The Initiative on Neuroscience and the Law

The hormone dopamine is responsible for the cravings of addiction, but when levels are abnormally low it causes the muscular twitches of Parkinson's disease

Modern technology provides a fresh perspective on the most famous case study in the history of neuroscience

Anyone who has studied psychology or neuroscience will be familiar with the incredible case of Phineas Gage, the railroad worker who had a metre-long iron rod propelled straight through his head at high speed in an explosion. Gage famously survived this horrific accident, but underwent dramatic personality changes afterwards.

In recent years researchers reconstructed his skull and the passage of the rod through it, to try to understand how these changes were related to his brain damage. Now, neuroscientists from the University of California, Los Angeles have produced Gage's connectome - a detailed wiring diagram of his brain, showing how its long-range connections were altered by the injury.

The new research, led by Jack Van Horn of UCLA's Laboratory of Neuroimaging (LONI), is part of the Human Connectome Project. Launched in July 2009, with tens of millions of dollars of funding from the National Institutes of Heath to several large consortia, this ambitious project aims to build a comprehensive map of the connections in the human brain, in the hope that it will aid our understanding of how the organ works and what goes wrong in conditions such as Alzheimer's Disease, autism, and schizophrenia.

The hundreds of researchers involved use a variety of techniques to collect data about the connectivity of the human brain, including magnetic resonance imaging (MRI), which can be used to obtain data about the structure and function of the live human brain. A related method, which has become increasingly popular in recent years, is diffusion tensor imaging (DTI), which can be used to visualize the large white matter tracts which form long-range connections between different parts of the brain.

But how does one reconstruct the connectome of someone who died more than 150 years ago, and whose brain no longer even exists? Van Horn and his colleagues used high-resolution CT scans of Gage's skull, from a 2004 study that digitally reconstructed the trajectory of the iron rod as it passed through his brain, and examined the data again to re-estimate its path as accurately as possible.

They then selected structural MRI and DTI data from 110 healthy people from the LONI Image Data Archive. All of these data came from men aged between 25 (Gage's age at the time of his accident) and 36 (the age at which he died). The researchers combined these data to produce a generalized map of the long-range connections in the human brain, and used computational modelling to project the passage of the rod onto it.

John Martyn Harlow, the doctor who attended to Gage at the scene of the accident, described the passage of the rod in a letter to the editor of the Boston Medical and Surgical Journal:

Taking a direction upward and backward... [it] entered the cranium, passing through the anterior left lobe of the cerebrum, and made its exit in the median line, at the junction of the coronal and sagittal sutures... breaking up considerable portions of brain, and protruding the globe of the left eye from its socket, by nearly one half its diameter.

The digital renderings below show the new model of the rod's path, and how it may have affected the structure of the white matter tracts. The image on the left shows the best-fit trajectory of the rod through Gage's skull, and some of the neural pathways in the left hemisphere that would have been damaged. The one on the right shows the inside of his skull from above, and the likely extent of the damage:

Finally, Van Horn and his colleagues crunched their data to visualize the connectivity in a healthy brain and in Gage's brain as 'connectograms,' circular diagrams depicting the brain's major white matter tracts. In these diagrams, the major brain regions - the frontal lobe, insula, limbic system, temporal lobe, parietal lobe, occipital lobe, brain stem and cerebellum - are colour-coded and arranged on the outer ring of the diagram, according to their position from the front.

The inner rings represent various other measures, such as the average volume, thickness and surface area of each area. The left half of the diagram represents the left hemisphere, the right half represents the right hemisphere, while the brain stem is shown at the bottom. The inner-most ring shows the degree of connectivity within and between the two hemispheres, as measured by DTI.

Here's the connectogram showing the major pathways in the healthy human brain, averaged from the 110 data sets:

Van Horn and his colleagues estimate that the rod destroyed about 4% of Gage's cerebral cortex, and about 11% of the total white matter in the frontal lobe. According to their model, the accident damaged some of the major white matter tracts in left the frontal lobe, including the uncinate fasciculus, which connects parts of the frontal cortex to the limbic system, and the superior longitudinal fasciculus, which runs the entire length of the brain to connect all four lobes in each hemisphere to each other. It also damaged the frontal cortex connector hubs, localized regions that contain a high density of connections to other areas.

This would have disrupted global network organization, making the damage far more profound and widespread than previously thought. Gage's connectogram looks quite different from that of an average healthy brain, and is dominated by white matter tracts that were either lost entirely (shown below in shades of grey) or partially severed (shades of brown) by the rod as it passed through his head:

This is all very well, but it doesn't tell us much more than we already know about how Gage's brain damage affected his behaviour. Gage is said to have undergone major personality changes following his accident, becoming quick-tempered and foul-mouthed and behaving sexually inappropriately. In a subsequent report, published 20 years after the accident, Harlow described the changes thus:

His contractors, who regarded him as the most efficient and capable foreman in their employ previous to his injury, considered the change in his mind so marked that they could not give him his place again. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint of advice when it conflicts with his desires, at times pertinaciously obstinent, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. In this regard, his mind was radically changed, so decidedly that his friends and acquaintances said he was "no longer Gage".

Damage to the connections between the frontal cortex and limbic system is in keeping with such behaviour, because these pathways are known to be involved in the regulation of emotions. The researchers also note that the global network changes they observed in their model are similar to those seen in fronto-temporal dementia and related neurodegenerative conditions, and suggest that they may explain Gage's apparent deficits in executive function.

According to Malcolm Macmillan, the accounts of Gage's behavioural changes are based largely on anecdotal reports that are not substantiated by the little evidence there is. "Phineas' story," Macmilllan writes in his book An Odd Kind of Fame, "is worth remembering because it illustrates how easily a small stock of facts becomes transformed into popular and scientific myth."

Macmillan's own research suggests that the reported changes in Gage's behaviour and personality lasted for only a short time after the injury. Indeed, we now know that the brain can recover from traumatic brain injury and other insults by forming new pathways, and DTI is increasingly being used to investigate these organizational changes.

There's little doubt that Gage sustained extensive frontal lobe damage in the accident, but we'll never know the true extent of the damage, and that calls in to question the accuracy and usefulness of his connectome. Nevertheless, the study is an early attempt at using these methods to assess whole brain connectivity following brain injury, and it seems quite fitting that the researchers used Gage as their subject.

Reference: Van Horn, J. D., et al. (2012). Mapping Connectivity Damage in the Case of Phineas Gage. PLoS ONE, 7(5): e37454. DOI: 10.1371/journal.pone.0037454

Researchers have reached a milestone in 'mind control' by creating a robot arm that can be controlled by a brain implant. A woman paralysed for the past 15 years has learned to use the system to serve herself coffee

The BrainGate implant can decode a patient's brain signals and instruct a robotic arm to reach and grasp objects

A woman who lost the use of her limbs after a devastating stroke nearly 15 years ago has taken a sip of coffee by guiding a robotic arm with her thoughts.

The 58-year-old used a brain implant to control the robot and bring a flask of the coffee to her lips, the first time she had picked up anything since she was paralysed and left unable to speak by a catastrophic brain stem stroke.

Doctors hailed the feat as the first demonstration of an implant that directly controls a reaching and gripping robotic arm by sensing and decoding the patient's brain signals.

The work is part of a US clinical trial of an experimental implant called BrainGate that doctors see as a first step towards devices that can bypass damage to the nervous system and allow paralysed people to regain control of their limbs or amputees to move prosthetics.

"At the very beginning I had to concentrate and focus on the muscles I would use to perform certain functions," the woman said. "BrainGate felt natural and comfortable, so I quickly got accustomed to the trial."

Writing in the journal Nature, researchers described trials in which the woman, known only as S3, and a 66-year-old man referred to as T2, used the implant to control two different designs of robotic arm. The pill-sized device is surgically implanted a few millimetres into the motor cortex on the surface of the brain, where its 96 hair-thin electrodes pick up the patient's neural activity.

In a series of sessions, the patients learned to control the robot arm and pick up foam balls by imagining moving their own arm and hand. Neither patient could control the robotic arm as well as natural arm movements, but doctors were still delighted with their progress.

"These results are the first peer-reviewed demonstration of a three-dimensional reaching and grasping task using direct brain control of a robotic device," said Leigh Hochberg, a neuroengineer at Brown University in Rhode Island.

"One of the participants was also able to use the investigational BrainGate system to pick up a bottle of coffee and drink from it. This was the first time in nearly 15 years that she had been able to pick up anything solely of her own volition. The smile on her face when she did this is something that I and our whole research team will never forget," he added.

The man who took part in the trial had a brain stem stroke in 2006. Describing the experience afterwards – by spelling out letters with his gaze – he said: "I just imagined moving my own arm and [the robotic] arm moved where I wanted it to go."

The BrainGate device plugs directly into the brain, but protrudes through the skull where it is connected to a computer by a cable. More advanced devices are planned that can operate wirelessly and be implanted out of sight, beneath the skin.

One concern with brain implants is that they steadily lose their ability to sense neural signals as scar tissue forms around the ultrafine electrodes. An encouraging sign from the latest trial is that doctors could still record useful signals from the woman's brain five years after her implant was fitted.

John Donoghue, a co-author on the paper, and director of the Brain Institute at Brown University, said there was still much work to do. "We'll have truly met our goal when someone who lost mobility to neurological injury or disease can truly interact with their environment without anyone knowing that they are employing a brain-computer interface," he said.

In an accompanying article, Andrew Jackson at the Institute of Neuroscience at Newcastle University, said the study underlined how basic research was a crucial driver for such technological advances. In previous years, patients have used BrainGate to control a cursor on a computer screen and clench the outstretched fingers of a prosthetic hand into a fist.

"At a time when experimentation using nonhuman primates is increasingly controversial, it is worth noting that the results reported … draw directly on previous neural interface demonstrations in monkeys and on decades of basic research into the control of arm movements," Jackson writes.

"Although robotic arms may be of practical assistance, restoring movements of the patients' own limbs should remain the ultimate goal," he adds.

Man, 71, regains some use of hands after surgeons use healthy nerves to bridge damaged area between brain and forearm

A man who was paralysed in a car crash four years ago has regained some use of his hands after doctors rewired the nerves in his arms.

In a pioneering operation, US doctors took healthy nerves from the man and used them to bridge the damaged wiring that stopped signals getting from the man's brain to his hands.

Surgeons at Washington University's school of medicine said the operation may prove to be a breakthrough for some patients paralysed by spinal cord injuries.

The 71-year-old broke his neck in a car crash in 2008 that left him unable to walk. Though he could still move his arms, he had lost the ability to grasp or hold things in either hand.

In the operation surgeons used healthy nerves to bypass the damaged area and connect working nerves above the spinal breakage to those in the anterior interosseous nerve in the forearm that ultimately controls hand movement.

The man received extensive therapy after the operation and began to move the thumb and fingers of his left hand eight months after surgery. He could move the fingers of his right hand 10 months afterwards.

The patient can now feed himself and write to some extent. Though slight, his improvement is nonetheless remarkable, given the severity of the injury and the 22 months that passed before surgery.

"To our knowledge, this is the first reported case of thumb and finger flexor reinnervation after a spinal cord injury. While the results in this patient are usually modest, due to the severe joint stiffness, his function has improved significantly with his ability to feed himself," the team writes in the Journal of Neurosurgery.

"The use of nerve transfers may represent a significant breakthrough toward improved independent function in select patients with cervical spinal cord injuries," the authors said.

Despite their success, doctors said the procedure would never restore normal function to patients. The limited improvement came after the patient learned to use a nerve that normally bends the arm at the elbow to make hand grasping movements.

Mark Bacon, director of research at the charity Spinal Research, told the BBC: "One of the issues with techniques such as this is the permanence of the outcome – once done it is hard to reverse.

"There is an inevitable sacrifice of some healthy function above the injury in order to provide more useful function below. This may be entirely acceptable when we are ultimately talking about providing function that leads to a greater quality of life.

"For the limited number of patients that may benefit from this technique this may be seen as a small price to pay."

The operation is only suitable for those patients who suffered damaged spines at the base of the neck.

When injuries are higher, there are no nerves to tap into to bypass the damage. And if the spinal cord is severed lower down, the patients are unlikely to lose the use of their hands.

Doctors said further research was needed to work out how reliable the procedure was in patients and the best time to perform surgery.

The downside to having a good memory

A genetic variant associated with an enhanced capacity for emotional memories is also linked to increased susceptibility to post-traumatic stress disorder (PTSD), according to new research published yesterday in Proceedings of the National Academy of Sciences.

The study, led by Dominique de Quervain of the University of Basel, used a combination of behavioural genetics and functional neuroimaging, and was carried out in three phases, two involving healthy European volunteers and the third involving Rwandan refugees who fled the 1994 civil war. I describe the work in more detail in this news story for Nature.

It's widely believed that memories are formed by the strengthening of connections within distributed networks of neurons. This process involves the orchestrated activity of dozens of proteins – the neurotransmitter receptors embedded in the nerve cell membranes, and their "effectors," the components of the biochemical signalling pathways inside the cells that are activated by the receptors. These molecules work together to make the signalling between neurons more efficient, so that synapses are strengthened.

The gene in question here, called PRKCA encodes an enzyme called protein kinase C-α (PKCα), and contributes to these processes by chemically modifying the receptors and their effectors. It does so by catalysing a reaction called phosphorylation, in which a phosphate group – a small organic compound consisting of one phosphorous and four oxygen atoms – is added to specific sites on the target protein. This enhances the activity of the protein, but the reaction is reversible – the phosphate group can be removed by another enzyme, called a phosphatase, which has the opposite effect on the function of the target protein.

In 2007, de Quervain and his colleagues reported that variations in the gene encoding the α2B-adrenoreceptor are related to emotional memories, and that the variants are associated with differences in susceptibility to stress but not with an increased risk of PTSD.

In their latest study, the researchers found that a variant of the PRKCA gene is associated with an enhanced capacity for emotional memories in a large group of healthy Swiss volunteers. In phase two, they showed that the same variant is also linked to differences in brain activity during memory encoding. Finally, they examined the DNA of a large group of Rwandan refugees, all of whom had experienced multiple traumatic events during the civil war, and found that those carrying the variant were twice as likely to suffer from PTSD than those who don't.

The variant is referred to as the A allele, because it contains an adenine residue at a specific position in the DNA sequence. The G allele, by contrast, has a guanine residue at the same position, but was not linked to enhanced memory. Intriguingly, the effect of the A allele on memory was dose-dependent – it was, in other words, influenced by the number of copies of the A allele that an individual carries. People with two copies of the A allele performed best on the memory test, and those carrying two copies of the G allele performed worst. The performance of people carrying one copy of each was somewhere in between.

It's almost certain that these variants encode slightly different versions of the PKCα that function differently from one another. The A allele may, for example, encode a version that is more active than the one encoded by the G allele, and this is something that can easily be tested. Exactly how this would lead to increased activity in the brain networks encoding emotional memories is, however, a more difficult question to answer, but this will probably be addressed in future work.

"This is an elegant study that uses multiple measures to validate the genetic findings with fMRI and behavior, and replicates the observations in a traumatized group," says neuropsychiatrist Rachel Yehuda, director of the Traumatic Stress Studies Division at Mount Sinai School of Medicine in New York. She urges caution, however, about how the findings could translate in the clinic.

"Most of the time, the distress of PTSD is caused by avoidance of traumatic memories, or the inability to remember key aspects of the trauma," she says, "so while it is important to gain as much understanding as possible of the biological basis of PTSD, we have to be careful to not misinterpret the findings to suggest that treatment involves tampering with or obliterating memory."

Reference: de Quervain, D. J. -F., et al. PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors. PNAS, DOI: 10.1073/pnas.1200857109 [PDF]

This week on Science Weekly, Claudia Hammond talks to Ian Sample about how we perceive the passage of time, the subject of her new book Time Warped: Unlocking the Mysteries of Time Perception. From body temperature to attention deficit hyperactivity disorder (ADHD), Claudia reveals how our calculation of time can be affected by a range of physical and mental conditions.

Alok Jha is joined by two fans of science geekdom, Mark Henderson author of The Geek Manifesto: Why Science Matters, and Angela Saini, author of Geek Nation: How Indian Science is Taking Over the World.

Angela and Mark discuss why science geeks are valued in India but not in the UK and the possibility of a "geek vote" to lobby for change. They will host a debate entitled "In defence of geeks" on 19 May at the Bristol Festival of Ideas.

Angela and Mark also review some of this week's science news including the Royal Society of Chemistry's first woman president Professor Lesley Yellowlees and her comments that the UK is half a century behind the US in terms of opportunities for women scientists, and the latest in the debate about open access to scientific research.

Subscribe for free via iTunes to ensure every episode gets delivered. (Here is the non-iTunes URL feed).

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An addict turned neuroscientist is both fascinating and irritating

"Probably a crab would be filled with a sense of personal outrage if it could hear us class it without ado or apology as a crustacean and thus dispose of it. 'I am no such thing,' it would say; 'I am myself, myself alone."

It's worth keeping William James's moment of empathy with arthropods in mind during any discussion of the way thoughts and feelings emerge from the brain. Marc Lewis's brilliant – if not wholly sympathetic – account of his many mind-bludgeoning drug experiences wears its biological determinism on its sleeve. Our selves are the product of excitation and inhibition in those "fleshy computers we carry around in our skulls", he says. But however true this may be, it is not necessarily useful in the study of personality. An individual is not just the product of his or her own brain, but of the way it interacts with the world, with other brains, with experience.

Lewis has certainly woven his experiences into an unusual and exciting book. Each chapter deals with a different phase of his life (along with a different drug), and the vivid accounts of external events are married with descriptions of the neurology behind them. His first school-skipping experiments with alcohol introduce us to GABA and glutamate, the brain's chemical "zeros and ones". Lonely and bullied, he swallows a bottle of cough medicine and thus explains the neuronal blockade that results in "dissociation" – when sensory information from the cortex is detached from meaning supplied by the limbic system. The result is a fragmented puzzle, a welling up of significance ungrounded in reality.

His scientific glosses are easy to understand but do not feel dumbed-down. The insights they offer are surprising. Serotonin, for example, rather than simply being a "happiness molecule", is used throughout the brain as a brake on excitation. It dampens and regulates neuronal firing, allowing us to filter input from the outside world without being overwhelmed. LSD, which the author discovers – almost too perfectly – while at Berkeley in the 60s, works by squatting in receptor sites normally activated by serotonin. The result: no regulation, no brakes, and a tsunami of sensation. In the absence of the gatekeeper, the doors of perception really do swing open.

Similarly, cannabinoids, which the brain produces naturally, allow neurons to continue firing after an initial burst, when in normal circumstances they would become unresponsive for a short period. This allows the focused thought and absorption in a particular mode of thinking or behaviour that is sometimes essential. Smoking marijuana, Lewis explains, floods the brain with an external cannabinoid, THC, hence the drug's bizarre effects: an obsession with tiny details, brighter colours or more intense sounds, "self-mesmerisation".

Heroin is more straighforward. It mimics, but hugely eclipses in intensity, the chemicals produced by the brain to alleviate suffering. And crucially – for this is the motor of addiction – in its soothing wake comes a surge of the chemical that reinforces desire, "the dopamine … that tops this dark lake with an electric sheen of attraction".

Lewis – sensitive, hurt, and far from risk-averse – seemed destined to fall for heroin. There are the usual addict's stories of narrow escape and extraordinary consumption here: the week-long hit-after-hit binge in his father's apartment in San Francisco, punctuated only by trips to dodgy neighbourhoods to get more of the stuff. And later, with a different drug, the biggest of all his falls from grace: three days of psychotic insomnia on amphetamine stolen from doctors' offices. Lewis had become an intern in a psychiatric hospital, of all places. His escapades lead to expulsion and arrest.

But by this point, he is less likeable. He has turned from lost, wide-eyed young man, stumbling across the riches of the counterculture, into a thieving, obsessive commitment-phobe. He says of his wife, "I was trapped. Crushed by the collapsed coalmine of her needs," and one wonders where the emotional deficiency really lies. Our cooling towards him may reflect the way society treats addicts: young people are the victims of upbringing and influence, not masters of their own destiny. Once they're adults, a less forgiving attitude creeps in, which seems unfair. But it's very hard to feel the same towards Lewis once he admits giving his partner a black eye, before "explaining" it with neuroscience.

This is where the so-far-avoided question of responsibility pokes its nose in. Biological determinism is all very well, up to a point. But Lewis is overplaying his hand if he believes it can be marshalled in quite the same way to address domestic violence. Though I don't doubt he feels thoroughly ashamed of his actions, there's something obtuse about dealing with this incident using the same framework as the drug experiences – that is, following it with a mini-essay on the dorsal anterior cingulate cortex.

For, like James's imagined crab, Lewis is a person – a self. The brain is the ground from which a personality emerges, but whether neuroscience can satisfyingly answer moral questions, or help us navigate the impossible situations life sometimes puts us in, is moot. This memoir is as strange, immediate and artfully written as any Oliver Sacks case-study, with the added scintillation of having been composed by its subject. But, for all its scientific dazzle, it is no more complete a portrait of real life.

Houston hospital pioneered live-tweeting last month during an open heart surgery, will answer questions and tweet pictures

Houston's Memorial Hermann hospital for the first time ever live-tweeted a brain surgery, performed by a leading surgeon in the field.

Dr Dong Kim, one of the surgeons who led the team that treated former congresswoman Gabrielle Giffords after she was shot in the head in 2011, removed a cavernous angioma tumor from a 21-year-old woman's brain.

The patient, who is not being identified, discovered the tumor after suffering a seizure.

Kim and his surgical team are using neuronavigation, a set of computer-assisted technologies, to identify the entry point and the precise location of the tumor in the patient's brain, according to the hospital.

A craniotomy is being performed to remove a portion of the skull bone. A microscope will then be used to take out the tumor deep in the right side of the patient's brain.

Finally, the team replaced the skull bone and completed the surgery.

A social media team that includes another neurosurgeon is sitting in an adjacent room answering questions on Twitter and posting photos and videos throughout the procedure.

Today's pioneering surgery follows closely behind the hospital's first foray into the medium, in which a 57-year-old's open heart surgery was tweeted in March.

"Our intent is for this to be an educational opportunity for the public – for high school, college, medical students and residents, and for anyone that may ever have a brain tumor or know of someone in need of brain surgery in the future," a hospital spokeswoman wrote in an email to the Guardian.

"By sharing this experience through photos, videos and text and by being available to answer questions and comments in real time, we are opening the curtain to the OR and giving the public the knowledge and the insight to make educated decisions for themselves when it comes to their choice of treatment."

A sample tweet:

"Social media is a powerful vehicle to help demystify brain surgery, a source of much fascination to people," Kim said in a statement to the Guardian. "We think that by providing this up-close glimpse of the OR, we can educate the public, particularly future patients, about what happens during brain surgery, about what to expect."

That's why the hospital will live-tweet all aspects of the surgery, from room temperature to the head shaving process, and post photos and video on Pinterest and YouTube after the procedure is finished. Follow a live stream from @houstonhospital in the widget below.

CT scans of an Australopithecine skull provide clues to the forces that shaped human brain evolution

One of the things that makes our species unique is our exceptionally large brain relative to body size. Brain size more than tripled during the course of human evolution, and this size increase was accompanied by a significant reorganization of the cerebral cortex, the prominent convoluted structure responsible for complex mental functions, which accounts for something like 85% of total brain volume.

What evolutionary forces drove this dramatic increase in brain size? Many theories have been put forward over the years, a popular one being that our ancestors' brains expanded to accommodate the faculty of language. A fossilized skull fragment belonging to a human ancestor that lived several million years ago provides yet more clues. A new analysis of the skull suggests that human brain evolution may have been shaped by changes in the female reproductive system that occurred when our ancestors stood upright.

At some point in evolution, our ancestors switched from walking on all four limbs to just two, and this transition to bipedalism led to what is referred to as the obstetric dilemma. The switch involved a major reconfiguration of the birth canal, which became significantly narrower because of a change in the structure of the pelvis. At around the same time, however, the brain had begun to expand.

One adaptation that evolved to work around the problem was the emergence of openings in the skull called fontanelles. The anterior fontanelle enables the two frontal bones of the skull to slide past each other, much like the tectonic plates that make up the Earth's crust. This compresses the head during birth, facilitating its passage through the birth canal.

In humans, the anterior fontanelle remains open for the first few years of life, allowing for the massive increase in brain size, which occurs largely during early life. The opening gets gradually smaller as new bone is laid down, and is completely closed by about two years of age, at which time the frontal bones have fused to form a structure called the metopic suture. In chimpanzees and bononbos, by contrast, brain growth occurs mostly in the womb, and the anterior fontanelle is closed at around the time of birth.

When this growth pattern appeared is one of the many unanswered questions about human brain evolution. The new study, led by Dean Falk of Florida State University, sought to address this. Working in collaboration with researchers from the Anthropological Institute and Museum at the University of Zürich, Falk compared the skulls of humans, chimps and bonobos of various ages to the fossilized skull of the so-called Taung Child.

Taung Child was found in 1924 in a limestone quarry near Taung, South Africa, and was the first Australopithecine specimen to be discovered. It belonged to an infant of three to four years of age, and is estimated to be approximately 2.5 million years old. The skull is incomplete, including the face, jaw and teeth, but it contains a complete cast of the brain case, which formed naturally from minerals that were deposited inside it and then solidified.

"Most of Taung child's brain case is no longer present, but you see all kinds of interesting structures in the endocast, like the imprints of the cortical convolutions," says study co-author Christoph Zollikofer. "We looked at the imprints of the sutures. These features are very well preserved, and have been known about for 50 years, but nobody paid attention to them."

In 1990, researchers from Washington University Medical School published a three-dimensional CT scan of the Taung Child endocast, and Falk subsequently reconstructed it again using more advanced computer technology. Comparison of this more recent reconstruction with scans of other species now reveal that the skull of Taung Child has a small, triangle-shaped remnant of the anterior fontanelle.

This suggests that Taung Child had a partially fused metopic suture at the time of death and, therefore, that the pattern of brain development in this Australopithecine species was similar to that of anatomically modern humans. Delayed fusion of the metopic suture indicates that fast brain growth in the period following birth came before the emergence of Homo, the genus that evolved from Australopithecines and eventually gave rise to our own species, Homo sapiens.

"There's a trade-off between walking bipedally in an optimal way, which narrows or constricts the birth canal, and evolving fat, big-brained babies which need a wide birth passage," says Zollikofer. "Bipedalism and big brains are independent evolutionary processes. Hominins started walking bipedally long before the brain expanded, but these trends collided at birth, and we believe this happened much earlier than previously thought."

Evolution is an opportunistic process - species change over time, but only some of these changes prove to be advantageous to an organism's survival. Some of them can prove advantageous in different and unrelated ways, and this seems to be the case for evolution of the human brain. Delayed fusion of the metopic suture apparently evolved to overcome the obstetric dilemma that arose when our ancestors stood upright, but had the added advantage of allowing for the pattern of modern human brain growth.

There are other ways in which bipedalism could have led to increased brain size. It would, for example, have freed up the forelimbs, and this would likely have led to the expansion and reorganization of the sensory and motor brain areas that process sensation and control movement. Similarly, standing upright would have led to big changes in what our ancestors saw, which may have led to an expansion of the visual areas at the back of the brain.

The new findings suggest that further brain expansion, as well as reorganization of the prefrontal cortex, could have occurred as an indirect result of the pelvic modifications that followed the transition to bipedalism.

All evolutionary changes are due to changes that occur at the genetic level, and the dramatic increase in brain size that occurred during human evolution is no exception. Numerous genes have been implicated in human brain evolution, but it is difficult to link any of them to specific changes in brain organization or structure.

Last week, however, Evan Eichler and colleagues reported that a gene known to be involved in development of the cerebral cortex was duplicated multiple times, and that this occurred exclusively in humans. They also estimate that these duplications took place between two and three million years ago, so it is tempting to speculate that they are somehow linked to the changes that may have occurred as a result of bipedalism.

Reference: Falk, D., et al. (2012). Metopic suture of Taung (Australopithecus africanus) and its implications for hominin brain evolution. PNAS, DOI: 10.1073/pnas.1119752109