Neurons See What We Tell Them to See

Neurons programmed to fire at specific faces—such as the famously reported “Jennifer Aniston neuron”—may be more in line with the conscious recognition of faces than the actual images seen. Subjects presented with a blended face, such as an amalgamation of Bill Clinton and George W. Bush, had significantly more firing of such face-specific neurons when they recognized the blended or morphed face as one person or the other. Results of the study led by Christof Koch at the Allen Institute for Brain Science, and carried out by neuroscientists Rodrigo Quian Quiroga at the University of Leicester, Alexander Kraskov at University College London and Florian Mormann at the University of Bonn, under the clinical supervision of the neurosurgeon Itzhak Fried at the University of California at Los Angeles Medical School, are published online today in the journal Neuron.

Some neurons in the region of the brain known as the medial temporal lobe are observed to be extremely selective in the stimuli to which they respond. A cell may only fire in response to different pictures of a particular person who is very familiar to the subject (such as loved one or a celebrity), the person’s written or spoken name, or simply recalling the person from memory.

“These highly specific cells are an entry point to investigate how the brain makes meaning out of visual information,” explains Christof Koch, Chief Scientific Officer at the Allen Institute for Brain Science and senior author on the paper. “We wanted to know how these cells responded not just to a simple image of a person’s face, but to a more ambiguous image of that face averaged or morphed with another person’s face.”

For the trials, subjects were shown either the face of individuals such as Bill Clinton or George W. Bush (the “adaptor” image), and then an ambiguous face which was a blend of both faces. Primed with the Clinton image, subjects tended to recognize Bush’s face in the blended image, while subjects who saw Bush’s face first recognized the blended face as Clinton. That is, even though the blended images were identical, subjects tended to consciously perceive the identity of face to which they were not adapted.

Researchers wanted to know whether these selective neurons responded to the actual image on the screen, or whether they responded more to the perception that the image caused in the brain of the subject. When subjects recognized the ambiguous face as belonging to Clinton, their Clinton-specific neurons fired. However, when subjects recognized that same face as Bush, the neurons fired significantly less. These results indicated that conscious recognition of the face played a crucial role in whether the neurons fired, rather than the raw visual stimulus.

“This study provides further evidence that stimulus-specific neurons in the medial temporal lobe follow the subjective perception of the person, as opposed to faithfully reporting the visual stimulus the person sees,” explains Koch. “This distinction may help us glean insight into how the brain takes raw visual information and transforms it into something meaningful, which can be further modulated by other aspects of experience in the brain.”

How physical exercise protects the brain from stress-induced depression

Physical exercise has many beneficial effects on human health, including the protection from stress-induced depression. However, until now the mechanisms that mediate this protective effect have been unknown. In a new study in mice, researchers at Karolinska Institutet in Sweden show that exercise training induces changes in skeletal muscle that can purge the blood of a substance that accumulates during stress, and is harmful to the brain. The study is being published in the prestigious journal Cell.

“In neurobiological terms, we actually still don’t know what depression is. Our study represents another piece in the puzzle, since we provide an explanation for the protective biochemical changes induced by physical exercise that prevent the brain from being damaged during stress,” says Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institutet.

It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).

These mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behaviour, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.

“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain. We actually found the opposite: well-trained muscle produces an enzyme that purges the body of harmful substances. So in this context the muscle’s function is reminiscent of that of the kidney or the liver,” says Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet.

The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness. In this study, the researchers demonstrated that when normal mice were given kynurenine, they displayed depressive behaviour, while mice with increased levels of PGC-1a1 in muscle were not affected. In fact, these animals never show elevated kynurenine levels in their blood since the KAT enzymes in their well-trained muscles quickly convert it to kynurenic acid, resulting in a protective mechanism.

“It’s possible that this work opens up a new pharmacological principle in the treatment of depression, where attempts could be made to influence skeletal muscle function instead of targeting the brain directly. Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness,” says Jorge Ruas.

Depression is a common psychiatric disorder worldwide. The World Health Organization (WHO) estimates that more than 350 million people are affected.

Strategic or Random? How the Brain Chooses

Many of the choices we make are informed by experiences we’ve had in the past. But occasionally we’re better off abandoning those lessons and exploring a new situation unfettered by past experiences. Scientists at the Howard Hughes Medical Institute’s Janelia Research Campus have shown that the brain can temporarily disconnect information about past experience from decision-making circuits, thereby triggering random behavior.

In the study, rats playing a game for a food reward usually acted strategically, but switched to random behavior when they confronted a particularly unpredictable and hard-to-beat competitor. The animals sometimes got stuck in a random-behavior mode, but the researchers, led by Janelia lab head Alla Karpova and postdoctoral fellow Gowan Tervo, found that they could restore normal behavior by manipulating activity in a specific region of the brain. Because the behavior of animals stuck in this random mode bears some resemblance to that of patients affected by a psychological condition called learned helplessness, the findings may help explain that condition and suggest strategies for treating it. Karpova, Tervo and their colleagues published their findings in the September 25, 2012, issue of the journal Cell.

The brain excels at integrating information from past experiences to guide decision-making in new situations. But in certain circumstances, random behavior may be preferable. An animal might have the best chance of avoiding a predator if it moves unpredictably, for example. And in a new environment, unrestricted exploration might make more sense than relying on an internal model developed elsewhere. So scientists have long speculated that the brain may have a way to switch off the influence of past experiences so that behavior can proceed randomly, Karpova says. But others disagreed. “They argue that it’s inefficient, and that it would be at odds with what some people call one of the most central operating principles of the brain – to use our past experience and knowledge to optimize behavioral choices,” she notes.

Karpova and her colleagues wanted to see if they could create a situation that would force animals to switch into this random mode of behavior. “We tried to create a setting that would push the need to create behavioral variability and unpredictability to its extreme,” she says. They did this by placing rats in a competitive setting in which a computer-simulated competitor determined which of two holes in a wall would provide a sugary reward. The virtual competitor, whose sophistication was varied by the experimenters, analyzed the rats’ behavior to predict their future choices.

“We thought if we came up with very sophisticated competitors, then the animals would eventually be unable to figure out how to outcompete them, and be forced to either give up or switch into this [random] mode, if such a mode exists,” Karpova says. And that’s exactly what happened: When faced with a weak competitor, the animals made strategic choices based on the outcomes of previous trials. But when a sophisticated competitor made strong predictions, the rats ignored past experience and made random selections in search of a reward.

Now that they had evidence that the brain could generate both strategic and random behavior, Karpova and her colleagues wanted to know how it switched between modes. Since that switch determines whether or not an animal’s internal model of the world influences its behavior, the scientists suspected it might involve a brain region called the anterior cingulate cortex, where that internal model is likely encoded.

They found that they could cause animals to switch between random and strategic behavior by manipulating the level of a stress hormone called norepinephrine in the anterior cingulate cortex. Increasing norepinephrine in the region activated random behavior and suppressed the strategic mode.  Inhibiting release of the hormone had the opposite effect.

Karpova’s team observed that animals in their experiments sometimes continued to behave randomly, even when such behavior was no longer advantageous. “If all they’ve experienced is this really sophisticated competitor for several sessions that thwarts their attempts at strategic, model-based counter-prediction, they go into this [random mode], and they can get stuck in it for quite some time after that competitor is gone,” she says. This, she says, resembles the condition of learned helplessness, in which strategic decision-making is impaired following an experience in which a person finds they are unable to control their environment.

The scientists could release the animals from this “stuck” state by suppressing the release of norepinephrine in the anterior cingulate cortex. “Just by manipulating a single neuromodulatory input into one brain area, you can dramatically enhance the strategic mode. The effect is strong enough to rescue animals out of the random mode and successfully transform them into strategic decision makers,” Karpova says. “We think this might shed light on what has gone wrong in conditions such as learned helplessness, and possibly how we can help alleviate them.” 

Karpova says that now that her team has uncovered a mechanism that switches the brain between random and strategic behavior, she would like to understand how those behaviors are controlled in more natural settings. “We normally try to use all of our knowledge to think strategically, but sometimes we still need to explore,” she says. In most cases, that probably means brief bouts of random behavior during times when we are uncertain that past experience is relevant, followed by a return to more strategic behavior – a more subtle balance that Karpova intends to investigate at the level of changes in activity in individual neural circuits.

New findings on how brain handles tactile sensations

The traditional understanding in neuroscience is that tactile sensations from the skin are only assembled to form a complete experience in the cerebral cortex, the most advanced part of the brain. However, this is challenged by new research findings from Lund University in Sweden that suggest both that other levels in the brain play a greater role than previously thought, and that a larger proportion of the brain’s different structures are involved in the perception of touch.

“It was believed that a tactile sensation, such as touching a simple object, only activated a very small part of the cerebral cortex. However, our findings show that a much larger part is probably activated. The assembly of sensations actually starts in the brainstem”, said neuroscience researcher Henrik Jörntell at Lund University.

According to his colleague Fredrik Bengtsson, who also participated in the research, this is the first study to show how complex tactile sensations from the skin are coded at the cellular level in the brain.

“Our findings have given us a new key to understanding how the perception of touch in the skin is processed and communicated to the brain”, he said.

The Lund researchers have worked in collaboration with researchers in Paris to study how individual nerve cells receive information from the skin. They used a ‘haptic interface’, which created controlled sensations of rolling and slipping movements and of contact initiating and ceasing. Movements proved decisive for the perception of touch – something that was not previously technically possible to study.

The findings of the Swedish-French research group have been published in the distinguished journal Neuron. The work is based on animal experiments and is first and foremost basic research, which aims to increase knowledge of the function of the brain. However, there are also possible areas of application.

“Normal hand and arm prostheses do not give any feedback and therefore no sensation of being a ‘real’ hand or arm. However, there are new, advanced prostheses with sensors that can supply information to the amputated arm. Our research could contribute to the further development of such sensors”, said Henrik Jörntell.

The new findings could also have a bearing on psychiatric illness and brain diseases such as stroke and Parkinson’s disease. Detailed knowledge of how the brain and its various parts process information and create a picture of a tactile experience is important to understanding these conditions.

“If we know how a healthy brain operates, we can compare it with the situation in different diseases. Then perhaps we can help patients’ brains to function more normally”, said Henrik Jörntell.

(Image caption: This is a coronal view of the hippocampus brain region of a patient with Alzheimer’s disease. Image courtesy of Daniel Tranel’s Laboratory at the UI’s Department of Neurology.)

Alzheimer’s patients can still feel the emotion long after the memories have vanished

A new University of Iowa study further supports an inescapable message: caregivers have a profound influence—good or bad—on the emotional state of individuals with Alzheimer’s disease. Patients may not remember a recent visit by a loved one or having been neglected by staff at a nursing home, but those actions can have a lasting impact on how they feel.

The findings of this study are published in the September 2014 issue of the journal Cognitive and Behavioral Neurology.

UI researchers showed individuals with Alzheimer’s disease clips of sad and happy movies. The patients experienced sustained states of sadness and happiness despite not being able to remember the movies.

“This confirms that the emotional life of an Alzheimer’s patient is alive and well,” says lead author Edmarie Guzmán-Vélez, a doctoral student in clinical psychology, a Dean’s Graduate Research Fellow, and a National Science Foundation Graduate Research Fellow.

Guzmán-Vélez conducted the study with Daniel Tranel, UI professor of neurology and psychology, and Justin Feinstein, assistant professor at the University of Tulsa and the Laureate Institute for Brain Research.

Tranel and Feinstein published a paper in 2010 that predicted the importance of attending to the emotional needs of people with Alzheimer’s, which is expected to affect as many as 16 million people in the United States by 2050 and cost an estimated $1.2 trillion.

“It’s extremely important to see data that support our previous prediction,” Tranel says. “Edmarie’s research has immediate implications for how we treat patients and how we teach caregivers.”

Despite the considerable amount of research aimed at finding new treatments for Alzheimer’s, no drug has succeeded at either preventing or substantially influencing the disease’s progression. Against this foreboding backdrop, the results of this study highlight the need to develop new caregiving techniques aimed at improving the well-being and minimizing the suffering for the millions of individuals afflicted with Alzheimer’s.

For this behavioral study, Guzmán-Vélez and her colleagues invited 17 patients with Alzheimer’s disease and 17 healthy comparison participants to view 20 minutes of sad and then happy movies. These movie clips triggered the expected emotion: sorrow and tears during the sad films and laughter during the happy ones.

About five minutes after watching the movies, the researchers gave participants a memory test to see if they could recall what they had just seen. As expected, the patients with Alzheimer’s disease retained significantly less information about both the sad and happy films than the healthy people. In fact, four patients were unable to recall any factual information about the films, and one patient didn’t even remember watching any movies.

Before and after seeing the films, participants answered questions to gauge their feelings. Patients with Alzheimer’s disease reported elevated levels of either sadness or happiness for up to 30 minutes after viewing the films despite having little or no recollection of the movies.

Quite strikingly, the less the patients remembered about the films, the longer their sadness lasted. While sadness tended to last a little longer than happiness, both emotions far outlasted the memory of the films.

The fact that forgotten events can continue to exert a profound influence on a patient’s emotional life highlights the need for caregivers to avoid causing negative feelings and to try to induce positive feelings.

“Our findings should empower caregivers by showing them that their actions toward patients really do matter,” Guzmán-Vélez says. “Frequent visits and social interactions, exercise, music, dance, jokes, and serving patients their favorite foods are all simple things that can have a lasting emotional impact on a patient’s quality of life and subjective well-being.”