells exist in the human brain, however. Obtaining solid evidence would involve implanting electrodes into the brain, which is unfeasible in healthy participants. Epileptic patients undergoing pre-surgical evaluation afford a unique opportunity to investigate neuronal function directly; perhaps researchers will try to investigate the cellular basis of spatial navigation in this situation.
Nevertheless, this study suggests that the human brain, like that of mice and rats, uses a regularly repeating grid-like geometry to encode representations of space. The hippocampus and surrounding areas are known to be the first to degenerate in Alzheimer’s Disease, so the findings present may also help to explain why disorientation is one of the first behavioural manifestations of the condition.
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Doeller, C., et al. (2010). Evidence for grid cells in a human memory network Nature DOI: 10.1038/nature08704.