Differences in brain development between males and females may hold clues to mental health disorders

Differences in brain development between males and females may hold clues to mental health disorders
November 17th, 2010 in Medicine & Health / Neuroscience


Many mental health disorders, such as autism and schizophrenia, produce changes in social behavior or interactions. The frequency and/or severity of these disorders is substantially greater in boys than girls, but the biological basis for this difference between the two sexes is unknown.

Researchers at the University of Maryland School of Medicine have discovered differences in the development of the amygdala region of the brain – which is critical to the expression of emotional and social behaviors – in animal models that may help to explain why some mental health disorders are more prevalent among boys. They also found a surprising variable – a difference between males and females in the level of endocannabinoid, a natural substance in the brain that affected their behavior, specifically how they played.

The study results have been published online this month in the Proceedings of the National Academy of Sciences.

Margaret M. McCarthy, Ph.D., the senior author and a professor of physiology and psychiatry at the University of Maryland School of Medicine, says, "Our findings help us to better understand the differences in brain development between males and females that may eventually provide the biologic basis for why some mental health conditions are more prevalent in males. We need to determine if these neural differences in the developing brain that we've seen in rats may cause similar behavioral effects in human babies."

Dr. McCarthy and her colleagues found that female rats have about 30 to 50 percent more glial cells in the amygdala region of the temporal lobe of the brain than their male litter mates. They also found that the females had lower amounts of endocannabinoids, which have been dubbed the brain's own marijuana because they activate cannabinoid receptors that are also stimulated by THC, the main psychoactive ingredient of cannabis.

Researchers also found that the female rats also played 30 to 40 percent less than male rats. However, when these newborn female rats were given a cannabis-like compound to stimulate their natural endocannabinoid system, their glial cell production decreased and they displayed increased play behavior later as juveniles. In fact, the level of play exhibited by females treated with a cannabis-like compound was very similar to levels in male rats, the researchers found. Yet exposure to this cannabis-like compound did not appear to have any discernible effect on newborn male rats.

Dr. McCarthy, who is also associate dean for Graduate Studies and interim chair of the Department of Pharmacology & Experimental Therapeutics, notes, "We have never before seen a sex difference such as this in the developing brain involving cell proliferation in females that is regulated by endocannabinoids."

E. Albert Reece, M.D., Ph.D., M.B.A., vice president of medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine, says, "The results of this study provide important clues to brain differences between males and females and may increase our knowledge about how these differences may affect both normal and aberrant brain development, thereby enhancing our understanding of many mental health disorders."

Provided by University of Maryland Medical Center

Studying our emotional life

Studying our emotional life
November 16th, 2010 in Medicine & Health / Psychology & Psychiatry


Lisa Feldman Barrett, a psychology professor, says that our mood has a direct effect on our perception of the world. When we’re happy, she says, we’ll see neutral faces as smiling. When we’re sad, they’ll appear as scowls.

"People treat their feelings about the world as evidence for how the world really is," says Barrett, who joined the College of Science this fall after almost 20 years at Boston College and the Pennsylvania State University.

Barrett, who studies how emotions function in the mind by using experiential, behavioral, psychophysiological, and brain-imaging methods, is also co-director of the Laboratory of Aging and Emotion at Massachusetts General Hospital.

Collaborators include cognitive neuroscientists at Mass General Hospital, Harvard Medical School, Emory University and the University of Colorado.

For one study, she employed a technique in visual neuroscience called binocular rivalry, in which one image — say, a house — is presented to a subject’s left eye and a very different image — a smiling or scowling face — is presented to the other.

She measured which image the subject saw first and for how long he looked at it. The results were clear, says Barrett: "Our feelings influence whether we’re conscious of seeing something or how we see something."

Her research is backed by federally funded grants from the National Science Foundation, National Institutes of Health and Army Research Institute.

In 2007, she earned the NIH Director’s Pioneer Award, which is awarded to scientists who take transformative approaches to solving challenges in biomedical and behavioral research.

She also studies how language affects our ability to recognize emotions using a technique called semantic satiation.

Say the word "anger" over and over again, until it "sounds like mumbo jumbo," she says, and you won’t know the meaning of the furious scowl on the face of the person sitting next to you on the subway.

Repeat the word "smile" over and over, and you won’t be able to tell whether two happy kids with ear-to-ear grins are conveying the same emotion.

"Disabling the semantic processing of words reduces our ability to see emotions," she says.

Words, she explains, act like glue to shape our perceptions. Interfering with the processing of a word "interferes with our perceptions" in the same way that unfamiliarity with a word — like, say, "cow" — makes it impossible to find the animal in an abstract design.

"If you make language inaccessible to a subject by taking away the word ‘cow,’ he won’t know what it means as a physical entity," she says. "When you give him a black and white blot, he’ll never find the cow."

Provided by Northeastern University

Research reveals deaf adults see better than hearing people

Research reveals deaf adults see better than hearing people
November 11th, 2010 in Medicine & Health / Research


Adults born deaf react more quickly to objects at the edge of their visual field than hearing people, according to groundbreaking new research by the University of Sheffield.

The study, which was funded by the Royal National Institute for Deaf People (RNID), has, for the first time ever, seen scientists test how peripheral vision develops in deaf people from childhood to adulthood.

Dr Charlotte Codina, from the University's Academic Unit of Ophthalmology and Orthoptics, led the research and found that children born deaf are slower to react to objects in their peripheral vision compared to hearing children. However, deaf adolescents and adults who have been without hearing since birth can react to objects in their peripheral vision more quickly.

The findings of Dr Codina's study, which were published in Development Science today (Thursday 11 November 2010), showed that deaf children aged between five to 10 years old had a slower reaction time to light stimuli in their peripheral vision than hearing children of the same age. By the age of 11 and 12 however, hearing and deaf children react equally quickly and deaf adolescents between 13 and 15 reacted more quickly than their hearing peers.

The study tested profoundly deaf children (aged five to 15 years) using a self-designed visual field test, and compared this to age-matched hearing controls as well as to deaf and hearing adult data.

The children tested sat with their head positioned in the centre of a grey acrylic hemisphere into which 96 LEDs were implanted. The participants then had to watch a central glowing ring in which a camera was hidden to monitor their eye movements.

The LEDs were then each briefly illuminated at three different light intensities all in random order. The test was designed to be like a computer game and called the Star Catcher. If the LED flash occurred above, the child had to 'catch the star' by moving the joystick upwards, and if it occurred to the left they would have to move the joystick to that position. In this way, the team were able to verify that the child had seen the light and not just guessed, as has been the problem with previous visual field tests in children.

Dr Charlotte Codina, who undertook the study as part of her RNID-funded PhD said: "We found that deaf children see less peripherally than hearing children, but, typically, go on to develop better than normal peripheral vision by adulthood. Important vision changes are occurring as deaf children grow-up and one current theory is that they have not yet learnt to focus their attention on stimuli in the periphery until their vision matures at the age of 11 or 12.

"As research in this area continues, it will be interesting to identify factors which can help deaf children to make this visual improvement earlier."

RNID's Research Programme Manager, Dr Joanna Robinson, said: "This research shows that adults who have been deaf since birth may have advantages over hearing people in terms of their range of vision. For example, deaf people could be more proficient in jobs which depend on the ability to see a wide area of activities and respond quickly to situations, such as sports referees, teachers or CCTV operators.

"On the other hand, the findings suggest that parents of deaf children need to be aware that their child's initially delayed reaction to peripheral movements may mean they are slower to spot and avoid potential dangers such as approaching traffic."

More information: Dr Charlotte Codina's 'Deaf and hearing children: a comparison of peripheral vision development' report is published in the November issue of Development Science. To view the latest issue of Developmental Science, please visit: http://onlinelibra … e-6/issuetoc


Provided by University of Sheffield

Researchers find learning in the visual brain

Researchers find learning in the visual brain
November 10th, 2010 in Medicine & Health / Neuroscience


A team of researchers from the University of Minnesota's College of Liberal Arts and College of Science and Engineering have found that an early part of the brain's visual system rewires itself when people are trained to perceive patterns, and have shown for the first time that this neural learning appears to be independent of higher order conscious visual processing.

The researchers' findings could help shape training programs for people who must learn to detect subtle patterns quickly, such as doctors reading X-rays or air traffic controllers monitoring radars. In addition, they appear to offer a resolution to a long-standing controversy surrounding the learning capabilities of the brain's early (or low-level) visual processing system.

The study by lead author Stephen Engel, a psychology professor in the College of Liberal Arts, is published in the Nov. 10 issue of the Journal of Neuroscience.

"We've basically shown that learning can happen in the earliest stages of visual processing in the brain," Engel said.

The researchers looked at how well subjects could identify a faint pattern of bars on a computer screen that continuously decreased in faintness. They found that over a period of 30 days, subjects were able to recognize fainter and fainter patterns. Before and after this training, they measured brain responses using EEG, which records electrical activity along the scalp produced by the firing of neurons within the brain.

"We discovered that learning actually increased the strength of the EEG signal," Engel said. "Critically, the learning was visible in the initial EEG response that arose after a subject saw one of these patterns. Even a tiny fraction of a second after a pattern was flashed, subjects showed bigger responses in their brain."

In other words, this part of the brain shows local "plasticity," or flexibility, that seems independent of higher order processing, such as conscious visual processing or changes in visual attention. Such higher order processing would take time to occur and so its effects would not be seen in the earliest part of the EEG response.

Engel says these finding may also help adults with visual deficits such as lazy eye by accelerating the development of training procedures to improve the eye's capabilities.

More information: "Perceptual Learning Increases the Strength of the Earliest Signals in Visual Cortex," Journal of Neuroscience.

Replacing faulty neurons

Replacing faulty neurons
November 5th, 2010 in Medicine & Health / Neuroscience

Purkinje neurons (yellow) generated from embryonic stem cells integrate into the cerebellum (red) when transplanted into the fetal mouse brain.

Reproduced from 2010 K. Muguruma et al.
Researchers from the RIKEN Center for Developmental Biology, Kobe, have shown that neurons called Purkinje cells can not only be generated from embryonic stem (ES) cells, but can also become fully integrated into existing neuronal circuits when transplanted into the brains of mouse fetuses.

Purkinje cells are the largest neuronal subtype in the mammalian brain, and their output in the brain region called the cerebellum controls balance, co-ordination and movement.

Yoshiki Sasai and his colleagues cultured ES cells and then treated them at different times with the hormone insulin, the naturally occurring chemical cyclopamine, and a protein called fibroblast growth factor 2, which normally induces the differentiation of Purkinje cells at a specific location in the developing hindbrain.

This treatment caused the ES cells to express genes that are specific for Purkinje cells, and then to differentiate into mature neurons with the extensive, two-dimensional dendritic tree and electrical properties that are characteristic of Purkinje cells. They found that the differentiation of the cells recapitulate the events that take place during neural development. The Purkinje cell-specific genes were expressed in the same sequence as in the embryo, and the immature cells exited the cell cycle, or stopped dividing, on a timescale comparable to that of the neurons in the developing cerebellum.

Sasai and colleagues then separated immature Purkinje cells from the ES cell cultures, and transplanted them into the brains of embryonic mice, injecting approximately 10,000 cells into each animal. They found that the transplanted cells integrated effectively into their proper location within the circuitry of the cerebellum. The majority began to express Purkinje cell genes between 1 to 4 weeks after transplantation, and then differentiated into mature neurons, each with a long axon projecting down into the deep cerebellar nuclei.

The methods of Sasai and his team significantly improve on earlier methods for generating Purkinje cells from ES cell cultures. By successfully reproducing the microenvironment of the developing cerebellum, they generated up to 30-fold more Purkinje cells than previous methods.

These results therefore raise the possibility of developing cell transplantation therapies the cerebellar ataxias, a group of movement disorders characterized by severe motor in-coordination, which occur because of Purkinje cell degeneration.

“As a next step, we are attempting to generate Purkinje cells from human ES cells,” says Sasai. “This technology would be useful in establishing an in vitro disease model for spinocerebellar ataxia, to investigate its pathogenesis and to explore the possibility of gene therapy for this genetic disease.”

More information: Muguruma, K., et al Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nature Neuroscience 13, 1171–1180 (2010).

Scientists show universality in the brain evolution

Scientists show universality in the brain evolution
November 4th, 2010 in Biology / Evolution


The ancestors of tree shrew (left) and bush baby (right) have been on separate evolutionary paths since 65 million years. Visual processing centers of their brains, nevertheless, display a common design. Picture source: Wikimedia Commons

Scientists have uncovered a self-organizing biological principle in the brains of three very different, genetically diverse mammals -- but in all three they found the same mathematically precise "pinwheel" organization and orientation of neurons.

The scientists found that this visual cortex is self-organized, through neuronal activity and not through genes or environment (for example, ferrets raised in the dark still have this type of organization in their developing brains).

The most straightforward way to summarize the importance of this work is to say that this new study demonstrates that complex patterns of connections in the brain are capable of self-organizing with mathematical precision.

In fact, the notion that a complex pattern can appear in a dynamical system without a central authority or planner has been understood, for example, in the field of physics.

However, in the biological sciences, and in the field neuroscience in particular, self-organization as a developmental force seldom has been recognized. This study, of which Duke researcher Leonard White, PhD., in Duke neurobiology was an author, provides, if not the first, certainly the most well documented case for this agency in brain development. This precise structure arises both from ongoing activity and lateral interactions of the neurons as well as across a neural network.



Enlarge


This image shows an orientation preference map from a prosimian primate, the galago. In this image, the colors represent the activity of columns of neurons that respond preferentially to particular angles in the visual world, such as horizontal (red regions) and vertical (blue regions). The brightness of the colors indicates how selective is the response of neurons in any given position in the map. Pinwheels are those smaller regions in the map where all colors are organized around a central dark point. The entire image shows about 60 square millimeters of the primary visual processing area in the brain of a galago. Image credit: Duke University

The findings, published today in Science, may cause scientists to think in new ways about how such a complex system as the human brain with its 100 billion neurons, gets wired up to begin with, given the relative dearth of genes in the human genome and the relative lack of environmental experiences in the newborn that already has advanced neural architecture in its cerebral cortex.
This demonstration of self-organization in brain development may also have implications for rehabilitation in the brains of people recovering from neurological injury or disease. As neural circuits in the recovering brain reactivate growth programs that shaped development earlier in life, it seems likely that self-organization will continue to influence the architecture of neural circuits whenever they are plastic and capable of changing their strength and the distribution of their connections.

The challenge for future studies will be to understand how genetic instructions and early life experiences interact within a self-organizing network of brain cells, and how such interactions can be optimized to enhance function in normal developing brains, as well as in mature brains that have to adapt to injury and disease.

A word about the orientation of the neurons: The orientation is such that from any central neuron, the surrounding neurons are in a repeat pattern of orientation, and that central neuron is also a part of the repeat pattern in a neighboring pinwheel, with mathematical precision. Neurons respond to vertical, horizontal or oblique patterns to create the images that brains can assimilate and process as our 3-D world.

More information: Universality in the Evolution of Orientation Columns in the Visual Cortex, Matthias Kaschube et al., Science, November 5, 2010.


Provided by Duke University

Collecting your thoughts: You can do it in your sleep!

Collecting your thoughts: You can do it in your sleep!
November 2nd, 2010 in Medicine & Health / Neuroscience
It is one thing to learn a new piece of information, such as a new phone number or a new word, but quite another to get your brain to file it away so it is available when you need it.
A new study published in the Journal of Neuroscience by researchers at the University of York and Harvard Medical School suggests that sleep may help to do both.

The scientists found that sleep helps people to remember a newly learned word and incorporate new vocabulary into their "mental lexicon".

During the study, which was funded by the Economic and Social Research Council, researchers taught volunteers new words in the evening, followed by an immediate test. The volunteers slept overnight in the laboratory while their brain activity was recorded using an electroencephalogram, or EEG. A test the following morning revealed that they could remember more words than they did immediately after learning them, and they could recognise them faster demonstrating that sleep had strengthened the new memories.

This did not occur in a control group of volunteers who were trained in the morning and re-tested in the evening, with no sleep in between. An examination of the sleep volunteers' brainwaves showed that deep sleep (slow-wave sleep) rather than rapid eye movement (REM) sleep or light sleep helped in strengthening the new memories.

When the researchers examined whether the new words had been integrated with existing knowledge in the mental lexicon, they discovered the involvement of a different type of activity in the sleeping brain. Sleep spindles are brief but intense bursts of brain activity that reflect information transfer between different memory stores in the brain -- the hippocampus deep in the brain and the neocortex, the surface of the brain.

Memories in the hippocampus are stored separately from other memories, while memories in the neocortex are connected to other knowledge. Volunteers who experienced more sleep spindles overnight were more successful in connecting the new words to the rest of the words in their mental lexicon, suggesting that the new words were communicated from the hippocampus to the neocortex during sleep.

Co-author of the paper, Professor Gareth Gaskell, of the University of York's Department of Psychology, said: "We suspected from previous work that sleep had a role to play in the reorganisation of new memories, but this is the first time we've really been able to observe it in action, and understand the importance of spindle activity in the process."

These results highlight the importance of sleep and the underlying brain processes for expanding vocabulary. But the same principles are likely to apply to other types of learning.

Lead author, Dr Jakke Tamminen, said: "New memories are only really useful if you can connect them to information you already know. Imagine a game of chess, and being told that the rule governing the movement of a specific piece has just changed. That new information is only useful to you once you can modify your game strategy, the knowledge of how the other pieces move, and how to respond to your opponent's moves. Our study identifies the brain activity during sleep that organizes new memories and makes those vital connections with existing knowledge."

More information: The paper ‘Sleep spindle activity is associated with the integration of new memories and existing knowledge’ is published in the Journal of Neuroscience at link http://www.jneuros … /30/43/14356