A Load Off Your Mind

Engineering professors are devising a brain scanner that will sense when you’re going into information overload

Picture an air-traffic controller tracking 10 planes approaching an airport. Now imagine he’s having trouble focusing on all 10 aircraft, perhaps because he’s been up all night or just has a lot on his mind. What would happen if his computer sensed his mental fatigue, removed one plane from his oversight and reassigned it to a controller who just started her shift?

The scenario might seem like science fiction, but with new technology being developed by Tufts researchers Robert Jacob and Sergio Fantini, it could be quite real someday. Jacob and Fantini have developed a brain-scanning device that allows a computer to sense the level of mental exertion of its user and adjust tasks accordingly to achieve the correct balance between boredom and overload.

“Humans and computers are two powerful information processors connected by this miserably narrow bandwidth—a mouse and a keyboard,” says Jacob, a professor of computer science in the School of Engineering. Jacob’s challenge is to find ways to create a more direct connection between machine and human brain to make both more efficient.

Read more

Pinpointing the Brain’s Arbitrator

We tend to be creatures of habit. In fact, the human brain has a learning system that is devoted to guiding us through routine, or habitual, behaviors. At the same time, the brain has a separate goal-directed system for the actions we undertake only after careful consideration of the consequences. We switch between the two systems as needed. But how does the brain know which system to give control to at any given moment? Enter The Arbitrator.

Researchers at the California Institute of Technology (Caltech) have, for the first time, pinpointed areas of the brain—the inferior lateral prefrontal cortex and frontopolar cortex—that seem to serve as this “arbitrator” between the two decision-making systems, weighing the reliability of the predictions each makes and then allocating control accordingly. The results appear in the current issue of the journal Neuron.

According to John O’Doherty, the study’s principal investigator and director of the Caltech Brain Imaging Center, understanding where the arbitrator is located and how it works could eventually lead to better treatments for brain disorders, such as drug addiction, and psychiatric disorders, such as obsessive-compulsive disorder. These disorders, which involve repetitive behaviors, may be driven in part by malfunctions in the degree to which behavior is controlled by the habitual system versus the goal-directed system.

"Now that we have worked out where the arbitrator is located, if we can find a way of altering activity in this area, we might be able to push an individual back toward goal-directed control and away from habitual control," says O’Doherty, who is also a professor of psychology at Caltech. "We’re a long way from developing an actual treatment based on this for disorders that involve over-egging of the habit system, but this finding has opened up a highly promising avenue for further research."

In the study, participants played a decision-making game on a computer while connected to a functional magnetic resonance imaging (fMRI) scanner that monitored their brain activity. Participants were instructed to try to make optimal choices in order to gather coins of a certain color, which were redeemable for money.

During a pre-training period, the subjects familiarized themselves with the game—moving through a series of on-screen rooms, each of which held different numbers of red, yellow, or blue coins. During the actual game, the participants were told which coins would be redeemable each round and given a choice to navigate right or left at two stages, knowing that they would collect only the coins in their final room. Sometimes all of the coins were redeemable, making the task more habitual than goal-directed. By altering the probability of getting from one room to another, the researchers were able to further test the extent of participants’ habitual and goal-directed behavior while monitoring corresponding changes in their brain activity.

With the results from those tests in hand, the researchers were able to compare the fMRI data and choices made by the subjects against several computational models they constructed to account for behavior. The model that most accurately matched the experimental data involved the two brain systems making separate predictions about which action to take in a given situation. Receiving signals from those systems, the arbitrator kept track of the reliability of the predictions by measuring the difference between the predicted and actual outcomes for each system. It then used those reliability estimates to determine how much control each system should exert over the individual’s behavior. In this model, the arbitrator ensures that the system making the most reliable predictions at any moment exerts the greatest degree of control over behavior.

"What we’re showing is the existence of higher-level control in the human brain," says Sang Wan Lee, lead author of the new study and a postdoctoral scholar in neuroscience at Caltech. "The arbitrator is basically making decisions about decisions."

In line with previous findings from the O’Doherty lab and elsewhere, the researchers saw in the brain scans that an area known as the posterior putamen was active at times when the model predicted that the habitual system should be calculating prediction values. Going a step further, they examined the connectivity between the posterior putamen and the arbitrator. What they found might explain how the arbitrator sets the weight for the two learning systems: the connection between the arbitrator area and the posterior putamen changed according to whether the goal-directed or habitual system was deemed to be more reliable. However, no such connection effects were found between the arbitrator and brain regions involved in goal-directed learning. This suggests that the arbitrator may work mainly by modulating the activity of the habitual system.

"One intriguing possibility arising from these findings, which we will need to test in future work, is that being in a habitual mode of behavior may be the default state," says O’Doherty. "So when the arbitrator determines you need to be more goal-directed in your behavior, it accomplishes this by inhibiting the activity of the habitual system, almost like pressing the breaks on your car when you are in drive."

Sociable receptors: in pairs, in groups or in a crowd

When cells migrate in the body, for instance, during development, or when neurons establish new connections, cells need to know where they are going. A ‘wrong turn’ will generally cause disease or developmental disorders. The cells take direction cues from other cells with which they interact, and which they then repel after a short period of contact. Among those direction cues are ephrin ligands, recognized by Eph receptors on the cell. Together with colleagues from the Max Planck Institute of Molecular Physiology in Dortmund, scientists at the Max Planck Institute of Neurobiology in Martinsried have discovered that Eph receptors must form groups of three or four in order to become active and transmit the signal. Furthermore, the ratio of such multimers to inactive dimers determines the strength of the cellular repulsion response. The new findings help scientists understand how cells communicate and offer a point of departure for studying diseases related to breakdowns in this guidance system.

When people get together, there is usually a lot of interaction. Our cells behave similarly. When cells grow close to each other during development, they need to communicate with the surrounding cells to establish whether they are in the right place in the organism and which cells they should connect with. This communication is especially critical in the brain, where adhesion and repulsion processes between neurons occur continuously. It is only when the right cells connect that something new can be learned, for example. Emerging tumours also must exchange information with the cells around them to be able to grow. “It is of fundamental importance to understand how cells communicate with one another”, says Rüdiger Klein, Director at the Max Planck Institute of Neurobiology. He has been studying the language of the cells for years together with colleagues in his department. Their research focuses on the so-called Eph receptors and their ephrin ligands.

Cell communication via ephrin/Eph receptors comes into play in most encounters between cells. As a result of this communication, one cell usually repels the other, which continues to grow in another direction. Many such instances of interaction guide the cell to the right place. The guidance system itself – the ephrins and Eph receptors – are found on the cell surface. When the ephrin and the Eph receptor of two opposing cells meet, they form an ephrin/Eph complex. This triggers cellular processes in one or both of the cells, which eventually cause the detachment of the ephrin/Eph complex and the repulsion of the two cells from one another.

“Many receptor systems have developed a security mechanism to prevent false alarms from triggering the cellular processes”, explains Rüdiger Klein. “A signal is only transmitted to the cell if two receptor/ligand pairs form a dimer.” However, in the case of ephrins and Eph receptors, things are different. Ephrin/Eph complexes form dimers, but often also larger groups on the cell membranes. Scientists were previously not sure how this affects repulsion and repulsive signalling strength.

The neurobiologists in Martinsried and their colleagues from the Max Planck Institute of Molecular Physiology in Dortmund have now been able to artificially trigger and study the formation of groups of Eph receptors in cell culture. The results show that the otherwise usual dimers are inactive when made up of Eph receptors. Only trimers and tetramers triggered the signals that caused cell repulsion. However, the scientists’ working hypothesis that a larger group would trigger a stronger signal turned out to be too simple. “It took us quite some time to figure out the system”, says Andreas Schaupp, first author of the study. “In fact, it is not the size of each individual group that matters, but the composition of the entire population of groups.”

The more trimers and tetramers and the fewer dimers present in the cell membrane, the stronger the repulsion signal. In contrast, a higher abundance of dimers and a smaller number of multimers produce a weaker reaction or none at all. “Thanks to this mechanism, a cell can grade its response from forcing another cell to make a U-turn to simply guiding it past at close range”, Rüdiger Klein says. This is an important step in understanding how migrating and growing cells navigate, and why this guidance system breaks down in some diseases.

Vision is key to spatial skills

Try to conjure a mental image of your kitchen, or imagine the route that you take to work every day. For most people, this comes so naturally that we think nothing of it, but for neuroscientists, there is still much to learn about how the brain develops this critical skill, known as spatial imagery.

Sensory information from the eyes, ears, and sense of touch all contribute to our ability to imagine spatial structures, but questions remain about the influence of each sensory system. A new study from MIT neuroscientists suggests that visual input plays a special role in developing these skills, particularly for more complex tasks.

By studying children in India who were born blind but whose blindness could be treated, the researchers found that the children’s ability to perform more complex spatial imagery tasks improved markedly following surgery that restored their sight.

“Just four months of vision seems to have a significant impact on spatial imagery skills,” says Pawan Sinha, an MIT professor of brain and cognitive sciences and senior author of the paper. “That seems to be consistent with the greater richness of spatial information that vision provides. With audition and touch we get a coarser sense of the environment. With vision we have a much more fine-grained appreciation of the environment.”

The study, which appeared in a recent issue of the journal Psychological Science, grew out of Project Prakash, a charitable effort Sinha launched to identify and treat children in India suffering from curable forms of blindness, such as cataracts or corneal scarring.

Tapan Gandhi, a postdoc in Sinha’s lab, is the paper’s lead author; Suma Ganesh, an ophthalmologist at Dr. Shroff’s Charity Eye Hospital in New Delhi, is also an author.

Read more

Image caption: When adult mice were kept in the dark for about a week, neural networks in the auditory cortex, where sound is processed, strengthened their connections from the thalamus, the midbrain’s switchboard for sensory information. As a result, the mice developed sharper hearing. This enhanced image shows fibers (green) that link the thalamus to neurons (red) in the auditory cortex. Cell nuclei are blue. Image by Emily Petrus and Amal Isaiah

A Short Stay in Darkness May Heal Hearing Woes

Call it the Ray Charles Effect: a young child who is blind develops a keen ability to hear things others cannot. Researchers have known this can happen in the brains of the very young, which are malleable enough to re-wire some circuits that process sensory information. Now researchers at the University of Maryland and Johns Hopkins University have overturned conventional wisdom, showing the brains of adult mice can also be re-wired, compensating for a temporary vision loss by improving their hearing.

The findings, published Feb. 5 in the peer-reviewed journal Neuron, may lead to treatments for people with hearing loss or tinnitus, said Patrick Kanold, an associate professor of biology at UMD who partnered with Hey-Kyoung Lee, an associate professor of neuroscience at JHU, to lead the study.

"There is some level of interconnectedness of the senses in the brain that we are revealing here," Kanold said.

"We can perhaps use this to benefit our efforts to recover a lost sense," said Lee. "By temporarily preventing vision, we may be able to engage the adult brain to change the circuit to better process sound."

Kanold explained that there is an early “critical period” for hearing, similar to the better-known critical period for vision. The auditory system in the brain of a very young child quickly learns its way around its sound environment, becoming most sensitive to the sounds it encounters most often. But once that critical period is past, the auditory system doesn’t respond to changes in the individual’s soundscape.

"This is why we can’t hear certain tones in Chinese if we didn’t learn Chinese as children," Kanold said. "This is also why children get screened for hearing deficits and visual deficits early. You cannot fix it after the critical period."

Kanold, an expert on how the brain processes sound, and Lee, an expert on the same processes in vision, thought the adult brain might be flexible if it were forced to work across the senses rather than within one sense. They used a simple, reversible technique to simulate blindness: they placed adult mice with normal vision and hearing in complete darkness for six to eight days.

After the adult mice were returned to a normal light-dark cycle, their vision was unchanged. But they heard much better than before.

The researchers played a series of one-note tones and tested the responses of individual neurons in the auditory cortex, a part of the brain devoted exclusively to hearing. Specifically, they tested neurons in a middle layer of the auditory cortex that receives signals from the thalamus, a part of the midbrain that acts as a switchboard for sensory information. The neurons in this layer of the auditory cortex, called the thalamocortical recipient layer, were generally not thought to be malleable in adults.

But the team found that for the mice that experienced simulated blindness these neurons did, in fact, change. In the mice placed in darkness, the tested neurons fired faster and more powerfully when the tones were played, were more sensitive to quiet sounds, and could discriminate sounds better. These mice also developed more synapses, or neural connections, between the thalamus and the auditory cortex.

The fact that the changes occurred in the cortex, an advanced sensory processing center structured about the same way in most mammals, suggests that flexibility across the senses is a fundamental trait of mammals’ brains, Kanold said.

"This makes me hopeful that we would see it in higher animals too," including humans, he said. "We don’t know how many days a human would have to be in the dark to get this effect, and whether they would be willing to do that. But there might be a way to use multi-sensory training to correct some sensory processing problems in humans."

The mice that experienced simulated blindness eventually reverted to normal hearing after a few weeks in a normal light-dark cycle. In the next phase of their five-year study, Kanold and Lee plan to look for ways to make the sensory improvements permanent, and to look beyond individual neurons to study broader changes in the way the brain processes sounds.

Brain Scans Show We Take Risks Because We Can’t Stop Ourselves

A new study correlating brain activity with how people make decisions suggests that when individuals engage in risky behavior, such as drunk driving or unsafe sex, it’s probably not because their brains’ desire systems are too active, but because their self-control systems are not active enough.

This might have implications for how health experts treat mental illness and addiction or how the legal system assesses a criminal’s likelihood of committing another crime.

Researchers from The University of Texas at Austin, UCLA and elsewhere analyzed data from 108 subjects who sat in a magnetic resonance imaging (MRI) scanner — a machine that allows researchers to pinpoint brain activity in vivid, three-dimensional images — while playing a video game that simulates risk-taking.

The researchers used specialized software to look for patterns of activity across the whole brain that preceded a person’s making a risky choice or a safe choice in one set of subjects. Then they asked the software to predict what other subjects would choose during the game based solely on their brain activity. The software accurately predicted people’s choices 71 percent of the time.

“These patterns are reliable enough that not only can we predict what will happen in an additional test on the same person, but on people we haven’t seen before,” said Russell Poldrack, director of UT Austin’s Imaging Research Center and professor of psychology and neuroscience.

When the researchers trained their software on much smaller regions of the brain, they found that just analyzing the regions typically involved in executive functions such as control, working memory and attention was enough to predict a person’s future choices. Therefore, the researchers concluded, when we make risky choices, it is primarily because of the failure of our control systems to stop us.

“We all have these desires, but whether we act on them is a function of control,” said Sarah Helfinstein, a postdoctoral researcher at UT Austin and lead author of the study that appears online this week in the journal Proceedings of the National Academy of Sciences.

Helfinstein said that additional research could focus on how external factors, such as peer pressure, lack of sleep or hunger, weaken the activity of our brains’ control systems when we contemplate risky decisions.

“If we can figure out the factors in the world that influence the brain, we can draw conclusions about what actions are best at helping people resist risks,” said Helfinstein.

To simulate features of real-world risk-taking, the researchers used a video game called the Balloon Analogue Risk Task (BART) that past research has shown correlates well with self-reported risk-taking such as drug and alcohol use, smoking, gambling, driving without a seatbelt, stealing and engaging in unprotected sex.

While playing the BART, the subject sees a balloon on the screen and is asked to make either a risky choice (inflate the balloon a little and earn a few cents) or a safe choice (stop the round and “cash out,” keeping whatever money was earned up to that point). Sometimes inflating the balloon causes it to burst and the player loses all the cash earned from that round. After each successful balloon inflation, the game continues with the chance of earning another standard-sized reward or losing an increasingly large amount. Many health-relevant risky decisions share this same structure, such as when deciding how many alcoholic beverages to drink before driving home or how much one can experiment with drugs or cigarettes before developing an addiction.

The data for this study came from the Consortium for Neuropsychiatric Phenomics at UCLA, which recruited adults from the Los Angeles area for researchers to examine differences in response inhibition and working memory between healthy adults and patients diagnosed with bipolar disorder, schizophrenia, or adult attention deficit hyperactivity disorder (ADHD). Only data collected from healthy participants were included in the present analyses.