Improving Babies’ Language Skills Before They’re Even Old Enough to Speak

In the first months of life, when babies begin to distinguish sounds that make up language from all the other sounds in the world, they can be trained to more effectively recognize which sounds “might” be language, accelerating the development of the brain maps which are critical to language acquisition and processing, according to new Rutgers research.

The study by April Benasich and colleagues of Rutgers University-Newark is published in the October 1 issue of the Journal of Neuroscience.

The researchers found that when 4-month-old babies learned to pay attention to increasingly complex non-language audio patterns and were rewarded for correctly shifting their eyes to a video reward when the sound changed slightly, their brain scans at 7 months old showed they were faster and more accurate at detecting other sounds important to language than babies who had not been exposed to the sound patterns. 

“Young babies are constantly scanning the environment to identify sounds that might be language,” says Benasich, who directs the Infancy Studies Laboratory at the University’s Center for Molecular and Behavioral Neuroscience. “This is one of their key jobs – as between 4 and 7 months of age they are setting up their pre-linguistic acoustic maps. We gently guided the babies’ brains to focus on the sensory inputs which are most meaningful to the formation of these maps.” 

Acoustic maps are pools of interconnected brain cells that an infant brain constructs to allow it to decode language both quickly and automatically – and well-formed maps allow faster and more accurate processing of language, a function that is critical to optimal cognitive functioning. Benasich says babies of this particular age may be ideal for this kind of training.

“If you shape something while the baby is actually building it,” she says, “it allows each infant to build the best possible auditory network for his or her particular brain. This provides a stronger foundation for any language (or languages) the infant will be learning. Compare the baby’s reactions to language cues to an adult driving a car. You don’t think about specifics like stepping on the gas or using the turn signal. You just perform them. We want the babies’ recognition of any language-specific sounds they hear to be just that automatic.”

Benasich says she was able to accelerate and optimize the construction of babies’ acoustic maps, as compared to those of infants who either passively listened or received no training, by rewarding the babies with a brief colorful video when they responded to changes in the rapidly varying sound patterns. The sound changes could take just tens of milliseconds, and became more complex as the training progressed.

Looking for lasting improvement in language skills

“While playing this fun game we can convey to the baby, ‘Pay attention to this. This is important. Now pay attention to this. This is important,’” says Benasich, “This process helps the baby to focus tightly on sounds in the environment that ‘may’ have critical information about the language they are learning. Previous research has shown that accurate processing of these tens-of-milliseconds differences in infancy is highly predictive of the child’s language skills at 3, 4 and 5 years.”  

The experiment has the potential to provide lasting benefits. The EEG (electroencephalogram) scans showed the babies’ brains processed sound patterns with increasing efficiency at 7 months of age after six weekly training sessions. The research team will follow these infants through 18 months of age to see whether they retain and build upon these abilities with no further training. That outcome would suggest to Benasich that once the child’s earliest acoustic maps are formed in the most optimal way, the benefits will endure.  

Benasich says this training has the potential to advance the development of typically developing babies as well as children at higher risk for developmental language difficulties. For parents who think this might turn their babies into geniuses, the answer is – not necessarily.  Benasich compares the process of enhancing acoustic maps to some people’s wishes to be taller. “There’s a genetic range to how tall you become – perhaps you have the capacity to be 5’6” to 5’9”,” she explains. “If you get the right amounts and types of food, the right environment, the right exercise, you might get to 5’9” but you wouldn’t be 6 feet. The same principle applies here.”

Benasich says it’s very likely that one day parents at home will be able to use an interactive toy-like device – now under development – to mirror what she accomplished in the baby lab and maximize their babies’ potential. For the 8 to 15 percent of infants at highest risk for poor acoustic processing and subsequent delayed language, this baby-friendly behavioral intervention could have far-reaching implications and may offer the promise of improving or perhaps preventing language difficulties.

Memory loss associated with Alzheimer’s reversed for first time

Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.

In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.

Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.

While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”

The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.

Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.

“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well—the drug may have worked, a single “hole” may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

Bredesen’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:

(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.

The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.

Cognitive decline is a major concern of the aging population. Already, Alzheimer’s disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it’s estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease is on the rise—recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

(Image: Corbis)

Using the brain to forecast decisions

You’re waiting at a bus stop, expecting the bus to arrive any time. You watch the road. Nothing yet. A little later you start to pace. More time passes. “Maybe there is some problem”, you think. Finally, you give up and raise your arm and hail a taxi. Just as you pull away, you glimpse the bus gliding up. Did you have a choice to wait a bit longer? Or was giving up too soon the inevitable and predictable result of a chain of neural events?

In research published on 09/28/2014 in the journal Nature Neuroscience, scientists show that neural recordings can be used to forecast when spontaneous decisions will take place. “Experiments like this have been used to argue that free will is an illusion,” says Zachary Mainen, a neuroscientist at the Champalimaud Centre for the Unknown, in Lisbon, Portugal, who led the study, “but we think that interpretation is mistaken.”

The scientists used recordings of neurons in an area of the brain involved in planning movements to try to predict when a rat would give up waiting for a delayed tone. “We know they were not just responding to a stimulus, but spontaneously deciding when to give up, because the timing of their choice varied unpredictably from trial to trial” said Mainen. The researchers discovered that neurons in the premotor cortex could predict the animals’ actions more than one second in advance. According to Mainen, “This is remarkable because in similar experiments, humans report deciding when to move only around two tenths of a second before the movement.”

However, the scientists claim that this kind of predictive activity does not mean that the brain has decided. “Our data can be explained very well by a theory of decision-making known as an ‘integration-to-bound’ model” says Mainen. According to this theory, individual brain cells cast votes for or against a particular action, such as raising an arm. Circuits within the brain keep a tally of the votes in favor of each action and when a threshold is reached it is triggered. Critically, like individual voters in an election, individual neurons influence a decision but do not determine the outcome. Mainen explained: “Elections can be forecast by polling, and the more data available, the better the prediction, but these forecasts are never 100% accurate and being able to partly predict an election does not mean that its results are predetermined. In the same way, being able to use neural activity to predict a decision does not mean that a decision has already taken place.”

The scientists also described a second population of neurons whose activity is theorized to reflect the running tally of votes for a particular action. This activity, described as “ramping”, had previously been reported only in humans and other primates. According to Masayoshi Murakami, co-author of the paper, “we believe these data provide strong evidence that the brain is performing integration to a threshold, but there are still many unknowns.” Said Mainen, “what is the origin of the variability is a huge question. Until we understand that, we cannot say we understand how a decision works”.

Sleep twitches light up the brain

A University of Iowa study has found twitches made during sleep activate the brains of mammals differently than movements made while awake.

Researchers say the findings show twitches during rapid eye movement (REM) sleep comprise a different class of movement and provide further evidence that sleep twitches activate circuits throughout the developing brain. In this way, twitches teach newborns about their limbs and what they can do with them.

“Every time we move while awake, there is a mechanism in our brain that allows us to understand that it is we who made the movement,” says Alexandre Tiriac, a fifth-year graduate student in psychology at the UI and first author of the study, which appeared this month in the journal Current Biology. “But twitches seem to be different in that the brain is unaware that they are self-generated. And this difference between sleep and wake movements may be critical for how twitches, which are most frequent in early infancy, contribute to brain development.”

Mark Blumberg, a psychology professor at the UI and senior author of the study, says this latest discovery is further evidence that sleep twitches— whether in dogs, cats or humans—are connected to brain development, not dreams.

“Because twitches are so different from wake movements,” he says, “these data put another nail in the coffin of the ‘chasing rabbits’ interpretation of twitches.”

For this study, Blumberg, Tiriac and fellow graduate student Carlos Del Rio-Bermudez studied the brain activity of unanesthetized rats between 8 and 10 days of age. They measured the brain activity while the animals were awake and moving and again while the rats were in REM sleep and twitching.

What they discovered was puzzling, at first.

“We noticed there was a lot of brain activity during sleep movements but not when these animals were awake and moving,” Tiriac says.

The researchers theorized that sensations coming back from twitching limbs during REM sleep were being processed differently in the brain than awake movements because they lacked what is known as “corollary discharge.”

First introduced by researchers in 1950, corollary discharge is a split-second message sent to the brain that allows animals—including rats, crickets, humans and more—to recognize and filter out sensations generated from their own actions. This filtering of sensations is what allows animals to distinguish between sensations arising from their own movements and those from stimuli in the outside world.

So, when the UI researchers noticed an increase in brain activity while the newborn rats were twitching during REM sleep but not when the animals were awake and moving, they conducted several follow-up experiments to determine whether sleep twitching is a unique self-generated movement that is processed as if it lacks corollary discharge.

The experiments were consistent in supporting the idea that sensations arising from twitches are not filtered: And without the filtering provided by corollary discharge, the sensations generated by twitching limbs are free to activate the brain and teach the newborn brain about the structure and function of the limbs.

“If twitches were like wake movements, the signals arising from twitching limbs would be filtered out,” Blumberg says. “That they are not filtered out suggests again that twitches are special—perhaps special because they are needed to activate developing brain circuits.”

The UI researchers were initially surprised to find the filtering system functioning so early in development.

“But what surprised us even more,” Blumberg says, “was that corollary discharge appears to be suspended during sleep in association with twitching, a possibility that – to our knowledge – has never before been entertained.”

Modeling shockwaves through the brain

Since the start of the military conflicts in Iraq and Afghanistan, more than 300,000 soldiers have returned to the United States with traumatic brain injury (TBI) caused by exposure to bomb blasts — and in particular, exposure to improvised explosive devices, or IEDs. Symptoms of traumatic brain injury can range from the mild, such as lingering headaches and nausea, to more severe impairments in memory and cognition.

Since 2007, the U.S. Department of Defense has recognized the critical importance and complexity of this problem, and has made significant investments in traumatic brain injury research. Nevertheless, there remain many gaps in scientists’ understanding of the effects of blasts on the human brain; most new knowledge has come from experiments with animals.

Now MIT researchers have developed a scaling law that predicts a human’s risk of brain injury, based on previous studies of blasts’ effects on animal brains. The method may help the military develop more protective helmets, as well as aid clinicians in diagnosing traumatic brain injury — often referred to as the “invisible wounds” of battle.

“We’re really focusing on mild traumatic brain injury, where we know the least, but the problem is the largest,” says Raul Radovitzky, a professor of aeronautics and astronautics and associate director of the MIT Institute for Soldier Nanotechnologies (ISN). “It often remains undetected. And there’s wide consensus that this is clearly a big issue.”

While previous scaling laws predicted that humans’ brains would be more resilient to blasts than animals’, Radovitzky’s team found the opposite: that in fact, humans are much more vulnerable, as they have thinner skulls to protect much larger brains.

A group of ISN researchers led by Aurélie Jean, a postdoc in Radovitzky’s group, developed simulations of human, pig, and rat heads, and exposed each to blasts of different intensities. Their simulations predicted the effects of the blasts’ shockwaves as they propagated through the skulls and brains of each species. Based on the resulting differences in intracranial pressure, the team developed an equation, or scaling law, to estimate the risk of brain injury for each species.

“The great thing about doing this on the computer is that it allows you to reduce and possibly eventually eliminate animal experiments,” Radovitzky says.

The MIT team and co-author James Q. Zheng, chief scientist at the U.S. Army’s soldier protection and individual equipment program, detail their results this week in the Proceedings of the National Academy of Sciences.

Air (through the) head

A blast wave is the shockwave, or wall of compressed air, that rushes outward from the epicenter of an explosion. Aside from the physical fallout of shrapnel and other chemical elements, the blast wave alone can cause severe injuries to the lungs and brain. In the brain, a shockwave can slam through soft tissue, with potentially devastating effects.

In 2010, Radovitzky’s group, working in concert with the Defense and Veterans Brain Injury Center, a part of the U.S. military health system, developed a highly sophisticated, image-based computational model of the human head that illustrates the ways in which pressurized air moves through its soft tissues. With this model, the researchers showed how the energy from a blast wave can easily reach the brain through openings such as the eyes and sinuses — and also how covering the face with a mask can prevent such injuries. Since then, the team has developed similar models for pigs and rats, capturing the mechanical response of brain tissue to shockwaves.

In their current work, the researchers calculated the vulnerability of each species to brain injury by establishing a mathematical relationship between properties of the skull, brain, and surrounding flesh, and the propagation of incoming shockwaves. The group considered each brain structure’s volume, density, and celerity — how fast stress waves propagate through a tissue. They then simulated the brain’s response to blasts of different intensities.

“What the simulation allows you to do is take what happens outside, which is the same across species, and look at how strong was the effect of the blast inside the brain,” Jean says.

In general, they found that an animal’s skull and other fleshy structures act as a shield, blunting the effects of a blast wave: The thicker these structures are, the less vulnerable an animal is to injury. Compared with the more prominent skulls of rats and pigs, a human’s thinner skull increases the risk for traumatic brain injury.

Shifting the problem

This finding runs counter to previous theories, which held that an animal’s vulnerability to blasts depends on its overall mass, but which ignored the role of protective physical structures. According to these theories, humans, being more massive than pigs or rats, would be better protected against blast waves.

Radovitzky says this reasoning stems from studies of “blast lung” — blast-induced injuries such as tearing, hemorrhaging, and swelling of the lungs, where it was found that mass matters: The larger an animal is, the more resilient it may be to lung damage. Informed by such studies, the military has since developed bulletproof vests that have dramatically decreased the number of blast-induced lung injuries in recent years.

“There have essentially been no reported cases of blast lung in the last 10 years in Iraq or Afghanistan,” Radovitzky notes. “Now we’ve shifted that problem to traumatic brain injury.”

In collaboration with Army colleagues, Radovitzky and his group are performing basic research to help the Army develop helmets that better protect soldiers. To this end, the team is extending the simulation approach they used for blast to other types of threats.

His group is also collaborating with audiologists at Massachusetts General Hospital, where victims of the Boston Marathon bombing are being treated for ruptured eardrums.

“They have an exact map of where each victim was, relative to the blast,” Radovitzky says. “In principle, we could simulate the event, find out the level of exposure of each of those victims, put it in our scaling law, and we could estimate their risk of developing a traumatic brain injury that may not be detected in an MRI.” 

Joe Rosen, a professor of surgery at Dartmouth Medical School, sees the group’s scaling law as a promising window into identifying a long-sought mechanism for blast-induced traumatic brain injury. 

“Eighty percent of the injuries coming off the battlefield are blast-induced, and mild TBIs may not have any evidence of injury, but they end up the rest of their lives impaired,” says Rosen, who was not involved in the research. “Maybe we can realize they’re getting doses of these blasts, and that a cumulative dose is what causes [TBI], and before that point, we can pull them off the field. I think this work will be important, because it puts a stake in the ground so we can start making some progress.”