When the amount of SynCAM1 was increased in experiments, the neurons formed a much greater number of synapses (cf.: picture on the right with increased SynCAM1). However, in the learning test, these mice performed worse than animals that lacked the protein. (Credit: Valentin Stein)

GoogleNews.com, Yale University, December 9, 2010 — Yale University researchers have found that a single molecule not only connects brain cells but also changes how we learn. The findings, reported in the December 9 issue of the journal Neuron, may help researchers discover ways to improve memory and could lead to new therapies to correct neurological disorders.

The junctions between brain cells over which nerve pulses pass — called synapses — are crucial for regulating learning and memory and how we think. Aberrations in the structure and function of synapses have been linked to mental retardation and autism, while synapses are lost in the aging brains of Alzheimer’s patients.

However, the mechanisms that organize synapses in the living brain remain a puzzle. Yale scientists identified one critical piece of this puzzle, a molecule called SynCAM 1 that spans across synaptic junctions.

“We hypothesized that this molecule might promote new synapses in the developing brain, but were surprised that it also impacts the maintenance and function of these structures,” said Thomas Biederer, associate professor of molecular biophysics and biochemistry and senior author of the study. “We can now define how this molecule supports the brain’s ability to wire itself.”

The Yale team focused on SynCAM 1, an adhesion molecule that helps to hold synaptic junctions together. They found that when the SynCAM 1 gene was activated in mice, more synaptic connections formed. Mice without the molecule produced fewer synapses.

When we learn, new synapses can form. However, the strength of synaptic connections also changes during learning, based on the amount of stimuli received — a quality scientists termed “plasticity.” Together with a group in Germany led by Valentin Stein, the team was surprised to find that SynCAM 1 controls an important form of synaptic plasticity.

Unexpectedly, Biederer and colleagues also found that mice with high amounts of SynCAM 1 are unable to learn while mice lacking SynCAM 1 — and having fewer synapses — learn better. Apparently an excess of the molecule can be damaging. This builds on recent theories suggesting that having too many connections isn’t always better and that the balance of synaptic activity is crucial for proper learning and memory.

“Synapses are dynamic structures. It appears that SynCAM 1 ties synapses together; some of this molecule is needed to promote contact but too much glues down the synapse and inhibits its function. It may act a bit like a sculptor who helps give synapses their shape.” Biederer also said that the molecule is almost identical in mice and man, and likely has the same roles in human brains.

Other Yale authors on the paper are Elissa Robbins and Karen Perez de Arce.

The work was funded by the National Institutes of Health and the March of Dimes Foundation.

Comparing images of brain activity in response to the “self-remember” and “self-future” event cues, researchers found a surprisingly complete overlap among regions of the brain used for remembering the past and those used for envisioning the future. (Image courtesy of Washington University in St. Louis)

Washington University, ST. LOUIS  —  Human memory, the ability to recall vivid mental images of past experiences, has been studied extensively for more than a hundred years. But until recently, there’s been surprisingly little research into cognitive processes underlying another form of mental time travel — the ability to clearly imagine or “see” oneself participating in a future event.

Researchers from Washington University in St. Louis have used advanced brain imaging techniques to show that remembering the past and envisioning the future may go hand-in-hand, with each process sparking strikingly similar patterns of activity within precisely the same broad network of brain regions.

“In our daily lives, we probably spend more time envisioning what we’re going to do tomorrow or later on in the day than we do remembering, but not much is known about how we go about forming these mental images of the future,” says Karl Szpunar, lead author of the study and a psychology doctoral student in Arts & Sciences at Washington University.

“Our findings provide compelling support for the idea that memory and future thought are highly interrelated and help explain why future thought may be impossible without memories.”

Published in Proceedings of the National Academy of Sciences, the study sheds new light on how the human mind relies on the vivid recollection of past experiences to prepare itself for future challenges, suggesting that envisioning the future may be a critical prerequisite for many higher-level planning processes.

Other study co-authors are Jason M. Watson, a Washington University doctoral graduate now assistant professor of psychology at the University of Utah; and Kathleen McDermott, an associate professor of psychology in Arts & Sciences and of radiology in the School of Medicine at Washington University.

McDermott, principal investigator for the University’s Memory and Cognition Lab, where the research is based, suggests that the findings are notable for two reasons.

First, the study clearly demonstrates that the neural network underlying future thought is not isolated in the brain’s frontal cortex, as some have speculated. Although the frontal lobes play a well-documented role in carrying out future-oriented executive operations, such as anticipation, planning and monitoring, the spark for these activities may well be the very process of envisioning oneself in a specific future event, an activity based within and reliant upon the same neurally distributed network used to retrieve autobiographical memories.

Second, within this neural network, patterns of activity suggest that the visual and spatial context for our imagined future often is pieced together using our past experiences, including memories of specific body movements and visual perspective changes — data stored as we navigated through similar settings in the past.

These findings, McDermott suggests, offer strong support for a relatively recent theory of memory, which posits that remembering the past and envisioning the future draw upon many of the same neural mechanisms. Previous speculation has been based largely on the anecdotal observation of very young children, cases of severe depression and brain damaged persons with amnesia.

“There’s a little known and not that well investigated finding that if you have an amnesic person who can’t remember the past, they’re also not at all good about thinking about what they might be doing tomorrow or envisioning any kind of personal future,” McDermott explains. They comprehend time and can consider the future in the abstract sense (e.g., that global warming is a concern for the future), but they cannot vividly envision themselves in a specific future scenario.

“The same is true with very small children — they don’t remember particularly what happened last month and they can’t really tell you much of anything about what they envision happening next week. This is also the case with suicidally depressed people. So, there’s this theory that it all goes hand-in-hand, but nobody has looked closely enough to explain exactly how or why this occurs.”

In this study, researchers relied on functional magnetic resonance imaging (fMRI) to capture patterns of brain activation as college students were given 10 seconds to develop a vivid mental image of themselves or a famous celebrity participating in a range of common life experiences.

Presented with a series of memory cues, such as getting lost, spending time with a friend or attending a birthday party, participants were asked to recall a related event from their own past; to envision themselves experiencing such an event in their future life; or, to picture a famous celebrity — specifically former U.S. President Bill Clinton — participating in such an event.

The “Clinton-Imagine” task was introduced to help researchers establish a baseline level of brain activity for a cognitive event that was in many ways similar to the other two tasks but did not involve the mental projection of oneself through time. Bill Clinton was chosen because pre-testing showed he was easy for participants to visualize in a variety of situations.

Comparing images of brain activity in response to the “self-remember” and “self-future” event cues, researchers found a surprisingly complete overlap among regions of the brain used for remembering the past and those used for envisioning the future — every region involved in recollecting the past was also used in envisioning the future.

During the experiment, participants were not required to describe details or explain the origin of mental images elicited by the memory cues, but in post-testing questionnaires most indicated that they tended to place future-oriented images in the context of familiar places (e.g. home, school) and familiar people (e.g. family, friends), which would require the reactivation of those images from neural networks responsible for the storage and retrieval of autobiographical memories.

Conversely, the neural networks associated with personal mental time travel showed significantly less activity when participants imagined scenarios involving Bill Clinton. The reason, researchers suggest, is that participants had no personal memories of direct interaction with Clinton, and thus, any images of him had to be derived from neural networks responsible for semantic memory — our context-free general knowledge of the world. In fact, participants later reported that their mental images of Clinton tended to be less vivid (e.g. “I see Bill Clinton at a party in the White House, alongside several faceless senators”).

“Results of this study offer a tentative answer to a longstanding question regarding the evolutionary usefulness of memory,” McDermott concludes. “It may just be that the reason we can recollect our past in vivid detail is that this set of processes is important for being able to envision ourselves in future scenarios. This ability to envision the future has clear and compelling adaptive significance.”

ScienceDaily.com, 2010  —  Entirely different signal paths and parts of the brain are involved when you try to remember something and when you just happen to remember something, prompted by a smell, a picture, or a word, for instance. This is shown by Kristiina Kompus in her dissertation at Umeå University in Sweden.

Imagine you are asked to remember what you were doing exactly one week ago. You would probably have to make quite a mental effort to sift through your memories. On another occasion, a smell, a picture, or a word might suddenly and unexpectedly trigger a vivid memory of something that happened to you. Science still does not fully understand why our brain sometimes automatically supplies us with a memory that we have done nothing to deliberately call to mind, whereas why, on other occasions, we cannot remember things even though we make efforts to recall them.

The studies in Kristiina Kompus’s dissertation show that these two different ways of remembering things are initiated by entirely different signal paths in the brain. Efforts to retrieve a specific memory are dealt with by the upper part of the frontal lobe. This area of the brain is activated not only in connection with memory-related efforts but also in all types of mental efforts and intentions, according to the dissertation. This part of the brain is not involved in the beginning of the process of unintentionally remembering something as a response to external stimuli. Instead, such memories are activated by specific signals from other parts of the brain, namely those that deal with perceived stimuli like smells, pictures, and words. Sometimes such memories are thought to be more vivid and emotional; otherwise they would not be activated in this way. But Kristiina Kompus’s dissertation shows that this is not the case — memories do not need to be emotionally charged to be revived spontaneously, unintentionally. Nor do memories that are revived spontaneously activate the brain more than other memories.

The studies also reveal that our long-term memory is more flexible that was previously believed. There is not just one single neurological signaling path for reliving old memories but rather several paths that are anatomically separate. This discovery is important, since it helps us understand how we can help people who have a hard time remembering things, regardless of whether this is related to aging or to some disorder in the brain. It may also help people who are plagued by unpleasant memories that constantly haunt them. This can happen following traumatic experiences, but also in depression.

The dissertation uses a combination of two imaging methods for the brain: functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The methods yield different information about the function of the brain. By combining them, Kristiina Kompus has been able both to determine what part of the brain is activated and how the activation proceeds over extremely brief time intervals, on the order of milliseconds.

GoogleNews.com, UCLA, LOS ANGELES — Many neuroscientists believe the loss of the brain region known as the amygdala would result in the brain’s inability to form new memories with emotional content. New UCLA research indicates this is not so and suggests that when one brain region is damaged, other regions can compensate.

The research appears in the online edition of the journal Proceedings of the National Academy of Sciences (PNAS).

“Our findings show that when the amygdala is not available, another brain region called the bed nuclei can compensate for the loss of the amygdala,” said the study’s senior author, Michael Fanselow, a UCLA professor of psychology and a member of the UCLA Brain Research Institute.

“The bed nuclei are much slower at learning, and form memories only when the amygdala is not learning,” he said. “However, when you do not have an amygdala, if you have an emotional experience, it is like neural plasticity (the memory-forming ability of brain cells) and the bed nuclei spring into action. Normally, it is as if the amygdala says, ‘I’m doing my job, so you shouldn’t learn.’ With the amygdala gone, the bed nuclei do not receive that signal and are freed to learn.”

The amygdala is believed to be critical for learning about and storing the emotional aspects of experience, Fanselow said, and it also serves as an alarm to activate a cascade of biological systems to protect the body in times of danger. The bed nuclei are a set of forebrain gray matter surrounding the stria terminalis; neurons here receive information from the prefrontal cortex and hippocampus and communicate with several lower brain regions that control stress responses and defensive behaviors.

“Our results suggest some optimism that when a particular brain region that is thought to be essential for a function is lost, other brain regions suddenly are freed to take on the task,” Fanselow said. “If we can find ways of promoting this compensation, then we may be in a better position to help patients who have lost memory function due to brain damage, such as those who have had a stroke or have Alzheimer’s disease.

“Perhaps this research can eventually lead to new drugs and teaching regimens that facilitate plasticity in the regions that have the potential to compensate for the damaged areas,” he said.

While the current study shows this relationship for emotional learning, additional research in Fanselow’s laboratory is beginning to suggest this is a general property of memory.

Fanselow’s PNAS study was federally funded by the National Institute of Mental Health.

Co-authors include lead author Andrew Poulos, a research scientist in Fanselow’s laboratory; Ravikumar Ponnusamy, also a research scientist in Fanselow’s laboratory; and Hong-Wei Dong, UCLA assistant adjunct professor of neurology and a member of UCLA’s Laboratory of Neuro Imaging.

This research provides the first direct evidence that brain connectivity is missing in people with ADHD.

UC Davis Center for Mind and Brain, 2010  —  Two brain areas fail to connect when children with attention deficit hyperactivity disorder attempt a task that measures attention, according to researchers at the UC Davis Center for Mind and Brain and M.I.N.D. Institute.

“This is the first time that we have direct evidence that this connectivity is missing in ADHD,” said Ali Mazaheri, postdoctoral researcher at the Center for Mind and Brain. Mazaheri and his colleagues made the discovery by analyzing the brain activity in children with ADHD. The paper appears in the current online issue of the journal Biological Psychiatry.

The researchers measured electrical rhythms from the brains of volunteers, especially the alpha rhythm. When part of the brain is emitting alpha rhythms, it shows that it is disengaged from the rest of the brain and not receiving or processing information optimally, Mazaheri said.

In the experiments, children with diagnosed ADHD and normal children were given a simple attention test while their brain waves were measured. The test consisted of being shown a red or blue image, or hearing a high or low sound, and having to react by pressing a button. Immediately before the test, the children were shown either a letter “V” to alert them that the test would involve a picture (visual), or an inverted “V” representing the letter “A” to alert them that they would hear a sound (auditory).

The experiments were conducted by researchers in the laboratories of Ron Mangun, professor of psychology and neurology, and Blythe Corbett, associate clinical professor of psychiatry and behavioral sciences and a researcher at the M.I.N.D. Institute.

According to current models of how the brain allocates attention, signals from the frontal cortex — such as the “V” and “A” cues — should alert other parts of the brain, such as the visual processing area at the back of the head, to prepare to pay attention to something. That should be reflected in a drop in alpha wave activity in the visual area, Mazaheri said.

And that is what the researchers found in the brain waves of children without ADHD. But children with the disorder showed no such drop in activity, indicating a disconnection between the center of the brain that allocates attention and the visual processing regions, Mazaheri said.

“The brains of the children with ADHD apparently prepare to attend to upcoming stimuli differently than do typically developing children,” he said.

Children with ADHD did improve their reaction times when properly cued, but they don’t seem to allocate resources as efficiently, Mazaheri said.

This is the first evidence from brain electrical patterns for a functional disconnection in cortical attention systems in ADHD, he said. Current definitions of ADHD are based only on behavior.

The research was originally inspired by a desire to combine laboratory and clinical research to go beyond existing measures of ADHD and get a better understanding of the condition, Corbett said.

“Clearly the crosstalk from bedside to bench has been fruitful,” she said.

Other co-authors on the paper are staff research associate Sharon Corina, postdoctoral fellow Evelijn Bekker and research assistant Anne Berry.

The study was funded by the grants from the National Institutes of Health, the Netherlands Organization for Scientific Research, the Perry Family Foundation, the Debber Family Foundation and the Aristos Academy.

About UC Davis

For more than 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has 32,000 students, an annual research budget that exceeds $600 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges — Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science. It also houses six professional schools — Education, Law, Management, Medicine, Veterinary Medicine and the Betty Irene Moore School of Nursing.

GoogleNews.com, FORBES.com, December 9, 2010, NEW YORK — A new government report shows U.S. life expectancy has dropped slightly after mostly inching up over the years.

Life expectancy dropped about a month, from 77.9 years in 2007 to 77.8 years in 2008. The author of the report called the change minuscule and says it will take many years to see whether it’s a trend. A similar decline occurred in 2005.

For the first time in 50 years, stroke fell from the No. 3 leading cause of death. It was surpassed by chronic lower respiratory diseases, which include asthma, emphysema and chronic bronchitis.

The preliminary report for 2008 was released Thursday by the National Center for Health Statistics.