Young animals can quickly forget negative (or positive) experiences. Young rats, for instance, easily forget fearful experiences with extinction training. Neuroscientist Andreas Lüthi of the Friedrich Miescher Institute for Biomedical Research in Switzerland and his colleagues designed an experiment to try to find out why.
The team focused on nets of highly organized systems that surround neurons and play a role in neuronal plasticity in the visual system. When the researchers injected an enzyme to degrade these nets before exposing the mice to a fearful experience, adults reverted to a juvenile-like state in which they were later able to forget the fear.
“This is a beautiful proof of principle that the adult brain is not fixed but you can reverse engineer it to a [juvenile-like] state,” said neuroscientist Takao Hensch of Harvard University, who did not participate in the research. This discovery may eventually be relevant to the success of therapies for anxiety disorders, he added.
|Image: Wikimedia commons
“This is an extremely important observation because it suggests a mechanism for why fear memories are so indelible,” neuroscientist Gregory Quirk of the University of Puerto Rico School of Medicine, who was not involved in the work, wrote in an email to The Scientist.
Memories of traumatic events can induce excessive fear in inappropriate situations, in some cases leading to post traumatic stress disorder (PTSD). One treatment for PTSD involves re-exposing individuals to elements of the bad event without the associated emotional trauma, in order to decrease the fear stirred up by the memory. In adults, this process, known as extinction, involves learning a new association — between the event and safety — as opposed to unlearning the original memory. Because the original association remains, however, the fear can resurface unexpectedly later in life.
Quirk pointed out that incorporating these findings into a clinical setting may not be easy, however. Forgetting the fear took more than time; the animals still needed extinction training to get rid of the fear response, and inducing plasticity after the fear had been learned did not boost the effectiveness of the extinction training. This suggests that the mechanism acts during fear memory formation, not forgetting, and thus may limit the clinical application of manipulating these neural nets, he said.
“A treatment based on this approach could not be given as an adjunct to extinction-based therapies,” Quirk said. “Instead, the treatment would have to be given prior to the trauma, perhaps to individuals with a high likelihood of experiencing traumatic events.”
Furthermore, the method used in this study was highly invasive, Hensch said. “We need to know better how these extracellular factors are regulated in the first place, so we could come up with some noninvasive behavioral therapy.”
The next step, Lüthi said, is nailing down the mechanism of fear memory acquisition. The nets form specifically around a certain class of inhibitory neurons, suggesting that reorganization of inhibitory pathways may be involved. “[But] we don’t really understand what synaptic connections [are involved and how] neurons change during normal extinction learning in adults,” he said. “This will definitely require further experiments.”
A study published in the July 10, 2009, issue of the journal Science shows that new brain cells help us find our way around.
According to senior author Fred Gage of the Salk Institute new brain cells “help us to distinguish between memories that are closely related in space.”
“Adding new neurons could be a very problematic process if they don’t integrate properly into the existing neural circuitry,” says Gage. “There must be a clear benefit to outweigh the potential risk.”
Most neurogenesis happens in the hippocampus, a small horn-shaped region in the brain’s interior. The hippocampus prepares information for recall and then send it off for storage. Experiences involving time, emotion, intent, touch, smell etc., arise in the cortex and gets channeled to the hippocampus.
Previous studies had indicated that new neurons contributed to learning and memory but the details were unclear.
The dentate gyrus divides and distributes incoming signals. This process, known as pattern separation, increases the number of active cells by a factor of ten. To find out whether the brain was using new cells to aid in pattern separation, the study team devised two sets of experiments:
1. To find food presented relative to the location of an earlier meal within an eight-spoke radial maze. “Mice without neurogenesis had no trouble finding the new location as long as it was far enough from the original location,” says Clelland, “but couldn’t differentiate between the two when they were close to each other.”
2. To differentiate close points on a touch screen. Again, mice in which neurogenesis had been curtailed could not discriminate between closely set points on the screen, but had no trouble recalling spatial information in general.
“Neurogenesis helps us to make finer distinctions and appears to play a very specific role in forming spatial memories,” says Clelland. Adds Gage, “There is value in knowing something about the relationship between separate events and the closer they get the more important this information becomes.”
Obviously, it is very unlikely that new cells only assist with pattern separation. For instance, the researchers also discovered that “newborn neurons actually form a link between individual elements of episodes occurring closely in time,” says Gage.
Gage and his team will go on to investigate whether neurons also enable the encoding of relationships of time and context.
A recent study by the MIND Research Network’s Rex Jung, a research scientist at MRN and an assistant professor at The University of New Mexico Department of Neurosurgery, shows that intelligent minds operate differently when forming creative thoughts.
By scanning the brains of 56 college-age students he found that a chemical associated with creativity called N-acetylaspartate, or NAA, works more discretely in the frontal lobe of those with high IQs (120 and above, or the top 9%) than it does in those with average IQs.
“It’s a funny kind of finding, and I wish I knew why,” Jung said. “This is the first time we’ve seen real biological evidence that creativity works differently in highly intelligent people. Why that is, though, is the real $64,000 question.”
(The team defined creativity as having the “cognitive skills necessary to produce something both ‘novel and useful,’ ” and used a standard IQ test and the Torrance Test of Creative Thinking for their study.)
People of average intelligence who are creative have more NAA than those in the high IQ group. And whereas in the average IQ group NAA operated broadly across the brain’s frontal lobe, in the high IQ group, the NAA was more focused in very specific areas of the frontal lobe, Jung said.
“I’ve been speculating, and mind you it’s just speculating, that in the average intelligence group, you need to hit more nodes in your brain to hunt that novel and unique idea,” Jung said. “In the high IQ folks, and that’s really a small percent of the population, it seems that the ideas they generate may be more novel to begin with, and so the mind tends to rely more on its knowledge base.”
“The IQ is a very precise scale of behavior that’s over 100 years old,” Jung said. “It’s a reliable, precise measure of brain function, and a stable measure of brain capacity and problem solving. But it’s limited in its ability to measure things like creativity or personality.”
Measuring creativity, and comparing it to intelligence, is a much harder task, he said.
Jung aims to understand the biological aspects of creativity and its relationship with intelligence. His next paper looks at the neural cortex and studies which areas are thicker or thinner in more creative people.
“With intelligence, usually more neurons are better, but with creativity it’s this complexity of more in some areas and less in others,” Jung said.
In a study of dieters, scientists found that everyone used a part of their brains called the ventromedial prefrontal cortex (a region behind the forehead) BUT, those who exercised restraint also used the dorsolateral prefrontal cortex, a smaller part of the brain further back. This region has been previously associated with working memory and meeting goals.
“This is the first time people have looked at the mechanism of self-control in people who are making real-life decisions,” said Todd Hare, a Caltech neuroscientist and leader of the study.
Hare and his colleagues scanned the brains of 37 people who considered themselves dieters while they rated over 50 different foods according to taste and healthiness.
Scientists then showed each volunteer a food that they had labeled “neutral” and asked them to choose between it and each of 49 other foods.
Based on the brain scan results scientists identified two distinct groups: those who chose the healthy food and those who didn’t.
Choosing healthy foods over tasty foods involved the activation of dorsolateral prefrontal cortex.
The results were detailed in the May 1 issue of the journal Science.
“It’s unlikely that self-control is just one little nodule in the brain,” cautioned Scott Huettel, neuroscience professor at Duke University who was not involved in the study. “There are undoubtedly many things that contribute to the way people make decisions.” However, Huettel added, the regions Hare’s team studied seemed to correspond to the decisions people make.
This reminds me of a similar study in which researchers asked participants to choose between unhealthy (cake) and healthy food (salad). Most chose the healthy option. But when the researchers deliberately overloaded participants’ working memory by asking them to remember specific words, they overwhelmingly chose cake.
This leads to a conclusion that working memory itself is involved in willpower. Certainly in our experience with customers of Brain Fitness Pro, this is one benefit of the training that keeps coming up — willpower, task completion, reduction of procrastination.
Scientists have linked low levels of a particular brain growth factor (fibroblast growth factor 2) to a disposition toward anxiety. The University of Michigan study on rats appears in the May 13 issue of The Journal of Neuroscience. Since FGF2 increases the survival rate of new brain cells, the findings also highlight the role of neurogenesis, or cell birth and integration in the adult brain, in reducing anxiety. These findings may offer new possibilities for the treatment of anxiety and potentially depression.
Previous human studies led by the senior author, Huda Akil, PhD, at the University of Michigan and team at the Pritzker Consortium, showed that people with severe depression had low levels of FGF2, but couldn’t say whether low FGF2 levels caused the disease or were caused by it.
Javier Perez, PhD, also at the University of Michigan, bred rats for high or low anxiety for over 19 generations. The researchers found lower FGF2 levels in rats bred for high anxiety compared to those bred for low anxiety.
The study also found that providing a more stimulating and interesting environment for the rats increased FGF2 levels and reduced anxiety. They also found that FGF2 treatment alone reduced anxiety behaviors in the high-anxiety rats.
“We have discovered that FGF2 has two important new roles: it’s a genetic vulnerability factor for anxiety and a mediator for how the environment affects different individuals. This is surprising, as FGF2 and related molecules are known primarily for organizing the brain during development and repairing it after injury,” Perez said.
The findings further indicate that FGF2 may in part reduce anxiety because it increases the survival of new cells in the hippocampus. Previous research has suggested that depression decreases the production and incorporation of new brain cells (neurogenesis). High-anxiety rats produced the same number of new brain cells as low-anxiety rats, but more of these new cells died off. FGF2 treatment and environmental enrichment each restored brain cell survival.
“This discovery may pave the way for new, more specific treatments for anxiety that will not be based on sedation — like currently prescribed drugs — but will instead fight the real cause of the disease,” said Pier Vincenzo Piazza, MD, PhD, Director of the Neurocentre Magendie an INSERM/University of Bordeaux institution in France, an expert on the role of neurogenesis in addiction and anxiety (not involved in the current study).
A study by the Pasteur Institute shows that new brain cells respond more readily to stimulation and more readily “learn” new skills and information. This enhanced plasticity lasts for about twelve weeks, at which point they become only as plastic as existing brain cells.
This discovery could explain the failure of therapeutic strategies based on grafts, which deliver large quantities of new neurons that then lose their special properties very quickly.
Scientists have also demonstrated that, two weeks after their formation, only 50% of these new cells succeed in integrating into neuronal circuits – an essential condition for their survival.
In the 1990s, grafts for patients suffering from Parkinson’s disease brought about only a temporary recovery of motor ability. If new neurons demonstrate significant properties only for a few weeks, attempts at recovering certain cerebral functions by relying solely on the grafting of cells can never be successful. It would be better to look towards stimulating the brain’s natural capacity to produce neurons continuously.
- Neurogenesis promotes synaptic plasticity in the adult olfactory bulb, Nature Neurosciences, published online on May 3d, 2009.
Antoine Nissant, Cedric Bardy, Hiroyuki Katagiri, Kerren Murray & Pierre-Marie Lledo
Institut Pasteur, Perception and Memory unit, CNRS, URA 2182, 25 rue du Dr. Roux, F-75724 Paris Cedex 15, France.
- Mouret A, Gheusi G, Gabellec MM, de Chaumont F, Olivo-Marin JC et Lledo P-M. Learning and survival of newly generated neurons: when time matters. J. Neurosci. 28, 11511-16, 2008
A Tour of MIT's Picower Institute
Researchers from MIT’s Picower Institute for Learning and Memory have identified two proteins – dubbed Shank and Homer – that work together to control the formation and pruning of synaptic connections as the brain both forms connections and lets them go.
A better understanding of this mechanism may lead to a better understanding of how to treat brain disorders such as autism, mental retardation, and Fragile X syndrome. Researchers believe these conditions are tied to abnormalities in synapses.
“Increase in the size of synapses and memory formation are closely linked,” said Mariko Hayashi, a Picower Institute research affiliate and co-author of the study. “Synapses get larger when we learn something and smaller when we forget something or unused connections are pruned. This happens in infants’ growing brains and in learning and memory during adulthood. ”
Read the full MIT article.
With great perspicacity, PC Mag online has picked Mind Sparke’s Brain Fitness Pro as one of its Top Ten Mother’s Day Gifts for Under $50. Brain training gaining force in the mainstream software realm!
If you’re reading this and you have a Digg account and could thumbs up my Digg, that would be great. Also feel free to pass the story around!!
Here’s the Digg link:
As reported in today’s issue of Neuron, researchers from the department of neuroscience at Georgetown University Medical Center have identified neurons that show a preference for complete, real words. They found them in the brain’s “visual word form” area.
“Although some theories of reading, as well as some neuropsychological and experimental data, have argued for the existence of a neural representation for whole real words, experimental evidence for such a representation has been elusive,” said Dr. Maximilian Riesenhuber.
As with other recent studies the researchers used real-time brain scans of participants to detect activation of specific regions of the brain as they completed tasks involving real words and nonsense words.
The left visual word form area consistently displayed a highly selective preference for real words over jibberish.
According to Riesenhuber, “These results are not just relevant for theories of reading and reading acquisitions, but also for our understanding of the mechanisms underlying experience-driven cortical plasticity in general.”
By which I suppose he means that our brains most likely develop specific and highly targeted responses to information that makes sense and has meaning.
“It will be interesting in future studies to investigate how the specificity of the representation in the VWFA changes during development, and how it might differ in individuals with reading disorders,” he added.
Stroke Victim Retrains Sight
A study by Scientists at the University of Rochester Eye Institute has shown that patients can recover sight loss caused by a stroke. The patients engaged in intensive prolonged visual brain training, stimulating neuroplastic change.
“We were very surprised when we saw the results from our first patients,” said Krystel Huxlin, Ph.D., the neuroscientist and associate professor who led the study of seven patients. “This is a type of brain damage that clinicians and scientists have long believed you simply can’t recover from. It’s devastating, and patients are usually sent home to somehow deal with it the best they can.”
A stroke affects the brain not the eyes, visual information still reaches the brain but the brain cannot construct images from it. The team used this “blindsight” – unprocessed visual information that still reaches the brain.
“The question is whether we can we recruit other, healthy regions of the brain to benefit the person’s vision. Can we train those brain regions so hard and stimulate the brain to such a degree that this visual information is brought to consciousness, so the person is aware of what they’re seeing?” said Huxlin.
The four women and three men in the study in their 30s through their 80s had suffered substantial damage to the primary visual cortex.
The team focused on motion perception, critical for most everyday tasks, aiming to see whether they could stimulate the brain’s middle temporal region, healthy in the participants, to take on some of the tasks normally handled by the visual cortex.
The five participants who performed the training and completed the experiment had significantly improved vision. They were able to see in ways they weren’t able to before the experiment began. A few found the experiment life-changing – a couple of participants are driving again, for instance, or have gained the confidence to go shopping and exercise frequently.
Following the dancing dots that can’t be “seen”
Participants fix their gaze on a small black square in the middle of a computer screen.
Every few seconds, a group of about 100 small dots appears within a circle on the screen, somewhere in the person’s damaged visual field – when the patients stare at the square, they don’t initially see the dots. The dots twinkle into existence, appear to move as a group either to the left or the right, then disappear after about one-half second. Then the patient has to choose whether the dots are moving left or right. A chime indicates whether he or she chose correctly, providing feedback that lets the brain know whether it made the right choice and speeding up learning.
But how do patients choose if they can’t consciously see the dots?
“The patients can’t see the dots, but they’re aware that there is something happening that they can’t quite see. They might say, ‘I know that there’s something there, but I can’t make any sense of it,’” said Huxlin, who is also a faculty member in the departments of Ophthalmology, Neurobiology and Anatomy, Brain and Cognitive Sciences, and in the Center for Visual Science.
But the brain is able to make some sense of it all, even though the patient is unaware that he or she is seeing anything. When forced to make a choice, patients typically start out with a success rate of around 50 percent by guessing. Over a period of days, weeks or months, that number goes to 80 or 90 percent, as the brain learns to “see” a new area, and the visual information moves from blindsight to consciousness. Patients eventually become aware of the dots and their movement.
As patients improve, researchers move the dots further and further into what was the patient’s blind area, as a way to challenge the brain, to coax it to see a new area.
“Basically, it’s exercising the visual part of the brain every day,” said Huxlin. “It’s very hard work, very grueling. By forcing patients to choose, you’re helping the brain re-develop.”
The patients in the study did about 300 tests at a time, which translated roughly to sitting in front of a computer for 15 to 30 minutes once or twice a day, every day, for nine to 18 months. It’s an exhausting task, especially for someone whose brain is working extra-hard to accomplish it.
Working with Huxlin on the work were Tim Martin, Ph.D., post-doctoral research associate; Kristin Kelly, formerly a technical associate and now a medical student; former graduate student Meghan Riley; neuro-ophthalmologist Deborah Friedman, M.D.; neurologist W. Scott Burgin, M.D.; and Mary Hayhoe, Ph.D., formerly of the Department of Brain and Cognitive Sciences at the University of Rochester, and now at the University of Texas at Austin. The University of Rochester has filed a patent on the technology.
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