One day in January 2007, a US federal government construction contractor called Doug Reitmeyer arrived at the offices of a brain-fitness software company called Posit Science, in downtown San Francisco. Reitmeyer’s son, Ryan, had had a devastating boat accident two years earlier. At about 9.45pm, four of Ryan’s friends had asked him to take them back to their car across the lake.
Ryan, 29, was driving the small Sea Ray boat across lake Travis, a reservoir on the Colorado River in Texas, when it collided with a ten-metre black Carver cabin cruiser that had no lights on. The Sea Ray’s five occupants went overboard and Ryan’s head was crushed between the two boats. Surgery to remove the shattered bone that had pierced his brain lasted several hours and he was in a coma for two weeks. Surgeons had to remove part of his brain’s frontal lobes, leaving him with an indentation in his head, where parts of his brain and skull were missing. When Doug Reitmeyer asked the surgeon if he could save his son’s life, the surgeon said that he could, but that Ryan would probably never be able to speak or live independently again. Reitmeyer was willing to prove the medics wrong, so he took early retirement and dedicated his life to helping his son make a full recovery. He researched brain-damage therapies and attended conferences and seminars, until he came upon the work of Michael Merzenich, a neuroscientist at the University of California, San Francisco, and founder of Posit Science, a company pioneering brain-fitness software to improve memory and processing speed in older adults. Reitmeyer scheduled a meeting.

Merzenich has silver hair and exudes bonhomie. He talks with the confidence of someone who believes he’s usually right. One of his mantras is to hear, feel and taste as if he were a child again.

Every day he goes for walks and, comically, he varies his pace and the length of his stride, as a way of exercising his brain. He drives a Fiat 500 and refuses to use a GPS, or indeed any other technology that may act as a substitute for his brain. At the weekend he usually repairs to his villa in Santa Rosa, a 60-minute car journey north of San Francisco, where he tends to a small vegetable garden and vineyards. (His wife calls him “the farmer and the farmer’s wife”.) He is a member of the US National Academy of Sciences and, despite not being a medical doctor, is also a member of the Institute of Medicine, making him one of the few to have been elected to both academies.

Merzenich listened as Reitmeyer described the challenges facing his son Ryan, whose daily schedule at the time included sessions of neurofeedback, speech, physical and occupational therapies. Ryan had made some progress recovering his speech and movement but his memory and cognitive control remained deficient: Reitmeyer could take Ryan to a restaurant and his son would ask him when they were going to eat right after they’d had a meal. Merzenich reviewed Ryan’s brain scans and medical records. Ryan was highly cognitively impaired, “down in the first few percentiles in cognitive ability”.

He had very restricted syntactic ability. He couldn’t hold much of a conversation. He couldn’t sustain attention and couldn’t memorise something for more than a couple of minutes. Merzenich’s software had been tested on patients with traumatic brain injury, but this case was so severe that Merzenich didn’t even know if Ryan would be able to initiate the exercises. But when Reitmeyer asked Merzenich if he could help his son, the doctor said of course he could.

Merzenich tailored a programme of regimented brain-fitness training for Ryan. It was heavily focused on redeveloping language and auditory abilities, with further emphasis on other skills, such as cognitive control and visual-processing. Ryan had spent more than 50 hours completing Posit Science’s brain-fitness exercises when he came to see Merzenich some months later. “They came to thank us and to show how well Ryan was doing,” Merzenich recalls. Ryan had recovered his memory and had made astonishing progress with his language and ability to control his attention. He could also hold a conversation and even use wit in his responses. Merzenich recalls Reitmeyer asking Ryan to pick something from a local drug store a couple of blocks away, a neighbourhood where Ryan had never been before. “And he did it. That would have been impossible a few months ago. They were so thankful. They knew that Ryan had come back into real life from such a deep hole,” Merzenich says.

“We can improve and often fix it, whether you’re 90 or when you’re nine.”
Michael Merzenich -

Merzenich keeps in touch with the Reitmeyers. Last time he spoke to Ryan, he was driving again, playing the guitar, had a job and was talking about getting married. “I choose not to talk about these things publicly because I don’t want people to think that if you have 30 per cent of your frontal lobes removed you can expect this kind of recovery,” Merzenich says. “One thing is clear though. Ryan would have never have recovered from such an injury if the human brain didn’t have a remarkable capacity to change.”

Merzenich is one of the few scientists and doctors who, in the past 30 years, have transformed the field of neurology by overturning the dogma that our mental abilities are immutable and fixed early in life. Cognitive impairment associated with neurological maladies, such as schizophrenia, strokes, autism and traumatic brain injury, were considered largely untreatable. Normal age-related cognitive decline was considered unavoidable. The capacity to train and improve the diverse mental abilities that make up our intelligence was not considered possible. But Merzenich and other researchers have shown that the brain is what they call “plastic” – it can physically remodel itself. The notion that the brain we are born with is not a fixed structure with a set of weaknesses and strengths, but a mutable organ that is adaptable and can be trained to overcome its deficiencies, has profound implications for how we perceive our brain and its associated capacities. Not only can brain plasticity be manipulated in ways that treat and prevent neuronal disease that was deemed permanent, but it can also keep our brains fit and resilient. “It means you’re not stuck with it,” Merzenich says. “We can improve and often fix it, whether you’re 90 or when you’re nine.”

In 1968, Merzenich made his first breakthrough. He was a recent neuroscience graduate, studying at the University of Wisconsin-Madison under the supervision of a neurophysiologist called Clinton Woolsey. Merzenich was an expert in a technique called “micromapping”, a precise but time-consuming way of finding which parts of the brain responded to external stimuli, using extremely small electrodes that measure the electrical activity of a single neuron. Merzenich used macaque monkeys, measuring neuronal activity as he tapped different parts of the monkey’s hand, in order to see which areas of it stimulated electrical activity in the monitored part of the brain. Mapping a whole hand using this method could take between 20 and 40 hours.

When he arrived at Madison, Woolsey asked Merzenich to supervise two young neurosurgeons, Ron Paul and Herbert Goodman, and the three set out to find what happened in the brain of adult macaque monkeys after a severe hand injury. The mainstream view at the time was that the brain reached a fixed state after just one year of existence. If, for instance, one of the main nerves in the hand were cut, then the corresponding area in the brain was supposed to be rendered silent and unused from the lack of sensorial input.

Merzenich, Paul and Goodman, however, found that this wasn’t the case. After the injury, neighbouring areas in the brain would expand into the vacant territory. Later, as the nerve regenerated, its corresponding brain connections would reclaim much of its original neurological real estate. This dynamic remodelling of the brain that Merzenich and his colleagues observed was completely at odds with the conventional view that the structure of a brain was immutable. In their scientific report, they wrote a lengthy discussion section about what these observations implied. Woolsey thought it was too conjectural and deleted it.

When, in 1971, Merzenich moved to the University of California, San Francisco, he continued his experiments at the department of otolaryngology, and showed again and again that adult brains remained plastic. The scientific establishment, however, was slow to accept it. Early reviews of his scientific papers often came back with sarcastic comments, and at conferences he was subjected to insults. That didn’t bother him. He was sure that the scientific truth always wins in the end. “What irritated me is that I was also arguing that this discovery could be used for all sorts of therapies,” Merzenich says. “I became a sort of missionary going to people and saying,

‘Listen, you should take this research seriously, it can help people.'” It took a couple of decades. In the late 80s, he met a neuroscientist from Rutgers University in New Jersey, called Paula Tallal. Tallal was interested in children who had difficulties reading and speaking, such as dyslexics. Her studies showed that children with dyslexia had something wrong with their brains. At the time, scientists believed that dyslexics had a deficiency with their eyes, but Tallal suspected that instead their brains were too slow in processing sound. “People thought dyslexia had something to do with seeing letters backwards,” says Tallal. “However, words are made of smaller units of sound represented by letters. It was becoming clear that the majority of dyslexic children find it difficult to be aware that words can be broken down into sounds.This in turn will affect their reading ability, because reading stands on the shoulders of spoken language. And because learning to read requires matching symbols to sounds, the child will be affected in understanding words and speech.”

At the time, Merzenich had been conducting experiments with adult macaque monkeys that showed how radically their brains rewired after they learned new skills, such as being able to distinguish sounds in shorter and shorter periods of time. “We would progressively train them to an extent that their initially sluggish brains were fast and accurate,” Merzenich says. When Tallal told him about her findings, Merzenich wondered if he could train these kids who lacked the necessary neurological circuitry to process sounds at speed. “Paula, if these kids were monkeys, I’m almost certain I could fix them,” he told her.

Tallal and Merzenich decided to collaborate. In six months, with the help of a team of language specialists, neuroscientists and computer scientists, they developed language-training software called Fast ForWord. Fast ForWord consisted of games that used acoustically enhanced speech, which initially made very rapid acoustic changes longer and louder and then would slowly revert back into a normal speech range. For a month during the summer of 1994, seven dyslexic children came to Tallal’s lab in Newark, New Jersey, to exercise their brains with the software. “At the time, the software was still very limited,” Merzenich says. “The difference it made on the children, however, was amazing.”

He remembers a quiet five-year-old boy who had the language abilities of a 30-month-old. “He was very limited, but when we returned to Newark after the tests he was a confident chatterbox. His tests indicated that his language ability was now normal after a month,” Merzenich says.

Tallal and Merzenich decided to conduct a larger-scale controlled trial with improved software and more children, the results of which were later published in the journal Science. Within days of the report coming out, Merzenich and Tallal received thousands of messages from parents and therapists desperate to try the new treatment on their children. In 1996, Tallal and Merzenich, along with two other neuroscientists, founded the Scientific Learning Corporation, a company that produces Fast ForWord today. It was the first company to provide a brain-fitness programme online. To date, according to Tallal, Fast ForWord has helped more than two million children overcome learning disabilities.

Merzenich was CEO of Scientific Learning Corporation for only 18 months. He returned to the lab to continue to file patents for brain-plasticity-based methods that could help adults with normal, age-related cognitive decline and clinical impairments such as schizophrenia, autism and brain trauma. At board meetings he would insist the company needed to invest in plasticity therapies for adults, but the board wanted to keep the focus on treating children with learning disabilities. He was proud that they could help children to read and write, but that wasn’t enough. So in 2003, he cofounded Posit Science with the goal of using the science of brain plasticity to help everybody else.

Merzenich runs Posit Science from a suite of offices in downtown San Francisco. He has a team of 36 people, including neurologists, computer scientists and game designers. Using the same brain-plasticity principles that he and Tallal used to treat children with Fast ForWord, Posit has developed an online software package called BrainHQ, a set of brain-training exercises aimed not only at treating neurological conditions, but also to arrest the normal cognitive decline that comes with age, and to improve the cognitive abilities of normal individuals. “I’ve looked at old brains, brains of animals we’d expected would die within months,” Merzenich says. “And you look at the various capabilities of these brains and everything that disadvantages them. And which of these capabilities can we reverse by intensive, progressive training? All of them. Their decline is inherently reversible. As far as we can see, the same is true for humans.”

To understand how Posit Science tackles neurological diseases, let’s consider schizophrenia. Schizophrenics typically suffer from hallucinations, delusion and disorganised reasoning. These symptoms result from an excess of dopamine and noradrenaline, the neurotransmitters that modulate the reward feedback-loop control-arousal levels in the brain. Underlying this chemical reaction are what Merzenich calls “failure modes of the plastic brain”: weaknesses in the neurological apparatus, specifically in working memory – a cognitive skill that indicates a person’s capacity to manipulate information, such as computing sums – and the ability to make predictions. Antipsychotic medication, which suppresses these neurotransmitters, is effective in mitigating symptoms such as hallucinations but doesn’t fix the cognitive structure.

“We’re transforming neuroscience-based software into medicine.”
Michael Merzenich -

“Drugs are an extremely primitive method to treat the neurology,” Merzenich says. “We’re manipulating machinery that is controlled by dozens of variables, by powerfully distorting one particular chemical. What we’re doing instead is replacing that chemical approach with strategies that actually correct the neurological underpinnings of these problems. And the only way is to have the brain correct itself.” Using BrainHQ, monitored schizophrenic patients can work on computer exercises that specifically target those cognitive weaknesses. Two recent studies led by Sophia Vinogradov, vice chair of psychiatry at the UCSF, have shown that 50 to 80 hours of using BrainHQ significantly improved not only patients’ working memory and learning, but also their social functioning and ability to distinguish reality. Posit Science is currently conducting studies to gain US Food and Drug Administration approval to treat schizophrenia, brain injury and stroke. “We’re transforming neuroscience-based software into medicine,” Merzenich says.

To show how BrainHQ’s exercises work, Merzenich instructs Wired to take a 36-part cognitive assessment that lasts three hours and purports to measure everything about cognitive abilities. “It allows us to tailor a programme to someone’s specific needs,” says Merzenich. In all, there were more than 40 exercises. One, called Hawk Eye, aims to sharpen visual perception and expand one’s field of view. A set of identical birds flashes briefly on-screen, except for one of a different colour that needs to be identified. A simpler exercise is Sound Sweeps, which tests auditory accuracy by requiring subjects to identify whether a sound, which might last only milliseconds, is going up or down in frequency. Even harder is Mixed Signals, which requires subjects to watch a string of symbols, listen to a piece of information and react when they match. As new levels are unlocked, colourful fireworks explode on-screen. The exercises in Merzenich’s brain gym are simple but strangely compelling.

On average, cognitive decline in humans starts when we’re between the ages of 20 and 30. At the onset of this steady downfall, the brain slows down and its reliability deteriorates. Listening becomes less accurate. Peripheral vision narrows. Attention and memory begins to falter. To make matters worse, this gradual decline is usually accompanied by social withdrawal, egocentrism and a loss of confidence. As Merzenich likes to put it, everything is going to hell.

This problem is compounded by our laziness. When we get older, we rest on our laurels, auto-piloting our behaviours, operating effectively throughout the day using skills that we learned when we were younger. The problem with that approach is that our brain can be maintained only by a life of continual learning – but, as older people effectively decide to stop challenging the brain, like an unused car, the learning machinery slowly seizes up. “Like every organ in our bodies, the brain undergoes changes in how it performs. You see it in your muscles, your bones, your hair – and you feel it in your brain,” says Adam Gazzaley, a neuroscientist at the University of California, San Francisco. “That is not helped by people seeking comfort and a less demanding life when they are older. The fact is that the brain is still plastic even when they are 70 or 80 years old. It can still be optimised – but instead, many people unwittingly accelerate its deterioration.”

Gazzaley is best known for demonstrating some of the mechanisms behind cognitive decline. He showed, for instance, that as we get older we are more susceptible to interference – be that in the form of distractions, irrelevant information or multitasking. The problem with older adults is that they don’t filter information, and consequently they overprocess irrelevant information that they can’t seem to ignore. One of the consequences of interference is poor memory: it’s difficult to recall something that was never properly imprinted in the brain in the first place.

One evening in 2008, Gazzaley had a strange, vivid dream about a video game. In that game, the player was driving a car along a winding road in the mountains and, at random intervals, a sign would pop up on the screen. If the sign had the right shape and colour, the player had to shoot it down while steering the car.

Gazzaley realised that he could design a video game to induce improvements in the brain. Later that day, Gazzaley called Matt Omernick, a friend who worked at the now-defunct games company LucasArts Entertainment, and recounted his dream. Omernick liked the idea and spoke to Eric Johnston, the legendary games developer who created the classicMonkeyIslandseries, and Noah Falstein, who had been one of LucasArts’ first game designers and was now Google’s chief game designer. “I explained to them the concept and Matt drew it out,” Gazzaley says. “I didn’t have any funding, but they wanted to work on it anyway. They said to me, ‘We spent our whole careers teaching teenagers how to kill aliens. We’re ready to use our skills to do something of impact.'”

Like Fast ForWord, Gazzaley’s game, called NeuroRacer, was designed according to the rules of how plasticity is induced in the brain. Gazzaley’s team used an “adaptive staircase algorithm” that constantly matched the difficulty of the game to the player’s skill. “Adaptivity is at the core of our game mechanics because that’s how you tap into plasticity,” Gazzaley says. “Between 70 to 80 per cent difficulty is the sweet spot. That’s where the player gets into a flow state and plasticity is maximal.” When the game was completed, Gazzaley recruited 174 people, with ages ranging from 20 to 80. In the first phase of the study, they tested the multitasking skills of their participants, confirming that older players had more multitasking deficiencies than younger ones. They then recruited 46 participants aged 60 to 85 and put them through a four-week training period with NeuroRacer. “After the training period, the multitasking skill levels of the older guys exceeded even the levels of the 20-year-olds who had played the game once,” says Gazzaley, “Those levels were sustained six months later.” Also, Gazzaley found that the older players not only improved their ability to multitask, which the game explicitly trained, but other abilities, such as working memory and sustained attention.

Last year, Gazzaley cofounded a company called Akili Interactive Labs, which is developing an upgrade of NeuroRacer called EVO. Like Posit Science, Akili is seeking FDA approval forEVOas a possible software-based treatment for ADHD. “Most people associate medicine with drugs, and that’s the result of a big, successful brainwashing campaign by pharma companies,” Gazzaley says. “But when it comes to brain health, drugs don’t work very well – and the drug companies know that. If you look across the world’s top-ten pharma companies, four have withdrawn research from neuroscience. That’s not because we’ve cured any of these diseases. Hopefully now we’ll start thinking of software and hardware as a form of medicine.”

Gazzaley has been preparing to open a new neuroscience laboratory at the University of California, San Francisco. “We’re going to be able to record real-time EEG data as you play one of our games,” Gazzaley says. “The challenge won’t just be correlated to your performance, but also directly by neural processes in your brain.” He gives Wired a copy of the November 2013 issue of the scientific journal Nature. The cover headline is “Game Changer” and the image shows the cartoon of an old balding man driving a car through NeuroRacer’s mountainous roads. “Before I’d developed NeuroRacer, I used to give talks to groups of colleagues and present my data on cognitive decline and its mechanisms, and they would love it, find it fascinating.

But when I gave a talk about it to a public audience of older people, like the American Association of Retired Persons, it was horrifying. If you give a lot of talks you get good at reading subtle signs in the audience. Every year at the AGM, I had over a thousand people in the audience, all grey, and at the end of my talk, I could just see them asking “Is this it? Is this the end of the movie?” There was this feeling like that was not really the right ending.” He points to the Nature cover. “That is the right ending.”

Older adults are often advised to keep their minds sharp, but such advice is so general as to be useless. “It’s true that we lose abilities as we get older, but I believe that most of that loss is driven by a lack of effort to sustain brain fitness,” says Alvaro Pascual-Leone, a neurologist at Harvard Medical School and one of the most-cited scientists in the field of brain plasticity. “We’re lazy, we don’t get out of our comfort zones, we stop learning new things. The fact is that whatever you do, from activities to relationships to thoughts, ultimately enters the brain and affects it. But we can harness that property of the brain for our own benefit. Ultimately, it’s a message of hope for people.”

The science of neuroplasticity illuminates the dynamic evolution of our brains throughout life, documenting how different experiences can dramatically change it. Its most pertinent insight, however, is that we can take control of such transformation.

Merzenich’s and Gazzaley’s brain-training exercises provide us with a tool to do it. They are a gym for the brain, a place where we can go to strengthen and expand our cognitive capabilities, which, to a very large extent, define who we are and determine what we are capable of.

This article was original published in May 2014 and has been updated to include the clinical trial. João Medeiros is WIRED’s senior comissioning editor. He wrote about Prozone in 01.14.

Update: 10.04.2017: On 5 April, Akili Interactive Labs announced the results of a study demonstrating its cognitive-training computer game, Project: EVO, improves the symptoms of children with cognitive deficits.

In the clinical study, 57 children with sensory processing disorder, a condition that affects how the brain receives and responds to sensorial information, played Project: EVO for four weeks.
After the treatment, the symptoms in 33 per cent of the patients had improved to the extent that they no longer met the criteria for the disorder.

“These findings are quite exciting given that they both reproduce critical elements of the study of this technology in older adults and suggest that this treatment approach can have powerful effects across the lifespan and in distinct populations with specific cognitive deficits,” said Joaquin Anguera, from the Departments of Neurology and Psychiatry at UCSF and lead author of the study.
Akili’s Project: EVO is currently still under evaluation in a large clinical trial with ADHD patients, a study that aims to get the game FDA approved as a medical treatment.

Source: https://www.wired.co.uk/article/game-your-brain