London taxi drivers are renowned throughout the world for their detailed knowledge of the streets, traffic configurations, and one-way systems of the big city. Unlike most of their counterparts around the world, it’s seemingly second nature for them to navigate the streets of the British capital without recourse to a map. On average it takes a rookie driver two years to absorb the information required to be able to do this, and to eventually pass an ominous oral exam tellingly called “The Knowledge.” These drivers have chosen a career that places a huge burden on their memory, specifically on their working memory, where rules and facts have to be kept constantly in mind in determining ongoing actions.
In 2000 Eleanor Maguire and her colleagues at University College London were intrigued by the question of whether London cab drivers would show any physical changes in their brains as a result of the very unusual daily experience of constantly using their working memory. Amazingly, they saw in brain scans that a particular area of the brain related to working memory (the hippocampus) was actually bigger in the taxi drivers than in others of the same age.1 Nor was it the case that having a big hippocampus predisposed these individuals to drive cabs, as the difference in hippocampal size was larger the longer the subjects had been plying their trade. This study captured the attention and fascination of the media, as well as of London taxi drivers, of course, and it remains to this day one of the best and simplest examples of the “use it or lose it” principle. Neurons, like the muscles of the body, grow stronger and larger with whatever activity is rehearsed. Even though such adaptation is shared not only by mammals but also by far simpler organisms such as the octopus2 and even the humble sea slug,3 humans have been able to exploit this talent superlatively, well beyond any other species.
Changes in the brain as a result of experience were actually first shown as long ago as 1783 by the Swiss naturalist Charles Bonnet and the Piedmontese anatomist Michele Vincenzo Malacarne: they discovered that training dogs and birds led to an increase in the number of folds in a part of the brain (the cerebellum), compared to dog littermates or birds from the same clutch of eggs.4 However, this finding did little to overthrow the dogma of the time, that the brain was unchangeable, until the idea was revisited in 1872 by the philosopher Alexander Bain: “For every act of memory, every exercise of bodily aptitude, every habit, recollection, train of ideas, there is a specific grouping or coordination of sensations and movements, by virtue of specific growths in the cell junctions.” Almost twenty years later, in 1890, the pioneering psychologist William James had a flash of insight: “When two elementary brain-processes have been active together or in immediate succession, one of them, on recurring, tends to propagate its excitement into the other.” The actual term for this process, plasticity, was first introduced a few years later, in 1894, by the great Spanish anatomist Santiago Ramón y Cajal, who borrowed the word from the Greek root meaning “to be molded,”5 well before the advent of the ubiquitous synthetic material.
“Give me a child until he is seven, and I will give you the man,” guaranteed the Jesuits. Just as plasticity had been anticipated by Michele Malacarne and Charles Bonnet long before modern scientists such as Eleanor Maguire produced experimental data, so too has it been widely accepted that a young, developing brain is more impressionable and more vulnerable. Of course this sensitivity of the young brain to external influence highlights the importance of shaping the right kind of early environment for the next generation. As Hillary Clinton pointed out in 1997, the experiences of children between birth and age three “can determine whether children will grow up to be peaceful or violent citizens, focused or undisciplined workers, attentive or detached parents themselves.”6
In the first years of life the brain has windows of opportunity, characterized by the exuberant growth of connections between neurons, which allows for astonishing possibilities. For example, in infants the visual and auditory compartments of the outer layer of the brain (cortex) appear to be functionally interchangeable, equally effectively stimulated by either hearing or vision. Consequently, when there is a loss of vision in early childhood, some form of hearing ends up sharper through a process known as cortical remapping.7 Because the visual sector is not being used for its normal job, it adapts to whatever inputs are available and takes on an alternative role, helping the brain process hearing with a resulting greater prowess.
This obliging adaptation by the central nervous system is not restricted to the senses. One example of the power of the young brain in compensating for damage was the case of Luke Johnson. Luke made the headlines in a British newspaper in 2001 when he was just a toddler. Soon after he was born, his right arm and leg appeared limp and motionless. Doctors diagnosed severe brain damage due to a stroke in the left side of his brain while in the womb or shortly after birth. But within a few years Luke had recovered the full use of his legs and arms. Over the course of the first two years of his life, his brain had been busy rewiring itself, reorganizing nerve pathways to bypass the damaged tissue.8
Sadly, these critical periods do not always ensure a positive outcome. Take the case of children who develop cataracts on one or both of their eyes. Visual deprivation through a cataract or another abnormality that impairs sight that occurs between birth and five years, leads to permanent damage to vision. But for children who encounter this problem when they are older, vision typically recovers after treatment.9 Interestingly, different types of vision have different critical periods, meaning that a child who develops a cataract within a certain time frame may have impairments in, say, the detection of motion, yet develop normal acuity. As with Luke Johnson, the brain of a young child with a cataract will rewire itself, but this time with the tragic consequences that the territory normally used by the nonoperational eye would have been usurped for other purposes.
The notion that there are critical periods of brain development is intuitively easy to grasp, and the changes seen at these particular crucial stages of even normal development are indeed marked. However, it is clear from the remarkable recovery often seen in adult stroke patients that even though “land grabs” in the brain may be less striking later in life, they do not cease with age. In adults as well, various sensory systems can cross the official boundaries between one and another, as when the visual cortex of blind people is activated during the reading of Braille. By the same token, the neuroscientist Helen Neville has demonstrated how auditory impairment induces specific compensation in enhancing vision, while conversely the blind process fast auditory stimulation better.10
The same fundamental brain mechanisms driving plasticity during learning in the intact immature brain are also pressed into service during relearning in the damaged or diseased brain. Recovery of function after brain damage falls into three stages: (1) restoration: restoring function to the residual brain area, (2) recruitment: recruiting new brain areas to aid in the performance of the original function, and (3) retraining: training these other brain areas to perform the new function efficiently.11 With language, the right hemisphere, which is not normally dominant for speech, can take over from the traditional left when it is damaged.12 Meanwhile, in the case of a nonfunctioning hand in monkeys, just one hour per day of training will keep its neuronal representation in the brain from shriveling to uselessness. This effect has also been demonstrated in humans. Many patients with a malfunctioning hand as the result of brain damage will prefer to use the healthy counterpart, but such a strategy impairs recovery of function. So a sleeve is often placed over the good hand to encourage use of the impaired hand, thereby making it as operational as possible.13
The brain does not tolerate “vacant space”—a situation where neurons would not be put to work. The overquoted old idea that we use only 10 percent of our brains is a complete myth, and easy to refute. First, there is no area of the brain that can be damaged without loss of ability of some sort, but if the 10 percent myth held true, we could afford for 90 percent of our brains to be damaged. Second, the brain is the greediest organ of our bodies at rest, guzzling up 20 percent of our energy supplies even though it constitutes only 2 percent of body weight. Why would we use so many resources to maintain 90 percent of neurons to do nothing? Third, brain-imaging techniques reveal that, with the exception of cases of severe damage (such as that seen with a persistent vegetative state), no brain areas show up in scans as completely inactive and silent. Fourth, all brain areas appear to contribute to functions: there is no structure in the brain that doesn’t have a job, even though we may not understand exactly how the contributions from different brain areas all fit together to give rise to an ultimate net behavior. Finally, as we’ve just seen, the brain operates on an unambiguous “use it or lose it” principle when it comes to neuronal survival and connectivity. Were 90 percent of the brain to remain unused, autopsies would reveal large-scale degeneration of up to 90 percent: but this isn’t the case.14
The harder specific neurons work away at a particular activity, the more brain territory they will take up. In one experiment, Michael Merzenich showed that owl monkeys trained to rotate a disk with two digits only had an enlarged area of the touch (somatosensory) cortex relating to those two digits.15 This finding has a fascinating counterpart in humans: musicians who play string instruments exercise their left hands more than their right and, in string players, the section of cortex related to touch is accordingly larger for the left hand than the right.16 Many other examples of plasticity in the sensory system of adults abound, and the impact of repeated experiences on brain functioning are the bedrock of Mind Change, so it’s worth getting an idea of just how sweeping and dramatic plasticity can be.
First there are snapshot studies, rather like the one with the taxi drivers, where the brains of a group of people who do something unusual or very frequently on a daily basis show differences compared to the rest of us. Quite generally, for example, brain structures differ between musicians and nonmusicians. Anatomical scans of professional musicians (keyboard players), amateur musicians, and nonmusicians showed size differences in a range of structures: motor, auditory, and visuo-spatial brain regions.17 It’s worth noting that there are strong relationships between musician status and practice intensity, suggesting the anatomical differences are linked to learning and not to a predisposition to music. Meanwhile, substantial time spent doing math induces an increase in gray matter density in specific (parietal) areas of the cortex known to be involved in either arithmetic processing or visuo-spatial imagery/mental creation/manipulation of 3-D objects.18
Then there’s sport. Experience-dependent plasticity is detectable in the brains of basketball players: when players were compared to healthy controls, there was an enlargement in the brain’s “autopilot,” the cerebellum.19 Comparable changes can also be seen in the skilled golfer’s brain, albeit in a different cerebral structure, in contrast to those who were less proficient.20 However, since there was also no linear relationship between a golfer’s handicap level and the anatomical changes, it is impossible to say whether the skilled golfers were already predisposed to this particular talent. This chicken-and-egg conundrum is one of the big disadvantages, more generally, of snapshot studies of different groups of people.
An alternative type of experiment that can differentiate cause and effect is to observe changes in the brain over time as normal human subjects with no particular skill or talent are trained from scratch in some standardized experimental task.21 In one case, it was juggling. Subjects underwent daily training for three months to learn a three-ball juggling task, where perception and anticipation were key to determining upcoming movements accurately. Scans were performed before training, after three months of training, and then after another three months in which no juggling was attempted, by which time performance had deteriorated back to baseline: use it or you will lose it. Meanwhile, the brain scans over this time showed that structural changes occurred within seven days of beginning training and were most rapid during the early stages, when performance level was low. This result suggests that it is the learning of a new task that is pivotal in changing the structure of the brain, rather than ongoing rehearsal of something already learned.
Most comforting of all is the observation that such training can still induce brain structure changes in the elderly. In a juggling task like the one just discussed, the performance of the elderly wasn’t quite as good as that of a younger population, but gray matter changes did occur in identical brain regions.22 More generally, memory training can induce growth in the cortex in the elderly. When an intensive eight-week training program is deployed, memory performance improves and cortical thickness increases in the experimental group undergoing the memory training.23 And if older people show brain changes as a result of increased mental activity, it should come as no surprise that younger people do too.
Preparation for the German basic medical exam, the Physikum, can have a demonstrable effect on the brain.24 This exam “includes both oral and written tests in biology, chemistry, biochemistry, physics, social sciences, psychology, human anatomy and physiology demanding a high level of encoding, retrieval and content recall.”25 Structural changes related to learning occurred in a variety of brain regions related to memory: hippocampus, parahippocampal gray matter, and posterior parietal cortex. But it’s not just the acute and stressful experience of exam preparation that’s key. Learning a second language increases the density of gray matter, the changes observed being correlated with skill level.26 Five months of second-language learning, in this case with native English-speaking exchange students learning German in Switzerland, resulted in structural changes that matched up with the increase in second-language proficiency. Once again, the individual amount of learning achieved was reflected in brain structure changes.
The exciting and scary fact of life is that you don’t have to actively engage in a specific training task to change your brain: it will happen in any case as a result of the experiences you have and of the environment you are in. In her revealing and fascinating book The Plastic Mind, Sharon Begley writes about how “new synapses, connections between one neuron and another, are the physical manifestation of memories. In this sense, the brain undergoes continuous physical change.… The brain remakes itself throughout life, in response to outside stimuli to its environment and to experience.”27
The earliest demonstration of the impact of the outside world was with what was eventually to be called an “enriched” environment and dates back to the 1940s, when the visionary psychologist Donald Hebb did what would be impossible nowadays: he took some of his lab rats home.28 The actual reason for this bizarre game plan is lost in the mists of time. However, after some weeks in the house, these “free range” rats turned out to have superior problem-solving abilities, such as maze running, compared to the less fortunate counterparts that had remained in standard lab cages.
Since then, more formal studies have shown just how powerful a factor the environment can be, especially when it is stimulating and novel and invites exploration. The very first mention of the term “environmental enrichment” in a scientific article was by Mark Rosenzweig and his team at the University of California in 1964, when they demonstrated for the first time physical changes in neural circuits through experience. The scientists had actually set out to identify the neural mechanisms underlying individual differences in behavior and problem solving in different strains of rats, but they quickly realized the enormous influence that experience had on the behavioral performance relative to their standard caged counterparts.29
Over the ensuing decades, neuroscientists have learned that an enriched environment leads to a whole host of physical changes in the brain, all of them for the good: increased neuron cell body size, increased overall brain weight, increased thickness of cortex, greater number of dendritic spines (protuberances on branches of cells that increase surface area), increase in the size of synaptic junctions and hence of connections, and increased number of glial cells (the housekeeping cells of the brain, which ensure a benign microenvironment for neurons). These effects are more pronounced in younger animals but can still be observed in adult or even old rats. There is also increased production of new brain cells in parts of the brain associated with memory and learning (hippocampus, dentate gyrus, and cerebellar Purkinje cells), as well as a greater blood supply and an increase in the amount of growth factors and protein synthesis.
This type of stimulating environment, where there is no fixed task to perform but which nonetheless generates different types of experience, can have a surprising impact even when destiny seems otherwise to be determined strongly by genes. In an experiment done fifteen years ago that has now become a much-cited classic, mice were deliberately genetically engineered to develop Huntington’s disease, a neurological disorder that manifests in wild, involuntary movements known as chorea (after the Greek for “dance”).30 The mice left in typical lab cages lived out their genetic fate as they aged, scoring worse and worse each day on a variety of movement tests, while a genetically identical group were exposed to an enriched environment, a world consisting of greater space to explore and more objects (wheels, ladders and so forth) with which to interact. The study conclusively demonstrated that mice living in such a stimulating environment developed movement problems much later and with a far more modest degree of impairment. Even here, with a disorder linked to a single gene and in the less complex brains of mice, nature and nurture interact.
Research since the early 1990s on animals living in an enriched environment have revealed a wide range of physical changes in the brain at the level of individual neuronal networks, as well as demonstrating that the duration of the enrichment experience is a significant factor. For example, in one study a single week of environmental enrichment had no effect, but four weeks of enrichment had behavioral effects that lasted two months, while eight weeks of enrichment led to behavioral effects lasting six months.31
Given all these physical changes in the structure and chemistry of the brain, it comes as no surprise that animals in enriched environments are superior in tests of spatial memory and show general increases in cognitive functioning such as learning ability, spatial and problem-solving skills, and processing speed. They also have reduced levels of anxiety. In addition, enrichment attenuates the persistent effects engendered by past negative experiences such as prenatal stress or neonatal separation from the mother. The protective effects of enrichment are particularly apparent in animals that are highly anxious or when the task is extremely challenging for the subject.
Enriched environments can also be beneficial in animal models of recovery from brain injury. For instance, transfer to an enriched environment improves the outcome after an experimentally induced stroke, as well as significantly improving motor performance in spontaneously hypertensive rats previously housed in standard laboratory cages, compared with controls remaining in the less stimulating environment.32 Moreover, an enriched environment will reduce programmed cell death (apoptotic cell death) in the rat hippocampus by 45 percent. And if that were not enough, these environmental conditions can also protect against experimentally induced seizures.33
The beneficial and widespread effects of environmental enrichment also persist in aged rats and across a diverse range of species: mice, gerbils, squirrels, cats, monkeys, birds, fish, even fruit flies and spiders—every animal “from flies to philosophers.”34 There is still some controversy as to whether enrichment actually represents a super-special experience or is only a relative improvement over standard laboratory animal housing. However, the main point is that it is the difference between the two types of experience, the relatively greater stimulation, that counts.
But to go back to the question asked at the beginning of the previous chapter: how can an external experience literally leave an internalized mark on the brain? Just as muscle grows with exercise, so too do neurons respond to physical changes, by growing more branches. When it has more branches, a brain cell will have an increased surface area, which makes it an easier target and leads to the possibility of more connectivity with other brain cells. Back in 1949 Donald Hebb came up with the startling suggestion that repeatedly stimulating the same chain of neurons so that they are active at the same time will make them stronger and more effective: as he put it, “cells that fire together wire together.”35 But how exactly? Fastforward another few decades to when sophisticated techniques became available to monitor the activity of single brain cells (done by inserting microelectrodes inside them and recording the voltage they generate). Using this technology, Swedish physiologist Terje Lomo and British neuroscientist Tim Bliss gained their place in the history of brain research for their breakthrough description of the actual step-by-step process of Hebb’s idea. Neuroscientists can now describe the specific physico-chemical steps by which signaling between two brain cells will become more effective as a result of repetition—that is, experience.36
While it would be hard to impose a standardized enriched environment on humans, and even harder to justify an experimental “control” group of people deprived of stimulation, the effect of different types of environment has been examined in older healthy adults by investigating the relationship between lifestyle and “cognitive reserve,”37 namely “the degree to which the brain can create and use networks or cognitive paradigms that are more efficient or flexible, and thus less susceptible to disruption.”38 The findings, perhaps not surprisingly, indicate that a greater involvement in intellectual and social activities is linked with less cognitive decline. It seems that a mentally active lifestyle may defend against cognitive deterioration by increasing the density of synapses (thereby improving the efficacy of communication within intact neurons) and the efficiency of normal and alternative brain networks.39 Then again, just as in animals, unless the enrichment or stimulation is maintained, performance may decline after previously successful rehabilitation, leading to negative changes. This could be as a result of withdrawal from social situations or reduced levels of activity and/or communication.40 Even when IQ, age, and general health are all taken into account, older individuals living in a community perform better in cognitive tests than those who are institutionalized.41
Most fascinating of all is that even brisk walking may stimulate the production of new neurons (neurogenesis). First, exercise increases the blood supply to the brain, and along with it the all-important oxygen the blood carries. Increased oxygen then enables stem cells (the universal progenitor cells from which different cells derive) to convert to neurons at maximum capacity, as well as stimulating the release of chemicals that help cells grow. But that’s not all. While physical activity increases the manufacture of neural stem cells, additional stimulation from an enriched environment increases the connectivity and the stability of those connections.42 Although it has only recently become possible to study cell production in the human brain,43 changes in brain processes and composition as a result of enriching social, mental, and physical activities are now thought to help stave off cognitive decline as we age,44 and in turn prevent the underlying loss of cells that characterizes the cycle of death in Alzheimer’s disease.45
It is also possible for mere thinking to actually change the physical brain, bizarre though this might sound. One of the most-cited examples of how a thought can drive a physical brain change was conducted by Alvaro Pascual-Leone and his research group back in 1995 with three groups of adult human volunteers, none of whom could play the piano.46 Over a five-day period, the control group was exposed to the experimental environment but not to the all-important factor of learning the exercises. A second group learned five-finger piano exercises, and over the five days showed an astonishing change in their brain scans. But a third group were more remarkable still. The subjects in this group were required merely to imagine that they were playing the piano, yet their brain scans showed changes almost identical to those seen in the group undergoing physical practice!
Many additional and amazing examples have followed of the tangible impact of thinking on the brain. Fred “Rusty” Gage, professor at the Laboratory of Genetics at the Salk Institute, has demonstrated that in order for exercise to generate the production of new brain cells, the exercise has to be voluntary: the animal must decide to enter the exercise wheel and run in it.47 Similarly in humans, it appears that plasticity occurs only when movements are volitional and/or the subject is paying conscious attention. But if paying attention at the critical moment is essential for adaptive changes in the brain, then of still more importance is the individual’s state of mind. Perhaps the most familiar but still seemingly improbable example would be the placebo effect, whereby the simple belief that an inert substance has therapeutic properties is sufficient in itself to cure an illness.
We know that this effect works via naturally occurring morphine-like chemicals in the brain, the enkephalins, as research has demonstrated that the drug naloxone, which blocks enkephalins, will correspondingly block the placebo effect.48 It also turns out that the effects are not merely due to the presence of the enkephalin molecule; rather, it is necessary to believe that the placebo is in fact an active drug. Again, what’s all-important is a conscious thought, not just the appropriate bottom-up landscape of brain cells and chemicals.
A further illustration of the key role played by conscious thought can be seen in clinical depression. It turns out that there’s a big difference for depressed patients between bottom-up intervention in their condition, with antidepressants such as Prozac, and intervention via various talking techniques such as cognitive behavioral therapy. Psychotherapy differs from antidepressant medication in that the therapist targets the patient’s beliefs, encouraging the patient to see the world in a new, more positive way. The cause of the depression—for example, the loss of a loved one—is not diminished but rather is placed in a context that enables the patient to have a more positive outlook. Thus cognitive behavioral therapy for depression works similarly to a placebo. In both cases, the brain is operating from the top down: a belief, which occurs on a macro scale of neuronal networking, which will then trigger chemical changes in the brain, although understanding precisely how this happens is still a great puzzle in neuroscience.
Meanwhile, medication with drugs works differently, by directly modifying from the bottom up. It directly modifies the availability of neurotransmitters, bypassing any personalized neuronal circuitry. And that personalized circuitry, what we can equate with the personal mind, could be all-important. A big difference between cognitive behavioral therapy and direct drug intervention is that the probability of relapse in depression is greater with drugs. Presumably the plasticity changes in personalized neuronal networking shaped by routine cognitive behavioral therapy are more enduring and powerful than a general but essentially transient change in the chemical brain landscape, where drugs are directly manipulating the individual’s feelings and conscious state over a much shorter time.
Interestingly enough, in depressed individuals the brain region where new neurons are created from stem cells (the dentate gyrus) shrinks.49 If these new cells normally would have made it easier to form new connections, Sharon Begley has suggested, then this physical change in the brain might account for why depressed patients are not so receptive to new things, why they persist in seeing the world in an unchanging, unexciting, monochromatic way.50
In summary, the brains of a whole range of animals are astonishingly plastic, and the human brain exceptionally so. It is constantly adapting physically to repeated types of behaviors on a “use it or lose it” basis. Such endless neuronal updating is particularly marked in critical time frames during development but continues throughout life into older age. Yet plasticity doesn’t stop at the rehearsal of certain skills. The mere experience of living and interacting in a certain environment leaves its mark on the brain, which in turn leads to a unique, personalized brain circuitry (state of mind) that can ultimately lead to further physical changes in the brain and body. But that leaves us with some exasperating riddles. How can an insubstantial thought modify a physical state? And, conversely, how can a drug that affects chemicals that modify physical states modify insubstantial thoughts? In short, what is the neuroscientist’s story about the possible physical basis of the mind and consciousness?