Secrets of Human Speech Uncovered

A team of researchers at UC San Francisco has uncovered the neurological basis of speech motor control, the complex coordinated activity of tiny brain regions that controls our lips, jaw, tongue and larynx as we speak.

Described this week in the journal Nature, the work has potential implications for developing computer-brain interfaces for artificial speech communication and for the treatment of speech disorders. It also sheds light on an ability that is unique to humans among living creatures but poorly understood.

“Speaking is so fundamental to who we are as humans – nearly all of us learn to speak,” said senior author Edward Chang, MD, a neurosurgeon at the UCSF Epilepsy Center and a faculty member in the UCSF Center for Integrative Neuroscience. “But it’s probably the most complex motor activity we do.”

The complexity comes from the fact that spoken words require the coordinated efforts of numerous “articulators” in the vocal tract – the lips, tongue, jaw and larynx – but scientists have not understood how the movements of these distinct articulators are precisely coordinated in the brain.

To understand how speech articulation works, Chang and his colleagues recorded electrical activity directly from the brains of three people undergoing brain surgery at UCSF, and used this information to determine the spatial organization of the “speech sensorimotor cortex,” which controls the lips, tongue, jaw, larynx as a person speaks. This gave them a map of which parts of the brain control which parts of the vocal tract.

They then applied a sophisticated new method called “state-space” analysis to observe the complex spatial and temporal patterns of neural activity in the speech sensorimotor cortex that play out as someone speaks. This revealed a surprising sophistication in how the brain’s speech sensorimotor cortex works.

They found that this cortical area has a hierarchical and cyclical structure that exerts a split-second, symphony-like control over the tongue, jaw, larynx and lips.

“These properties may reflect cortical strategies to greatly simplify the complex coordination of articulators in fluent speech,” said Kristofer Bouchard, PhD, a postdoctoral fellow in the Chang lab who was the first author on the paper.

In the same way that a symphony relies upon all the players to coordinate their plucks, beats or blows to make music, speaking demands well-timed action of several various brain regions within the speech sensorimotor cortex.

Brain Mapping in Epilepsy Surgery

The patients involved in the study were all at UCSF undergoing surgery for severe, untreatable epilepsy. Brain surgery is a powerful way to halt epilepsy in its tracks, potentially completely stopping seizures overnight, and its success is directly related to the accuracy with which a medical team can map the brain, identifying the exact pieces of tissue responsible for an individual’s seizures and removing them.

The UCSF Comprehensive Epilepsy Center is a leader in the use of advanced intracranial monitoring to map out elusive seizure-causing brain regions. The mapping is done by surgically implanting an electrode array under the skull on the brain’s outer surface or cortex and recording the brain’s activity in order to pinpoint the parts of the brain responsible for disabling seizures. In a second surgery a few weeks later, the electrodes are removed and the unhealthy brain tissue that causes the seizures is removed.

This setting also permits a rare opportunity to ask basic questions about how the human brain works, such as how it controls speaking. The neurological basis of speech motor control has remained unknown until now because scientists cannot study speech mechanisms in animals and because non-invasive imaging methods lack the ability to resolve the very rapid time course of articulator movements, which change in hundredths of seconds.

But surgical brain mapping can record neural activity directly and faster than other noninvasive methods, showing changes in electrical activity on the order of a few milliseconds.

Prior to this work, the majority of what scientists knew about this brain region was based on studies from the 1940’s, which used electrical stimulation of single spots on the brain, causing a twitch in muscles of the face or throat. This approach using focal stimulation, however, could never evoke a meaningful speech sound. 

Chang and colleagues used an entirely different approach to studying the brain activity during natural speaking brain using the implanted electrodes arrays. The patients read from a list of English syllables – like bah, dee, goo. The researchers recorded the electrical activity within their speech-motor cortex and showed how distinct brain patterning accounts for different vowels and consonants in our speech.

“Even though we used English, we found the key patterns observed were ones that linguists have observed in languages around the world – perhaps suggesting universal principles for speaking across all cultures,” said Chang.

Males’ superior spatial ability likely is not an evolutionary adaptation

Males and females differ in a lot of traits (besides the obvious ones) and some evolutionary psychologists have proposed hypotheses to explain why. Some argue, for example, that males’ slight, but significant, superiority in spatial navigation over females – a phenomenon demonstrated repeatedly in many species, including humans – is probably “adaptive,” meaning that over the course of evolutionary history the trait gave males an advantage that led them to have more offspring than their peers.

A new analysis published in The Quarterly Review of Biology found no support for this hypothesis. The researchers, led by University of Illinois psychology professor Justin Rhodes, looked at 35 studies that included data about the territorial ranges and spatial abilities of 11 species of animals: cuttlefish, deer mice, horses, humans, laboratory mice, meadow voles, pine voles, prairie voles, rats, rhesus macaques and talastuco-tucos (a type of burrowing rodent). Rhodes and his colleagues found that in eight out of 11 species, males demonstrated moderately superior spatial skills to their female counterparts, regardless of the size of their territories or the extent to which males ranged farther than females of the same species.

The findings lend support to an often-overlooked hypothesis, Rhodes said. The average superiority of males over females in spatial navigation may just be a “side effect” of testosterone, he said. (Previous studies have shown that women who take testosterone tend to see an improvement in their spatial navigation skills, he said.)

The analysis adds a new dimension to an ongoing debate about the evolutionary significance of some baffling human traits. Rhodes and his colleagues object to “creation stories” that seek to explain sexual phenomena like the female orgasm, rape or menopause by hypothesizing that they evolved because they provided an evolutionary advantage. Some evolutionary psychologists describe rape, for example, as an alternate mating strategy for males who otherwise are reproductively unsuccessful. Others say menopause evolved in women to enhance the survival of their genes by increasing the time spent nurturing their grandchildren. Some of these hypotheses seem intuitive, Rhodes said. “But these stories generally are not testable.”

Researchers tend to overlook the fact that many physical and behavioral traits arise as a consequence of random events, or are simply side effects of other changes that offer real evolutionary advantages, he said.

“For example, women have nipples because it’s an adaptation; it promotes the survival of their offspring,” Rhodes said. “Men get it because it doesn’t harm them. So if we see something that’s advantageous for one sex, the other sex will get it because it’s inheriting the same genes – unless it’s bad for that sex.”

Similarly, scientists who claim that the different spatial skills in men and women are adaptive must explain why women failed to inherit the superior spatial skills of their navigationally enhanced fathers, Rhodes said.

“The only way you will get a sex difference (in an adaptive trait) is where a trait is good for one sex and bad for the other,” he said. “But how is navigation bad for women? This is a flaw in the logic.”

“When people hear arguments made or stories told, particularly about human behaviors being products of adaptation, I think they should ask the question: ‘Where is the evidence?’ ” Rhodes said.

Engineering control theory helps create dynamic brain models

Models of the human brain, patterned on engineering control theory, may some day help researchers control such neurological diseases as epilepsy, Parkinson’s and migraines, according to a Penn State researcher who is using mathematical models of neuron networks from which more complex brain models emerge.

"The dual concepts of observability and controlability have been considered one of the most important developments in mathematics of the 20th century," said Steven J. Schiff, the Brush Chair Professor of Engineering and director of the Penn State Center for Neural Engineering. "Observability and controlability theorems essentially state that if you can observe and reconstruct a system’s variables, you may be able to optimally control it. Incredibly, these theoretical concepts have been largely absent in the observation and control of complex biological systems."

Those engineering concepts were originally designed for simple linear phenomena, but were later revised to apply to non-linear systems. Such things as robotic navigation, automated aircraft landings, climate models and the human brain all require non-linear models and methods.

"If you want to observe anything that is at all complicated — having more than one part — in nature, you typically only observe one of the parts or a small subset of the many parts," said Schiff, who is also professor of neurosurgery, engineering science and mechanics, and physics, and a faculty member of the Huck Institutes of the Life Sciences. "The best way of doing that is make a model. Not a replica, but a mathematical representation that uses strategies to reconstruct from measurements of one part to the many that we cannot observe."

This type of model-based observability makes it possible today to create weather predictions of unprecedented accuracy and to automatically land an airliner without pilot intervention.

"Brains are much harder than the weather," said Schiff. "In comparison, the weather is a breeze."

There are seven equations that govern weather, but the number of equations for the brain is uncountable, according to Schiff. One of the problems with modeling the brain is that neural networks in the brain are not connected from neighbor to neighbor. Too many pathways exist.

"We make and we have been making models of the brain’s networks for 60 years," Schiff said at the recent annual meeting of the American Association for the Advancement of Science in Boston. “We do that for small pieces of the brain. How retina takes in an image and how the brain decodes that image, or how we generate simple movements are examples of how we try now to embody the equations of motion of those limited pieces. But we never used the control engineer’s trick of fusing those models with our measurements from the brain. This is the key — a good model will synchronize with the system it is coupled to.”

(Image: Photograph by Anne Keiser, National Geographic; model by Yeorgos Lampathakis)

Momentum builds in quest to find cure for childhood brain disease

Rasmussen Encephalitis strikes healthy kids; only known treatment removing half the brain.

How do you find a cure for a devastating pediatric brain disease so rare that it can take decades to build a meaningful research base?

In 2010, the parents of a patient created the Rasmussen Encephalitis (RE) Children’s Project to help solve this problem. In a short amount of time, the foundation has raised funds to establish a consortium of top researchers, build a collection of samples of the disease from around the world and support projects to study the disease tissue and search for genetic links. The goal is to find a cure.

Researchers at the David Geffen School of Medicine at UCLA have played a vital role in the ongoing research, and the foundation recently provided a second round of funding to continue their work. The gift of $125,000 builds on the organization’s donation of $111,000 made in 2011. 

"We are still in the early stages of research, but our momentum is building," said Seth H. Wohlberg, founder of the RE Children’s Project, and father of Grace, 15, who was stricken by the disease when she was 10 years old. "One of our key accomplishments has been to create an international system so that we can coordinate and transfer RE brain tissue and DNA material from the patients and parents. Collecting these samples is vital to advancing the research."

With the additional funding, UCLA researchers will apply cutting-edge DNA sequencing technology to determine whether a virus, or some other infectious agent, causes RE. They also plan to develop an animal model of the disease using cells obtained from the RE samples. 

The researchers include Dr. Gary Mathern, professor of pediatric neurosurgery and director of the UCLA Pediatric Epilepsy Program at Mattel Children’s Hospital; Carol Kruse, professor of neurosurgery; and Geoffrey Owens, visiting assistant researcher in neurosurgery.

"I am grateful to collaborate with a devoted father who has taken on the enormous task of advancing research for RE," said Mathern. "Thanks to his leadership, we now have the network to collect the tissue and DNA needed to study the brain, immunologic cells and genetics to unlock what causes this disease and develop new treatments or a cure. The RE Children’s Project has truly helped accelerate our research, bringing new information and resources that could have taken 10 more years to develop to the forefront today."

Rasmussen Encephalitis is a neurological disease that causes intractable seizures, cognitive deficits and paralysis of half of the body.  It is very rare and only a few hundred cases have been reported worldwide. RE typically affects previously normal children between the ages of two and ten years old. The disease process can run its course over a one to two year period during which time one half of the body is rendered useless and epileptic seizures continue unabated. 

An unusual feature of the disease is that it is usually confined to one hemisphere of the brain and is resistant to standard anti-seizure medicines. Currently the only known “cure” is radical- the surgical removal or disconnection of the affected side of the brain known as a hemispherectomy.

In the summer of 2008, the Wohlberg’s 10-year-old daughter Grace started to experience epileptic seizures. After months of testing, her parents learned that she had the extremely rare neurological disorder. Grace underwent an initial hemispherectomy surgery in February 2009. However, her seizures recurred so her parents then brought Grace to UCLA to complete the hemispherectomy which was performed by Mathern in March 2010. 

Today, Grace attends high school with the assistance of a full-time aide. While the surgery has stopped the seizures, Grace faces lifelong disabilities including partial blindness, cognitive issues and learning how to walk again. She is also active in helping her father promote the RE Children’s Project.

"It’s really supportive to let people know our story," said Grace. "Every year, my dad does a fundraiser and a lot of people come out to support it. It’s fun to be there and see all the people who care and want to help."

(Image: Wikimedia Commons)

It’s Not Just Amyloid: White Matter Hyperintensities and Alzheimer’s Disease

New findings by Columbia researchers suggest that along with amyloid deposits, white matter hyperintensities (WMHs) may be a second necessary factor for the development of Alzheimer’s disease.

Most current approaches to Alzheimer’s disease focus on the accumulation of amyloid plaque in the brain. The researchers at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, led by Adam M. Brickman, PhD, assistant professor of neuropsychology, examined the additional contribution of small-vessel cerebrovascular disease, which they visualized as white matter hyperintensities (WMHs).

The study included 20 subjects with clinically defined Alzheimer’s disease, 59 subjects with mild cognitive impairment, and 21 normal control subjects. Using data from the Alzheimer’s Disease Neuroimaging Initiative public database, the researchers found that amyloid and WHMs were equally associated with an Alzheimer’s diagnosis. Amyloid and WMHs were also equally predictive of which subjects with mildcognitive impairment would go on to develop Alzheimer’s. Among those with significant amyloid, WMHs were more prevalent in those with Alzheimer’s than in normal control subjects.

Because the risk factors for WMHs—which are mainly vascular—can be controlled, the findings suggest potential ways to prevent the development of Alzheimer’s in those with amyloid deposits.

“White Matter Hyperintensities and Cerebral Amyloidosis” was published online in JAMA Neurology.

New study shows how seals sleep with only half their brain at a time

A new study led by an international team of biologists has identified some of the brain chemicals that allow seals to sleep with half of their brain at a time.

The study was published this month in the Journal of Neuroscience and was headed by scientists at UCLA and the University of Toronto. It identified the chemical cues that allow the seal brain to remain half awake and asleep. Findings from this study may explain the biological mechanisms that enable the brain to remain alert during waking hours and go off-line during sleep.

“Seals do something biologically amazing — they sleep with half their brain at a time. The left side of their brain can sleep while the right side stays awake. Seals sleep this way while they’re in water, but they sleep like humans while on land. Our research may explain how this unique biological phenomenon happens” said Professor John Peever of the University of Toronto.

The study’s first author, University of Toronto PhD student Jennifer Lapierre, made this discovery by measuring how different chemicals change in the sleeping and waking sides of the brain. She found that acetylcholine – an important brain chemical – was at low levels on the sleeping side of the brain but at high levels on the waking side. This finding suggests that acetylcholine may drive brain alertness on the side that is awake.

But, the study also showed that another important brain chemical – serotonin – was present at the equal levels on both sides of the brain whether the seals were awake or asleep. This was a surprising finding because scientist long thought that serotonin was a chemical that causes brain arousal.

These findings have possible human health implications because “about 40% of North Americans suffer from sleep problems and understanding which brain chemicals function to keep us awake or asleep is a major scientific advance. It could help solve the mystery of how and why we sleep” says the study’s senior author Jerome Siegel of UCLA’s Brain Research Institute.

(Image: AFP)

Researchers develop tool for reading the minds of mice

If you want to read a mouse’s mind, it takes some fluorescent protein and a tiny microscope implanted in the rodent’s head.

Stanford scientists have demonstrated a technique for observing hundreds of neurons firing in the brain of a live mouse, in real time, and have linked that activity to long-term information storage. The unprecedented work could provide a useful tool for studying new therapies for neurodegenerative diseases such as Alzheimer’s.

The researchers first used a gene therapy approach to cause the mouse’s neurons to express a green fluorescent protein that was engineered to be sensitive to the presence of calcium ions. When a neuron fires, the cell naturally floods with calcium ions. Calcium stimulates the protein, causing the entire cell to fluoresce bright green.

A tiny microscope implanted just above the mouse’s hippocampus – a part of the brain that is critical for spatial and episodic memory – captures the light of roughly 700 neurons. The microscope is connected to a camera chip, which sends a digital version of the image to a computer screen.

The computer then displays near real-time video of the mouse’s brain activity as a mouse runs around a small enclosure, which the researchers call an arena.

The neuronal firings look like tiny green fireworks, randomly bursting against a black background, but the scientists have deciphered clear patterns in the chaos.

"We can literally figure out where the mouse is in the arena by looking at these lights," said Mark Schnitzer, an associate professor of biology and of applied physics and the senior author on the paper, recently published in the journal Nature Neuroscience.

When a mouse is scratching at the wall in a certain area of the arena, a specific neuron will fire and flash green. When the mouse scampers to a different area, the light from the first neuron fades and a new cell sparks up.

"The hippocampus is very sensitive to where the animal is in its environment, and different cells respond to different parts of the arena," Schnitzer said. "Imagine walking around your office. Some of the neurons in your hippocampus light up when you’re near your desk, and others fire when you’re near your chair. This is how your brain makes a representative map of a space."

The group has found that a mouse’s neurons fire in the same patterns even when a month has passed between experiments. “The ability to come back and observe the same cells is very important for studying progressive brain diseases,” Schnitzer said.

We know when we’re being lazy thinkers

New study shows that human thinkers are conscious cognitive misers

Are we intellectually lazy? Yes we are, but we do know when we take the easy way out, according to a new study by Wim De Neys and colleagues, from the CNRS in France. Contrary to what psychologists believe, we are aware that we occasionally answer easier questions rather than the more complex ones we were asked, and we are also less confident about our answers when we do. The work is published online in Springer’s journal Psychonomic Bulletin & Review.

Research to date on human thinking suggests that our judgment is often biased because we are intellectually lazy, or so-called cognitive misers. We intuitively substitute hard questions for easier ones. What is less clear is whether or not we realize that we are doing this and notice our mistake.

Using an adaptation of the standard ‘bat-and-ball’ problem, the researchers explored this phenomenon. The typical ‘bat-and-ball’ problem is as follows: a bat and ball together cost $1.10. The bat costs $1 more than the ball. How much does the ball cost? The intuitive answer that immediately springs to mind is 10 cents. However, the correct response is 5 cents.

The authors developed a control version of this problem, without the relative statement that triggers the substitution of a hard question for an easier one: A magazine and a banana together cost $2.90. The magazine costs $2. How much does the banana cost?A total of 248 French university students were asked to solve each version of the problem. Once they had written down their answers, they were asked to indicate how confident they were that their answer was correct.

Only 21 percent of the participants managed to solve the standard problem (bat/ball) correctly. In contrast, the control version (magazine/banana) was solved correctly by 98 percent of the participants. In addition, those who gave the wrong answer to the standard problem were much less confident of their answer to the standard problem than they were of their answer to the control version. In other words, they were not completely oblivious to the questionable nature of their wrong answer. The key reason seems to be that reasoners tend to minimize cognitive effort and stick to intuitive processing.

The authors comment: “Although we might be cognitive misers, we are not happy fools who blindly answer erroneous questions without realizing it.”

Indeed, although people appear to unconsciously substitute hard questions for easier ones, in reality, they are less foolish than psychologists might believe because they do know they are doing it.