Thursday, January 16th, 2014

Time	Event
5:00a	In the blink of an eye Imagine seeing a dozen pictures flash by in a fraction of a second. You might think it would be impossible to identify any images you see for such a short time. However, a team of neuroscientists from MIT has found that the human brain can process entire images that the eye sees for as little as 13 milliseconds — the first evidence of such rapid processing speed. That speed is far faster than the 100 milliseconds suggested by previous studies. In the new study, which appears in the journal Attention, Perception, and Psychophysics, researchers asked subjects to look for a particular type of image, such as “picnic” or “smiling couple,” as they viewed a series of six or 12 images, each presented for between 13 and 80 milliseconds. “The fact that you can do that at these high speeds indicates to us that what vision does is find concepts. That’s what the brain is doing all day long — trying to understand what we’re looking at,” says Mary Potter, an MIT professor of brain and cognitive sciences and senior author of the study. image: Christine Daniloff/MIT This rapid-fire processing may help direct the eyes, which shift their gaze three times per second, to their next target, Potter says. “The job of the eyes is not only to get the information into the brain, but to allow the brain to think about it rapidly enough to know what you should look at next. So in general we’re calibrating our eyes so they move around just as often as possible consistent with understanding what we’re seeing,” she says. Other authors of the paper are former MIT postdoc Brad Wyble, now at Pennsylvania State University, postdoc Carl Hagmann, and research assistant Emily McCourt. Rapid identification After visual input hits the retina, the information flows into the brain, where information such as shape, color, and orientation is processed. In previous studies, Potter has shown that the human brain can correctly identify images seen for as little as 100 milliseconds. In the new study, she and her colleagues decided to gradually increase the speeds until they reached a point where subjects’ answers were no better than if they were guessing. All images were new to the viewers. The researchers expected they might see a dramatic decline in performance around 50 milliseconds, because other studies have suggested that it takes at least 50 milliseconds for visual information to flow from the retina to the “top” of the visual processing chain in the brain and then back down again for further processing by so-called “re-entrant loops.” These processing loops were believed necessary to confirm identification of a particular scene or object. However, the MIT team found that although overall performance declined, subjects continued to perform better than chance as the researchers dropped the image exposure time from 80 milliseconds to 53 milliseconds, then 40 milliseconds, then 27, and finally 13 — the fastest possible rate with the computer monitor being used. “This didn’t really fit with the scientific literature we were familiar with, or with some common assumptions my colleagues and I have had for what you can see,” Potter says. Potter believes one reason for the subjects’ better performance in this study may be that they were able to practice fast detection as the images were presented progressively faster, even though each image was unfamiliar. The subjects also received feedback on their performance after each trial, allowing them to adapt to this incredibly fast presentation. At the highest rate, subjects were seeing new images more than 20 times as fast as vision typically absorbs information. “We think that under these conditions we begin to show more evidence of knowledge than in previous experiments where people hadn’t really been expecting to find success, and didn’t look very hard for it,” Potter says. Simon Thorpe, director of the Centre de Recherche Cerveau & Cognition at the University of Toulouse, says the results “illustrate beautifully” that the brain can make sense of briefly presented images. “This new paper shows that the meaning of an image can be extracted even when an image is mixed up in a sequence of six or even 12 images presented at 13 milliseconds per image — a rate of about 75 frames a second. Another striking finding was that the effect is also seen when the question concerning the target is only presented after the sequence has been run, meaning that the brain can extract meaning even when there is no way to predict what will be shown,” says Thorpe, who was not part of the research team. The findings are consistent with a 2001 study from researchers at the University of Parma and the University of St. Andrews, who found that neurons in the brains of macaque monkeys that respond to specific types of image, such as faces, could be activated even when the target images were each presented for only 14 milliseconds in a rapid sequence. “That was the only background that suggested maybe 14 milliseconds was sufficient to get something meaningful into the brain,” Potter says. One-way flow The study offers evidence that “feedforward processing” — the flow of information in only one direction, from retina through visual processing centers in the brain — is enough for the brain to identify concepts without having to do any further feedback processing. It also suggests that while the images are seen for only 13 milliseconds before the next image appears, part of the brain continues to process those images for longer than that, Potter says, because in some cases subjects weren’t asked whether a specified image was present until after they had seen the sequence. “If images were wiped out after 13 milliseconds, people would never be able to respond positively after the sequence. There has to be something in the brain that has maintained that information at least that long,” she says. This ability to identify images seen so briefly may help the brain as it decides where to focus the eyes, which dart from point to point in brief movements called fixations about three times per second, Potter says. Deciding where to move the eyes can take 100 to 140 milliseconds, so very high-speed understanding must occur before that. The researchers are now investigating how long visual information presented so briefly can be held in the brain. They are also scanning subjects’ brains with a magnetoencephalography (MEG) scanner during the task to see what brain regions are active when a person successfully completes the identification task. The research was funded by the National Institutes of Health. (Comment on this)
5:00p	Erasing traumatic memories Nearly 8 million Americans suffer from posttraumatic stress disorder (PTSD), a condition marked by severe anxiety stemming from a traumatic event such as a battle or violent attack. Many patients undergo psychotherapy designed to help them re-experience their traumatic memory in a safe environment so as to help them make sense of the events and overcome their fear. However, such memories can be so entrenched that this therapy doesn’t always work, especially when the traumatic event occurred many years earlier. MIT neuroscientists have now shown that they can extinguish well-established traumatic memories in mice by giving them a type of drug called an HDAC2 inhibitor, which makes the brain’s memories more malleable, under the right conditions. Giving this type of drug to human patients receiving psychotherapy may be much more effective than psychotherapy alone, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory. “By inhibiting HDAC2 activity, we can drive dramatic structural changes in the brain. What happens is the brain becomes more plastic, more capable of forming very strong new memories that will override the old fearful memories,” says Tsai, the senior author of a paper describing the findings in the Jan. 16 issue of Cell. The new study also reveals the molecular mechanism explaining why older memories are harder to extinguish. Lead authors of the paper are former Picower Institute postdoc Johannes Graff and Nadine Joseph, a technical assistant at the Picower Institute. Genes and memories Tsai’s lab has previously shown that when memories are formed, neurons’ chromatin — DNA packaged with proteins — undergoes extensive remodeling. These chromatin modifications make it easier to activate the genes necessary to create new memories. In this study, the researchers focused on chromatin modifications that occur when previously acquired memories are extinguished. To do this, they first trained mice to fear a particular chamber — by administering a mild foot shock — and then tried to recondition the mice so they no longer feared it, which was done by placing the mice in the chamber where they received the shock, without delivering the shock again. This training proved successful in mice that had experienced the traumatic event only 24 hours before the reconditioning. However, in mice whose memories were 30 days old, it was impossible to eliminate the fearful memory. The researchers also found that in the brains of mice with 24-hour-old memories, extensive chromatin remodeling occurred during the reconditioning. For several hours after the mice were placed back in the feared chamber, there was a dramatic increase in histone acetylation of memory-related genes, caused by inactivation of the protein HDAC2. That histone acetylation makes genes more accessible, turning on the processes needed to form new memories or overwrite old ones. In mice with 30-day-old memories, however, there was no change in histone acetylation. This suggests that re-exposure to a fearful memory opens a window of opportunity during which the memory can be altered, but only if the memory has recently been formed, Tsai says. “If you do something within this window of time, then you have the possibility of modifying the memory or forming a new trace of memory that actually instructs the animal that this is not such a dangerous place,” she says. “However, the older the memory is, the harder it is to really change that memory.” Based on this finding, the researchers decided to treat mice with 30-day-old memories with an HDAC2 inhibitor shortly after re-exposure to the feared chamber. Following this treatment, the traumatic memories were extinguished just as easily as in the mice with 24-hour-old memories. The researchers also found that HDAC2 inhibitor treatment turns on a group of key genes known as immediate early genes, which then activate other genes necessary for memory formation. They also saw an increase in the number of connections among neurons in the hippocampus, where memories are formed, and in the strength of communication among these neurons. “Our experiments really strongly argue that either the old memories are permanently being modified, or a new much more potent memory is formed that completely overwrites the old memory,” Tsai says. “This could be a very promising way to bring older memories back, process them in the hippocampus, and then extinguish them with the correct paradigm,” says Jelena Radulovic, a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine who was not part of the research team. Treating anxiety Some HDAC2 inhibitors have been approved to treat cancer, and Tsai says she believes it is worth trying such drugs to treat PTSD. “I hope this will convince people to seriously think about taking this into clinical trials and seeing how well it works,” she says. Such drugs might also be useful in treating people who suffer from phobias and other anxiety disorders, she adds. Tsai’s lab is now studying what happens to memory traces when re-exposure to traumatic memories occurs at different times. It is already known that memories are formed in the hippocampus and then transferred to the cortex for longer-term storage. It appears that the HDAC2 inhibitor treatment may somehow restore the memory to the hippocampus so it can be extinguished, Tsai says. The research was funded by the National Institutes of Health, the Picower Neurological Disorder Fund, the Stanley Medical Foundation, and the Howard Hughes Medical Institute. (Comment on this)

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