Creativity: Humour

Human cognition depends upon slow-firing neurons

Good mental health and clear thinking depend upon our ability to store and manipulate thoughts on a sort of "mental sketch pad."

In a new study, Yale School of Medicine researchers describe the molecular basis of this ability -- the hallmark of human cognition -- and describe how a breakdown of the system contributes to diseases such as schizophrenia and Alzheimer's disease.

Prof Amy Arnsten

"Insults to these highly evolved cortical circuits impair the ability to create and maintain our mental representations of the world, which is the basis of higher cognition," said Amy Arnsten, professor of neurobiology and senior author of the paper published in the Feb. 20 issue of the journal Neuron.

High-order thinking depends upon our ability to generate mental representations in our brains without any sensory stimulation from the environment.

These cognitive abilities arise from highly evolved circuits in the prefrontal cortex.

Mathematical models by former Yale neurobiologist Xiao-Jing Wang, now of New York University, predicted that in order to maintain these visual representations the prefrontal cortex must rely on a family of receptors that allow for slow, steady firing of neurons.

The Yale scientists show that NMDA-NR2B receptors involved in glutamate signaling regulate this neuronal firing.

These receptors, studied at Yale for more than a decade, are responsible for activity of highly evolved brain circuits found especially in primates.

Earlier studies have shown these types of NMDA receptors are often altered in patients with schizophrenia.

The Neuron study suggests that those suffering from the disease may be unable to hold onto a stable view of the world.

Also, these receptors seem to be altered in Alzheimer's patients, which may contribute to the cognitive deficits of dementia.

The lab of Dr. John Krystal, chair of the department of psychiatry at Yale, has found that the anesthetic ketamine, abused as a street drug, blocks NMDA receptors and can mimic some of the symptoms of schizophrenia.

The current study in Neuron shows that ketamine may reduce the firing of the same higher-order neural circuits that are decimated in schizophrenia.

"Identifying the receptor needed for higher cognition may help us to understand why certain genetic insults lead to cognitive impairment and will help us to develop strategies for treating these debilitating disorders," Arnsten said.

The above story is reprinted from materials provided by Yale University.

Far from the Tree: Dyslexia, Down Syndrome, Autism, Schizophrenia, disability, etc.

Far from the Tree (BBC website)

The time-worn adage says that the apple doesn't fall far from the tree, meaning that a child resembles his or her parents.

The children described in this book are apples that have fallen elsewhere - some a couple of orchards away, some on the other side of the world.

Yet myriad families learn to tolerate, accept and finally celebrate children who are not what they originally had in mind.

Andrew Solomon introduces us to families coping with deafness, Down syndrome, autism, schizophrenia, and disability - as well as families who have children who are prodigies, who are gay, or who become criminals.

Episode 1:
Growing up gay and also struggling with dyslexia led Andrew Solomon to reflect on those situations where a child arrives in a family and is immediately an 'outsider'. 'Parenthood,' he writes, 'abruptly catapults us into a permanent relationship with a stranger'.

Read by Kerry Shale
Abridged and produced by Jill Waters

Read more about the book: Far From the Tree

BiPolar Disorder: Cannabis increases neuro-cognitive performance

According to a study published online in the journal Psychiatry Research, individuals with bipolar disorder who used cannabis showed higher neuro-cognitive performance than patients who did not use cannabis.

The Researchers; The Zucker Hillside Hospital in Long Island, NY, in collaboration with a team at the Mount Sinai School of Medicine and the Albert Einstein College of Medicine in New York City.

They examined the difference in cognitive performance among 50 individuals with bipolar disorder who had a history of cannabis use, with 150 bipolar patients who had no history of cannabis use.

Both groups of patients were similar in age at bipolar onset. In addition, the groups did not differ in racial background, age, or highest education level achieved.

The team discovered that patients who used cannabis showed superior neuro-cognitive performance than those who did not. However, patients who used cannabis did not differ considerably on estimates of premorbid IQ.

The researchers explained: "Results from our analysis suggest that subjects with bipolar disorder and history of (cannabis use) demonstrate significantly better neurocognitive performance, particularly on measures of attention, processing speed, and working memory.

These findings are consistent with a previous study that demonstrated that bipolar subjects with history of cannabis use had superior verbal fluency performance as compared to bipolar patients without a history of cannabis use.

Similar results have also been found in schizophrenia in several studies."

They concluded, "The data could be interpreted to suggest that cannabis use may have a beneficial effect on cognitive functioning in patients with severe psychiatric disorders.

However, it is also possible that these findings may be due to the requirement for a certain level of cognitive function and related social skills in the acquisition of illicit drugs."

What is Bipolar Disorder?  
Bipolar disorder, more commonly known in the past as manic depression or manic depressive illness, is a mental disorder in which the patient has mood instability, often severe. In severe cases the illness can be very disabling, psychologically and socially.

An individual with bipolar disorder typically has unusual shifts in mood, energy, and the ability to function - these changes can last for weeks and sometimes months.

The fluctuations present in bipolar disorder are much more severe than the "ups-and-downs" we all go through. The changes are much steeper and last longer.

They can damage relationships, destroy job prospects, and undermine school performance. Some patients find their symptoms so unbearable that they attempt to commit suicide.

Health Risks: Being Left-Handed

Left-handers have been the subject of curiosity, stigma and even fear over the centuries.

Researchers now, however, are recognizing the scientific importance of understanding why people use one hand or the other to write, eat or toss a ball.

Handedness, as the dominance of one hand over the other is called, provides a window into the way our brains are wired, experts say and it may help shed light on disorders related to brain development, like dyslexia, schizophrenia and attention deficit hyperactivity disorder, or ADHD, which are more common in left-handed people.

Other recent research suggests that mixed-handedness—using different hands for daily tasks and not having a dominant one—may be even more strongly linked than left-handedness to ADHD and possibly other conditions.

About 10% of people are left-handed, according to expert estimates. Another 1% of the population is mixed-handed.

What causes people not to favour their right hand is only partly due to genetics—even identical twins, who have 100% of the same genes, don't always share handedness.

More important, researchers say, are environmental factors—especially stress—in the womb.

Babies born to older mothers or at a lower birth weight are more likely to be lefties, for example and mothers who were exposed to unusually high levels of stress during pregnancy are more likely to give birth to a left-handed child.

A review of research, published in 2009 in the journal Neuropsychologia, estimated that about 25% of the variability in handedness is due to genetics.

On average there is no significant difference in IQ between righties and lefties, studies show, belying popular perceptions.

There is some evidence that lefties are better at divergent thinking, or starting from existing knowledge to develop new concepts, which is considered an element of creativity.

Oddly, left-handed people have salaries that on average are about 10% lower than righties, according to recent research performed at Harvard University that analyzed large income data bases, although findings of some earlier studies were mixed.

Left-handedness appears to be associated with a greater risk for a number of psychiatric and developmental disorders.

While lefties make up about 10% of the overall population, about 20% of people with schizophrenia are lefties, for example.

Links between left-handedness and dyslexia, ADHD and some mood disorders have also been reported in research studies.

The Health Risks Of Being Left-Handed - WSJ.com

Social deficits associated with autism, schizophrenia induced in mice

Researchers at Stanford University School of Medicine have been able to switch on, and then switch off, social-behavior deficits in mice that resemble those seen in people with autism and schizophrenia, thanks to a technology that allows scientists to precisely manipulate nerve activity in the brain.

In synchrony with this experimentally induced socially aberrant behavior, the mice exhibited a brain-wave pattern called gamma oscillation that has been associated with autism and schizophrenia in humans, the researchers say.

The findings, to be published online in Nature on July 27, lend credence to a hypothesis that has been long floated but hard to test, until now.

They mark the first demonstration, the researchers said, that elevating the brain's susceptibility to stimulation can produce social deficits resembling those of autism and schizophrenia, and that then restoring the balance eases those symptoms.

Autism spectrum disorder and schizophrenia each affect nearly 1 percent of all people. At present, there are no good drugs for mitigating the social-behavioral deficits of either disorder.

While they differ in many ways, each syndrome is extremely complex, involving diverse deficits including social dysfunction. Mice are social animals, and there are many well-established tests of sociability in these animals.

Social behavior can't be ascribed to a single brain region, said Karl Deisseroth, MD, PhD, associate professor of psychiatry and behavioral sciences and of bioengineering and the study's senior author.

"To form a coherent pattern of another individual, you need to quickly integrate all kinds of sensations. And that's just the tip of the iceberg," said Deisseroth, a practicing psychiatrist who routinely sees autistic-spectrum patients.

"It's all changing, millisecond by millisecond, as both you and the other individual act and react. You have to constantly alter your own predictions about what's coming next. This kind of interaction is immensely more uncertain than, for example, predator/prey activity. It seems that it has to involve the whole brain, not just one or another part of it."

One intriguing hypothesis holds that social dysfunctions characteristic of autism and schizophrenia may stem from an altered balance in the propensity of excitatory versus inhibitory nerve cells in the brain to fire, resulting in an overall hyper-responsiveness to stimulation.

Evidence for this hypothesis includes the higher seizure rate among patients with autism, and the fact that many autistic children's brains exhibit elevated levels of a high-frequency brain-wave pattern -- known as "gamma oscillation" -- that can be picked up by an electroencephalogram.

Many schizophrenics also exhibit social deficits as well as higher levels of this anomalous brain-wave pattern, even at rest.

In addition, said Deisseroth, "autistic kids seem to be over-responding to environmental stimuli." For instance, they find eye contact overwhelming, or may cover their ears if there are too many people talking at once.

Filters That Reduce ‘brain Clutter’ Identified

Until now, it has been assumed that people with conditions like ADHD, Tourette syndrome, obsessive compulsive disorder and schizophrenia, all of whom characteristically report symptoms of "brain clutter," may suffer from anomalies in the brain's prefrontal cortex.

Damage to this brain region is often associated with failure to focus on relevant things, loss of inhibitions, impulsivity and various kinds of inappropriate behaviour.

So far, exactly what makes the prefrontal cortex so essential to these aspects of behaviour has remained elusive, hampering attempts to develop tools for diagnosing and treating these patients.

But new research by Julio Martinez-Trujillo, a professor in McGill University's Department of Physiology and Canada Research Chair in Visual Neuroscience, has brought new hope to these patients.

He believes the key to the "brain clutter" and impulsivity shown by individuals with dysfunctional prefrontal cortices lies in a malfunction of a specific type of brain cell. Martinez-Trujilo and his team have identified neurons in the dorsolateral sub-region of the primate prefrontal cortex that selectively filter out important from unimportant visual information.

The key to the normal functioning of these "filter neurons" is their ability to, in the presence of visual clutter, selectively and strongly inhibit the unimportant information, giving the rest of the brain access to what is relevant.

"Contrary to common beliefs, the brain has a limited processing capacity. It can only effectively process about one per cent of the visual information that it takes in," Martinez-Trujilo said. "This means that the neurons responsible for perceiving objects and programming actions must constantly compete with one another to access the important information.

"What we found when we looked at the behaviour of the neurons in the prefrontal cortex, was that an animal's ability to successfully accomplish a single action in the presence of visual clutter, was dictated by how well these units suppressed distracting information."

These results could be highly relevant for identifying the causes and improving the diagnosis and treatments of a wide range of mental disorders including ADHD and schizophrenia.

The research was conducted by Therese Lennert, a PhD student who holds a Vanier Scholarship, and it was funded by the Canada Research Chair program, Canadian Institutes of Health Research (CIHR), EJLB Foundation, and Natural Sciences and Engineering Research Council of Canada (NSERC).

Primary symptoms of psychosis may be evident in 12-year-olds

Children normally experience flights of fancy, including imaginary friends and conversations with stuffed animals, but some of them are also having hallucinations and delusions which might be the early signs of psychosis.

A study of British 12-year-olds that asked whether they had ever seen things or heard voices that weren't really there, and then asked careful follow-up questions, has found that nearly 6 percent may be showing at least one definite symptom of psychosis.

The children who exhibited these symptoms had many of the same risk factors that are known to correlate with adult schizophrenia, including genetic, social, neurodevelopmental, home-rearing and behavioral risks.

"We don't want to be unduly alarmist, but this is also not something to dismiss," said co-author Terrie Moffitt, the Knut Schmidt Nielsen professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke University. The study appears in the April issue of Archives of General Psychiatry.

The children were participants in the long-term Environmental Risk Longitudinal Twin Study in Britain, which includes 2,232 children who have been tracked since age 5 and reassessed at 7, 10 and 12.

The British study is an outgrowth of research that the same group did earlier with a long-term cohort in Dunedin, New Zealand. At age 11, those children were asked about psychotic symptoms, but the researchers waited 15 years to see how, as adults, their symptoms matched what they reported at 11. By age 26, half of the people who self-reported symptoms at age 11 were found to be psychotic as adults.

"It looks like a non-trivial minority of children report these symptoms," said co-author Avshalom Caspi, the Edward M. Arnett professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke.

The findings provide more clues to the development of schizophrenia, but don't solve any questions by themselves, said co-author Richard Keefe, director of the schizophrenia research group in the department of psychiatry and behavioral sciences at Duke.

Schizophrenia often goes undetected until adolescence, when the first overt symptoms -- antisocial behavior, self-harm, delusions -- begin to manifest in an obvious way. But nobody knows whether the disease is triggered by the process of adolescence itself, or brain development or hormone changes. "It's my impression that all of those things interact," Keefe said.

Psychotic symptoms in childhood also can be a marker of impaired developmental processes, and are something caregivers should look for, Moffitt said. "There is not much you can do except monitoring and surveillance," Moffitt said. "But we feel we should be alerting clinicians that there's a minority to pay attention to."

While the incidence of psychotic symptoms in this study was around 5 or 6 percent, the adult incidence of schizophrenia is believed to be about 1 percent, Keefe added. There are some recent findings however, that many more people experience hallucinations and delusions without being diagnosed as psychotic, he said.

The research was supported by the U.S. National Institutes of Health, UK Medical Research Council, The National Alliance of Research on Schizophrenia and Depression, the Health Research Board of Ireland and the William T. Grant Foundation.

Etiological and Clinical Features of Childhood Psychotic Symptoms, Guilherme Polanczyk et al, Archives of General Psychiatry, April 2010 http://archpsyc.ama-assn.org/cgi/content/full/67/4/328

Link: http://www.duke.edu/

Could Autism and Schizophrenia be Genetic?

Autism and schizophrenia may be two sides of the same coin, suggests a review of genetic data associated with the conditions. The finding could help design complementary treatments for the two disorders.

Though autism was originally described as a form of schizophrenia a century ago, evidence for a link has remained equivocal. One theory puts the conditions at opposite ends of a developmental spectrum.

To investigate, Bernard Crespi, an evolutionary biologist at Simon Fraser University in Vancouver, Canada, and colleagues gathered data on all known genetic variants associated with each condition, then looked for patterns of co-occurrence.

The researchers found four regions in the genome which dramatically affect the risk of autism or schizophrenia. Called "copy-number variants", these are stretches of DNA with seemingly accidental duplications or deletions. Crespi's team found that the presence of a particular variant – a duplication, say – was often associated with autism while the opposite variation – a deletion of the genetic material – was linked to schizophrenia.

The results fit with other evidence that autism may be caused by overdevelopment of specific brain regions and schizophrenia by underdevelopment, says Crespi.

If they are indeed opposites, work on one disorder may inform work on its counterpart, he says.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0906080106