The Neurotech 2015 symposium presents talks by neurotechnology pioneers whose cutting-edge innovations are changing the face of neurobiological research from molecules to cognition. The symposium is open to the public, and registration is required, but seating is limited.
For more information and to register for this event, visit neurotech.mit.edu
About 8 million Americans suffer from nightmares and flashbacks to a traumatic event. This condition, known as post-traumatic stress disorder (PTSD), is particularly common among soldiers who have been in combat, though it can also be triggered by physical attack or natural disaster.
Studies have shown that trauma victims are more likely to develop PTSD if they have previously experienced chronic stress, and a new study from MIT may explain why. The researchers found that animals who underwent chronic stress prior to a traumatic experience engaged a distinctive brain pathway that encodes traumatic memories more strongly than in unstressed animals.
Blocking this type of memory formation may offer a new way to prevent PTSD, says Ki Goosens, the senior author of the study, which appears in the journal Biological Psychiatry.
“The idea is not to make people amnesic but to reduce the impact of the trauma in the brain by making the traumatic memory more like a ‘normal,’ unintrusive memory,” says Goosens, an assistant professor of neuroscience and investigator in MIT’s McGovern Institute for Brain Research.
The paper’s lead author is former MIT postdoc Michael Baratta.
Strong memories
Goosens’ lab has sought for several years to find out why chronic stress is so strongly linked with PTSD. “It’s a very potent risk factor, so it must have a profound change on the underlying biology of the brain,” she says.
To investigate this, the researchers focused on the amygdala, an almond-sized brain structure whose functions include encoding fearful memories. They found that in animals that developed PTSD symptoms following chronic stress and a traumatic event, serotonin promotes the process of memory consolidation. When the researchers blocked amygdala cells’ interactions with serotonin after trauma, the stressed animals did not develop PTSD symptoms. Blocking serotonin in unstressed animals after trauma had no effect.
“That was really surprising to us,” Baratta says. “It seems like stress is enabling a serotonergic memory consolidation process that is not present in an unstressed animal.”
Memory consolidation is the process by which short-term memories are converted into long-term memories and stored in the brain. Some memories are consolidated more strongly than others. For example, “flashbulb” memories, formed in response to a highly emotional experience, are usually much more vivid and easier to recall than typical memories.
Goosens and colleagues further discovered that chronic stress causes cells in the amygdala to express many more 5-HT2C receptors, which bind to serotonin. Then, when a traumatic experience occurs, this heightened sensitivity to serotonin causes the memory to be encoded more strongly, which Goosens believes contributes to the strong flashbacks that often occur in patients with PTSD.
“It’s strengthening the consolidation process so the memory that’s generated from a traumatic or fearful event is stronger than it would be if you don’t have this serotonergic consolidation engaged,” Baratta says.
“This study is a very nice dissection of the mechanism by which chronic stress seems to activate new pathways not seen in unstressed animals,” says Mireya Nadal-Vicens, medical director of the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital, who was not part of the research team.
Drug intervention
This memory consolidation process can take hours to days to complete, but once a memory is consolidated, it is very difficult to erase. However, the findings suggest that it may be possible to either prevent traumatic memories from forming so strongly in the first place, or to weaken them after consolidation, using drugs that interfere with serotonin.
“The consolidation process gives us a window in which we can possibly intervene and prevent the development of PTSD. If you give a drug or intervention that can block fear memory consolidation, that’s a great way to think about treating PTSD,” Goosens says. “Such an intervention won’t cause people to forget the experience of the trauma, but they might not have the intrusive memory that is ultimately going to cause them to have nightmares or be afraid of things that are similar to the traumatic experience.”
The Food and Drug Administration has already approved a drug called agomelatine that blocks this type of serotonin receptor and is used as an antidepressant.
Such a drug might also be useful to treat patients who already suffer from PTSD. These patients’ traumatic memories are already consolidated, but some research has shown that when memories are recalled, there is a window of time during which they can be altered and reconsolidated. It may be possible to weaken these memories by using serotonin-blocking drugs to interfere with the reconsolidation process, says Goosens, who plans to begin testing that possibility in animals.
The findings also suggest that the antidepressant Prozac and other selective serotonin reuptake inhibitors (SSRIs), which are commonly given to PTSD patients, likely do not help and may actually worsen their symptoms. Prozac enhances the effects of serotonin by prolonging its exposure to brain cells. While this often helps those suffering from depression, “There’s no biological evidence to support the use of SSRIs for PTSD,” Goosens says.
“The consolidation of traumatic memories requires this serotonergic cascade and we want to block it, not enhance it,” she adds. “This study suggests we should rethink the use of SSRIs in PTSD and also be very careful about how they are used, particularly when somebody is recently traumatized and their memories are still being consolidated, or when a patient is undergoing cognitive behavior therapy where they’re recalling the memory of the trauma and the memory is going through the process of reconsolidation.”
In 2011, MIT neuroscientist Rebecca Saxe and colleagues reported that in blind adults, brain regions normally dedicated to vision processing instead participate in language tasks such as speech and comprehension. Now, in a study of blind children, Saxe’s lab has found that this transformation occurs very early in life, before the age of 4.
The study, appearing in the Journal of Neuroscience, suggests that the brains of young children are highly plastic, meaning that regions usually specialized for one task can adapt to new and very different roles. The findings also help to define the extent to which this type of remodeling is possible.
“In some circumstances, patches of cortex appear to take on other roles than the ones that they most typically have,” says Saxe, a professor of cognitive neuroscience and an associate member of MIT’s McGovern Institute for Brain Research. “One question that arises from that is, ‘What is the range of possible differences between what a cortical region typically does and what it could possibly do?’”
The paper’s lead author is Marina Bedny, a former MIT postdoc who is now an assistant professor at Johns Hopkins University. MIT graduate student Hilary Richardson is also an author of the paper.
Brain reorganization
The brain’s cortex, which carries out high-level functions such as thought, sensory processing, and initiation of movement, is made of sheets of neurons, each dedicated to a certain role. Within the visual system, located primarily in the occipital lobe, most neurons are tuned to respond only to a very specific aspect of visual input, such as brightness, orientation, or location in the field of view.
“There’s this big fundamental question, which is, ‘How did that organization get there, and to what degree can it be changed?’” Saxe says.
One possibility is that neurons in each patch of cortex have evolved to carry out specific roles, and can do nothing else. At the other extreme is the possibility that any patch of cortex can be recruited to perform any kind of computational task.
“The reality is somewhere in between those two,” Saxe says.
To study the extent to which cortex can change its function, scientists have focused on the visual cortex because they can learn a great deal about it by studying people who were born blind.
A landmark 1996 study of blind people found that their visual regions could participate in a nonvisual task — reading Braille. Some scientists theorized that perhaps the visual cortex is recruited for reading Braille because like vision, it requires discriminating very fine-grained patterns.
However, in their 2011 study, Saxe and Bedny found that the visual cortex of blind adults also responds to spoken language. “That was weird, because processing auditory language doesn’t require the kind of fine-grained spatial discrimination that Braille does,” Saxe says.
She and Bedny hypothesized that auditory language processing may develop in the occipital cortex by piggybacking onto the Braille-reading function. To test that idea, they began studying congenitally blind children, including some who had not learned Braille yet. They reasoned that if their hypothesis were correct, the occipital lobe would be gradually recruited for language processing as the children learned Braille.
However, they found that this was not the case. Instead, children as young as 4 already have language-related activity in the occipital lobe.
“The response of occipital cortex to language is not affected by Braille acquisition,” Saxe says. “It happens before Braille and it doesn’t increase with Braille.”
Language-related occipital activity was similar among all of the 19 blind children, who ranged in age from 4 to 17, suggesting that the entire process of occipital recruitment for language processing takes place before the age of 4, Saxe says. Bedny and Saxe have previously shown that this transition occurs only in people blind from birth, suggesting that there is an early critical period after which the cortex loses much of its plasticity.
The new study represents a huge step forward in understanding how the occipital cortex can take on new functions, says Ione Fine, an associate professor of psychology at the University of Washington.
“One thing that has been missing is an understanding of the developmental timeline,” says Fine, who was not involved in the research. “The insight here is that you get plasticity for language separate from plasticity for Braille and separate from plasticity for auditory processing.”
Language skills
The findings raise the question of how the extra language-processing centers in the occipital lobe affect language skills.
“This is a question we’ve always wondered about,” Saxe says. “Does it mean you’re better at those functions because you have more of your cortex doing it? Does it mean you’re more resilient in those functions because now you have more redundancy in your mechanism for doing it? You could even imagine the opposite: Maybe you’re less good at those functions because they’re distributed in an inefficient or atypical way.”
There are hints that the occipital lobe’s contribution to language-related functions “takes the pressure off the frontal cortex,” where language processing normally occurs, Saxe says. Other researchers have shown that suppressing left frontal cortex activity with transcranial magnetic stimulation interferes with language function in sighted people, but not in the congenitally blind.
This leads to the intriguing prediction that a congenitally blind person who suffers a stroke in the left frontal cortex may retain much more language ability than a sighted person would, Saxe says, although that hypothesis has not been tested.
Saxe’s lab is now studying children under 4 to try to learn more about how cortical functions develop early in life, while Bedny is investigating whether the occipital lobe participates in functions other than language in congenitally blind people.
Researchers discover neurons in the brain that weigh costs and benefits to drive formation of habits.
It has been recognized for decades that the brain produces rhythmic patterns of electrical activity, colloquially known as “brain waves.” These rhythmic patterns reflect the activity of thousands or millions of neurons, each with its own intrinsic rhythmic tendencies. If each neuron is firing independently of its neighbors, the overall effect will appear as noise, but when they become synchronized, their combined effect can be detected as rhythmic oscillations, which in some cases are strong enough to penetrate the skull, allowing them to be recorded noninvasively with electrodes on the scalp.
This video illustrates a mechanical analogy for how this synchronization occurs; the ticking metronomes influence each other through the side-to-side movements of the board on which they sit, and over time this causes them to lock into a synchronous pattern.
