Can Happiness Be Inherited?

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ScienceDaily (May 14, 2009) — A new study suggests that our feelings in our lifetime can affect our children.

Dr. Halabe Bucay suggests that a wide range of chemicals that our brain generates when we are in different moods could affect 'germ cells' (eggs and sperm), the cells that ultimately produce the next generation. Such natural chemicals could affect the way that specific genes are expressed in the germ cells, and hence how a child develops.
In his article in the latest issue of Bioscience Hypotheses, Dr Alberto Halabe Bucay of Research Center Halabe and Darwich, Mexico, suggested that the hormones and chemicals resulting from happiness, depression and other mental states can affect our eggs and sperm, resulting in lasting changes in our children at the time of their conception.
Brain chemicals such as endorphins, and drugs, such as marijuana and heroin are known to have significant effects on sperm and eggs, altering the patterns of genes that are active in them.
"It is well known, of course, that parental behavior affects children, and that the genes that a child gets from its parents help shape that child's character." said Dr. Halabe Bucay. "My paper suggests a way that the parent's psychology before conception can actually affect the child's genes."
"This is an intriguing idea" commented Dr. William Bains, Editor of Bioscience Hypotheses. "We wanted to publish it to see what other scientists thought, and whether others had data that could support or disprove it. That is what our journal is for, to stimulate debate about new ideas, the more groundbreaking, the better."
Journal reference:
Halabe Bucay et al. Endorphins, personality, and inheritance: Establishing the biochemical bases of inheritance. Bioscience Hypotheses, May 7, 2009; DOI: 10.1016/j.bihy.2009.03.003
Adapted from materials provided by Elsevier, via EurekAlert!, a service of AAAS.

When Senses Intersect: The neurologist Richard Cytowic discusses what synesthesia can teach us about ordinary perception, creativity and V.Nabokov

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Dr. Richard Cytowic is one of the leading researchers of synesthesia, a condition in which two normally separated sensations - such as sight and sound, or touch and taste - occur at the same time. As a result, a synesthetic person might experience the taste of a dish on her fingertips, or be convinced that the letter X is a vibrant turquoise. Mind Matters editor Jonah Lehrer chats with Cytowic about his new book, Wednesday is Indigo Blue, which he co-wrote with David Eagleman.

LEHRER: What first got you interested in synesthesia?
CYTOWIC: It was an accident. I like etymology and so knew the word, whereas my colleagues back in 1979 had never heard of synesthesia. In fact, they refused to believe it could be real, and warned that looking into such “weird” and “New Age” nonsense would ruin my career. Their denial was the typical reaction of orthodoxy to something it can’t explain.
It is said that chance favors the prepared mind, so I guess I was ready when a dinner host apologized that there weren’t “enough points on the chicken.” For Michael Watson, who I later wrote about as “The Man Who Tasted Shapes,” flavor was more than a mouthful. Taste was also a touch sensation felt on his face and in his hands. “With an intense flavor,” he explained, “a feeling sweeps down my arm and I feel weight, shape, texture, and temperature as if I’m actually grasping something.”
Fortunately, I could use university resources to quietly study Michael in depth and write papers. What interested me most was pondering an experience that “wasn’t supposed to be.”
LEHRER: How has our scientific understanding of synesthesia changed in recent years?
CYTOWIC: It has to do with possibilities of how the senses couple in the brain. My first idea that the emotional brain served as the link gave way, based on observations in neonatal synesthesia, to the possibility of faulty pruning. That is, the gene in synesthesia might fail to prune the extra synapses that are normally made in great excess in all newborns. We thought their persistence might plausibly explain why some people are synesthetes.
Today, we know that far from being rare, synesthesia is common––one in 23 individuals has some kind of synesthesia, and one in 90 has colored letters and numerals. That being so, in Wednesday is Indigo Blue David Eagleman and I favor a genetically–determined imbalance between excitation and inhibition. We’ve learned that the normal brain is already highly cross–wired. We think synesthesia occurs due to increased activity in existing wiring rather than the result of extra wiring.
LEHRER: What can synesthetes teach us about the nature of human perception?
CYTOWIC: Far from being a mere curiosity, synesthesia is a consciously elevated form of the perception that everyone already has. Minds that function differently are not so strange after all, and everyone can learn from them.
Synesthesia has opened up a window onto a broad expanse of the brain and perception. Younger researchers are now active in 15 countries. Because the trait runs strongly in families, it is easy to collect DNA from a large number of synesthetic relatives. This means that synesthesia may be the very first perceptual condition for which science can map its gene. This inherited quirk is teaching us that cross–talk among the senses is the rule rather than the exception––we are all inward synesthetes who are outwardly unaware of sensory couplings happening all the time.
For example, sight, sound, and movement normally map to one another so closely that even bad ventriloquists convince us that whatever moves is doing the talking. Likewise, cinema convinces us that dialogue comes from the actors’ mouths rather than the surrounding speakers. Dance is another example of cross–sensory mapping in which body rhythms imitate sound rhythms kinetically and visually. We so take these similarities for granted that we never question them the way we might doubt colored hearing.

LEHRER:In Wednesday Is Indigo Blue, you argue that investigations of synesthesia can help us better understand the neurological basis of metaphor and even creativity. Could you explain?
CYTOWIC: Artists are at ease using metaphors, and we have known for a long time that synesthesia is more common in creative individuals. Famous synesthetes include novelist Vladimir Nabokov, whose mother and son Dmitri also had it; composers Olivier Messiaen, Amy Beech and Billy Joel; and painters David Hockney and Wasily Kandinsky. Dmitri Nabokov, incidentally, wrote a charming afterword about his father and himself for “Indigo Blue.”
There is more to creativity than a capacity for metaphor, of course. Nonetheless, begin with the assumption that the gene for synesthesia lashes together normally unconnected brain areas, thus linking seemingly unrelated qualities such as sound and color. Having one kind of synesthesia gives a person a 50 percent chance of having a second or third kind, meaning that the gene expresses itself in two or three separate areas in that person’s brain. Suppose, however, that brain hyper–connectivity occurred not selectively here and there, but diffusely. One would have a generalized talent for cross connecting apparently unrelated concepts, which is the definition of metaphor: seeing the similar in the dissimilar.
And this is the reason several of us suspect that the synesthesia gene maintains itself at such a high frequency in the population. After all, one in 23 people are walking around with a mutation for an apparently useless trait. It must be doing something of inapparent value in order for evolution to select so strongly in its favor. When the gene expresses itself in sensory parts of the brain, people are outwardly synesthetic. But what are they like when the mutation expresses itself in non–sensory brain parts such as those concerned with memory, planning, or moral reasoning? Might it contribute to increased creativity, thereby making humans smarter as a whole?
We are beginning to find out. The strongest link so far is a region on chromosome 2 that is associated with autism and epilepsy, conditions that occur together with synesthesia more often than chance predicts. The autistic savant Daniel Tammet, whose best–selling autobiography is Born on a Blue Day, has all three conditions––indicating that they might share an underlying genetic mechanism. Tammet first shot to fame in Britain when he set a record for reciting 22,514 digits of pi from memory.
LEHRER: Has there been one case of synesthesia that you've been particularly astonished by?
CYTOWIC: What is astonishing about The Man Who Tasted Shapes is how rare Michael Watson’s type of flavor–touch synesthesia turned out to be in retrospect: less than one percent. So, the odds of him having been the first case were vanishingly small.
One feature that still fascinates me is the “screen” phenomenon that some people with colored hearing have. That is, they see their sound–triggered hues, geometric shapes, and moving configurations projected a foot or so in front of their face as if on a screen. One college professor particularly likes seeing rising and falling lines. Lines that go up are the best. “My favorite music,” she says, “makes the lines go right off the top of the screen.”
In the end, the most astonishing thing I’ve experienced over and over during 30 years of study has been the trust strangers placed in me and their willingness to allow me into their private worlds. That is a brave thing to do when no one has believed you all your life. So it is impossible not to remain fascinated with synesthesia, and even more so synesthetes themselves.
Are you a scientist? Have you recently read a peer-reviewed paper that you want to write about? Then contact Mind Matters editor Jonah Lehrer, the science writer behind the blog The Frontal Cortex and the book Proust Was a Neuroscientist. His latest book is How We Decide.

By Richard Cytowic

Meditation increases brain gray matter

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Push-ups, crunches, gyms, personal trainers -- people have many strategies for building bigger muscles and stronger bones. But what can one do to build a bigger brain? Meditate.

That's the finding from a group of researchers at UCLA who used high-resolution magnetic resonance imaging (MRI) to scan the brains of people who meditate. In a study published in the journal NeuroImage and currently available online (by subscription), the researchers report that certain regions in the brains of long-term meditators were larger than in a similar control group.
Specifically, meditators showed significantly larger volumes of the hippocampus and areas within the orbito-frontal cortex, the thalamus and the inferior temporal gyrus — all regions known for regulating emotions.
"We know that people who consistently meditate have a singular ability to cultivate positive emotions, retain emotional stability and engage in mindful behavior," said Eileen Luders, lead author and a postdoctoral research fellow at the UCLA Laboratory of Neuro Imaging. "The observed differences in brain anatomy might give us a clue why meditators have these exceptional abilities."
Research has confirmed the beneficial aspects of meditation. In addition to having better focus and control over their emotions, many people who meditate regularly have reduced levels of stress and bolstered immune systems. But less is known about the link between meditation and brain structure.
In the study, Luders and her colleagues examined 44 people — 22 control subjects and 22 who had practiced various forms of meditation, including Zazen, Samatha and Vipassana, among others. The amount of time they had practiced ranged from five to 46 years, with an average of 24 years.
More than half of all the meditators said that deep concentration was an essential part of their practice, and most meditated between 10 and 90 minutes every day.
The researchers used a high-resolution, three-dimensional form of MRI and two different approaches to measure differences in brain structure. One approach automatically divides the brain into several regions of interest, allowing researchers to compare the size of certain brain structures. The other segments the brain into different tissue types, allowing researchers to compare the amount of gray matter within specific regions of the brain.

The researchers found significantly larger cerebral measurements in meditators compared with controls, including larger volumes of the right hippocampus and increased gray matter in the right orbito-frontal cortex, the right thalamus and the left inferior temporal lobe. There were no regions where controls had significantly larger volumes or more gray matter than meditators.
Because these areas of the brain are closely linked to emotion, Luders said, "these might be the neuronal underpinnings that give meditators' the outstanding ability to regulate their emotions and allow for well-adjusted responses to whatever life throws their way."
What's not known, she said, and will require further study, are what the specific correlates are on a microscopic level — that is, whether it's an increased number of neurons, the larger size of the neurons or a particular "wiring" pattern meditators may develop that other people don't.
Because this was not a longitudinal study — which would have tracked meditators from the time they began meditating onward — it's possible that the meditators already had more regional gray matter and volume in specific areas; that may have attracted them to meditation in the first place, Luders said.
However, she also noted that numerous previous studies have pointed to the brain's remarkable plasticity and how environmental enrichment has been shown to change brain structure.
Source: University of California - Los Angeles

Brain's Problem-solving Function At Work When We Daydream

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ScienceDaily (May 12, 2009) — A new University of British Columbia study finds that our brains are much more active when we daydream than previously thought.

The study, published in the Proceedings of the National Academy of Sciences, finds that activity in numerous brain regions increases when our minds wander. It also finds that brain areas associated with complex problem-solving – previously thought to go dormant when we daydream – are in fact highly active during these episodes.
"Mind wandering is typically associated with negative things like laziness or inattentiveness," says lead author, Prof. Kalina Christoff, UBC Dept. of Psychology. "But this study shows our brains are very active when we daydream – much more active than when we focus on routine tasks."
For the study, subjects were placed inside an fMRI scanner, where they performed the simple routine task of pushing a button when numbers appear on a screen. The researchers tracked subjects' attentiveness moment-to-moment through brain scans, subjective reports from subjects and by tracking their performance on the task.
The findings suggest that daydreaming – which can occupy as much as one third of our waking lives – is an important cognitive state where we may unconsciously turn our attention from immediate tasks to sort through important problems in our lives.
Until now, the brain's "default network" – which is linked to easy, routine mental activity and includes the medial prefrontal cortex (PFC), the posterior cingulate cortex and the temporoparietal junction – was the only part of the brain thought to be active when our minds wander.
However, the study finds that the brain's "executive network" – associated with high-level, complex problem-solving and including the lateral PFC and the dorsal anterior cingulate cortex – also becomes activated when we daydream.
"This is a surprising finding, that these two brain networks are activated in parallel," says Christoff. "Until now, scientists have thought they operated on an either-or basis – when one was activated, the other was thought to be dormant." The less subjects were aware that their mind was wandering, the more both networks were activated.
The quantity and quality of brain activity suggests that people struggling to solve complicated problems might be better off switching to a simpler task and letting their mind wander.
"When you daydream, you may not be achieving your immediate goal – say reading a book or paying attention in class – but your mind may be taking that time to address more important questions in your life, such as advancing your career or personal relationships," says Christoff.
The research team included members who are now at Stanford University and University of California, Santa Barbara.
Journal reference:
Kalina Christoff, Alan M. Gordon, Jonathan Smallwood, Rachelle Smith, and Jonathan W. Schooler. Experience sampling during fMRI reveals default network and executive system contributions to mind wandering. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0900234106
Adapted from materials provided by University of British Columbia.

Impaired Brain Plasticity Linked To Angelman Syndrome Learning Deficits

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ScienceDaily (May 10, 2009) — How might disruption of a single gene in the brain cause the severe cognitive deficits associated with Angelman syndrome, a neurogenetic disorder? Researchers at the University of North Carolina at Chapel Hill School of Medicine and Duke University now believe they have the answer: impaired brain plasticity.

"When we have experiences, connections between brain cells are modified so that we can learn," said Benjamin Philpot, Ph.D., professor of cell and molecular physiology at UNC and senior author of the study published online May 10 in Nature Neuroscience. "By strengthening and weakening appropriate connections between brain cells, a process termed 'synaptic plasticity', we are able to constantly learn and adapt to an ever-changing environment."
Angelman syndrome occurs in one in 15,000 live births. The most common genetic defect of the syndrome is the lack of expression of the gene UBE3A on chromosome 15. The syndrome often is misdiagnosed as cerebral palsy or autism. Characteristics of the syndrome include intellectual and developmental delay, severe mental retardation lack of speech (minimal or no use of words), seizures, sleep disturbance, hand flapping and motor and balance disorders.
Philpot and his co-authors studied a mouse model of Angelman syndrome. In these mice, the gene UBE3A is functionally deficient. The study found that brain cells in the mice lacked the ability to appropriately strengthen or weaken their connections in the neocortex, a region of the brain that is important for cognitive abilities.
"If brain cells were unable to modify their connections with new experiences, then we would have difficulty learning," said Michael Ehlers, M.D., Ph.D., professor of neurobiology at Duke and co-senior author of the study. "We have found that a specific form of brain plasticity is severely impaired in a mouse model of Angelman syndrome and this prevents brain circuits from encoding information provided by sensory experiences. In addition, an exciting possibility is that the defect we have found may be a more general feature of other disorders of brain development including autism."
The inability of brain cells to encode information from experiences in the Angelman syndrome model suggests that this is the basis for the learning difficulties in these patients.
"It is difficult to study how experiences lead to changes in the brain in models of mental retardation," said Koji Yashiro, PhD, a former graduate student in Philpot's lab and lead author of the study, now a scientist with Urogenix, Inc. in Research Triangle Park, North Carolina. "Instead of studying a complex learning model, we studied how connections between brain cells change in visual areas of mice exposed to light or kept in darkness. This approach revealed that brain cells in normal mice can modify their connections in response to changes in visual experiences, while the brain cells in Angelman syndrome model mice could not."
An unexpected finding was that the plasticity of the cellular connections could be restored in visual areas of the brain after brief periods of visual deprivation. Philpot said the observation that the brain defect could be reversed "is very encouraging, as it suggests that viable behavioral or pharmacological therapies are likely to exist."
"By showing that brain plasticity can be restored in Angelman syndrome model mice, our findings suggest that brain cells in Angelman syndrome patients maintain a latent ability to express plasticity. We are now collaborating to find a way to tap into this latent plasticity, as this could offer a treatment, or even a cure, for Angelman syndrome," said Philpot.
Philpot added, "This same experimental approach could also reveal how brain cells encode information from experiences in other related disorders, such as autism, and may provide a model to find cures for a variety of neurodevelopmental disorders."
Other authors are, from Philpot's UNC lab: Thorfinn Riday, graduate student; Adam Roberts, Ph.D., postdoctoral fellow; Danilo Bernardo, medical student; and Rohit Prakash, former M.D./Ph.D. rotation student. Kathryn Condon, a graduate student in Ehler's lab and the department of neurobiology at Duke University; and Richard Weinberg, Ph.D., professor of cell and developmental biology at UNC, also participated in the research.
Support for the work came from grants from the National Institutes of Health, the Howard Hughes Medical Institute, the Angelman Syndrome Foundation and the Simons Foundation.
Adapted from materials provided by University of North Carolina School of Medicine, via EurekAlert!, a service of AAAS.

Gene Key To Alzheimer's-like Reversal Identified: Success In Restoring Memories In Mice Could Lead To Human Treatments

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ScienceDaily (May 7, 2009) — A team led by researchers at MIT's Picower Institute for Learning and Memory has now pinpointed the exact gene responsible for a 2007 breakthrough in which mice with symptoms of Alzheimer's disease regained long-term memories and the ability to learn.

In the latest development, reported in the May 7 issue of Nature, Li-Huei Tsai, Picower Professor of Neuroscience, and colleagues found that drugs that work on the gene HDAC2 reverse the effects of Alzheimer's and boost cognitive function in mice.
"This gene and its protein are promising targets for treating memory impairment," Tsai said. "HDAC2 regulates the expression of a plethora of genes implicated in plasticity — the brain's ability to change in response to experience — and memory formation.
"It brings about long-lasting changes in how other genes are expressed, which is probably necessary to increase numbers of synapses and restructure neural circuits, thereby enhancing memory," she said.
The researchers treated mice with Alzheimer's-like symptoms using histone deacetylase (HDAC) inhibitors. HDACs are a family of 11 enzymes that seem to act as master regulators of gene expression. Drugs that inhibit HDACs are in experimental stages and are not available by prescription for use for Alzheimer's.
"Harnessing the therapeutic potential of HDAC inhibitors requires knowledge of the specific HDAC family member or members linked to cognitive enhancement," Tsai said. "We have now identified HDAC2 as the most likely target of the HDAC inhibitors that facilitate synaptic plasticity and memory formation.
"This will help elucidate the mechanisms by which chromatin remodeling regulates memory," she said. It also will shed light on the role of epigenetic regulation, through which gene expression is indirectly influenced, in physiological and pathological conditions in the central nervous system.
"Furthermore, this finding will lead to the development of more selective HDAC inhibitors for memory enhancement," she said. "This is exciting because more potent and safe drugs can be developed to treat Alzheimer's and other cognition diseases by targeting this HDAC specifically," said Tsai, who is also a Howard Hughes Medical Institute investigator. Several HDAC inhibitors are currently in clinical trials as novel anticancer agents and may enter the pipeline for other diseases in the coming two to four years. Researchers have had promising results with HDAC inhibitors in mouse models of Huntington's disease.
Remodeling structures
Proteins called histones act as spools around which DNA winds, forming a structure in the cell nucleus known as chromatin. Histones are modified in various ways, including through a process called acetylation, which in turn modifies chromatin shape and structure. (Inhibiting deacetylation with HDAC inhibitors leads to increased acetylation.)
Certain HDAC inhibitors open up chromatin. This allows transcription and expression of genes in what had been a too tightly packaged chromatin structure in which certain genes do not get transcribed.
There has been exponential growth in HDAC research over the past decade. HDAC inhibitors are currently being tested in preclinical studies to treat Huntington's disease. Some HDAC inhibitors are on the market to treat certain forms of cancer. They may help chemotherapy drugs better reach their targets by opening up chromatin and exposing DNA. "To our knowledge, HDAC inhibitors have not been used to treat Alzheimer's disease or dementia," Tsai said. "But now that we know that inhibiting HDAC2 has the potential to boost synaptic plasticity, synapse formation and memory formation, in the next step, we will develop new HDAC2-selective inhibitors and test their function for human diseases associated with memory impairment to treat neurodegenerative diseases."
The researchers conducted learning and memory tasks using transgenic mice that were induced to lose a significant number of brain cells. Following Alzheimer's-like brain atrophy, the mice acted as though they did not remember tasks they had previously learned.
But after taking HDAC inhibitors, the mice regained their long-term memories and ability to learn new tasks. In addition, mice genetically engineered to produce no HDAC2 at all exhibited enhanced memory formation.
The fact that long-term memories can be recovered by elevated histone acetylation supports the idea that apparent memory "loss" is really a reflection of inaccessible memories, Tsai said. "These findings are in line with a phenomenon known as 'fluctuating memories,' in which demented patients experience temporary periods of apparent clarity," she said.
In addition to Tsai, co-authors are Picower postdoctoral associate Ji-Song Guan; and colleagues from Massachusetts General Hospital; Harvard Medical School; the Whitehead Institute for Biomedical Research; MIT's Department of Biology; the Dana Farber Cancer Institute; and the Netherlands Cancer Institute.
This work is supported by the National Institute for Neurological Disorders and Stroke, the Stanley Center for Psychiatric research at the Broad Institute of Harvard and MIT; the NARSAD, a mental health foundation, the National Cancer Institute, the Damon-Runyon Cancer Research Foundation; the Dutch Cancer Society; the National Institutes of Health; and the Robert A. and Renee E. Belfer Institute for Applied Cancer Science.
Journal reference:
Guan et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature, 2009; 459 (7243): 55 DOI: 10.1038/nature07925
Adapted from materials provided by Massachusetts Institute of Technology.

Brain Cell Mechanism For Decision Making Also Underlies Judgment About Certainty

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ScienceDaily (May 8, 2009) — Countless times a day people judge their confidence in a choice they are about to make -- that they now can safely turn left at this intersection, that they aren't sure of their answer on a quiz, that their hot coffee has cooled enough to drink.

University of Washington (UW) researchers who study how the brain makes decisions are uncovering the biological mechanisms behind the belief that a choice is likely to be correct.
"Choice certainty," noted one of the researchers, Dr. Roozbeh Kiani, "allows us to translate our convictions into suitable actions." Several other research projects have shown that choice certainty is closely associated with reaction time and with decision accuracy.
Kiani and the co-author of the new May 8 Science article, Michael N. Shadlen are members of the UW Department of Physiology and Biophysics and of the National Primate Research Center. Shadlen is also an investigator in the Howard Hughes Medical Institute.
The researchers tested the possibility that the same brain cell mechanism that underlies decision making might also underlie judgments about certainty. In their study, rhesus monkeys played a video game in which they watched a dynamic, random dot display. They then had to determine the direction of motion. The difficulty of the task was varied by both the percentage of moving dots and the viewing time. After a short delay, the fixation point faded. This cued the monkey to indicate its choice of direction by moving its eyes toward one of two targets. The monkey would receive a reward for each correct choice, and no reward for an incorrect choice.
On a random half of the trials, the monkey could pass on making a choice and instead pick a third, fixed-position target that guaranteed a small reward. While watching the moving dots, the monkeys didn't know whether this third option would be offered. The sure bet was shown during the short delay.
"The monkeys opted for the sure target when the chance of making a correct decision about the motion direction was small," the researchers noted. They picked the sure bet more frequently when the visual evidence was weaker and duration shorter.
According to the researchers, when the monkeys waived the sure-bet option, they more accurately picked the correct direction than when the wager wasn't offered. This occurred at all levels of difficulty, suggesting that the monkeys chose the sure bet because of uncertainty, not because that round of the game was too hard.
The researchers recorded activity from 70 brain cells while the monkeys made their decisions. The cells were located in the lateral intraparietal cortex of the brain. The parietal lobe is located just under the crown of the head and plays a role in spatial sensations. In rhesus monkeys, the lateral area of the parietal lobe is attuned to movement.
The researchers found that the pattern of firing activity in these brain nerve cells could predict the direction choice and whether the monkey would opt out of the direction decision by taking the sure bet when it was offered. Normally, these brain cells change their firing rates as evidence accrues for one direction or the other, ultimately giving rise to a clear decision through high or low firing rates.
On some trials, however, these same brain cells seemed to dilly-dally and achieve an intermediate "gray zone" of activity. Those were the trials where the monkey declared uncertainty by choosing the sure-bet target.
Analysis of the detailed data from the study results show that the mechanism underlying certainty in these brain cells is linked to the same evidence accumulation that underlies choice and decision time.
"Some research has suggested that brain cells in an area associated with reward expectation or conflict are associated with decision uncertainty," Kiani noted. "However, these brain cells presumably receive this information from neurons involved in decision making."
The results of this study, according to the authors, advance the understanding of brain cell mechanisms that underlie decision making by coupling for the first time the mechanisms that lead to decision formation and the establishment of a degree of confidence in that decision.
"This simple mechanism," the authors said, "brings certainty, which is commonly conceived as a subjective aspect of decision making, under the same rubric as choice and reaction time."
According to the researchers, it is likely that these cells also carry the relevant signals for assigning the probability of receiving a reward. The researchers noted that it seems likely that this computation of choice certainty is passed from the lateral parietal cortex to brain structures that anticipate reward, and that the response from these structures influence the decision to pick or forgo the sure bet if it is offered.
The authors went on to add, "Our findings suggest that when the brain embraces truth, it does so in a graded way so that even a binary [yes/no, true/false, left/right] choice leaves in its wake a quantity that represents a degree of belief. The neural mechanism of decision making doesn't flip into a fixed point, but instead approximates a probability distribution."
The Howard Hughes Medical Institute, the National Eye Institute of the National Institutes of Health, and the National Center for Research Resources supported the research.
Journal reference:
Roozbeh Kiani and Michael N. Shadlen. Representation of Confidence Associated with a Decision by Neurons in the Parietal Cortex. Science, 2009; DOI: 10.1126/science.1169405
Adapted from materials provided by University of Washington.

Schizophrenia: Blocking Errant Protein Could Stem Runaway Brain Activity In Psychosis

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ScienceDaily (May 6, 2009) — A study on schizophrenia has implicated machinery that maintains the flow of potassium in cells and revealed a potential molecular target for new treatments. Expression of a previously unknown form of a key such potassium channel was found to be 2.5 fold higher than normal in the brain memory hub of people with the chronic mental illness and linked to a hotspot of genetic variation.

An extensive series of experiments suggest that selectively inhibiting this suspect form could help correct disorganized brain activity in schizophrenia – without risk of cardiac side effects associated with some existing antipsychotic medications. Scientists at the National Institutes of Health and European colleagues report on threads of converging evidence in the May, 2009 issue of the journal Nature Medicine.
"The end game in linking genes with complex disorders like schizophrenia requires that we not only demonstrate statistical association, but also show how a gene version acts biologically to confer risk," explained Daniel Weinberger, M.D., director of National Institute of Mental Health's (NIMH) Genes Cognition and Psychosis Program, who led the research. "We found schizophrenia-like effects in brain circuitry and mental processing in perfectly healthy people who carry the risk-associated version of this potassium channel gene, even though they don't show any psychotic behavior."
Evidence suggests that schizophrenia stems from complex interactions between multiple genes and environmental factors. Several candidate genes have recently been statistically linked to the illness in large genome-wide association studies.
"Our study goes further, spanning discovery of a new gene variant, confirmation of its association with the illness, and multi-level probes into how it works – in human post mortem brain tissue, the living human brain, and neurons," added Weinberger.
By regulating the flow of potassium ions into the cell, potassium channels control when neurons fire – electrically discharge and release a chemical messenger that signals neighboring neurons in a circuit. This flow is regulated, in part, by activity of the chemical messenger dopamine, the main target of antipsychotic medications used to treat schizophrenia.
One type of potassium channel, called KCNH2, attracted the researchers' interest for its potential role in sustaining the type of neuronal firing that supports the higher mental functions disturbed in schizophrenia. Spurred by hints from postmortem studies of genetic variation linked to schizophrenia in the genomic neighborhood of KCNH2, the researchers analyzed the gene's association with the illness in 5 independent samples comprising hundreds of families. This pinpointed 4 variations associated with schizophrenia within a small region of the KCNH2 gene.
"Yet this statistical association didn't imply a mechanism," said Weinberger. "It didn't explain how KCNH2 might increase risk for schizophrenia. So we went back to the post-mortem brain tissue in search of an answer."
It was only then that the researchers discovered a previously unknown version of KCNH2, called Isoform 3.1, that soared to levels 2.5 times higher-than-normal in the hippocampus (memory hub) of people who had schizophrenia – especially those with the risk-associated variations. Isoform 3.1 was also higher-than-normal in healthy individuals who carried the risk-associated variations. This signaled the existence of a risk-associated version of the KCNH2 gene.
Healthy controls carrying the risk gene version also:
Performed significantly worse-than-normal on measures of IQ and mental processing speed. Previous studies have linked similar performance with genetic risk for schizophrenia.
Inefficiently processed memory in the hippocampus and working memory in the prefrontal cortex, as revealed by functional MRI (magnetic resonance imaging) scans. Although they performed similarly to controls on these tasks, their brains had to work harder to compensate for disordered tuning of circuitry – a phenomenon previously implicated in schizophrenia.
Showed significantly decreased volume in the hippocampus – a heritable trait – in anatomical MRI scans.
In addition, Isoform 3.1:
Showed levels 1,000 times lower in the heart than the other main form of KCNH2 and does not exist in lower animals, suggesting that it has evolved a unique role in the primate brain. Mutant forms of KCNH2 in the heart can lead to arrhythmias and even sudden death – a rare risk of taking antipsychotic medications, many of which interact with KCNH2. So targeting this brain-specific form potentially opens the way to development of new treatments free of such cardiac side-effects.
Dramatically changed activity in rodent brains toward a neuronal firing pattern that may be important for thinking and memory tasks unique to primates.
Is expressed much more prior to birth, compared to the other main form of KCNH2, suggesting that it plays a prominent role in the early stages of brain development.
Is associated with a hotspot of variation in an area that controls gene expression, hinting that the suspect variations may contribute to schizophrenia risk by over-expressing Isoform 3.1.
Even though it is normally important for our higher order executive functioning, such over expression of Isoform 3.1 in schizophrenia could result in "abnormally increased neuronal excitability, runaway circuit activity and inefficient information processing," suggested Stephen Huffaker, Ph.D., the article's lead author, now a medical student at Harvard. The researchers propose that a treatment designed to inhibit just Isoform 3.1, might spare any heart-related side effects while improving the disorganized neural firing characteristic of the brain in schizophrenia.
In addition to the NIMH, researchers from the NIH's National Institute on Child Health and Human Development (NICHD) also participated in the research.
Journal reference:
Huffaker et al. A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nature Medicine, May 3, 2009; DOI: 10.1038/nm.1962
Adapted from materials provided by NIH/National Institute of Mental Health.