Crossroads Newsletter August 2004

White Noise Delays Auditory Organization In Brain

University of California, San Francisco
2003-04-18

Exposure to continuous white noise sabotages the development of the auditory region of the brain, which may ultimately impair hearing and language acquisition, according to researchers from the University of California, San Francisco.

According to the scientists, the young rats used in their study were exposed to constant white noise that is relevant to the increasing, random noise encountered by humans in today's environment. They theorize that their findings could aid in explaining the increase in language-impairment developmental disorders over the last few decades.

The researchers, which included Howard Hughes Medical Institute medical student fellow Edward Chang and otolaryngology professor Michael Merzenich at the University of California at San Francisco, published their findings in the April 18, 2003, issue of the journal Science.

"While the rat is not a perfect model of human auditory development, it does allow us to investigate the fundamental role of early sensory experience in mammalian auditory development," said Chang. "For example, we do know that exposing infant rats to specific sound stimuli can induce long-standing representational changes in the brain. Other researchers have shown that there are striking parallels in humans and other animals."

Although past experiments have demonstrated the important effects that visual experience can have on brain development in animals and humans, Chang said very few comparable experiments have been reported that explore the effects of patterned early auditory experience on cortical development.

"Auditory experience is clearly an important factor in humans for learning language," he said. "We learn to speak and read through our sensitivities to speech sounds that are heard during early life."

Thus, Chang and Merzenich designed experiments in which they reared rat pups in an environment of moderate continuous background noise, which, while not injurious to their peripheral hearing, was loud enough to mask normal environmental sounds. They then used electrophysiological methods to gauge the organization of the auditory cortex in those animals, as well as in control animals raised in a normal auditory environment.

The mapping technique consisted of recording the responses of auditory cortex neurons to a variety of sounds presented to anesthetized animals.

"We knew from previous work that the rat auditory cortex normally undergoes a very dramatic, specific, and progressive development," said Chang. "During the first month of life, it becomes much more specific and well tuned to different frequencies and temporal patterns of sound. The brains of animals reared in noise, however, did not achieve the basic benchmarks of auditory development until they were three or four times older than normal animals," he said.

Additional tests on the maturing noise-reared rats showed that their auditory regions continued to be plastic -- they continued to reorganize their neural circuitry in response to exposure to sound stimuli alone, long after the brains of normal rats had ceased rewiring. This suggested that a "critical period" for exposure-based plasticity in the brain had been extended.

They performed supplementary long-term experiments that showed that although auditory development was delayed in the noise-exposed rats, it did mature to normal adult levels once the animals were removed from the noisy environment. And furthermore, they observed those plasticity effects consolidated during the extended critical period persisted into the future, suggesting that this exposure were indeed "critical." Chang summarized, "it's like the brain is waiting for some clearly patterned sounds in order to continue its development. And when it finally gets them, it is heavily influenced them, even when the animal is physically older."

Chang said that the findings "suggest that there are two sides to the coin. "On the negative side, these findings suggest that noise can have devastating effects on the rate of development of the brain. They emphasize the importance that children, especially those at risk, be exposed to salient features in speech sounds in order for their auditory development to be normal. On the positive side, our findings may mean that the time frame may be longer in which treatment of such children will allow them to catch up." According to Chang, the need for exposure to structured sounds underscores the importance of special therapy for children with disorders that might affect auditory processing.

"There are many linkages between neurons in the auditory system from the cochlea to the cortex where information has to be passed along," he said. "And in addition to environmental noise, a number of acquired or inherited disorders could potentially degrade the signal at any of these points, masking the sensory input. From these findings, we theorize that disorders, for example, such as focal epilepsies or defects in myelination, might affect the fidelity of this signal, disrupting normal development of the auditory cortex. A combination of external and internal elements would be highly detrimental"

Chang's future studies will address whether humans with developmental disorders have higher levels of noise in their auditory systems. Such studies, he said, could lead to diagnostic and predictive tests.

"If we knew that a child had a susceptibility to noise, we could intervene to enrich the child's acoustic experience to foster more normal auditory and language development," said Chang.

Georgetown Researchers Make Important Discovery About Areas Of Brain Used In Hearing

Georgetown University
2001-04-27

WASHINGTON, D.C. — Two specialized areas of the brain are responsible for certain auditory functions, a team of Georgetown researchers led by Josef P. Rauschecker, PhD, professor of physiology and biophysics, has found. This discovery has important implications for scientists seeking to learn more about how humans hear, a process that is still poorly understood. The findings were published in the journal Science.

Rauschecker’s research, conducted over the past two and a half years, involved four rhesus monkeys, whose brain structure is similar enough to that of humans to draw valid comparisons. He and his colleagues performed microelectrode recordings on the monkeys while they listened to rhesus-specific communication sounds coming from different locations.

It was known previously that virtually all higher hearing functions take place in the auditory cortex, which is located on either side of the head, above the ears, and receives information from the inner ear and brainstem. However, the Georgetown scientists were able to define certain specialized areas within the auditory cortex that the monkeys used specifically to identify the type and location of sound—areas that up until now had not been pinpointed.

“This is an interesting discovery for not only basic scientists, but for anyone who studies hearing and brain function,” Rauschecker said. “We hope that our findings can be more widely used to help solve neurological problems that are still not understood.”

Ongoing studies will examine functional specialization directly in the auditory cortex of the human brain using functional magnetic resonance imaging (fMRI). This technology allows researchers to observe brain activity in response to certain types of speech sounds and music. “Single-neuron studies in animals remain indispensable nevertheless,” Rauschecker says, “if one really wants to understand in sufficient detail how our brain processes such highly complex sounds.”

DYSLEXIA

Dyslexia May Involve Both Vision And Hearing

Wake Forest University Baptist Medical Center
2003-11-10

WINSTON-SALEM, N.C. – Dyslexia may stem from how the brain processes sight and sound together – rather than simply a problem "decoding" the written word – reported researchers from Wake Forest University Baptist Medical Center.

"For the first time, there is evidence that dyslexia is a multi-sensory disorder," says Mark Wallace, Ph.D., associate professor of neurobiology and anatomy. "It isn't solely a problem with visual processing or with language. This is a novel way of looking at the disorder."

Wallace said the finding could lead to a simple test for early diagnosis – even before school age – and better methods for teaching people with reading disabilities.

"Until now, experts have thought that dyslexia was either a visual processing problem or a problem involving language areas of the brain," said Wallace. "But our study suggests that it's actually a problem combining visual information with auditory information."

For the study, 36 people with dyslexia and 29 people without the disorder were tested on their ability to tell which of two lights appeared first. The participants sat in front of a video monitor and pushed a button to report their perception. In both dyslexic and non-dyslexic individuals, sounds presented through headphones were found to help performance.

When lights were accompanied by a sound, participants were better at discriminating lights presented very close together in time. For participants without dyslexia, the sound needed to occur within about 150 milliseconds of the light to get such a benefit. Longer intervals failed to help. People with dyslexia, however, showed benefits even with delays as long as 350 milliseconds.

. "In essence, the brain fuses things that happen very close together in time, and for dyslexics, this fusion appears to happen over longer periods of time than in non-dyslexic persons," said Wallace. "We believe this time difference is the fundamental problem that dyslexics have when learning to read. Early reading involves matching what you see with what you hear. But in dyslexics, we believe this matching process is disrupted. The sights and sounds of words are inappropriately matched. So, while the average person very quickly matches the written word "dog" with the sound "dog," a child with dyslexia may have much more difficulty."

Lynn Flowers, Ph.D., a co-researcher and assistant professor of neuropsychology, said the study demonstrates that lifelong dyslexic individuals integrate visual and auditory information differently than good readers. "The study did not use letters and speech sounds, suggesting that there may be a very basic sensory integration deficit in dyslexia that underlies reading difficulties," Flowers said.

Wallace said the finding suggests better ways to teach people with reading disabilities.

"We believe that the most effective approaches will use a combination of visual and auditory cues," he said. "Because the brain is very changeable in young children, we hope that by using such methods early, we could change the brain's architecture so that the children could process sight and sound normally."

He said the finding provides a basis for the effectiveness of a method called the Orton-Gillingham approach that relies on the use of sight and sound together to teach reading.

Wallace said the test could be used for early diagnosis because it doesn't involve reading, just the ability to push a button when a light comes on.

The researchers are now using functional magnetic resonance imaging, a technology for viewing the brain and seeing which areas "light up" when they are activated, to learn more about the disorder.

"We're exploring what happens in the brain when a person with dyslexia reads," said Wallace. "The future is exciting. We hope this is the first in a long series of studies to learn more about this common and often debilitating disorder."

Wake Forest University Baptist Medical Center is a health system comprised of North Carolina Baptist Hospital and Wake Forest University School of Medicine

More Evidence Shows That Children's Brains With Dyslexia Respond Abnormally To Language Stimuli

The University of Texas Health Science Center at Houston
2003-10-27

WASHINGTON -- Researchers have additional evidence that reading problems are linked to abnormal sound processing, thanks to high-precision pictures of the brain at work. In a recent study, when children without reading problems tried to distinguish between similar spoken syllables, speech areas in the left brain worked much harder than corresponding areas in the right brain, whose function is still unknown. But when children with dyslexia made the same attempt, those right-brain areas actually worked harder, going into overdrive after a brief delay. These findings appear in Neuropsychology, which is published by the American Psychological Association (APA).

Psychologists at The University of Texas Health Science Center at Houston targeted the suspect brain areas by isolating speech-processing sites from sites involved with other aspects of language, such as memory and meaning. As a result, they believe their research contributes to the identification of a central marker of the deficit that makes it hard for people with dyslexia to process similar but different sounds –- in both spoken and written form. The results parallel prior evidence gathered by the Houston team that brains of children with dyslexia also respond abnormally during reading.

The researchers studied the brain activity of 12 children with and 11 children without dyslexia during a simple speech perception task. The children were eight to 12 years old. Magnetoencephalography (MEG), a non-invasive, high-resolution form of functional imaging, highlighted precise activity in participants' left and right temporoparietal (TP) language areas while the children discriminated between spoken pairs of syllables, such as /ga/ and /ka/. This kind of task, known as phonological processing, is fundamental to acquiring reading skill. The temporoparietal areas are on the surface in the back of the brain.

While distinguishing between sounds, the non-impaired readers showed more relative activity in the speech part of the left TP area. During the same task, after a slight delay, impaired readers showed a sharp peak of relative activation in corresponding (but functionally mysterious) areas on the right side. The poorer the child's performance in phonological processing, the more their right brains "lit up" during that task.

The results, says co-author Joshua Breier, Ph.D., suggest that children with dyslexia "may lack the predominant involvement of left-hemisphere auditory association cortices" shown by children and adults without reading problems.

Dyslexia may affect up to 17 percent of the school-age population and can continue into adulthood. Reading experts have long suspected that many reading problems, especially in decoding letter sounds, are rooted in the brain and have more to do with sound than sight. Brain imaging studies have confirmed that suspicion and helped to put to rest any notion that dyslexia, although it can make a child feel "stupid" and be a problem in school, reflects visual problems or a lower overall intelligence.

"The neurological deficit appears to be specific to very restricted areas of the brain," says Breier, "and can occur in children with a wide range of general intellectual function."

Such findings are helping to shape national education policy. In fact, co-author Jack Fletcher, Ph.D., points out that most states, following federal guidelines, have for decades used a discrepancy between IQ and reading tests to determine eligibility for special education in the learning disability category, which accounts for more than half of all students in special education. However, several national bodies have, in the past year, proposed allowing states to use alternative means of establishing eligibility. Legislation is in progress. Breier explains that given the research, "The use of IQ in reading disability definitions, at least for these children, is not appropriate." Adds Fletcher, "It's poor reading that's important."

And, poor reading can improve. "The present study shows that reliable brain correlates can be identified in individual children," Breier points out. Given that effective teaching changes brain activation patterns, he says, "the brain in people with reading difficulties is responsive to intense intervention."

Further research will gauge the reliability of the findings, which were established with a participant number typical of a brain-imaging study, using high-precision measurements. In addition, the Houston researchers hope to determine under which treatment conditions MEG brain imaging might be associated with how well a child with dyslexia responds to intervention.

Article: "Abnormal Activation of Temporoparietal Language Areas During Phonetic Analysis in Children with Dyslexia," by Joshua I. Breier, Ph.D.; Panagiotis G. Simos, Ph.D.; Jack M. Fletcher, Ph.D.; Eduardo M. Castillo, Ph.D.; Wenbo Zhang, Ph.D.; and Andrew C. Papanicolaou, Ph.D.; The University of Texas Health Science Center at Houston; Neuropsychology, Vol. 17, No. 4.

Short-term Dyslexia Treatment Strengthens Key Brain Regions

American Academy Of Neurology
2003-07-28

ST. PAUL, MN – After only three weeks of reading instruction, brain scans in children with dyslexia develop activation patterns that match those of normal readers, according to a study published in Neurology, the scientific journal of the American Academy of Neurology. These findings indicate that children with dyslexia use the same regions of their brains as other readers, and that specialized instruction can rapidly compensate for some types of reading deficits.

Dyslexic children in this study had above average intelligence but scored approximately 30 percent lower than average on standard reading tests. The dyslexic children and a group of good readers of the same age underwent functional magnetic resonance imaging (fMRI) to map their brain activation patterns during two types of reading tests. The children with dyslexia then received a three-week training program based on principles outlined by the National Reading Panel (http://www.nationalreadingpanel.org), convened by the National Institute of Child Health and Human Development. Both groups of children then underwent a second brain scan. The experiment was conducted during the summer, to avoid confounding effects from school instruction.

The reading tests during the brain scan measured the ability of the children to decide whether certain letter combinations could stand for certain sounds (for example, could "ow" and "oa" make the same sound?) and whether certain letter patterns in words created meaningful relationships between words (for example, does the "er" in "builder" make it related to the word "build"? does the "er" in "corner" make it related to the word "corn"?). Both skills are key elements of the reading process.

Both dyslexic children and normal readers used the same specific parts of their brains to perform these tasks, says lead study author Elizabeth Aylward, PhD, with the department of radiology at the University of Washington in Seattle. However, the activation of these regions was much weaker in dyslexic children, reflecting their poorer performance on these tasks.

After the three-week reading program the levels of brain activation were essentially the same in the two groups. Aylward says these results indicate that instruction doesn't "rewire" the brain of the dyslexic child, but instead strengthens the normal circuits which are already in use.

One of the most encouraging results of the study, she says, is that "we can document changes in the brain even after a fairly short training period," suggesting that appropriate in-school training has great potential for improving the reading ability of dyslexic children.

Reading and spelling disabilities, which occur despite normal intelligence, affect 10 to 15 percent of school-age children in the United States. Early diagnosis and proper instruction significantly improve the dyslexic child's reading achievement outcome.

Rutgers Researcher: Brains In Dyslexic Children Can Be 'Rewired' To Improve Reading Skills

2003-03-05

(NEWARK) – In a scientific first, researchers have shown that the brains of dyslexic children can be "rewired" through intensive remedial training to function more like those found in normal readers.

Paula Tallal, Board of Governors Professor of Neuroscience at Rutgers-Newark, and other members of a multi-university research team used brain-imaging scans of dyslexic children to demonstrate that areas of the brain critical to reading skills became activated for the first time and began to function more normally after only eight weeks of special training. In addition, other regions of the brain also lit up on the functional magnetic resonance imaging (fMRI) scans in a compensatory process that the dyslexics may have used as they learned to read more fluently.

The researchers' groundbreaking findings were published Feb. 24 by the Proceedings of the National Academy of Sciences Early Edition. The other authors include faculty from Stanford and Cornell universities, the University of California's Los Angeles and San Francisco campuses, and one of the co-founders of Oakland-based Scientific Learning Corporation.

Dyslexia, sometimes called "word blindness," is a disorder that affects 5 to 10 percent of Americans, and is characterized by difficulties in processing language. Usually these problems are severe enough to interfere with performance in school, but they cannot be attributed to a poor education, personal motivation, or impaired sight or hearing.

The investigators, working at Stanford, extensively used Fast ForWord Language, a computer program designed by Tallal and other researchers at Scientific Learning Corporation. The program focuses on helping children become more adept at processing the rapidly changing sounds inside words. A dyslexic child may, for example, have difficulties distinguishing between letters that rhyme, such as B and D.

"If you hear the sound 'ba' in 'butter' and 'da' in 'Doug,' the only way we know the difference is in the first 40 milliseconds of the onset of those sounds," Tallal explained. "The ability to extract sounds out of words is what is called phonological awareness." Words can be broken into sounds, and these sounds have to be mentally connected with letters. Although the process might seem intuitive, it is actually a learned skill, Tallal said.

One portion of the study involved asking children if two letters of the alphabet rhymed, while their brains were imaged with fMRI scans. The scans of the 20 dyslexic children in the experiment – who struggled with the task – contrasted sharply with those of the 12 normal readers in the experiment's control group. The dyslexics' scans showed a lack of activity in the language-critical temporal regions of the brain.

The training program, which included dyslexic children aged 8 to 12 years, was designed to help them learn to process and interpret the very rapid sequence of sounds within words and sentences by exaggerating them and slowing them down.

"These are the building blocks you have to have in place before you can learn to read," Tallal said. "I think Fast ForWord is building the scaffolding for reading, and doing it based on scientific knowledge of the most efficient and effective way of helping the brain learn."

The dyslexic children used the Fast ForWord Language computer program for 100 minutes a day, five days a week, as part of their regular school day. The program consisted of seven exercises adapted as computer games. In one exercise, for example, when a picture of a boy and a toy was shown, a voice from the computer asked the player to point to the boy – a step that required understanding the very brief difference in the sound of each word's first consonant.

"Each child worked at his or her own level," Tallal said. The goal was to have the children process sounds correctly in words and sentences of increasing length and grammatical complexity, she added. The study's authors emphasized that continuous intervention would be necessary to make the dyslexics' improvements in reading skills stick and advance.

"In light of President [George W.] Bush's legislation, 'No Child Left Behind,' which mandates that only scientifically validated applications be used for intervening with children, this program has the potential to help address the crisis we are facing in the large number of children failing to meet [educational] standards," Tallal observed.

UCSF-Led Team Offers New Insight Into Neurological Basis Of Dyslexia

1999-05-26

Researchers are reporting direct neurological evidence that the region of the brain that processes brief, rapidly successive sounds is functionally abnormal in adults with the reading disability known as dyslexia.

The findings, documented through simultaneous brain imaging and behavioral tests, strongly indicate, the researchers said, that adult dyslexics have an enduring neurological deficit in their ability to process these brief, rapidly successive sounds.

They suspect that the deficiency contributes to difficulties in early speech and language learning, and leads to a weakness in the subsequent mental leap in abstraction to words on a page that enables people to learn to read.

The study was published in Proceedings of the National Academy of Science.

Perhaps the most provocative aspect of the finding, the researchers said, is the clear and direct neurological evidence that reading deficits are generated, at least in part, by a deficit at a very fundamental level of cortical processing of sound inputs.

"Our findings indicate that there is a basic problem in signal reception, as complex sound information streams into the cerebral cortical system underlying aural speech representation," said the senior author of the study, Michael Merzenich, PhD, the Francis A. Sooy Professor of Otolaryngology and a member of the Keck Center for Integrative Neuroscience at UC San Francisco. "The way that the brain processes sound in poor readers is very different from its processing and representation of rapidly changing sound inputs in competent readers."

"Our research indicates that adult dyslexics are representing the sound parts of words by the activation of cortical neuron populations in a weaker and less salient form within their cortical aural speech processing system. We believe that they, therefore, are not delivering the normal forms of representation of the separable sound parts of words to the regions of the brain involved in speech perception and reading," he said.

The authors emphasize that their findings do not discount the additional involvement of higher levels of brain processing in dyslexia, where more complex combinations of information lead to the recognition and interpretation of speech.

At the same time, they argue that the very elementary defect in the brain's processing of sound must be playing an important role in the generation of relatively weak neuronal representations of the sound parts of aural speech.

And this elementary neurological deficit, they said, could provide a target for remedial therapies aimed at training the brain to increase the speed and accuracy with which it processes rapidly successive and rapidly changing sounds.

The sound-processing function occurs at a base, or entry, level of sound processing in the brain, and is believed to be a primary step in the brain's representation of normal speech sounds and its creation of speech and language-reception abilities. The process ultimately culminates with a listener learning to recognize the sound parts of words, and to translate these word sounds as written letters.

Previous behavioral studies have suggested that the inability to parse the rapidly successive, changing sounds that make up words, the phonemes of language, may be the primary basis of language-learning impairments in children. Scientists have long argued that children who have difficulty parsing word sounds are destined to have difficulty successfully initiating reading.

Other behavioral studies have indicated that most people with dyslexia, characterized by a difficulty with reading, also have impairments in the fidelity of their auditory reception. However, because most dyslexics ultimately develop facile speech reception and production capabilities, the significance of this problem for the origin of reading impairments has been unclear.

The researchers conducted their current study in seven dyslexic adults who were of normal intelligence but severely challenged by reading, spelling and writing. Results were compared with those recorded in seven adults of normal intelligence who were competent readers.

The dyslexic adults performed poorly on standardized reading tests. And, as has been shown to be the case with the great majority of adult dyslexics, these poor readers (ages 18-42) also performed poorly on a variety of tests that measured their ability to discern rapidly successive sound stimuli.

In one of these sound-discerning tests, adults were exposed to two sounds that differed in frequency and that occurred a tenth or a fifth of a second apart. They were then asked to identify the sounds and to replay the sequence in which they were presented. Their brain activity was simultaneously recorded using magnetoencephalographic brain imaging, which measures magnetic field fluctuations generated by spatially localizable human brain activity with millisecond precision.

In these studies, the UCSF team focused on the activity generated by the rapidly successive sounds evoked from the "primary" auditory cortical areas, where information about aural speech flows into the cerebral cortex's processing system for language.

Poor readers did report hearing the two very brief sounds, and often knew that in some way they weren't the same, but they were unable to identify them, or to reliably reconstruct the sequence in which they were represented.

"The reason," said Srikantan Nagarajan, PhD, an assistant adjunct professor of otolaryngology and a member of the Keck Center for Integrative Neuroscience at UCSF, and the lead scientist of the study, "was demonstrated by the abnormal way that the brain of the poor-reading subjects responded to these rapidly successive sound events."

"In normal readers, the auditory cortex generated clear, separate representations of sounds occurring within the time dimensions of a syllable," said Nagarajan. "In poor readers, the brain separately generated only very weak representations of sound events past the first sound.

"In the normal reader, successive intra-syllabic sound events are separately represented in high fidelity within the processing channels of the 'primary' auditory cortex. In the impaired reader, they are not," he said.

"These findings are consistent with the increasing evidence," said Merzenich, "that language-impaired and reading-impaired children are a very broadly synonymous population. Scientists have historically argued that only a small percentage of dyslexics have a clear history of early language impairment and fundamental auditory processing deficits. To the contrary, we have seen that most poor readers and most language-impaired children share these same fundamental listening and brain processing abnormalities."

Moreover, he said, "The studies show that these fundamental listening problems clearly persist across a lifetime, even while the basic speech reception abilities of these individuals can ultimately achieve a relatively normal competency."

Co-authors of the study were Henry Mahncke, PhD, a research fellow in the Keck Center at UCSF; Talya Salz, of Scientific Learning Corporation in Berkeley, CA; Paula Tallal, PhD, co-director of the Center for Molecular and Behavioral Neuroscience at Rutgers University, Newark, NJ; and Timothy Roberts, PhD, assistant professor of radiology in the Biomagnetic Imaging Laboratory, Department of Radiology, at UCSF.

The study was funded by the National Institutes of Health, the Office of Naval Research, Hearing Research Inc., and the Coleman fund.

New Technique Developed For Deciphering Brain Recordings Can Capture Thinking As It Happens

University of California San Diego
2004-06-15

A team led by University of California San Diego neurobiologists has developed a new approach to interpreting brain electroencephalograms, or EEGs, that provides an unprecedented view of thought in action and has the potential to advance our understanding of disorders like epilepsy and autism.

The new information processing and visualization methods that make it possible to follow activation in different areas of the brain dynamically are detailed in a paper featured on the cover of the June 15 issue of the journal Public Library of Science Biology (plos.org) The significance of the advance is that thought processes occur on the order of milliseconds--thousandths of a second--but current brain imaging techniques, such as functional Magnetic Resonance Imaging and traditional EEGs, are averaged over seconds. This provides a "blurry" picture of how the neural circuits in the brain are activated, just as a picture of waves breaking on the shore would be a blur if it were created from the average of multiple snapshots.

"Our paper is the culmination of eight years of work to find a new way to parse EEG data and identify the individual signals coming from different areas of the brain," says lead author Scott Makeig, a research scientist in UCSD's Institute for Neural Computation of the Swartz Center for Computational Neuroscience . "This much more comprehensive view of brain dynamics was only made possible by exploiting recent advances in mathematics and increases in computing power. We expect many clinical applications to flow from the method and have begun collaborations to study patients with epilepsy and autism."

To take an EEG, recording electrodes--small metal disks--are attached to the scalp. These electrodes can detect the tiny electrical impulses nerve cells in the brain send to communicate with each other. However, interpreting the pattern of electrical activity recorded by the electrodes is complicated because each scalp electrode indiscriminately sums all of the electrical signals it detects from the brain and non-brain sources, like muscles in the scalp and the eyes.

"The challenge of interpreting an EEG is that you have a composite of signals from all over the brain and you need to find out what sources actually contributed to the pattern," explains Makeig. "It is a bit like listening in on a cocktail party and trying to isolate the sound of each voice. We found that it is possible, using a mathematical technique called Independent Component Analysis, to separate each signal or "voice" in the brain by just treating the voices as separate sources of information, but without other prior knowledge about each voice."

Independent component analysis, or ICA, looks at the distinctiveness of activity in each patch of the brain's cortex. It uses this information to determine the location of the patch and separate out the signals from non-brain sources. Because ICA can distinguish signals that are active at the same time, it makes it possible to identify the electrical signals in the brain that correspond to the brain telling the muscles to take an action --which in the paper was deciding whether or not to press a button in response to an image flashed on a computer screen--and to separate this signal from the signals the brain uses to evaluate the consequences of that action.

According to Makeig, UCSD was a leader in developing the earlier methods of interpreting EEGs forty years ago. "The new, more general 'ICA' method continues this tradition of UCSD excellence in cognitive electrophysiology research," he says.

The coauthors on the paper, in addition to Makeig, include Arnaud Delorme and Tzyy-Ping Jung, Swartz Center for Computational Neuroscience; Marissa Westerfield and Jeanne Townsend, UCSD's Department of Neurosciences; Eric Courchesne, Children's Hospital Research Center and UCSD's Department of Neurosciences; and Terrence Sejnowski, UCSD professor of biology and Howard Hughes Medical Institute professor at the Swartz Center for Computational Neuroscience and the Salk Institute for Biological Studies. The study was funded by the Swartz Foundation, the National Institutes of Health and the Howard Hughes Medical Institute.

Researchers Find Link Between Improved Memory And The Use Of Neurofeedback

Imperial College London at the Charing Cross
2003-01-23

Results announced in the International Journal of Psychophysiology this month show a link between neurofeedback training and improved memory in a 40 person trial.

Dr David Vernon, from Imperial College London at the Charing Cross hospital says: "Previous research has indicated that neurofeedback can be used to help treat a number of conditions including Attention Deficit Hyperactivity Disorder, epilepsy and alcoholism by training particular aspects of brain activity, but this is the first time we have shown a link between the use of neurofeedback, and improvements in memory."

Neurofeedback is a learning procedure that has been involved in treatments enabling participants to normalize behaviour, stabilize mood and improve their cognitive performance. It works by allowing people to watch their brain activity, and through this, find a way to correct or improve it.

Neurofeedback monitors brain activity through sensors attached to the scalp with the key frequency components filtered out. These filtered brainwaves are then 'fed back' to the individual in the form of a video game displayed on screen, and the participant learns to control the game by altering particular aspects of their brain activity. This alteration in brain activity can influence cognitive performance.

For the trial, the volunteers completed a number of neurofeedback sessions requiring them to enhance one aspect of brain activity while simultaneously inhibiting others. Participants completed two tests, both before and after the neurofeedback training had been completed, to see if neurofeedback would influence working memory performance. Working memory refers to the type of memory used to hold and manipulate information during the performance of a task, such as maintaining a telephone number in mind in order to recall it later.

In both tests, the volunteers were presented with a series of words from different categories, and following this were tested on how well they were able to recall all the words from a specific category. Across both tests those receiving neurofeedback increased their recall from 70.6 percent to 81.6 percent, while recall in the control group only increased from 72.5 percent to 75.1 percent.

Professor John Gruzelier, from Imperial College London at Charing Cross hospital adds: "Neurofeedback has been proven to be effective in altering brain activity, but the extent to which such alterations can influence behaviour are still unknown. Further tests are needed to confirm this, but if neurofeedback can positively influence the cognitive performance of healthy individuals, as we have previously shown on attention and musical performance, it opens up the possibility that such treatment may be beneficial for those suffering from cognitive deficits".

1. The effect of training distinct neurofeedback protocols on aspects of cognitive performance International Journal of Psychophysiology, Volume 47, Issue 1, pp 75-85.

2. Neurofeedback refers to a form of biofeedback, linked to a specific aspect of brain activity, such as frequency, location, amplitude or duration of specific EEG activity. 3. Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (10,000) and staff (5,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment - underpinned by a dynamic enterprise culture.

4. Charing Cross Hospital is part of the Hammersmith Hospitals NHS Trust, which also includes the Hammersmith, Queen Charlottes and Ravens Court Park hospitals.

The Medium And The Message: Eyes And Ears Understand Differently, Carnegie Mellon Scientists Report In The Journal Human Brain Mapping

Carnegie Mellon University
2001-08-15

PITTSBURGH - A new study by Carnegie Mellon University scientists shows that because of the way the brain works, we understand spoken and written language differently, something that has potential implications in the workplace and in education, among many other areas.

In the first imaging study that directly compares reading and listening activity in the human brain, Carnegie Mellon scientists discovered that the same information produces systematically different brain activation. And knowing what parts of the brain fire during reading or listening comprehension affects the answer to one of the classic questions about language comprehension: whether the means of delivery through eyes or ears makes a difference. "The brain constructs the message, and it does so differently for reading and listening. The pragmatic implication is that the medium is part of the message. Listening to an audio book leaves a different set of memories than reading does. A newscast heard on the radio is processed differently from the same words read in a newspaper," said Carnegie Mellon Psychology Professor Marcel Just, co-author of the report that appears in this month's issue of the journal Human Brain Mapping.

Just said that the most recent methods of functional magnetic resonance imaging (fMRI) were applied to measure brain activity during these high-level conceptual processes. Rather than examining the processing of single digits or words, his group is applying brain imaging to societal, workplace, and instructional issues. "We can now see how cell-phone use can affect driving, how reading differs from listening, and how visual thinking is integrated with verbal thinking," Just said.

Using the non-invasive fMRI, scientists were able to measure the amount of activity in each of 20,000 peppercorn-sized regions of the brain every three seconds and create visual maps of how the mental work of thinking was allocated throughout the brain from moment to moment. To the scientists' surprise, there were two big differences in the brain activity patterns while participants were reading or listening to identical sentences, even at the conceptual level of understanding the meaning of a sentence. First, during reading, the right hemisphere was not as active as anticipated, which opens the possibility that there were qualitative differences in the nature of the comprehension we experience in reading versus listening.

Second, while listening was taking place, there was more activation in the left-hemisphere brain region called the pars triangularis (the triangular section), a part of Broca's area that usually activates when there is language processing to be done or there is a requirement to maintain some verbal information in an active state (sometimes called verbal working memory). The greater amount of activation in Broca's area suggests that there is more semantic processing and working memory storage in listening comprehension than in reading.

Because spoken language is so temporary, each sound hanging in the air for a fraction of a second, the brain is forced to immediately process or store the various parts of a spoken sentence in order to be able to mentally glue them back together in a conceptual frame that makes sense. "By contrast," Just said, "written language provides an "external memory" where information can be re-read if necessary. But to re-play spoken language, you need a mental play-back loop, (called the articulatory-phonological loop) conveniently provided in part by Broca's area."

The study doesn't attempt to suggest that one means of delivering information is better than another, Just said. "Is comprehension better in listening or in reading? It depends on the person, the content of the text, and the purpose of the comprehension. In terms of persons, some people are more skilled at one form of comprehension and typically exercise a preference for their more skilled form where possible. It may be that because of their experience and biology they are better and more comfortable in listening or reading," he explained.

Just carries out his research on the human brain through the Center for Cognitive Brain Imaging at Carnegie Mellon. The language comprehension project is funded by the National Institutes of Health.

Rare Brain Mapping Procedure Provides Unique Picture Of Two Areas Concerned With Language Processing And Production

LOS ANGELES -- A unique opportunity to map and test the human brain has yielded new insights into two areas involved in producing and processing of language.

David Corina, an assistant professor of psychology at the University of Washington, reported on the roles of two brain regions called Broca's area and the supramarginal gyrus. The findings came from a rare case, a deaf person called S.T. who uses American Sign Language. S.T. underwent a procedure called an awake cortical stimulation mapping, which allows assessment of language and motor functions at specific sites in the brain's left hemisphere.

Corina, a fluent signer, and an interdisciplinary team of UW researchers tested the subject and found that electrical stimulation of Broca's area and the supramarginal gyrus created repeated but different kinds of errors in S.T.'s ability to name objects. When Broca's area, which is located in the frontal lobe, was stimulated, S.T. had difficulty making clear hand shapes and specific movements associated with signs. Nonetheless, these sloppy signs resembled the target sign. Corina likens these errors to "mumbling" made in spoken languages. The subject made no effort to self-correct these lax or imperfect signs.

Stimulation of the supramarginal gyrus, a small area in the parietal lobe, produced different kind of signing error. With stimulation, S.T. mixed up word meanings and word forms. For example, when shown a picture of a pig and asked to make the sign for it, S.T. made the sign for farm. The two signs are very similar in hand shape, movement and spatial location to the sign pig in American Sign Language, and would be distinct to skilled signer. Comparable errors in English might be saying oyster instead of lobster or plane instead of train. This type of error suggests that the supramarginal gyrus may be an area of the brain important in the selection and combining of word meanings with word forms.

Another interesting difference in these language errors was that with stimulation to Broca's area, S.T. made no effort to self-correct his imprecise signing. However, with stimulation to the supramarginal gyrus, he would make successive attempt to produce the correct sign (for oyster he would sign "loyster," then "lobster"). This suggests that stimulation of Broca's area was effecting only the final output of a correctly selected word, while supramarginal gyrus stimulation was effecting the compiling of the word forms, according to Corina.

Neuroscientists have long established that a region in the left hemisphere plays a role in language function. In the past decade it also has become evident that left hemis- phere specialization for language extends to deaf people who use sign languages, as well as for those who speak. However, scientists are just beginning to understand the particular contributions specific regions within the left hemisphere play in language processing.

The data Corina reported on came from an awake cortical stimulation mapping performed on S.T., a 50-year-old man who was suffering from epileptic brain seizures. The mapping was done prior to an operation called a temporal lobectomy which reduces severe seizures. The mapping procedure helps the neurosurgeon plan this delicate operation. In the mapping, a small electrical current is applied to the exposed cortex of the brain of an awake patient. During electrical stimulation, the patient is asked to name objects and imitate actions. This procedure is often used on speaking people undergoing the brain surgery, but Corina's report and an in press paper, are the first detailed accounts of its effects on a deaf signer.

"Although Broca's area has gotten considerable attention, its precise role in language behavior remains controversial," said Corina. "One controversy is whether Broca's areas is specialized just for speech or language in general. We have now been able to identify that Broca's area is involved in language production, not just speech production but any language spoken or signed. This is the best evidence that it is responsible for language independent of whether that language is expressed through the hands or the voice."

Corina noted the surprising finding that stimulation to areas next Broca's area resulted in movements of the mouth and lips, but not the hands.

"This study also strongly suggests that the supramarginal gyrus plays a critical role in blending semantic and phonetic information," he added, citing the word cat as an example. Cat has semantic features, being a "little furry critter that goes meow." It also has phonemic elements which correspond to the sound which make up the word cat --/k/ and /at/ in English -- and the hand shape and movements for a sign in American Sign Language. The supramarginal gyrus may be pulling together this kind of information, according to Corina.

"Some people have wondered if the human brain has specialized areas of language production and processing," he said. "This work provides new evidence in favor of specialized areas of the brain which are unique to language processing and production. People also have asked if there is a so-called language organ. Our work suggests that there is a whole network of areas responsible for speech and language. Broca's area and the supramarginal gyrus are just two pieces of that network."

The mapping procedure on S.T. lasted about 90 minutes prior to his surgery and was conducted while he was under a local anesthetic. The researchers tested a number of different left hemisphere sites for motor and language impairment by having S.T. do several tasks. He was shown pictures of 49 objects, such as a bird, chair, pig, bed and table, and asked to give the sign for each under normal conditions and while being electrically stimulated at each site. He also was asked to imitate signs and complex arm gestures. Only six sites showed any motor impairment and just two, Broca's area and the supramarginal gyrus, exhibited consistent impairments to language processing or production.

Corina said basic research such as this is important because science is very interested in being able to provide people with improved communications skills. "One way to improve communications is to discover all the sub parts that are involved in language. To do this, we need to understand where and what portions of the brain are involved so we can develop better interventions to assist people," he said.

"This work also has a practical application to help deaf people who, like hearing people, have seizures. The medical community needs to be aware that it can use the same standardized mapping procedures used on hearing people to identify language areas to ensure better post-operative outcomes on deaf patients. People need to realize that sign languages are real and naturally occurring human languages."

MEMORY

How Brain Gives Special Resonance To Emotional Memories

Duke University
2004-06-10

DURHAM, N.C. -- If the emotional memory of a traumatic car accident or the thrill of first love are remembered with a special resonance, it is because they engage different brain structures than do normal memories, Duke University researchers have discovered.

Their new study provides clear evidence from humans that the brain's emotional center, called the amygdala, interacts with memory-related brain regions during the formation of emotional memories, perhaps to give such memories their indelible emotional resonance.

The researchers said their basic insights could contribute to understanding of the role that the neural mechanisms underlying emotional memory formation play in post traumatic stress disorder and depression.

The study by Florin Dolcos, Kevin LaBar and Roberto Cabeza was reported in the June 10, 2004, issue of the journal Neuron. Dolcos is a research associate in the Brain Imaging and Analysis Center and LaBar and Cabeza are, respectively, assistant and associate professors of psychological and brain sciences. They are also faculty in the Center for Cognitive Neurosciences. Their research was supported by the National Institutes of Health.

According to Dolcos, in their experiments the researchers were seeking evidence for the "modulation hypothesis," which holds that the brain's emotional and memory centers interact during the formation of emotional memories.

"The basic idea was simple: to find evidence supporting the notion that the brain's emotional region modulates activity in the memory regions to form an emotional memory," said Dolcos. "This idea was supported by animal research, but the evidence from neurologically intact humans was scarce and indirect. So, our goal was to find the right method that would allow us to demonstrate that this phenomenon happens in human, too,” he said.

In their study, the researchers sought to establish that the memory-enhancing effect of emotion is due to interaction between emotion- and memory-related brain regions. Thus, they first exposed volunteer subjects to a collection of pictures that evoked both positive and negative emotions and those that were neutral. Emotional pictures depicted such negative events as aggressive acts or injured people and such positive events as romantic scenes or sporting triumphs. Neutral pictures included such subjects as buildings or scenes of routine shopping.

While viewing the emotional and neutral pictures, participants’ brains were scanned using functional magnetic resonance imaging. Such imaging involves the use of harmless magnetic fields and radio signals to measure blood flow to individual brain regions, which reflects greater activity in those regions. Then, following the scanning session, the researchers tested participants’ memory for the images they viewed during the scanning.

Two important features distinguish the new study from previous functional neuroimaging studies, said the researchers. First, to identify the brain regions associated with the memory-enhancing effect of emotion, the study identified the brain regions whose activity during memory formation predicts what items would be remembered or forgotten (encoding success). Thus, it was possible to compare successful encoding activity for emotional and neutral items.

Second, to delineate the contribution of the emotion and memory-related regions during emotional memory formation, the study used precise anatomical methods, which involved tracing of these regions on each subject's brain image. Thus, it was possible to precisely localize the signal coming from anatomically proximal brain regions. As expected, analysis of the behavioral data revealed evidence that the memories of emotional images were more strongly encoded than the neutral ones. And importantly, the brain scans showed that the emotional memories evoked activity in the amygdala as well as the "medial temporal lobe memory" structures. Specifically, these structures include the hippocampus and associated regions. Moreover, according to Dolcos, the analysis revealed a significant correlation between the strength of activity in the emotion- and memory-related brain regions.

"We found evidence that the interaction between the emotional and memory regions occurred more systematically and consistently during the formation of emotional memories than during the formation of neutral memories," Dolcos said. "More specifically, we found that the subjects showing greater successful encoding activity in the emotional region also had greater activity in the memory regions," said Dolcos.

Said Cabeza of the findings, "Other studies have focused on the general enhancing effects of emotion on memory, and the evidence for the modulation hypothesis was disparate and inconclusive. Thus, this is the first direct evidence for the modulation hypothesis in humans."

What's more, said Cabeza, "We also found indications that some regions within the medial temporal lobe may actually be more specialized for encoding neutral information. We don't know exactly what the processes involved are, or why these regions are engaged. But we speculate that the regions that were more activated for emotional stimuli are involved in semantic processing of the meaning of the images, whereas those that are more activated by neutral stimuli reflect perceptual processing."

Thus, said Cabeza, the findings not only establish the functional link between the emotional and memory areas; but also hint at differences within the memory areas that should be explored with further studies. As part of their research, the authors are now exploring the role of these brain regions during the retrieval of well-consolidated emotional memories.

While such studies are basic in nature, said Cabeza, better delineation of the role of the amygdala in emotional memory could aid understanding of post traumatic stress disorder -- especially such phenomena as flashbacks of traumatic memories. Said Dolcos, "Also, people who suffer depression ruminate obsessively on negative or unpleasant memories. This problem could reflect a pathology in how their memory systems have processed emotional memories."

Thus, said Cabeza, he and his collaborators are now exploring the nature of emotional memory encoding in people with depression, before and after therapy.

Individual Neurons Reveal Complexity Of Memory Within The Brain

University Of Washington
2002-01-04

An investigation of the activity of individual human nerve cells during the act of memory indicates that the brain’s nerve cells are even more specialized than many people think – no pun intended.

Although nerve cells that change activity during the use of memory are widely distributed in the brain, individual neurons generally respond to specific aspects of memory.

"For the first time, we’ve been able to show differences within regions of the temporal lobe in the way individual neurons respond to memory. Everything we’ve done to this point was to show that there are individual neurons that change activity --but we hadn’t been able to sort them out in any meaningful way. Now we can," says Dr. George Ojemann, professor of neurological surgery at the University of Washington.

The findings appear in the January 2002 issue of Nature Neuroscience.

Ojemann is an internationally renowned neurosurgeon who has developed surgical techniques for treating epilepsy, brain tumors and Parkinsonism, and ways to explore the detailed organization of the human brain for language, memory, thought and learning. He has co-authored two books for lay readers on the higher functions of the brain: Inside the Brain and Conversations with Neil's Brain.

This research involves patients with epilepsy who were awake during surgery and agreed to respond to requests to recall words, names of pictures and sounds. The recordings were from relatively healthy brain tissue that must be removed in order to reach problematic parts of the brain responsible for epileptic seizures. In a typical procedure, surgeons insert four microelectrodes and record the electrical activity as neurons communicate with other cells. After the microelectrodes are in place, patients are asked questions that measure stages of memory.

The microelectrodes, sharpened tungsten wire about the thickness of a human hair, identify electric impulses from neurons. There are only a few programs worldwide that have investigated neuronal activity changes with human cognition. Given the size and complexity of neurons and their interconnections, it is difficult to measure the activity of any given neuron for a given time. The electrodes pick up discharges of a pool of neurons that are then separated into activity of individual neurons based on the shape of their individual discharges.

The latest study was able to identify the behavior of 105 neurons at 57 sites in 26 patients; before, Ojemann says, his team’s largest sample was about 25 neurons.

The findings reinforce the message that neurons are very specialized. For example, researchers identified 16 of the 105 neurons that significantly changed activity with different stages of memory – encoding, storage and retrieval – and found that in 13 of those, changes were observed in only one modality (auditory, six; text, four; objects, three).

"We just don’t find neurons that are generic memory neurons. What we find are neurons that show statistically significant relationships to memory for a particular thing," Ojemann says.

There are three regional differences in brain activity that have not been noted before:

* There is a cluster of neurons that changes activity from encoding, to storage, to retrieval, in the basal temporal area, below the temporal lobe.

* Neurons that may help people recall something quickly after they have seen it earlier in the day – what scientists call ‘implicit memory’ -- seem very active in the superior temporal gyrus of the temporal lobe.

* There are neurons in the language-dominant hemisphere that respond to more than one modality – memory of both visual and auditory material.

At this point, the research is helping to illuminate the vast mysteries of the human brain. Someday, scientists may be able to use this knowledge to assist ailing brains. For example, it may be possible to externally activate neurons related to memory encoding in order to enhance memory.
These studies are supported by a grant from the National Institute of Neurological Disorders and Stroke, and are a collaborative project with Professor David Corina of the UW Department of Psychology.

Researchers Trace Roots Of Vivid Memories

Howard Hughes Medical Institute

September 26, 2000 — Researchers have found that calling up vivid memories—the face of a loved one or the chords of a favorite song—activates regions of the brain responsible for processing sensory experiences. When a person recalls a vivid memory, some of the sensory regions of the brain responsible for etching the original memory are reactivated.

In an article published in the September 26, 2000, Proceedings of the National Academy of Sciences, Howard Hughes Medical Institute investigator Randy L. Buckner, Mark E. Wheeler and Steven E. Petersen at Washington University in St. Louis describe how they used functional magnetic resonance imaging (fMRI) to probe the roots of a longstanding hypothesis in the field of memory research. According to the reactivation hypothesis, brain regions that are activated when a person has a sensory-specific experience are reactivated whenever the person remembers that experience.

"The question of how the brain represents memories as we experience them has been debated for more than a century with no clear answers," said Buckner. "We thought that fMRI, with its ability to see changes in brain activity on a moment-to-moment basis, would give us a prime opportunity to gain new insight into this fundamental question."

In fMRI, powerful magnetic fields and radio waves are used to image the brain and other body structures. In brain studies, these images reveal detailed changes in blood flow that occur when specific regions of the brain are activated.

According to Buckner, previous studies by other scientists indicated that stimulation of the brain's visual-processing region evoked visual memories. Likewise, studies showed that asking people to visualize scenes activated visual areas of the brain. But no one had done key experiments to "watch" the brain as sensory-specific memories were evoked in test subjects, said Buckner.

In their first set of experiments, Buckner and his colleagues presented volunteer subjects with a range of pictures of ordinary objects such as a dog, an airplane or a drum; or common sounds such as a dog barking, a plane's roar or a drum's tapping. Labels of descriptive text accompanied the images and sounds. After familiarizing the subjects with the images or sounds, the researchers placed each subject in an MRI scanner and presented them with the labels associated with the pictures or sounds. Each subject was then asked to recall the associated image or sound while the researchers used fMRI to take snapshots of brain activity. Analysis of the results showed that recalling images almost invariably activated the visual cortex while recalling sounds activated the auditory cortex.

"Perhaps we were seeing memory's echo in the brain—activity associated with the stored memory that momentarily bounces back to our awareness when we attempt to remember," said Buckner. While some of the findings were expected—and confirmed the reactivation hypothesis—others were a surprise.

"Given previous research, it was natural to expect that the same brain areas used to perceive visual and auditory information might also be involved in remembering seen and heard items. However, not all the areas involved in perceptions were reactivated during remembering.

"Instead, we found that a subset of these areas representing the highest-level areas in perception were reactivated. While we need to do more work to understand this discovery, it suggests that during remembering the brain areas reactivated do not include those involved with the earliest levels of perception, but rather selectively rely on high-level brain areas that already contain rather complex representations of sensory information."

Buckner emphasized that the findings confirm and extend the reactivation hypothesis. "For the first time, we have actually seen the brain areas that subserve the reactivation process," he said. "As we learn more about these perceptual areas we will begin to understand how they serve as building blocks for memories. This study gave us some initial insights into which brain areas might represent these building blocks." According to Buckner, an understanding of how the brain represents information during remembering is a resonant mystery for people.

"We have all shared the experience of closing our eyes and remembering what a family member looks like or what a new tune on the radio sounds like. And we are all interested in how our brains help us to do this. These findings that the brain reactivates sensory areas during remembering helps explain how this rich experience of remembering may result in part from the reactivation of multiple sensory areas." According to Buckner, the findings also represent a step along the pathway to understanding and possibly alleviating memory loss associated with various diseases.

"By understanding how such memories can be successfully accessed in healthy subjects, as we did in this study, we begin to build a foundation for exploring why such memories fail in patients with memory difficulties," he said.