New Thoughts On Language Acquisition: Toddlers As Data Miners
Indiana University researchers are studying a ground-breaking theory that young children are able to learn large groups of words rapidly by data-mining.
Their theory, which they have explored with 12- and 14-month-olds, takes a radically different approach to the accepted view that young children learn words one at a time — something they do remarkably well by the age of 2 but not so well before that.
Data mining, usually computer-assisted, involves analyzing and sorting through massive amounts of raw data to find relationships, correlations and ultimately useful information. It often is used and thought of in a business context or used by financial analysts, and more recently, a wide range of research fields, such as biology and chemistry. IU cognitive science experts Linda Smith and Chen Yu are investigating whether the human brain accumulates large amounts of data minute by minute, day by day, and handles this data processing automatically. They are studying whether this phenomenon contributes to a “system” approach to language learning that helps explain the ease by which 2- and 3-year-olds can learn one word at a time.
“This new discovery changes completely how we understand children’s word learning,” Smith said. “It’s very exciting.”
Smith, chair of the Department of Psychological and Brain Sciences at IU Bloomington, and Yu, assistant professor in the department, recently received a $1 million grant from the National Institutes of Health to fund this research for five years. Here are some recent findings:
*In one of their studies, published in the journal Cognition, Yu and Smith attempted to teach 28 12- to 14-month-olds six words by showing them two objects at a time on a computer monitor while two pre-recorded words were read to them. No information was given regarding which word went with which image. After viewing various combinations of words and images, however, the children were surprisingly successful at figuring out which word went with which picture.
*In the adult version of the study, which used the same eye-tracking technology used in the Cognition study, adults were taught 18 words in just six minutes. Instead of viewing two images at a time, they simultaneously were shown anywhere from three to four, while hearing the same number of words. The adults, like the children, learned significantly more than would be expected by chance. Many of the adult subjects indicated they were certain they had learned nothing and were “amazed” by their success. Yu and Smith wrote in the journal Psychological Science, “This suggests that cross-situational learning may go forward non-strategically and automatically, steadily building a reliable lexicon.”
Yu and Smith say it’s possible that the more words tots hear, and the more information available for any individual word, the better their brains can begin simultaneously ruling out and putting together word-object pairings, thus learning what’s what.
Yu, who has a doctorate in computer science and writes much of the software programming for their studies, said that if they can identify key factors involved in this form of learning and how it can be manipulated, they might be able to make learning languages easier, through training DVDs and other means, for children and adults. The learning mechanisms used by the children to learn words also could be used to further machine learning.
Cognition, Volume 106, Issue 3, March 2008, Pages 1558-1568
Infants rapidly learn word-referent mappings via cross-situational statistics
Linda Smith and Chen Yu
First word learning should be difficult because any pairing of a word and scene presents the learner with an infinite number of possible referents. Accordingly, theorists of children’s rapid word learning have sought constraints on word-referent mappings. These constraints are thought to work by enabling learners to resolve the ambiguity inherent in any labeled scene to determine the speaker’s intended referent at that moment. The present study shows that 12- and 14-month-old infants can resolve the uncertainty problem in another way, not by unambiguously deciding the referent in a single word-scene pairing, but by rapidly evaluating the statistical evidence across many individually ambiguous words and scenes.
Psychological Science May 2007 (Volume 18, Issue 5 Page 369-46 
Rapid Word Learning Under Uncertainty via Cross-Situational Statistics
There are an infinite number of possible word-to-word pairings in naturalistic learning environments. Previous proposals to solve this mapping problem have focused on linguistic, social, representational, and attentional constraints at a single moment. This article discusses a cross-situational learning strategy based on computing distributional statistics across words, across referents, and, most important, across the co-occurrences of words and referents at multiple moments. We briefly exposed adults to a set of trials that each contained multiple spoken words and multiple pictures of individual objects; no information about word-picture correspondences was given within a trial. Nonetheless, over trials, subjects learned the word-picture mappings through cross-trial statistical relations. Different learning conditions varied the degree of within-trial reference uncertainty, the number of trials, and the length of trials. Overall, the remarkable performance of learners in various learning conditions suggests that they calculate cross-trial statistics with sufficient fidelity and by doing so rapidly learn word-referent pairs even in highly ambiguous learning contexts.
Signaling Networks That Control Neuron Function Mapped For The First Time
Led by Richard Klemke, Ph.D., professor of pathology at UCSD School of Medicine and the Moores UCSD Cancer Center, the research team designed a new technology enabling them to, for the first time, isolate and purify neurites — long membrane extensions from the neuron that give rise to axons or dendrites. This technological breakthrough opens the door to understanding how neurites form and differentiate to regenerate neuronal connections and give rise to a functioning network. It also led to the discovery of how two key signaling molecules are regulated by a complex protein network that controls neurite outgrowth.
The formation of neurites, a process called neuritogenesis, is the first step in the differentiation of neurons, the basic information cells of the central nervous system.
“Understanding how neurites form is crucial, as these structures give rise to the specialized axons and dendrites which relay sensory input and enable us to see, hear, taste, reason and dream,” said Klemke.
Neurons regenerate by sending out one or several long, thin neurites that will ultimately differentiate into axons, which primarily receive signals, or dendrites, primarily involved in sending out signals. These long, branch-like protrusions have a specialized sensory structure called a growth cone that probes the extracellular environment to find its way and determine which direction the neurite should move in order to hook up with other neurites that will also differentiate into axons and dendrites.
The neural signaling network of dendrites and axons forms a huge information grid, which the UCSD team is studying in order to discover how neurons connect properly and regenerate to maintain proper wiring of the brain. Understanding the role that neuritogenesis plays in the regeneration of nerve connections damaged by diseases such as Alzheimer’s, Parkinson’s or other neurogenerative diseases is an important component of mapping the signaling network.
“Our primary goal is to identify unique proteins that cause the neurite to sprout and differentiate,” said Klemke. “We also want to understand the underlying signals that guide neurite formation and migration in response to directional cues.”
Klemke’s postdoctoral associates Olivier Pertz and Yingchun Wang identified a complex network of enriched proteins called GEFs and GAPs that control neuritogenesis by modulating signaling.
“This signaling provides external guidance cues to mechanical mechanisms inside the cell that make the neurite go forward, turn, or reverse direction,” Klemke said. “Understanding how the thousands of neurite proteins work in concert may someday help us guide neurites to the right place in the body to regenerate and reverse the impact of neural degenerative diseases or help facilitate spinal cord healing after injury.”
The researchers developed a unique microporous filter technology to separate the neurite from the cell body of the neuron, called the soma. The ability to slice millions of neurons into their soma and neurite components opened the door to using mass spectrometry, a tool able to identify the thousands of proteins that uniquely compose the two structures. Using information gleaned from published work, the researchers were then able to predict the function of most of the neurite proteins. This allowed them to construct a blueprint of how the thousands of proteins work together to facilitate neurite formation.
PNAS 2007 104: 8328-8333; published online before print as 10.1073/pnas.0701103104
Profiling signaling polarity in chemotactic cells
Yingchun Wang, Shi-Jian Ding, Wei Wang, Jon M. Jacobs, Wei-Jun Qian, Ronald J. Moore, Feng Yang, David G. Camp, II, Richard D. Smith, and Richard L. Klemke
Cell movement requires morphological polarization characterized by formation of a leading pseudopodium (PD) at the front and a trailing rear at the back. However, little is known about how protein networks are spatially integrated to regulate this process at the system level. Here, we apply global proteome profiling in combination with newly developed quantitative phosphoproteomics approaches for comparative analysis of the cell body (CB) and PD proteome of chemotactic cells. The spatial relationship of 3,509 proteins and 228 distinct sites of phosphorylation were mapped revealing networks of signaling proteins that partition to the PD and/or the CB compartments. The major network represented in the PD includes integrin signaling, actin regulatory, and axon guidance proteins, whereas the CB consists of DNA/RNA metabolism, cell cycle regulation, and structural maintenance. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive system-wide profile of proteins and phosphorylation sites that control cell polarization.
Brain Circuits: Method Applied To Learning And Memory Pathway
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Researchers at the Picower Institute for Learning and Memory at MIT report in the Jan. 24 online edition of Science that they have created a way to see, for the first time, the effect of blocking and unblocking a single neural circuit in a living animal.
The green-stained section of this mouse hippocampus represents where the new DICE-K technique blocked the neural-signal transmission in one of the hippocampal circuits of the brain. (Credit: Image / Toshi Nakashiba, MIT)This revolutionary method allowed Susumu Tonegawa, Picower Professor of Biology and Neuroscience, and colleagues to see how bypassing a major memory-forming circuit in the brain affected learning and memory in mice.“Our data strongly suggest that the hippocampal neural pathway called the tri-synaptic pathway, or TSP, plays a crucial role in quickly forming memories when encountering new events and episodes in day-to-day life,” Tonegawa said. “Our results indicate that the decline of these abilities, such as that which accompanies neurodegenerative diseases and normal aging in humans, is likely to be due, at least in part, to the malfunctioning of this circuit.”Combining several cutting-edge genetic engineering techniques, Tonegawa’s laboratory invented a method called doxycycline-inhibited circuit exocytosis-knockdown, or DICE-K-an acronym that also reflects Tonegawa’s admiration of ace Boston Red Sox pitcher Daisuke Matsuzaka. DICE-K allows researchers for the first time to induce and reverse a blockade of synaptic transmission in specific neural circuits in the hippocampus.
“The brain is the most complex machine ever assembled on this planet,” Tonegawa said. “Our cognitive abilities and behaviors are based on tens of thousands of molecules that compose several billion neurons, as well as how those neurons are connected.
“One effective way to understand how this immensely complex cellular network works in a major form of cognition like memory is to intervene in the specific neural circuit suspected to be involved,” he said.
Computing memories
The hippocampus, a seahorse-shaped brain region, plays a part in memory and spatial navigation. In Alzheimer’s disease, the hippocampus is one of the first regions to suffer damage; memory problems and disorientation are among the disease’s first symptoms.
The hippocampus is made up of several regions–CA1, CA3 and the dentate gyrus–that are wired up with distinct pathways.
The MIT study sought to determine how the interactions between neural pathways and the hippocampal regions affect learning and memory tasks.
Imagine that the three hippocampal regions are computers, and neural pathways are the conduits through which the computers get data from all over the brain. The computers perform different tasks, so the types of data processing will depend on which conduits the data travels through.
The hippocampus has two major, parallel information-carrying routes: the tri-synaptic pathway (TSP) and the shorter monosynaptic pathway (MSP). The TSP includes data processing from all three hippocampal regions, whereas the MSP skips through most of them.
Uisng DICE-K, the researchers were surprised to find that mice in which the major TSP pathway was shut down could still learn to navigate a maze. The shorter MSP pathway was sufficient for the job.
However, the maze is a task that is slowly learned over many repeated trials. When the mice were tested with a different task in a new environment that required rapid learning and memory formation, the researchers found that the mice with TSP shut down could not perform the task. Thus, the TSP pathway is required for animals to quickly acquire memories in a new environment. “This kind of learning results in the most sophisticated form of memory that makes animals more intelligent and is known to decline with age,” Tonegawa said.
Science. 2008 Jan 24 [Epub ahead of print] -
The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, RIKEN-MIT Neuroscience Research Center, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information from the entorhinal cortex –> dentate gyrus –> CA3 –> CA1 –> entorhinal cortex) and the monosynaptic pathway (which connects entorhinal cortex –> CA1 –> entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid, one-trial contextual learning, for pattern completionbased memory recall and for spatial tuning of CA1 cells.
Genes Predict Risk Of Getting Hooked On Cigarettes
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Cigarette smoking is the largest preventable source of death and disability in the USA, contributing to ~ 400,000 deaths annually. Despite widespread knowledge of the health dangers, ~ 1 in 8 American adults is a habitual heavy smoker.
For several decades, scientists have known that most of the risk for habitual heavy smoking (smoking a pack each day) is largely influenced by genetics. This conclusion comes from the study of identical and fraternal twins from Scandinavia, North America, Australia and (more recently) China. It has been estimated that ~ 2/3 of the risk to become a heavy habitual smoker is genetic. This does not imply that this genetic risk is due to a single gene. It is known that many genes are involved, each one contributing a small amount of risk.Finding the individual genes is a considerable challenge, but worth the effort, because it is hoped that the genes conveying risk for heavy smoking could be used to develop new medicines to help people quit. The development of new medicines to help people quit is particularly important, because the existing medications, including nicotine replacement (’the patch’ or gum), bupropion and varenicline are effective in the short-term (several months) for a minority of heavy smokers.
This paper describes the results of a genetic study of 14,000 people, from the USA and Europe, whose smoking histories were known. DNA samples from ~ 6000 people were analyzed at ~ 500,000 known variations in the human genome to determine whether any of these variations predicted cigarettes per day during the period of heaviest smoking for these individuals. The results implicated variations in two genes, both producing brain proteins to which nicotine binds in generating its addicting effects. These two proteins (are their genes) are termed the alpha 3 and alpha 5 nicotinic receptor subunits, so-called because they form (with other nicotinic receptor subunits) binding sites for nicotine on certain brain cells which are known to be activated during the process of addiction.
A second population of ~ 8000 people (whose smoking histories were known) was analyzed in a similar manner, the result again suggesting that variations in these two genes increased risk for heavy smoking. Taken together, these two studies provide convincing proof that variations in the alpha 3 and alpha 5 nicotinic receptor subunit genes play a significant role in risk for nicotine addiction. A previously published paper, using similar methods, also supports this conclusion.
These results suggest two important research activities. First, and foremost, the alpha 3 and alpha 5 nicotinic receptor subunits will be made targets for new smoking cessation medication development programs by pharmaceutical companies. Second, the implicated DNA variants can be used to determine whether they predict ability to quit using the one of the currently available smoking cessation medicines. This “personalized medicine” approach might allow for more efficient and productive use of those medicines, until improved ones can be created.
Mol Psychiatry. 2008 Jan 29 [Epub ahead of print]
Different Patterns Of Brain Activity In Creative And Noncreative Problem Solvers
Why do some people solve problems more creatively than others? Are people who think creatively somehow different from those who tend to think in a more methodical fashion?
These questions are part of a long-standing debate, with some researchers arguing that what we call “creative thought” and “noncreative thought” are not basically different. If this is the case, then people who are thought of as creative do not really think in a fundamentally different way from those who are thought of as noncreative. On the other side of this debate, some researchers have argued that creative thought is fundamentally different from other forms of thought. If this is true, then those who tend to think creatively really are somehow different.
A new study led by John Kounios, professor of psychology at Drexel University and Mark Jung-Beeman of Northwestern University addresses these questions by comparing the brain activity of creative and noncreative problem solvers. The study published in the journal Neuropsychologia, reveals a distinct pattern of brain activity, even at rest, in people who tend to solve problems with a sudden creative insight — an “Aha! Moment” — compared to people who tend to solve problems more methodically.
At the beginning of the study, participants relaxed quietly for seven minutes while their electroencephalograms (EEGs) were recorded to show their brain activity. The participants were not given any task to perform and told they could think about whatever they wanted. Later, they were asked to solve a series of anagrams — scrambled letters that can be rearranged to form words [MPXAELE = EXAMPLE]. These can be solved by deliberately and methodically trying out different letter combinations, or they can be solved with a sudden insight or “Aha!” in which the solution pops into awareness. After each successful solution, participants indicated in which way the solution had come to them.
The participants were then divided into two groups — those who reported solving the problems mostly by sudden insight, and those who reported solving the problems more methodically — and resting-state brain activity for these groups was compared. As predicted, the two groups displayed strikingly different patterns of brain activity during the resting period at the beginning of the experiment — before they knew they would have to solve problems or even knew what the study was about.
One difference was that the creative solvers exhibited greater activity in several regions of the right hemisphere. Previous research has suggested that the right hemisphere of the brain plays a special role in solving problems with creative insight, likely due to right-hemisphere involvement in the processing of loose or “remote” associations between the elements of a problem, which is understood to be an important component of creative thought. The current study shows that greater right-hemisphere activity occurs even during a “resting” state in those with a tendency to solve problems by creative insight. This finding suggests that even the spontaneous thought of creative individuals, such as in their daydreams, contains more remote associations.
Second, creative and methodical solvers exhibited different activity in areas of the brain that process visual information. The pattern of “alpha” and “beta” brainwaves in creative solvers was consistent with diffuse rather than focused visual attention. This may allow creative individuals to broadly sample the environment for experiences that can trigger remote associations to produce an Aha! Moment. For example, a glimpse of an advertisement on a billboard or a word spoken in an overheard conversation could spark an association that leads to a solution. In contrast, the more focused attention of methodical solvers reduces their distractibility, allowing them to effectively solve problems for which the solution strategy is already known, as would be the case for balancing a checkbook or baking a cake using a known recipe.
Thus, the new study shows that basic differences in brain activity between creative and methodical problem solvers exist and are evident even when these individuals are not working on a problem. According to Kounios, “Problem solving, whether creative or methodical, doesn’t begin from scratch when a person starts to work on a problem. His or her pre-existing brain-state biases a person to use a creative or a methodical strategy.”
In addition to contributing to current knowledge about the neural basis of creativity, this study suggests the possible development of new brain imaging techniques for assessing potential for creative thought, and for assessing the effectiveness of methods for training individuals to think creatively.
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Neuropsychologia. 2008;46(1):281-91. Epub 2007 Jul 27.
see also:
Cognitive Insight And Its Neural Mechanism
and
- Neural Activity When People Solve Verbal Problems with Insight
- Published April 13, 2004 - RESEARCH ARTICLE Jung-Beeman M, Bowden EM, Haberman J, Frymiare JL, Arambel-Liu S, et al. - PLoS Biology Vol. 2, No. 4, e97 doi:10.1371/journal.pbio.0020097
- The Prepared Mind: Neural Activity Prior to Problem Presentation Predicts Subsequent Solution by Sudden Insight
- Psychological Science October 2006 (Volume 17, Issue 10 Page 825-924)
Deep Brain Stimulation In Hypothalamus Triggers Memories
Deep brain stimulation (DBS) surgery, which is used to treat Parkinson’s disease and other movement disorders, is now being studied for its potential to treat a variety of conditions. A new study found that hypothalamic DBS performed in the treatment of a patient with morbid obesity unexpectedly evoked a sense of déjà vu and detailed personal memories.
Led by Andres Lozano, Professor of Neurosurgery and Canada Research Chair in Neuroscience and his team at the Toronto Western Hospital in Toronto, Ontario, researchers conducted an experimental study to treat a 50-year-old man with a lifelong history of obesity in whom a variety of treatment approaches had failed. While they were identifying potential appetite suppressant sites in the hypothalamus by stimulating electrode contacts that had been implanted there, the patient suddenly experienced a feeling of “déjà vu.”
He reported the perception of being in a park with friends from when he was around 20 years old and as the intensity of the stimulation was increased, the details became more vivid. These sensations were reproduced when the stimulation was performed in a double-blinded manner. The contacts that most readily induced the memories were located in the hypothalamus and estimated to be close to the fornix, an arched bundle of fibers that carries signals within the limbic system, which is involved in memory and emotions. Stimulation was shown to drive the activity the temporal lobe and the hippocampus, important components of the brain’s memory circuit.
At the first office visit two months after the patient was released from the hospital, the researchers were able to induce and videotape the memory effects seen in the operating room by turning on the electrical stimulation. They also tested the patient’s memory during and without stimulation and found that after three weeks of continuous hypothalamic stimulation he showed significant improvements in two learning tests. In addition, the patient was much more likely to remember unrelated paired objects when stimulation was on than when it was off. They conclude that “just as DBS can influence motor and limbic circuits, it may be possible to apply electrical stimulation to modulate memory function and, in so doing, gain a better understanding of the neural substrates of memory.”
DBS of the hypothalamus has also been used to treat cluster headaches and aggressiveness in humans, and stimulating this area influences feeding behavior in animals.
Annals of Neurology Volume 63, Issue 1, Date: January 2008, Pages: 119-123 DOI 10.1002/ana.21295
Memory enhancement induced by hypothalamic/fornix deep brain stimulation
Clement Hamani, Mary Pat McAndrews, Melanie Cohn, Michael Oh, Dominik Zumsteg, Colin M. Shapiro, Richard A. Wennberg, Andres M. Lozano
Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions.
Checking One Voice In A Noisy Room? New Findings On Selectively Interpreting Sounds
Scientists at Cold Spring Harbor Laboratory (CSHL) have reported new findings about how the mammalian brain interprets and fashions representations of sound that may help explain how we are able to focus on one particular sound among many in noisy environments such as offices or cocktail parties.
Neurons in the brain’s auditory cortex interpret incoming sound signals and send them to the rest of the nervous system, in the brain and spinal cord. Using rats, the CSHL team discovered that a very small minority of available auditory neurons react strongly when exposed to any specific sound.
“This finding challenges the standard model of sound representations in the auditory cortex, which predicts that neural representations of stimuli often engage a large fraction of neurons,” said Anthony Zador, Ph.D., CSHL professor and corresponding author of a new research paper.*
The researchers used a new technique called “in vivo cell-attached patch clamp recording” which measures the reaction of individual neurons. This recording technique samples neurons in a fair and unbiased way, unlike traditional approaches, which favored the largest and most active neurons. Using this technique, the team found that only 5% of neurons in the auditory cortex had a “high firing rate” when receiving a range of sounds of varying length, frequency, and volume. The experiment included white noise and natural animal sounds.
The team’s objective was to quantify the relative contributions of different sub-populations of neurons in response to the range of sounds. Most of what is known about the auditory cortex of the mammalian brain comes from studies of the anesthetized cortex. The results of the experiments reported today are important partly because they measure the response of neurons in rats that were not anesthetized. In animals that are awake, it’s possible to measure the response over an interval of time to one sound among many that are co-occurring.
This is the approach the Zador lab has taken to explain “selective attention,” or what Dr. Zador calls “the cocktail party problem.” Half of the neurons measured in the reported experiments showed no reaction at all to incoming stimuli. The researchers hypothesize that each neuron in the auditory cortex may have an “optimal stimulus” to which it is particularly sensitized.
“Your entire sensory apparatus is there to make successful representations of the outside world,” said Dr. Zador, who is director of the CSHL Swartz Center for Computational Neuroscience. “Sparse representations may make sensory stimuli easier to recognize and remember.” Recognizing the brain’s ability to distinguish “optimal stimuli” could help scientists find ways to improve how sounds are learned. Prior research has already yielded similar results when measuring sight, movement, and smell. This is the first evidence of a correlation between sparse representations and hearing.
“The goal of sensory processing is to take a signal, like a sound or a vision, from your environment and use it to drive behavior,” said Dr. Zador. “The brain needs to recognize and learn about these inputs in order to survive.”
PLoS Biol 6(1): e16 doi:10.1371/journal.pbio.0060016
1 Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold Spring Harbor, New York, United States of America, 2 Department of Physics and Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America, 3 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
‘Satiety Center’ Of The Mouse Brain
By pitting two forces — hunger and circadian rhythms — against each other, researchers at Rockefeller University have identified the region of the mouse brain that first registers changes in food availability. The research, as aforesaid in mice, suggests that shifting the timing of a meal increases mental alertness even during times when they are usually at rest, findings that, perhaps, may have implications for targeting health concerns such as obesity and diabetes as well as optimizing performance on tasks that require sustained vigilance in humans.
To pit the need for food against the need for sleep, scientists led by Donald Pfaff, head of the Laboratory of Neurobiology and Behavior, gradually shifted the mice’s mealtime during the night, when mice are most active, to a four-hour window during the day, when they are usually at rest. Three days after the mealtime shift, the mice began to show classic signs of anticipatory behavior: wheel-running an hour or two before the timed meal. Compared to control animals, the shifted mice ran three times the distance on the wheel — increased activity signaling a heightened sense of alertness. This behavior also suggests that the light-dark cycle no longer regulated the mice’s behavioral arousal; food did.
The researchers used immunocytochemistry to test where in the brain these two arousal pathways converge. Out of the 16 brain regions tested, only one had become activated: the ventromedial hypothalamus, a group of neurons known as the satiety center of the brain. Animals, including humans, tend to stop eating when this region is activated, and damage to this group of neurons leads to obesity. The activity of the paraventricular nucleus, a region that produces many hormones, was decreased.
“Since we examined the brain as close as possible to the development of this anticipatory behavior,” says postdoc Ana Ribeiro, “the neuronal changes we observed are the ones most likely causing the changes in behavioral arousal. These regions are thus the best targets for modulating arousal.”
As about implications for humans, first author Ribeiro daringly claims that to optimize performance on tasks that require sustained vigilance, ones performed by air-traffic controllers, physicians, the military and others, understanding the neural mechanisms and molecules involved in mediating arousal becomes important. “This research,” she says, “gives us a big clue as to what these mechanisms may be.”
PNAS | December 11, 2007 | vol. 104 | no. 50 | 20078-20083
Two forces for arousal: Pitting hunger versus circadian influences and identifying neurons responsible for changes in behavioral arousal
Ana C. Ribeiro*,
, Evelyn Sawa*, Isabelle Carren-LeSauter*, Joseph LeSauter
, Rae Silver,
,¶, and Donald W. Pfaff*,
*Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021; Department of Psychology, Barnard College, New York, NY 10027; Department of Psychology, Columbia University, New York, NY 10027; and ¶Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Contributed by Donald W. Pfaff, October 24, 2007 (received for review July 6, 2007)
The mechanisms underlying CNS arousal in response to homeostatic pressures are not known. In this study, we pitted two forces for CNS arousal against each other (circadian influences vs. restricted food availability) and measured the neuronal activation that occurs in a behaviorally defined group of animals that exhibited increased arousal in anticipation of feeding restricted to their normal sleeping time. The number of c-FOS+ neurons was significantly increased only in the ventromedial nucleus of the hypothalamus (VMH) in these mice, compared with control animals whose feeding was restricted to their normal active and feeding time (P < 0.01). Because the activation of VMH neurons coincides with the earliest signs of behavioral arousal preceding a change in meal time, we infer that VMH activation is involved in the increased arousal in anticipation of food.
Circuitry Of Feedback Perception
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Researchers have found the brain region that controls the decision to halt your midnight exploration of the refrigerator and commence enjoyment of that leftover chicken leg. What’s more, they said, such mechanisms governing exploration are among those that malfunction in addiction and mental illness.
In their experiments, the researchers presented monkeys with a choice of touch targets on a computer screen, requiring the monkeys to spend time exploring which target would trigger a juice reward. Once the monkeys discovered the reward target, the researchers then gave the animals a period during which they could repeatedly touch the reward target to obtain more juice.During the trials, the researchers recorded the electrical activity of hundreds of neurons in the anterior cingulate cortex (ACC), a brain region known to be active in adaptive behaviors such as the shift between exploring and exploiting.
In their analysis, the researchers measured the electrophysiological activity of cells during four different types of feedback–incorrect choices, first reward, repetition of the reward, and the ending of a trial by breaking fixation on the targets.
Analyzing the results, the researchers concluded that “Our data show that ACC discriminates between different types of feedback, allowing appropriate behavioral adaptations.”
Emmanuel Procyk and colleagues published their findings in the January 24, 2008, issue of the journal Neuron, published by Cell Press.
They wrote that “Thus, the function we attribute to ACC activations is clearly not only to evaluate feedbacks but is also to participate in monitoring the different steps of the task at hand to optimize action adaptation and valuation. A dysfunction of these mechanisms represents the core feature of cognitive alterations observed in addiction and mental illness.”
Wrote Procyk and colleagues, “The ACC produces signals that discriminate between various behaviorally relevant positive and negative feedbacks, suggesting a role in triggering appropriate adaptations. Our data reinforce the proposal that ACC is important for establishing action valuations. But they also emphasize a combined role in monitoring events/actions for behavioral regulation when task control is high, underlining the intimate link between control and action valuation.”
Neuron. 2008 Jan 24;57(2):314-25. -
Inserm, U846, Stem Cell and Brain Research Institute, 69500 Bron, France; Université de Lyon, Lyon 1, UMR-S 846, 69003 Lyon, France.
Rapid optimization of behavior requires decisions about when to explore and when to exploit discovered resources. The mechanisms that lead to fast adaptations and their interaction with action valuation are a central issue. We show here that the anterior cingulate cortex (ACC) encodes multiple feedbacks devoted to exploration and its immediate termination. In a task that alternates exploration and exploitation periods, the ACC monitored negative and positive outcomes relevant for different adaptations. In particular, it produced signals specific of the first reward, i.e., the end of exploration. Those signals disappeared in exploitation periods but immediately transferred to the initiation of trials-a transfer comparable to learning phenomena observed for dopaminergic neurons. Importantly, these were also observed for high gamma oscillations of local field potentials shown to correlate with brain imaging signal. Thus, mechanisms of action valuation and monitoring of events/actions are combined for rapid behavioral regulation
ADHD - Now, Is It Or Not?
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A new UCLA study shows that only about half of children diagnosed with attention-deficit hyperactivity disorder, or ADHD, exhibit the cognitive defects commonly associated with the condition.
The study also found that in populations where medication is rarely prescribed to treat ADHD, the prevalence and symptoms of the disorder are roughly equivalent to populations in which medication is widely used.ADHD is a common, chronic behavioral disorder characterized by inattention, hyperactivity and impulsivity that is thought to affect some 5 to 10 percent of school-age children worldwide.
In adolescence, ADHD is generally associated with cognitive deficits, particularly with working memory and inhibition, which have been linked to overall intelligence and academic achievement, according to UCLA psychiatry professor Susan Smalley, who headed the research. Interestingly, the study showed that these deficits are only present in about half of adolescents diagnosed with ADHD.
Part of the explanation may lie in the common method for diagnosing the disorder. ADHD is an extreme on a normal continuum of behavior that varies in the population, much like height, weight or IQ. Its diagnosis, and thus its prevalence, is defined by where health professionals “draw the line” on this continuum, based on the severity of the symptoms and overall impairment.
However, children with cognitive deficits do not show increased levels of inattention or hyperactivity when compared with other children diagnosed with ADHD, the study found, suggesting that behavior-rating scales alone are not sensitive enough to differentiate between the two groups. Additional psychological testing is recommended to confirm the presence of cognitive impairments.
Researchers also found surprising results regarding the effectiveness of medicine in treating ADHD. In contrast to children in United States, youth in northern Finland are rarely treated with medicine for ADHD, yet the ‘look’ of the disorder — its prevalence, symptoms, psychiatric comorbidity and cognition — is relatively the same as in the U.S., where stimulant medication is widely used. The researchers point out that this raises important issues about the efficacy of the current treatments of ADHD in dealing with the disorder’s long-term problems.
“We know medication is very effective in the short-term,” said Smalley, who authored or co-authored each of the papers. “But the study raises important questions concerning the long-term efficacy of ADHD treatment. Here we have two different cultures and two different approaches to treatment, yet at the time of adolescence, there are few differences in the presentation and problems associated with ADHD.”
Other findings from the wide-ranging study include:
- Further confirmation that ADHD symptoms do change with age: Hyperactivity and impulsivity decrease with age, while inattention increasingly predominates. In fact, about two-thirds of children with ADHD continue to exhibit significant levels of inattentiveness and impairment into adolescence.
- ADHD is associated with increased rates of other psychiatric problems. Most prominent in adolescence are depression; anxiety; oppositional behaviors, such as arguing, losing one’s temper and being easily annoyed; and conduct disorders like vandalism and truancy. Surprisingly, post-traumatic stress disorder is significantly elevated among adolescents with ADHD, compared with non-ADHD youth. The prevalence of these co-occurring disorders is comparable to that found in other ADHD populations worldwide.
- Two genes, labeled DBH and DRD2, involved in the regulation of dopamine — a neurotransmitter involved in attention, motivation and emotion — have also been associated with ADHD in the population of northern Finland. Although the researchers involved say they likely account for very little of the genetic variation underlying ADHD, the findings further support the involvement of the dopamine pathway in the etiology of the disorder.
“This set of articles brings to light the necessity of engaging in new ways of thinking about ADHD,” said Smalley, who is also a member of the Center for Neurobehavioral Genetics at UCLA. “Certainly it is a valid disorder in terms of its diagnosis; there are relatively similar prevalences around the world. But the predisposition to ADHD is a normal distribution in attention and activity level, much like diabetes and glucose tolerance, or dyslexia and reading disability.
And one cannot emphasize enough, what she added: “The continuous nature of liability to ADHD requires that we examine more carefully what environmental pressures may be leading to impairment, instead of broadening our diagnostic classifications even further.”
The results of the first large, longitudinal study of adolescents and ADHD, conducted among the population of northern Finland, appeared in several papers in a special section of the Journal of the American Academy of Child and Adolescent Psychiatry published in December and are currently online.
The study started in 1986, when researchers from Imperial College, London, and Finland’s University of Oulu began studying 9,432 children in northern Finland. They tracked the children from the early fetal period to adolescence (age 16 to 18). UCLA researchers then joined in the effort to examine the adolescents for ADHD behaviors, using a standard screening survey and diagnostic criteria. Among the 6,622 respondents to the survey, a subset of 457 likely cases and controls were evaluated for ADHD and other psychiatric disorders. The estimated prevalence of ADHD among these adolescents was 8.5 percent, with a male-female ratio of 5.7 to 1.
J Am Acad Child Adolesc Psychiatry. 2007 Dec;46(12):1575-83.OBJECTIVE: The purpose of the study was to estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its clinical characteristics in the Northern Finland Birth Cohort 1986. METHOD: A general population Northern Finland Birth Cohort 1986 of 9,432 children followed prospectively from the early fetal period was surveyed at adolescence (ages 16-1
for ADHD behaviors. Among 6,622 respondents to the survey, a subset of 457 likely cases and controls were evaluated for ADHD and other psychiatric disorders. Chi-square and descriptive statistics were used to examine clinical characteristics of ADHD in the subset, and logistic regression was used to estimate prevalence by weighted extrapolation in the larger cohort. RESULTS: The estimated prevalence of ADHD among adolescents in the Northern Finland Birth Cohort 1986 is 8.5% with a male/female ratio of 5.7:1. The distribution of ADHD subtypes among the ADHD adolescents is 28% Combined, 64% Inattentive, and 8% Hyperactive-Impulsive. A lifetime diagnosis of a broadly defined ADHD (probable or definite) had a prevalence of 18.2% with a male/female odds ratio (OR) of 3.2. This lifetime diagnosis of ADHD is significantly associated with anxiety (OR 2.4), mood (OR 2.9), and disruptive behavioral disorders (OR 17.3) in the cohort. CONCLUSIONS: ADHD is a common neurobehavioral disorder among Northern Finnish adolescents and significantly associated with psychiatric comorbidity in adolescence.see also:
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J Am Acad Child Adolesc Psychiatry. 2007 Dec;46(12):1594-604.
