When Albert Einstein died in April 1955, a pathologist had his brain on a slab within a day. There was of course only one big question: would the brain of a genius look the same as the brain of a mortal? It turned out that some parts of his brain appeared narrower than the norm, while others were wider; some areas were almost non-existent, but these were compensated for with others that had clearly once pulsed with frantic activity. The findings caused quite a fuss at the time, because our understanding of the human brain was still in its infancy. We could master relativity and quantum theory without any firm understanding of how our brain managed it.
But this is gradually changing. Thanks to technology, brain mapping has entered an exciting phase, a phase where we can actually see things that twenty years ago were purely theoretical. Partly this is due to the work of Einstein himself. And one of the things we’re beginning to grasp is how – and where – we are able to read a map.
It always amuses people to learn that Einstein couldn’t drive; he probably had other things on his mind. But every time he took a cab – say from his office at Princeton to Newark Airport an hour away – there was one thing he could be relatively certain of: the person driving him had a brain bigger than he did. Or at least a certain part of it was bigger, the bit that successfully selected the quickest route, taking into account traffic conditions, the newest roadblock and the time of day. It was bigger because Einstein’s cab drivers (okay, the better ones) had learnt a large map of the state of New Jersey, unknowingly broken it down into a system of molecules, cells and neurons, and reassembled them in just the right order to take their valuable cargo to his next assignment.
When Einstein came to London in the early 1930s to speak at the Royal Albert Hall it was the same: the cab driver would have the entire A-Z crammed up there. It was thought likely that this brain area in cab drivers would be larger than in those who, for example, were constantly getting lost on their way from their front door to the shops (apparently another Einstein occurrence). But it was only very recently that this theory was proven, in a scientifically elegant story that combines both everyday practical maps and the grander notion of the way we read and memorise them: the software and the hardware.
In 2000, a young woman called Eleanor Maguire and a group of colleagues at University College London published a paper in the Proceedings of the National Academy of Sciences that got its readers thinking about an obscure and vaguely mythical qualification called The Knowledge. London cabbies knew it only too well as the fiendishly frustrating series of routes or ‘runs’ they needed to learn before they could earn their licence. There used to be 400 runs to learn, and even though there are now only 320 (Run 4: Pages Walk SW4 to St Martin’s Theatre WC2, perhaps, or Run 65: St John’s Wood Station NW8 to Brompton Oratory SW7, each twisty enough to make you yearn for the Manhattan grid system) it takes an average of two to three years to learn them. Indeed, only about half of those who start on The Knowledge will stay the distance and get their badge (for as well as having to navigate some 25,000 streets, there are also about 20,000 ‘points of interest’ to memorise.)
Maguire is a cognitive neuroscientist, and thus concerned with how learned behaviour affects the structure, function and passageways of the brain. But there was also a personal reason for her interest in cab drivers and mental maps. ‘I am absolutely appalling at finding my way around,’ she explained. ‘I wondered, how are some people so good and I am so terrible? I still get lost in the Centre for Neuroimaging and I have been working here for fifteen years.’
Her breakthrough paper – Navigation-Related Structural Change in the Hippocampi of Taxi Drivers – produced headlines around the world for its key finding: that London cabbies who had the A-Z in their brains had a significantly larger right posterior hippocampus (the part responsible for spatial awareness and memory) than those who hadn’t taken The Knowledge. This news was so handy, and perhaps surprising, for the Public Carriage Office (the body that licenced the black-cab drivers), that they started using it in their recruitment ads, the best boost since the cab driver Fred Housego won Mastermind in 1980. But the findings also provided hope to people unable to read a map or find their way around. Or, rather, to those who say they are unable to find their way around, like Eleanor Maguire. Her work suggested the opposite was true: spatial awareness and erudition is not an inherited trait, but a learnt one. Anyone with regular brain capacity and without brain disease can follow a compass, read a map, remember a route, and find their way back to their car. Learning a lot of maps showed that the brain was malleable plastic.
The brain mapped. If your right posterior hippocampus is a lot bigger than this, you’re probably a London cab driver.
In 2001, a year after Maguire’s research was published, a new study of two slides of Einstein’s brain showed something equally intriguing. Einstein had significantly larger neurons on the left side of his hippocampus than on the right – that is, the opposite side to cab drivers. This suggested stronger nerve cell connections between the hippocampus and the neocortex, the part of the brain associated with analytical and innovative thinking, but no marked increase in cell growth on the part linked to the reinforcement of memory.
The methodology of the ‘plastic brain’ research did leave a few unanswered questions, however. Only sixteen cab drivers were used in the research – all male, right-handed, with a mean age of forty-four and a mean cab-driving duration of 14.3 years – and there was no way of being sure that they didn’t become cab drivers because they already had a larger hippocampus before they began driving, and thus a propensity to retain vast amounts of mapping information and a vocational urge to exploit it.
And so, buoyed by the initial enthusiasm towards her work, Maguire and her colleagues at UCL designed further studies. In 2006, many of the doubts surrounding her initial survey were dispelled when she plotted the grey matter in the hippocampus of cab drivers against that of London bus drivers. Both had an aptitude for driving and stress, but the bus drivers were not required to memorise anything but relatively simple and repetitive routes. The bus drivers chosen as the control group had driven for the same number of years as the cab drivers. Again, only the cab drivers showed a significant enlargement in the right posterior hippocampus. The cab drivers also fared better than the bus drivers on memory tests on London landmarks (learned information), but less well on short-term recollection. This was reflected in the larger anterior hippocampus of bus drivers.
The implications of this work are great, and represent a potentially exciting advance in our understanding of spatial skills and memory. It opens doors to other areas, including the possibility of repairing memory loss caused by Alzheimer’s, dementia and brain injury through accident. That is to say, the new mapping gives us structural knowledge of the brain and also functional knowledge, the possibility of clinical treatment. When it is complete, the mapping of a pulsing lump of protoplasm may hold the key to eradicating some of our most impenetrable diseases, and in so doing our greatest miseries.
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There is a very deep history to this. We are cave men, and we have learnt to walk upright, and our brains have suddenly become very big. Somehow, in the last four million years, we have transformed ourselves from Australopithecus to Homo habilis to Homo erectus to ancient Homo sapiens to modern Homo sapiens, and towards the end of this run the size of our brains has swelled, probably more than any other creature, and the tasks we can perform as a result have increased greatly. We can, for instance, imagine other worlds beyond our own, and we can anticipate life before and after our own, and we can contemplate our role in the universe, and our own death. Not bad for something that weighs about three pounds, and (we think) unique among the animal world.
One of the other tasks we can perform is to speculate how this brain expansion came about. There are several theories, and prominent among them is the development of language. At some point we managed to make recognisable and repeatable sounds, and to assign these sounds a meaning and a vocabulary. Without knowing why, we developed grammar too. Even the most primitive form of communication would make the most basic tasks easier, and so our talent to make ourselves understood continued to expand (and obviously continues to do so). Our larynx would have had to expand in size and capability as well, and the power to accommodate these changes and possibilities would have caused the brain to expand, feeding on its own possibilities.
Another theory, popularised by the neurophysiologist William Calvin, wonders whether the growth spurt wasn’t triggered by the physical, specifically the expansion of nervous tissue caused by our ability to throw and kill. The most successful hunter-gatherers were the ones who could lure their targets and dispose of them accurately and efficiently, and for this they needed a combination of strength, spatial awareness, cunning and timing. These are big things to lug around, and hence the need for more cranial computational space.
And there is a third theory, lucidly examined by Richard Dawkins in Unweaving the Rainbow, his celebration of the scientific imagination. Dawkins set out to find the deus ex machina that would have remodelled our brain capacity in the same way that the growth in personal computers coincided with the reduction in size and price of the transistor. Our brain capacity developed far more slowly than the capacity expansion of the computer, of course, but the metaphor is a hard one to resist: Dawkins looks for a revolutionary event that was to the brain what the development of the mouse and Graphical User Interface was to the birth of the Apple Mac and Microsoft Windows. And he may have found one.
Back on the African plains with the hunter-gatherers, the skill of tracking is invaluable. The ability to read footprints, dung deposits and disturbed vegetation will lead to edible rewards, but this knowledge is insufficient in itself. The expert tracker needs expert spear chuckers, and an ability to communicate expert findings. If there was as yet no language, our tracker may mime his intentions to kill an antelope – a silent watch followed by a stealthy stalk and a sudden pounce – but miming precise location of the prey would be trickier. Dawkins suggests there was another way. ‘He could point out objectives and planning manoeuvres on a map of the area.’ A tracker would be ‘fully accustomed to the idea of following a trail, and imagining it laid out on the ground as a life-size map and the temporal graph of the movements of an animal. What could be more natural than for the leader to seize a stick and draw in the dust a scale model of just such a temporal picture: a map of movement over a surface?’
This, of course, is also the beginning of cave paintings – humans and animals depicted in their daily round of survival, with representational figures standing for something else, and introducing the concept of scale and directional arrows and spatial difference.*
But as for the brain, we may have found the reason for expansion and sophistication. Richard Dawkins concludes with a question: ‘Could it have been the drawing of maps that boosted our ancestors beyond the critical threshold which the other apes just failed to cross?’
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In November 2010 Chris Clark, a colleague of Eleanor Maguire’s at University College London, delivered a talk on brain mapping at the British Library, part of a series to accompany its Magnificent Maps exhibition.
Clark had trained as an accountant before making the considerable career switch to neuroscience and is now head of the Imaging and Biophysics Unit at UCL’s Institute of Child Health, where he is concerned with a wide range of neurological diseases seen in children, including autism and cerebral palsy. The mapping of the brain – in particular the white matter consisting of connective tissue that links particular functions – may, he hopes, one day provide enough clues to explain the nature of why certain brain functions fail and allow us to understand how treatments might influence brain circuitry and ultimately restore function.
At the British Library, Clark began his presentation where modern scientific brain mapping started, with the Brodmann maps from 1909. Korbinian Brodmann was a German anatomist who, by examining stained sections of cortex under a microscope, managed to define 52 distinct regions according to their unique cellular make-up (cytoarchitectonics, as he called it). Area 4, for example, is the primary motor cortex, while Area 17 is the primary visual cortex. All of Brodmann’s areas were numbered at the time but only some were named, and even fewer had a defined function. (The most notable and widely accepted was the language/speech centre named Broca’s Area, the left frontal region named after a French anatomist who, during autopsy in the early 1860s, found lesions and other damage in speech-impaired patients; one of these patients was called Tan, the only word he could say.)
Brodmann’s revolutionary demarcations had a popular natural precursor, albeit one rooted less in advanced neuroanatomy than in pseudoscience. Phrenology – in its baldest sense the study of regions on the surface of the skull as indicators of behaviour traits and personal qualities – had been all the rage in the alternative quarters of Victorian science, and the maps are as amusing to us today as they were once perceived to be revelatory. Once one accepted that all human thought and emotion was processed in some way within the brain (rather than the heart or perhaps an ethereal/religious channel), then it made sense to locate particular attributes and values to particular areas; this is what Brodmann was doing in a more sophisticated form. What made less sense was to believe that these attributes could be somehow measured, gauged and differentiated by bumps and lumps on the brain’s bony casing – the equivalent of diagnosing a car engine by feeling the bonnet.*
That said, the Victorian maps popularised by leading proponents of phrenology, such as the German physiologist Franz Joseph Gall and the American Fowler brothers in New York, were complex, imaginative and crankily beguiling. The classic china bust of a skull now displayed sardonically in psychoanalysts’ waiting rooms shows the simplest cranial elements: Domestic, Aspiring, Animal, Self-Perfecting, Moral, Reflectives and Perceptives. These resemble nothing less than countries on a world map (or perhaps areas in a Disney theme park), and are usually broken down into regions. So Perceptives contains Order, Individuality and the sinister Eventuality (which actually just means an ability to recall events), while the Self-Perfecting zone has Cautiousness, Self-Esteem and Firmness.
The leading American Phrenological proselytisers, Orson Squire Fowler and Lorenzo Niles Fowler, travelled the US, Britain and Ireland giving lectures and selling their American Phrenological Journal and books. These days they’d be driven out of town for their conjectures, but in 1876, when their Illustrated New Self Instructor reached its 11th edition, their readers clearly thought the Fowlers were onto something. The book may have been used to find your ideal husband or spot your local psychopath, and the task was made easier by more than a hundred engravings, showing various forms of disjunction. Like the Brodmann maps, each part of the head was assigned a numbered function. Unlike Brodmann, the Fowlers’ diagrams had hair. Area number four for the Fowlers, about half way down the back of the head, represented Inhabitiveness, the propensity to live near one’s roots. A large bulge on the head indicated a large degree of domestic patriotism; but the lack of one indicated the life of a rambler. Similar markings were laid out for Amativeness at the very base of the skull (big sexual urges were revealed when this area was swollen, while a sunken area exposed modest frigidity).
The Fowler brothers’ phrenology bust with its map of the brain’s perceived activity areas. Oddly, no space for sex or shopping.
Fortunately for medical science, it is Brodmann’s work that has set the template for brain mapping for the last century, gradually refined into a neural jigsaw showing both brain function and connection (Broca’s Area was assigned Areas 44 and 45). But it’s only since the 1990s that we have been able to effectively map the function of these areas in a way that may prove clinically useful. The enabling technology – employed by Eleanor Maguire with her cab drivers and Chris Clark in his child health work – is that great forensic scanning tool Magnetic Resonance Imaging (MRI), and in particular the highly evolved specialisations known as Diffusion MRI and Functional MRI.
A few months after his talk I met Clark at his office in Bloomsbury. He shows me more slides – brain slices that display Ordnance Survey-style contours, images of thin long cylinders known as axons, fabulously coloured bundles of these axons known as tracts. And then there is a map of diffusion, an image that shows the passage of brain molecules moving through water in a random manner. And then an image of Einstein, who developed the coefficient establishing the ‘time-dependent’ process in which molecules move further and further away from their starting position as time increases.
Why is this significant? Because the movement of water through the underlying tissue structure – the slower the movement the darker the area on an image – suggests a concentration of structure that may be mapped over time. In the early 1990s diffusion MRI revolutionised the detection of brain damage only hours after a patient had suffered a stroke. Then tractography arrived to provide a method for mapping the connectivity of the brain, allowing the study of so-called disconnection syndromes such as Alzheimers disease and indeed normal aging.
The MRI scanner that lets us gather these images is an other-worldly-looking thing. But for clinical and experimental purposes it has one great advantage: unlike other forms of diagnostic imaging such as X-rays, it is thought to carry no risk of harm to the patient.
‘You should have a look at the journal Human Brain Mapping,’ Clark says. So I do. The March 2012 issue contains articles on changes in the hippocampus of bipolar patients who take (and do not take) lithium, and the results of localised brain activation in stroke patients after directed stimuli. These are not theoretical concerns, but may soon feed back into treatment programmes. Clark’s work also already has practical applications. His unit is frequently called upon to provide diffusion images of a patient before surgery, particularly in cases of epilepsy where a patient isn’t responding to drugs and requires the removal of a part of the temporal lobe. It’s an effective operation but also a particularly delicate one, as the surgeon needs to avoid damaging the adjacent area known as Meyer’s Loop for fear of causing a defect in the visual field. Tractography can play a crucial role in guiding the surgeon here, as it can with tumour removal; prior to the directional mapping of the neuro-pathways there was a much greater risk of cutting the motor cortex that attaches to the spinal cord. Clark says he does have ‘a little bit of uncertainty’ when patients submit themselves to the knife assisted by his imaging work. ‘The culture in science is to constantly question what we do. Is this correct? What are the sources of error? Can we improve on what we are currently doing?’
Where are we heading with all this? Somewhere exciting. Advances in brain mapping have mirrored the development of the human genome with something called the Human Connectome Project, a US-based enterprise that will eventually lead to an entire map of the brain’s physical wiring. Unlike the Genome Project, which shows what makes us who we are, this neural ID will demonstrate how we process and store information, and why we behave the way we do. This ‘anatomy of thought’ involves capturing some 150 trillion neural connections, and to do this the neuroimaging division of Massachusetts General Hospital took possession of a new scanner at the end of 2011 with some excitement (‘4 times the fieldcoils and 4 times as many water cooling layers!’ as the machine it replaced). It was hoped that the brain mapping of 1,200 people would begin in the middle of 2012, about half of whom would be twins.
Brodmann’s brain maps – in specific parts of the brain certain cell characteristics group together.
The study of connectivity is ‘as hot as hot can get,’ according to Susan Bookheimer, a UCLA neuropsychologist and the head of the Organisation of Human Brain Mapping. But Bookheimer and her colleagues were naturally reluctant to put a timeline on delivering practical applications from the completion of the Connectome. And of course even with completion there will be other, bigger, more contemplative questions to answer. The questions of consciousness and human purpose, for instance. The eternal question of how to produce a 3-D map of the planet.