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Feature: Magic memories

We seem to hold an internal map of the world in our heads. Understanding how the brain stores such maps could help people whose memory has been damaged by a stroke or other trauma.

In a study that generated considerable media interest (and won her an Ig Nobel Prize), in 2000 Dr Eleanor Maguire scanned the brains of 16 London black-cab drivers, who had spent an average of two years learning 'the Knowledge' – street names and routes in London. The taxi drivers had a larger right hippocampus than control subjects, and the longer they had been on the job, the larger their hippocampus was. These findings seem to indicate that the right hippocampus plays an important role in storing spatial memories.

Dr Maguire, a Wellcome Trust Senior Research Fellow at the Wellcome Department of Imaging Neuroscience at University College London, is continuing her investigations into what happens in our brains when we navigate large-scale space. "When we travel down a route we are familiar with, we often can't see our destination. Instead, we have an image of it in our mind, and a mental map of how to get there. But this mental map is very different from a street map. I'm trying to understand how we create internal three-dimensional representation of space and our position within it."

She is also interested in another form of memory, linked to spatial memory, which appears to be mediated by the left, rather than the right hippocampus. "Having created an internal representation of large-scale space, how do we structure episodic memories – particular events and personal experiences that occurred at a specific time and place – within that environment?"

Dr Maguire will be using magnetic resonance imaging (MRI) techniques * to establish which neural elements, or brain circuits, are involved in storing and recollecting these two types of memory: spatial and episodic. Results from the MRI scans will be combined with findings from psychological tests to shed light on the cognitive processes that support neural activity in the formation of memory.

Together, she hopes these neural and cognitive findings will provide an integrated, holistic picture of how we understand who and where we are, by locating ourselves in the world and recalling the personal experiences that constitute our recent and distant past.

Mimicking reality

Measuring someone's brain activity while they navigate large-scale space poses a challenge, since MRI techniques require the subject to lie in a brain scanner. Dr Maguire has therefore developed a series of virtual-reality tasks that the subject can carry out, without physically moving, on a screen inside a scanner. The complex, naturalistic nature of these tasks closely mimics 'real-life' situations.

"We ask subjects to find their way around a virtual city using a joystick or keypad, and scan their brains while they're doing it, to find out which brain regions are activated," explains Dr Maguire. "We vary factors like familiarity by allowing some subjects to practise first; or we get people to take detours or short-cuts or we put a road block in their normal route." Developing these virtual-reality environments can be done by adapting commercially available video games. "A lot of video games have good editors and are therefore adaptable. We take out all the shooting and monsters so we're left with the basic environment, which is ideal for our purposes."

She has adapted the same method of 'in-scanner' testing for tasks involving episodic memory. Unlike recall of facts or object recognition, memories of personal experiences are coloured with emotions and played out in a rich spatial, temporal and social context. To understand how the brain stores and recalls this form of memory, it is important to evoke the 'whole' memory during MRI scanning. One way of doing this is to project a photo of a party or wedding from a family album onto the screen, prompting the subject to recall and re-experience this particular event in their past.

Plastic brains

As well as understanding how these memories are structured in 'normal' healthy subjects, Dr Maguire also hopes to find out more about what happens in the brains of people who lose these abilities.

"The ability to find our way around an environment and to remember the events that occur within it – both thought to be mediated by the hippocampus – are fundamental to normal functioning in daily life," she says. "Unfortunately, the hippocampus is vulnerable to brain damage by epilepsy, dementia, and anoxia (when the brain is deprived of oxygen), which impacts on both these capacities, leaving patients severely debilitated and dependent on others for day-to-day living."

The symptoms can be very problematic. "If spatial cognition is affected, people literally don't know where they are, and if episodic memory is damaged, it can lead to amnesia," says Dr Maguire. People with amnesia live permanently in the present. Their speech and general intellect tends to remain intact, because remembering facts and general knowledge is not dependent on the hippocampus, but everything is frozen in time: they cannot remember anything that occurs after the damage took place. "If they do a couple of hours of tests with me, for example, and I leave the room for ten minutes and come back, they can't remember anything about me or what they had been doing. They can't live alone because they can't remember if they turned the gas off or paid their bills. Sometimes, which is very sad, if a spouse dies, they can't remember their loved one is now gone."

For people suffering from hippocampal damage and associated difficulties with spatial and episodic memory, the question of whether the brain can mend itself and memory be recovered is a pressing one. "It has long been thought that the adult brain only has a limited amount of plasticity," says Dr Maguire. "But findings like those from our study of London cab drivers show that structural changes can occur in healthy human brains. Perhaps in the future we could use that kind of understanding to help people with hippocampal damage."

Dr Maguire is therefore attempting to characterise the brain's plasticity in more detail by taking a unique lifespan approach to her study of memory. "We'll be measuring the effects of disease or injury on the brain and memory at all stages of life – from developmental disorders in children, to dementia in the elderly – and comparing these with healthy subjects." As well as examining memories at single points in time, she will also be tracking how people's brains change over short and longer timescales, again comparing diseased or injured brains with healthy brains of the same age. "If you see a measurable difference in the brain of a particular individual over time, such as growth of their hippocampus, then you know that structural changes have definitely occurred in that particular person's brain. This is different from simply comparing groups of people at one point in time."

Alongside these projects, Dr Maguire will be conducting further work on black-cab drivers. This time she will be testing retired cabbies to see if the plasticity goes both ways – whether the hippocampus shrinks again when they stop full-time navigation around London. She also wants to establish whether this plasticity is limited to navigation, or whether it is generalisable to other areas of the brain.

Findings from her research will be used to provide benchmarks for assessing the effects of disease or injury on memory, for people of different ages, and could aid development of clinical memory tests for early diagnosis of pathology. "In the long term, we hope we'll be able to use this information to develop new kinds rehabilitation programmes for people with hippocampal damage – but we still have a very long way to go."

The World Memory Championships

Dr Maguire's study on London black-cab drivers showed distinct structural changes to the brain linked to the memorising of large interconnected spatial environments. She was interested to find out if similar changes accompanied another feat of exceptional memory, those on show at the World Memory Championships, which take place every year in London.

"People entering the World Memory Championships can do amazing things," she says. "They can memorise the order of cards in deck after deck of cards, for example. One memory champion passed time waiting in reception prior to his scan by memorising pages from the phone book – pretty well too; I tested him on it."

Despite their high performance on memory tasks, however, Dr Maguire could find no structural changes. "I then asked them what strategies they used. Nine out of ten of them used the same strategy: an ancient Greek method, called the method of loci. It's based on navigation: they imagine going down a street they know well, place items at certain positions along the street, then mentally re-trace their route to find the items."

Although this strategy uses spatial memory to boost performance, the amount of large-scale space memorised is small, possibly accounting for the lack of structural changes in the right hippocampus. "Their brain doesn't have to change to accommodate a large map of London in their heads as it does for the cab drivers; the memory champions just need to memorise a couple of routes in detail."

* In collaboration with the Functional Imaging Laboratory, at the Institute of Neurology, University College London.

† In collaboration with the Institute of Cognitive Neuroscience, University College London.

‡ In collaboration with the National Hospital for Neurology and Neurosurgery.

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