Chapter 7. Life-Span Development of the Brain and Behavior
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by Bob Holmes Dying cells may play only a small role in the brain decline that accompanies ageing. That is the suggestion from the first computer simulation of brain function that can solve intelligence tests almost as well as university undergraduates. The model promises to reveal how our brains and behaviour are affected by age, and might even offer a way of testing drugs that compensate for cognitive decline. Psychologists have known for many years that our ability to think through novel problems – our "fluid intelligence" – gradually declines with age. However, the reasons for this decline aren't clear, because many features of the brain change as we age: neurons die; connections become sparser between regions of the brain and between individual brain cells; and our mental representation of different concepts becomes less distinct, among other changes. So far, psychologists have been unable to tease apart these possible explanations for cognitive decline. Enter Chris Eliasmith, a theoretical neuroscientist at the University of Waterloo in Ontario, Canada, and his student Daniel Rasmussen. The pair used a computer to simulate the behaviour of about 35,000 individual brain cells wired together in a biologically realistic way. Just like a real brain, their model encoded information as a pattern of electrical activity in particular sets of cells. The researchers set up the system to solve a widely used intelligence test known as Raven's Progressive Matrices, which involves predicting what abstract symbol comes next in a sequence. © Copyright Reed Business Information Ltd.
By KRISTIN WARTMAN THE solution to one of America’s most vexing problems — our soaring rates of obesity and diet-related diseases — may have its roots in early childhood, and even in utero. Researchers at the Monell Chemical Senses Center, a nonprofit research organization in Philadelphia, have found that babies born to mothers who eat a diverse and varied diet while pregnant and breast-feeding are more open to a wide range of flavors. They’ve also found that babies who follow that diet after weaning carry those preferences into childhood and adulthood. Researchers believe that the taste preferences that develop at crucial periods in infancy have lasting effects for life. In fact, changing food preferences beyond toddlerhood appears to be extremely difficult. “What’s really interesting about children is, the preferences they form during the first years of life actually predict what they’ll eat later,” said Julie Mennella, a biopsychologist and researcher at the Monell Center. “Dietary patterns track from early to later childhood but once they are formed, once they get older, it’s really difficult to change — witness how hard it is to change the adult. You can, but it’s just harder. Where you start, is where you end up.” This may have profound implications for the future health of Americans. With some 70 percent of the United States population now overweight or obese and chronic diseases skyrocketing, many parents who are eating a diet high in processed, refined foods are feeding their babies as they feed themselves, and could be setting their children up for a lifetime of preferences for a narrow range of flavors. The Monell researchers have identified several sensitive periods for taste preference development. One is before three and a half months of age, which makes what the mother eats while pregnant and breast-feeding so important. “It’s our fundamental belief that during evolution, we as humans are exposed to flavors both in utero and via mother’s milk that are signals of things that will be in our diets as we grow up and learn about what flavors are acceptable based on those experiences,” said Gary Beauchamp, the director of the Monell Center. © 2013 The New York Times Company
Ewen Callaway Certain fears can be inherited through the generations, a provocative study of mice reports1. The authors suggest that a similar phenomenon could influence anxiety and addiction in humans. But some researchers are sceptical of the findings because a biological mechanism that explains the phenomenon has not been identified. According to convention, the genetic sequences contained in DNA are the only way to transmit biological information across generations. Random DNA mutations, when beneficial, enable organisms to adapt to changing conditions, but this process typically occurs slowly over many generations. Yet some studies have hinted that environmental factors can influence biology more rapidly through 'epigenetic' modifications, which alter the expression of genes, but not their actual nucleotide sequence. For instance, children who were conceived during a harsh wartime famine in the Netherlands in the 1940s are at increased risk of diabetes, heart disease and other conditions — possibly because of epigenetic alterations to genes involved in these diseases2. Yet although epigenetic modifications are known to be important for processes such as development and the inactivation of one copy of the X-chromsome in females, their role in the inheritance of behaviour is still controversial. Kerry Ressler, a neurobiologist and psychiatrist at Emory University in Atlanta, Georgia, and a co-author of the latest study, became interested in epigenetic inheritance after working with poor people living in inner cities, where cycles of drug addiction, neuropsychiatric illness and other problems often seem to recur in parents and their children. “There are a lot of anecdotes to suggest that there’s intergenerational transfer of risk, and that it’s hard to break that cycle,” he says. © 2013 Nature Publishing Group
by Jessica Griggs HAVING type 2 diabetes may mean you are already on the path to Alzheimer's. This startling claim comes from a study linking the two diseases more intimately than ever before. There is some good news: the same research also offers a way to reverse memory problems associated with diabetes – albeit in rats – which may hint at a new treatment for Alzheimer's. "Perhaps you should use Alzheimer's drugs at the diabetes stage to prevent cognitive impairment in the first place," says Ewan McNay from the University at Albany in New York. Alzheimer's cost the US $130 billion in 2011 alone. One of the biggest risk factors is having type 2 diabetes. This kind of diabetes occurs when liver, muscle and fat cells stop responding efficiently to insulin, the hormone that tells them to absorb glucose from the blood. The illness is usually triggered by eating too many sugary and high-fat foods that cause insulin to spike, desensitising cells to its presence. As well as causing obesity, insulin resistance can also lead to cognitive problems such as memory loss and confusion. In 2005, a study by Susanne de la Monte's group at Brown University in Providence, Rhode Island, identified a reason why people with type 2 diabetes had a higher risk of developing Alzheimer's. In this kind of dementia, the hippocampus, a part of the brain involved in learning and memory, seemed to be insensitive to insulin. Not only could your liver, muscle and fat cells be "diabetic" but so it seemed, could your brain. © Copyright Reed Business Information Ltd.
By Tanya Lewis 20 hours ago To understand the human brain, scientists must start small, and what better place than the mind of a worm? The roundworm Caenorhabditis elegans is one of biology's most widely studied organisms, and it's the first to have the complete wiring diagram, or connectome, of its nervous system mapped out. Knowing the structure of the animal's connectome will help explain its behavior, and could lead to insights about the brains of other organisms, scientists say. "You can't understand the brain without understanding the connectome," Scott Emmons, a molecular geneticist at Albert Einstein College of Medicine of Yeshiva University in New York, said in a talk earlier this month at the annual meeting of the Society for Neuroscience in San Diego. In 1963, South African biologist Sydney Brenner of the University of Cambridge decided to use C. elegans as a model organism for developmental biology. He chose the roundworm because it has a simple nervous system, it's easy to grow in a lab and its genetics are relatively straightforward. C. elegans was the first multicellular organism to have its genome sequenced, in 1998. Brenner knew that to understand how genes affect behavior, "you would have to know the structure of the nervous system," Emmons told LiveScience.
By Neuroskeptic Claims that children with autism have abnormal brain white matter connections may just reflect the fact that they move about more during their MRI scans. So say a team of Harvard and MIT neuroscientists, including Nancy “Voodoo Correlations” Kanwisher, in a new paper: Spurious group differences due to head motion in a diffusion MRI study. Essentially, the authors show how head movement during a diffusion tensor imaging (DTI) scan causes apparant differences in the integrity of white matter tracts, like these ones: In comparisons of two randomized groups of healthy children – in whom no white matter differences ought to appear – spurious effects were seen whenever one group moved more than the other: As for autism, the authors found that kids with autism moved more, on average, than controls, and that matching the two groups by motion reduced the magnitude of the group differences in white matter (though many remained significant). Technically, the motion-related differences manifested as increases in RD and reductions in FA; these were localized: The pathways that exhibited the most substantial motion-induced group differences in our data were the corpus callosum and the cingulum bundle. Perhaps this is related to their proximity to non-brain voxels (such as the ventricles) … deeper brain areas appear to be more affected than more superﬁcial ones, thus distance from the head coils may also be a factor. The good news is that there’s a simple fix: entering the motion parameters, extracted from the DTI data itself, as a covariate in the analysis. The authors show that this is extremely effective. The bad news is that most researchers don’t do this.
By James Gallagher Health and science reporter, BBC News Steroids given to help premature babies develop may also be slightly increasing the risk of mental health disorders, say researchers. The drugs are often given to pregnant mothers at risk of a premature birth to help the baby's lungs prepare for life outside the womb. The study, in the journal PLoS One, showed there was a higher risk of attention disorders at age eight. The charity Bliss said it reinforced the need for regular health checks. Being born too soon can lead to long-term health problems and the earlier the birth the greater the problems. One immediate issue is the baby's lungs being unprepared to breathe air. Steroids can help accelerate lung development. However, the study by researchers at Imperial College London and the University of Oulu in Finland showed the drugs may also be affecting the developing brain. They compared what happened to 37 premature children whose mother was injected with steroids with 185 premature children, of the same weight and gestational age, who were not exposed to the extra dose of steroid. When the children were followed to the age of eight, there was a higher incidence of attention deficit hyperactivity disorder. No difference could be detected at age 16, but this may have been due to the small size of the study. BBC © 2013
One afternoon in October 2005, neuroscientist James Fallon was looking at brain scans of serial killers. As part of a research project at UC Irvine, he was sifting through thousands of PET scans to find anatomical patterns in the brain that correlated with psychopathic tendencies in the real world. “I was looking at many scans, scans of murderers mixed in with schizophrenics, depressives and other, normal brains,” he says. “Out of serendipity, I was also doing a study on Alzheimer’s and as part of that, had brain scans from me and everyone in my family right on my desk.” “I got to the bottom of the stack, and saw this scan that was obviously pathological,” he says, noting that it showed low activity in certain areas of the frontal and temporal lobes linked to empathy, morality and self-control. Knowing that it belonged to a member of his family, Fallon checked his lab’s PET machine for an error (it was working perfectly fine) and then decided he simply had to break the blinding that prevented him from knowing whose brain was pictured. When he looked up the code, he was greeted by an unsettling revelation: the psychopathic brain pictured in the scan was his own. Many of us would hide this discovery and never tell a soul, out of fear or embarrassment of being labeled a psychopath. Perhaps because boldness and disinhibition are noted psychopathic tendencies, Fallon has gone all in towards the opposite direction, telling the world about his finding in a TED Talk, an NPR interview and now a new book published last month, The Psychopath Inside. In it, Fallon seeks to reconcile how he—a happily married family man—could demonstrate the same anatomical patterns that marked the minds of serial killers. “I’ve never killed anybody, or raped anyone,” he says. “So the first thing I thought was that maybe my hypothesis was wrong, and that these brain areas are not reflective of psychopathy or murderous behavior.”
By Helen Briggs BBC News A condition where people experience a mixing of the senses, such as tasting words, has been linked with autism. Research suggests synaesthesia is nearly three times as common in adults with autism spectrum disorder than in the general population. The two conditions may share common features such as unusual wiring of the brain, say UK scientists. The study helps understanding of how people with autism experience life, says the National Autistic Society. Synaesthesia is a condition where one sense automatically triggers another. Some people experience tastes when they read or hear words, some perceive numbers as shapes, others see colours when they hear music. People with synaesthesia might say: "The letter q is dark brown," or: "The word 'hello' tastes like coffee," for example. Following anecdotal evidence of links between synaesthesia and Asperger's syndrome, researchers at the Autism Research Centre at Cambridge University set out to test the idea. More than 200 study participants - 164 adults diagnosed with high-functioning autism or Asperger's syndrome, and 97 adults without autism - were asked to fill in questionnaires to measure synaesthesia and autism traits. The study found one in five adults with autism spectrum conditions - a range of related developmental disorders, including autism and Asperger's syndrome - had synaesthesia compared with about 7% of people with no signs of the disorders. Prof Simon Baron-Cohen, who led the research, told BBC News: "Synaesthesia involves a mixing of the senses and it's a very subjective private experience, so the only way we know it's happening is if you ask people to report on their experiences. BBC © 2013
Link ID: 18948 - Posted: 11.20.2013
Dara Mohammadi At the beginning of next year, Clive Holmes will attempt to do something remarkable. But you'd never guess it from meeting this mild-mannered psychiatrist with a hint of a Midlands accent. In fact, you could be sitting in his office in the Memory Assessment and Research Centre at Southampton University and be unaware that he was up to anything out of the ordinary – save for a small whiteboard behind his desk, on which he's drawn a few amorphous blobs and squiggles. These, he'll assure you, are components of the immune system. As a psychiatrist, he's had little formal training in immunology, but has spent much of his time of late trying to figure how immune cells in the body communicate with others in the brain. These signals into the brain, he thinks, accelerate the speed at which neurons – nerve cells in the brain – are killed in late-stage Alzheimer's disease and at the beginning of next year he hopes to test the idea that blocking these signals can stop or slow down disease progression. If he shows any dent on disease progression, he would be the first to do so. Despite the billions of pounds pumped into finding a cure over the last 30 years, there are currently no treatments or prevention strategies. "Drug development has been largely focused on amyloid beta," says Holmes, referring to the protein deposits that are characteristically seen in the brains of people with Alzheimer's and are thought to be toxic to neurons, "but we're seeing that even if you remove amyloid, it seems to make no difference to disease progression." © 2013 Guardian News and Media Limited
Link ID: 18944 - Posted: 11.19.2013
by Jessica Griggs, San Diego Pregnant women may pass on the effects of stress to their fetus by way of bacterial changes in their vagina, suggests a study in mice. It may affect how well their baby's brain is equipped to deal with stress in adulthood. The bacteria in our body outnumber our own cells by about 10 to 1, with most of them found in our gut. Over the last few years, it has become clear that the bacterial ecosystem in our body – our microbiome – is essential for developing and maintaining a healthy immune system. Our gut bugs also help to prevent germs from invading our bodies, and help to absorb nutrients from food. A baby gets its first major dose of bacteria in life as it passes through its mother's birth canal. En route, the baby ingests the mother's vaginal microbes, which begin to colonise the newborn's gut. Chris Howerton, then at the University of Pennsylvania in Philadelphia, and his colleagues wanted to know if this initial population of bacteria is important in shaping a baby's neurological development, and whether that population is influenced by stress during pregnancy. The first step was to figure out what features of the mother's vaginal microbiome might be altered by stress, and then see if any of those changes were transmitted to the offspring's gut. © Copyright Reed Business Information Ltd
by Laura Sanders SAN DIEGO — Teenagers’ brains are wired to confront a threat instead of retreating, research presented November 10 at the annual Society for Neuroscience meeting suggests. The results may help explain why criminal activity peaks during adolescence. Kristina Caudle of Weill Cornell Medical College in New York City and colleagues tested the impulse control of 83 people between ages 6 and 29. In the experiment, participants were asked to press a button when a photo of a happy face quickly flashed before them. They were told not to press the button when a face had a threatening expression. When confronted with the threatening faces, people between the ages of 13 and 17 were more likely to impulsively push the button than children and adults were, the team found. Brain scans revealed that activity in an area called the orbital frontal cortex peaked in teens when they successfully avoided pushing the button, suggesting that this region curbs the impulse to react, Caudle said. It’s not clear why children don’t have the same impulsive reaction to threatening faces. More studies could determine how the relevant brain systems grow and change, Caudle said. © Society for Science & the Public 2000 - 2013.
by Laura Sanders SAN DIEGO — When stress during pregnancy disrupts a growing baby’s brain, blame bacteria. Microbes take part in an elaborate chain reaction, a new study finds: First, stress changes the populations of bacteria dwelling in a pregnant mouse’s vagina; those changes then affect which bacteria colonize a newborn pup’s gut; and the altered gut bacteria change the newborn’s brain. The research, presented at the annual Society for Neuroscience meeting, may help explain how a stressful environment early in life can make a person more susceptible to disorders such as autism or schizophrenia. The finding also highlights the important and still mysterious ways that the bacteria living in bodies can influence the brain. “This is really fascinating and promising work,” said neuroscientist Cory Burghy of the University of Wisconsin–Madison. “I am excited to take a look at how these systems interact in humans,” she said. Stress during pregnancy dramatically shifts the mix of bacteria that dwell in the vagina, Christopher Howerton of the University of Pennsylvania reported November 11. The alarming odor of foxes, loud noise, physical restraints and other stressful situations during a mouse’s pregnancy changed the composition of its vaginal bacteria, he and his colleagues found. The population of helpful Lactobacillus bacteria, for instance, decreased after stress. And because newborn mouse pups populate their guts with bacteria dwelling in their mother’s birth canal, microbes from mom colonize the baby’s gut. Mice born to moms with lower levels of Lactobacillus in the vagina had lower levels of Lactobacillus in their guts soon after they were born, the team reported. © Society for Science & the Public 2000 - 2013
By Melissa Hogenboom Science reporter, BBC News Changes to specific cells in the retina could help diagnose and track the progression of Alzheimer's disease, scientists say. A team found genetically engineered mice with Alzheimer's lost thickness in this layer of eye cells. As the retina is a direct extension of the brain, they say the loss of retinal neurons could be related to the loss of brain cells in Alzheimer's. The findings were revealed at the US Society for Neuroscience conference. The team believes this work could one day lead to opticians being able to detect Alzheimer's in a regular eye check, if they had the right tools. Alterations in the same retinal cells could also help detect glaucoma - which causes blindness - and is now also viewed as a neurodegenerative disease similar to Alzheimer's, the researchers report. Scott Turner, director of the memory disorders programme at Georgetown University Medical Center, said: "The retina is an extension of the brain so it makes sense to see if the same pathologic processes found in an Alzheimer's brain are also found in the eye." Dr Turner and colleagues looked at the thickness of the retina in an area that had not previously been investigated. This included the inner nuclear layer and the retinal ganglion cell layer. They found that a loss of thickness occurred only in mice with Alzheimer's. The retinal ganglion cell layer had almost halved in size and the inner nuclear layer had decreased by more than a third. BBC © 2013
SAN DIEGO, CALIFORNIA—Why do teens—especially adolescent males—commit crimes more frequently than adults? One explanation may be that as a group, teenagers react more impulsively to threatening situations than do children or adults, likely because their brains have to work harder to reign in their behavior, a research team reported here yesterday at the Society for Neuroscience meeting. Whether it's driving too fast on a slick road or experimenting with drugs, teenagers have a reputation for courting danger that is often attributed to immaturity or poor decision-making. If immaturity or lack of judgment were the only problem, however, one would expect that children, whose brains are at an even earlier stage of development, would have an equal or greater penchant for risk-taking, says Kristina Caudle, a neuroscientist at the Weill Cornell Medical College in New York City who led the study. But younger children tend to be more cautious than teenagers, suggesting that there is something unique about adolescent brain development that lures them to danger, she says. It's hard to generalize about teenage impulsivity, because some adolescents clearly have more self-control than many adults, says principal investigator B. J. Casey, a neuroscientist. Still, a growing body of evidence suggests that, in general, teens specifically struggle to keep their cool in social situations, she says. Because many crimes committed during adolescence involve emotionally fraught social situations, such as conflict, Caudle and colleagues decided to test whether teens perform badly on a common impulsivity task when faced with social cues of threat. They recruited 83 people, ranging in age from 6 to 29, to perform a simple "Go/No-Go" task, in which they watched a series of faces making neutral or threatening facial expressions flicker past on a computer screen. Each time the participants saw a neutral face, they were instructed to hit a button. They were also told to hold back from pressing the button when they saw a threatening face. As the participants performed the task, the researchers monitored their brain activity with functional magnetic resonance imaging. © 2013 American Association for the Advancement of Science.
Babies born to women who exercised during pregnancy have enhanced brain development compared with babies born to moms who didn’t exercise while they were pregnant, a new Canadian study suggests. The babies of 10 women who did as little as 20 minutes of moderate exercise three times a week during pregnancy showed more advanced brain activity when they were tested at eight to 12 days old than the babies of eight women who did not exercise during pregnancy, reported University of Montreal researcher David Ellemberg and his colleagues at the Neuroscience 2013 conference in San Diego on Sunday. “We are optimistic that this will encourage women to change their health habits, given that the simple act of exercising during pregnancy could make a difference for their child's future,” Ellemberg said in a statement. The women in the study were randomly assigned to an exercise group or a sedentary group at the beginning of their second trimester. Those in the exercise group had to spend at least 20 minutes three times a week doing exercise intense enough to lead to at least a slight shortness of breath. After their babies were born, the researchers tested them by placing a cap of electrodes on the babies' heads and then playing novel sounds while they slept. They measured the electrical response of the babies' brains to see how well they could distinguish between different sounds. The researchers found that the babies in the exercise group produced signals associated with more mature brains. The researchers said they plan to test the children’s cognitive, motor and language development at age one to see if there are lasting effects. © CBC 2013
Keyword: Development of the Brain
Link ID: 18916 - Posted: 11.12.2013
Jessica Wright A new test of mouse intelligence closely mimics the types of assays used with people and detects a subtle learning deficit reminiscent of one seen in teenagers with autism, according to findings presented Saturday at the2013 Society for Neuroscience annual meeting in San Diego. Another behavioral test, also presented Saturday, uncovers an unexpected social deficit in an autism mouse model. The test in the first study could be used to screen for drugs that improve cognitive deficits associated with autism, says Jill Silverman, a postdoctoral associate in Jacqueline Crawley’s lab at the University of California, Davis MIND Institute. Silverman presented the work at a poster session. To measure learning in mice, researchers typically place them in a water maze, or see if they learn to anticipate an electric shock. “But you don’t shock people or put them in a pool to swim,” notes Silverman. Silverman instead trained the mice in a human activity: using a touchscreen. In the most basic form of the test, the mice see two graphic images (such as a plane and a spider) and learn that they get “yummy” strawberry milkshake if they touch the spider, Silverman says. (She says she uses milkshakes because the mice work hard for them, even if they aren’t hungry.) BTBR mice, which have many autism-like features, learn to go for the spider just as readily as control mice do. So Silverman made things much more complicated. The complex test follows the logic of transitive properties. For example, if John is taller than Anne and Anne is taller than Jane, we are able to infer that John is taller than Jane. © Copyright 2013 Simons Foundation
Sarah DeWeerdt Parts of the brain that process vision and control movements are poorly connected in children with autism, according to results presented Saturday at the 2013 Society for Neuroscience annual meeting in San Diego. In addition to the social deficits that are a core feature of autism, children with the disorder often have clumsy movements. Studies have also found that people with autism have trouble imitating others. The new study uncovers patterns of brain activity suggesting all three of these deficits may be related. The researchers used functional magnetic resonance imaging (fMRI) to measure resting-state activation — brain activity that occurs while individuals are resting quietly in the scanner — in 45 children with autism and 45 controls. Parts of the brain that tend to activate and deactivate together during this procedure are said to be functionally connected. The researchers zeroed in on two sets of brain structures involved in motor activity. One of them, the ventral motor component, includes parts of the cortex, the thalamus and lobule 6 of the cerebellum. They also focused on three areas of the brain involved in visual processing. The most interesting is a region at the back of the brain responsible for complex interpretation of visual information. © Copyright 2013 Simons Foundation
by Laura Sanders Neonatal intensive care units are crammed full of life-saving equipment and people. The technology that fills these bustling hubs is responsible for saving the lives of fragile young babies. That technology is also responsible for quite a bit of noise. In the NICU, monitors beep, incubators whir and nurses, doctors and family members talk. This racket isn’t just annoying: NICU noise often exceeds acceptable levels set by the American Academy of Pediatrics, a 2009 analysis found. To dampen the din, many hospitals are shifting away from open wards to private rooms for preemies. Sounds like a no-brainer, right? Fragile babies get their own sanctuaries where they can recover and grow in peace. But in a surprising twist, a new study finds that this peace and quiet may actually be bad for some babies. Well aware of the noise problem in the NICU ward, Roberta Pineda of Washington University School of Medicine in St. Louis and colleagues went into their study of 136 preterm babies expecting to see benefits in babies who stayed in private rooms. Instead, the researchers found the exact opposite. By the time they left the hospital, babies who stayed in private rooms had less mature brains than those who stayed in an open ward. And two years later, babies who had stayed in private rooms performed worse on language tests. The results were not what the team expected. “It was extremely surprising,” Pineda told me. The researchers believe that the noise abatement effort made things too quiet for these babies. As distressing data from Romanian orphanages highlights, babies need stimulation to thrive. Children who grew up essentially staring at white walls with little contact from caregivers develop serious brain and behavioral problems, heartbreaking results from the Bucharest Early Intervention Project show. Hearing language early in life, even before birth, might be a crucial step in learning to talk later. And babies tucked away in private rooms might be missing out on some good stimulation. © Society for Science & the Public 2000 - 2013
Kenneth S. Kosik Twenty years of research and more than US$1-billion worth of clinical trials have failed to yield an effective drug treatment for Alzheimer's disease. Most neuroscientists, clinicians and drug developers now agree that people at risk of the condition will probably need to receive medication before the onset of any cognitive symptoms. Yet a major stumbling block for early intervention is the absence of tools that can reveal the first expression of the insidious disease. So far, researchers have tended to focus on macroscopic changes associated with the disease, such as the build up of insoluble plaques of protein in certain areas of the brain, or on individual genes or molecular pathways that seem to be involved in disease progression. I contend that detecting the first disruptions to brain circuitry, and tracking the anatomical and physiological damage underlying the steady cognitive decline that is symptomatic of Alzheimer's, will require tools that operate at the 'mesoscopic' scale: techniques that probe the activity of thousands or millions of networked neurons. Although such tools are yet to be realized, several existing technologies indicate that they are within reach. Charted territory All the current approaches that are used to diagnose Alzheimer's are crude and unreliable. Take the classic biomarkers of the disease: a build up of plaques of the protein β-amyloid in a person's cerebral cortex, for instance, or elevated levels of the tau protein and dampened levels of β-amyloid in their cerebrospinal fluid. Although such markers are predictive of the disease, the interval between their appearance and the onset of cognitive problems is hugely variable, ranging from months to decades. © 2013 Nature Publishing Group