Fear: A Justified Response or Faulty Wiring?

Fear is one of the most primal feelings known to man and beast. As we develop in society and learn, fear is hard coded into our neural circuitry through the amygdala, a small, almond-shaped nuclei of neurons within the medial temporal lobe of the brain. For psychologists and neurologists, the amygdala is a particularly interesting region of the brain because it plays a role in emotional learning and can have profound effects on human and animal behavior.

On June 3, 2013, a new article studying amygdala activity in human beings will be published as part of JoVE Behavior, a new section of the video journal that focuses on the behavioral sciences. The technique, developed by Dr. Fred Helmstetter and his research group at the University of Wisconsin-Milwaukee, studies how the brain responds to anticipated painful stimuli, in this case an electric shock, in volunteer test subjects.

“We’re interested in how the brain reacts to stimuli in the environment and how it changes when we form a memory of what we experience.” Dr. Helmstetter explains. “The amygdala is a part of the brain that’s important for the way we determine what is dangerous and what is safe around us and how we react to threat.  This experiment is novel in that we are able to look at activity in the amygdala on a very detailed time scale while it responds to human faces.“

The technique takes advantage of two neuroimaging techniques: magnetic resonance imaging and magnetoencephalography. Magnetic resonance imaging (MRI) is a method where a test subject’s brain can be imaged in high resolution while the test subject is immobilized, creating a map of the brain. Once this map has been obtained, magnetoencephalography (MEG) is used to record the magnetic fields created by the electrical activity within the brain. When the test subject is shocked, or anticipates a shock, amygdala activity is picked up by the MEG and mapped to the MRI computer model.

As an emotional control center in the brain, the amygdala serves as a key component in a line of neurological structures that identify and respond to perceived threat. Dr. Helmstetter tells us, “There is good evidence to suggest that anxiety disorders and other psychopathology might be directly related to altered functioning of the amygdala. Prior work with other non-invasive imaging modalities supports this idea but has only been able to average the results of neural activity over several seconds which results in a poor picture of how neurons react to a stimulus over time. This work represents a significant improvement and will allow new questions to be answered.”

The article is part of the launch of JoVE Behavior, the eighth section of JoVE. Founded in 2006, JoVE has rapidly expanded its scope from general biology to many disciplines by visualizing experimentation. Director of Content Aaron Kolski-Andreaco, PhD explains that, “By dedicating a section to behavior, JoVE has provided a platform for researchers to visualize experiments aimed at answering questions about how we think, feel, and communicate with one another.   Emphasizing this area of science is the next logical step for our journal, as the multidisciplinary study of behavior is enabled by technological advancements in physics, chemistry, and the life sciences - areas JoVE has already covered.”

New research shows how our bodies interact with our minds in response to fear and other emotions

New research has shown that the way our minds react to and process emotions such as fear can vary according to what is happening in other parts of our bodies.

In two different presentations today (Monday) at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London, researchers have shown for the first time that the heart’s cycle affects the way we process fear, and that a part of the brain that responds to stimuli, such as touch, felt by other parts of the body also plays a role.

Dr Sarah Garfinkel, a postdoctoral fellow at the Brighton and Sussex Medical School (Brighton, UK), told a news briefing: “Cognitive neuroscience strives to understand how biological processes interact to create and influence the conscious mind. While neural activity in the brain is typically the focus of research, there is a growing appreciation that other bodily organs interact with brain function to shape and influence our perceptions, cognitions and emotions.

“We demonstrate for the first time that the way in which we process fear is different dependent on when we see fearful images in relation to our heart.”

Dr Garfinkel and her colleagues hooked up 20 healthy volunteers to heart monitors, which were linked to computers. Images of fearful faces were shown on the computers and the electrocardiography (ECG) monitors were able to communicate with the computers in order to time the presentation of the faces with specific points in the heart’s cycle.

“Our results show that if we see a fearful face during systole (when the heart is pumping) then we judge this fearful face as more intense than if we see the very same fearful face during diastole (when the heart is relaxed). To look at neural activity underlying this effect, we performed this experiment in an MRI [magnetic resonance imaging] scanner and demonstrated that a part of the brain called the amygdala influences how our heart changes our perception of fear.

“From previous research, we know that if we present images very fast then we have trouble detecting them, but if an image is particularly emotional then it can ‘pop’ out and be seen. In a second experiment, we exploited our cardiac effect on emotion to show that our conscious experience is affected by our heart. We demonstrated that fearful faces are better detected at systole (when they are perceived as more fearful), relative to diastole. Thus our hearts can also affect what we see and what we don’t see – and can guide whether we see fear.

“Lastly, we have demonstrated that the degree to which our hearts can change the way we see and process fear is influenced by how anxious we are. The anxiety level of our individual subjects altered the extent their hearts could change the way they perceived emotional faces and also altered neural circuitry underlying heart modulation of emotion.”

Dr Garfinkel says that her findings might have the potential to help people who suffer from anxiety or other conditions such as post traumatic stress disorder (PTSD).

“We have identified an important mechanism by which the heart and brain ‘speak’ to each other to change our emotions and reduce fear. We hope to explore the therapeutic implications in people with high anxiety. Anxiety disorders can be debilitating and are very prevalent in the UK and elsewhere. We hope that by increasing our understanding about how fear is processed and ways that it could be reduced, we may be able to develop more successful treatments for these people, and also for those, such as war veterans, who may be suffering from PTSD.

“In addition, there is a growing appreciation about how different forms of meditation can have therapeutic consequences. Work that integrates body, brain and mind to understand changes in emotion can help us understand how meditation and mindfulness practices can have calming effects.”

In a second presentation, Dr Alejandra Sel, a postdoctoral researcher in the Department of Psychology at City University (London, UK), investigated a part of the brain called the somatosensory cortex – the area that perceives bodily sensations, such as touch, pain, body temperature and the perception of the body’s place in space, and which is activated when we observe emotional expressions in the faces of other people.

“In order to understand other’s people emotions we need to experience the same observed emotions in our body. Specifically, observing an emotional face, as opposed to a neutral face, is associated with an increased activity in the somatosensory cortex as if we were expressing and experiencing our own emotions. It is also known that people with damage to the somatosensory cortex find it difficult to recognise emotion in other people’s faces,” Dr Sel told the news briefing.

However, until now, it has not been clear whether activity in the somatosensory cortex was simply a by-product of the way we process visual information, or whether it reacts independently to emotions expressed in other people’s faces, actively contributing to how we perceive emotions in others.

In order to discover whether the somatosensory cortex contributes to the processing of emotion independently of any visual processes, Dr Sel and her colleagues tested two situations on volunteers. Using electroencephalography (EEG) to measure the brain response to images, they showed participants either a face showing fear (emotional) or a neutral face. Secondly, they combined the showing of the face with a small tap to an index finger or the left cheek immediately afterwards.

Dr Sel said: “By tapping someone’s cheek or finger you can modify the ‘resting state’ of the somatosensory cortex inducing changes in brain electrical activity in this area. These changes are measureable and observable with EEG and this enables us to pinpoint the brain activity that is specifically related to the somatosensory cortex and its reaction to external stimuli.

“If the ‘resting state’ of the somatosensory cortex when a fearful face is shown has greater electrical activity than when a neutral face is shown, the changes in the activity of the somatosensory cortex induced by the taps and measured by EEG also will be greater when observing fearful as opposed to neutral faces.

“We subtracted results of the first situation (face only) from the second situation (face and tap), and compared changes in the activity related with the tap in the somatosensory cortex when seeing emotional faces versus neutral faces. This way, we could observe responses of the somatosensory cortex to emotional faces independently of visual processes,” she explained.

The researchers found that there was enhanced activity in the somatosensory cortex in response to fearful faces in comparison to neutral faces, independent of any visual processes. Importantly, this activity was focused in the primary and secondary somatosensory areas; the primary area receives sensory information directly from the body, while the secondary area combines sensory information from the body with information related to body movement and other information, such as memories of previous, sensitive experiences.

“Our experimental approach allows us to isolate and show for the first time (as far as we are aware) changes in somatosensory activity when seeing emotional faces after taking away all visual information in the brain. We have shown the crucial role of the somatosensory cortex in the way our minds and bodies perceive human emotions. These findings can serve as starting point for developing interventions tailored for people with problems in recognising other’s emotions, such as autistic children,” said Dr Sel.

The researchers now plan to investigate whether they get similar results when people are shown faces with other expressions such as happy or angry, and whether the timing of the physical stimulus, the tap to the finger or cheek, makes any difference. In this experiment, the tap occurred 105 milliseconds after a face was shown, and Dr Sel wonders about the effect of a longer time interval.

(Image: Shutterstock)

What Predicts Distress After Episodes of Sleep Paralysis?

Ever find yourself briefly paralyzed as you’re falling asleep or just waking up? It’s a phenomenon is called sleep paralysis, and it’s often accompanied by vivid sensory or perceptual experiences, which can include complex and disturbing hallucinations and intense fear.

For some people, sleep paralysis is a once-in-a-lifetime experience; for others, it can be a frequent, even nightly, phenomenon.

Researchers James Allan Cheyne and Gordon Pennycook of the University of Waterloo in Canada explore the factors associated with distress after sleep paralysis episodes in a new article published in Clinical Psychological Science, a journal of the Association for Psychological Science.

The researchers used an online survey and follow-up emails to survey 293 people. They measured post-episode distress using a range of items, from post-episode rumination to interference with next-day functioning.

The level of distress following sleep paralysis episodes was associated with features of the sleep paralysis episode itself. For example, the results showed that the more fear people felt during sleep paralysis episodes, the more distress they felt afterward.

The researchers also found that sensory experiences during episodes of sleep paralysis predicted later distress. Feelings of threat and assault — such as sensing a presence in the room, feeling pressure on the chest, having difficulty breathing, or having a feeling of imminent death — were all associated with distress following sleep paralysis episodes. So, too, were vestibular-motor experiences, including feelings of floating or falling and out-of-body experiences.

Cheyne and Pennycook speculate that the sensory experiences that come with episodes of sleep paralysis could exacerbate people’s fear, creating a feedback loop that enhances memories of experiences later on.

Post-episode distress was also associated with a number of individual-level factors, including cognitive style, distress sensitivity, and supernatural beliefs about sleep paralysis.

People who held supernatural beliefs about sleep paralysis experiences also experienced greater post-episode distress. Those who had more analytic cognitive styles, on the other hand, experienced comparatively less distress after sleep paralysis episodes.

Taken together, these findings show that both situational factors and individual factors contribute to these common, and often stressful, personal experiences.

These findings are important, the researchers say, because they provide insight into a common experience of distress that is not well understood. Some participants lamented that their experiences of terror following episodes of sleep paralysis were often dismissed by clinicians.

Given that a large percentage of people report some carryover effects on their functioning the next day, sleep paralysis could “make a significant contribution to the billions of dollars, worldwide, in costs associated with accidents, illnesses, and lost productivity associated with sleep disturbances,” the researchers note.

Changes in patterns of brain activity predict fear memory formation

Psychologists at the University of Amsterdam (UvA) have discovered that changes in patterns of brain activity during fearful experiences predict whether a long-term fear memory is formed. The research results have recently been published in the prestigious scientific journal ‘Nature Neuroscience’.

Researchers Renee Visser MSc, Dr Steven Scholte, Tinka Beemsterboer MSc and Prof. Merel Kindt discovered that they can predict future fear memories by looking at patterns of brain activity during fearful experiences. Up until now, there was no way of predicting fear memory. It was also, above all, unclear whether the selection of information to be stored in the long-term memory occurred at the time of fear learning or after the event.

Picture predicts pain stimulus

During magnetic resonance brain imaging (MRI), participants saw neutral pictures of faces and houses, some of which were followed by a small electric shock. In this way, the participants formed fear memories. They showed fear responses when the pictures were shown that were paired with shocks. This fear response can be measured in the brain, but is also evident from increased pupil dilation when someone sees the picture. After a few weeks, the participants returned to the lab and were shown the same images. Brain activity and pupil diameter were once again measured. The extent to which the pupil dilated when seeing the images that were previously followed by a shock, was considered an expression of the previously formed fear memory.

Pattern Analysis

In order to analyse the fMRI data, (spatial) patterns of brain activity (Multi-Voxel Pattern Analysis, or MVPA) were analysed. By correlating patterns of various stimulus presentations with each other, it is possible to measure the extent to which the representation of two stimuli is the same. It appears that images that have nothing in common, such as houses and faces, lead to increasing neural pattern similarity when they predict danger. This does not occur when they do not predict danger. This leads to the formation of stronger fear responses. The extent to which this occurs is an indication of fear memory formation: the stronger the response during learning, the stronger the fear response will be in the long term.

These findings may lead to greater insights into the formation of emotional memory. As a result, it is possible to conduct experimental research into the mechanisms that strengthen, weaken or even erase fear memory in a more direct fashion, without having to wait until the fear memory is expressed.

Memory appears susceptible to eradication of fear responses

Fear responses can only be erased when people learn something new while retrieving the fear memory. This is the conclusion of a study conducted by scientists from the University of Amsterdam (UvA) and published in the leading journal Science.

Researchers Dieuwke Sevenster MSc, Dr Tom Beckers and Prof. Merel Kindt have developed a method to determine whether an acquired fear response is susceptible to modification. By doing so, they have revealed the circumstances under which an acquired fear response can be eradicated. In order to measure whether a person actually learnt something new, the researchers used a measure for Prediction Error – in other words, the discrepancy between a person’s anticipation of what is going to happen and what actually happens.

No fear response

Cognitive Behavioural Therapy is currently the most common and effective type of treatment for people suffering from anxiety disorders. However, the effects are often short-lived and the fear returns in many patients. One major finding of Van Kindt’s research lab is that when participants were given propranolol, a beta blocker, while retrieving a specific fear memory, the acquired fear response was shown to be totally erased a day or month later. The researchers repeatedly found that the fear did not come back, despite the use of techniques specifically aimed to make it return. This indicates that the fear memory was either fully eradicated, or could no longer be accessed. One crucial finding was that while participants could still remember the association with the fear, that particular memory no longer triggered the former fear response.

Fear conditioning

For their study the researchers used a fear conditioning procedure in which a specific picture was followed by a nasty painful stimulus. While the participants viewed the pictures, the researchers measured the anticipation of the painful stimulus as well as the more autonomous fear response on the basis of the startle reflex.

The current findings will contribute to the further development of more effective and efficient therapies for patients suffering from excessive anxiety disorders, such as trauma victims. There was no independent measure to indicate whether the memory is susceptible to modification up until now. The researchers have shown that the fear response can be eradicated completely, provided that the person concerned actually learns something new while retrieving the fear memory.

(Image: iStock)

Even the brains of people with anxiety states can get used to fear

Fear is a protective function against possible dangers that is designed to save our lives. Where there are problems with this fear mechanism, its positive effects are cancelled out: patients who have a social phobia become afraid of perfectly normal, everyday social situations because they are worried about behaving inappropriately or being thought of as stupid by other people. Scientists from the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna have now discovered that this fear circuit can be deactivated, at least in part.

In a study by Ronald Sladky, led by Christian Windischberger (Centre for Medical Physics and Biomedical Technology), which has recently been published in the magazine PLOS One, functional magnetic resonance tomography was used to measure the changes in the brain activity of socially phobic patients and healthy test subjects while they were looking at faces. This experiment simulates social confrontation with other people without actually placing the individual in an intolerable situation of anxiety.

Permanent confrontation has a diminishing effect on anxiety
“The study demonstrated that people with social phobia initially exhibit greater activity in the amygdala and in the medial, prefrontal cortex of the brain, however after a few faces this activity recedes,” says Sladky. This contradicts the assumption made thus far that the emotional circuit of socially phobic individuals is unable to adapt adequately to this stress-inducing situation.

Permanent confrontation with the test task not only led to a solution to the “problem” being found more quickly among the patients with anxiety, but also to some areas of the brain being bypassed which otherwise were over-stimulated, a characteristic typical of anxiety. Says Sladky: “We therefore concluded that there are functional control strategies even in the emotional circuits of people with social phobia, although the mechanisms take longer to take effect in these individuals. The misregulation of these parts of the brain can therefore be compensated to a degree.”

These findings could, according to Sladky, provide a starting point for the development of personalised training programmes that will help affected individuals to conquer unpleasant situations in their everyday lives more effectively. In Austria, around 200,000 people a year are affected by some form of social phobia. The number of people who suffer this condition without seeking help for it is likely to be very high, since many affected individuals fail to seek assistance or do so only too late as a result of their anxiety.

Neuroscientists pinpoint location of fear memory in amygdala

A rustle of undergrowth in the outback: it’s a sound that might make an animal or person stop sharply and be still, in the anticipation of a predator. That “freezing” is part of the fear response, a reaction to a stimulus in the environment and part of the brain’s determination of whether to be afraid of it.

A neuroscience group at Cold Spring Harbor Laboratory (CSHL) led by Assistant Professor Bo Li Ph.D., together with collaborator Professor Z. Josh Huang Ph.D., today release the results of a new study that examines the how fear responses are learned, controlled, and memorized. They show that a particular class of neurons in a subdivision of the amygdala plays an active role in these processes.

Locating fear memory in the amygdala

Previous research had indicated that structures inside the amygdalae, a pair of almond-shaped formations that sit deep within the brain and are known to be involved in emotion and reward-based behavior, may be part of the circuit that controls fear learning and memory. In particular, a region called the central amygdala, or CeA, was thought to be a passive relay for the signals relayed within this circuit.

Li’s lab became interested when they observed that neurons in a region of the central amygdala called the lateral subdivision, or CeL, “lit up” in a particular strain of mice while studying this circuit.

“Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded,” Li says, “but nobody had been able to actually show this.”

This led the team to further probe into the role of these neurons in fear responses and furthermore to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?

To examine the behavior of mice undergoing a fear test the team first trained them to respond in a Pavlovian manner to an auditory cue. The mice began to “freeze,” a very common fear response, whenever they heard one of the sounds they had been trained to fear.

To study the particular neurons involved, and to understand them in relation to the fear-inducing auditory cue, the CSHL team used a variety of methods. One of these involved delivering a gene that encodes for a light-sensitive protein into the particular neurons Li’s group wanted to look at.

By implanting a very thin fiber-optic cable directly into the area containing the photosensitive neurons, the team was able to shine colored laser light with pinpoint accuracy onto the cells, and in this manner activate them. This is a technique known as optogenetics. Any changes in the behavior of the mice in response to the laser were then monitored.

A subset of neurons in the central amygdala controls fear expression

The ability to probe genetically defined groups of neurons was vital because there are two sets of neurons important in fear-learning and memory processes. The difference between them, the team learned, was in their release of message-carrying neurotransmitters into the spaces called synapses between neurons. In one subset of neurons, neurotransmitter release was enhanced; in another it was diminished. If measurements had been taken across the total cell population in the central amygdala, neurotransmitter levels from these two distinct sets of neurons would have been averaged out, and thus would not have been detected.

Li’s group found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons – neurons that suppress the activity of other neurons – in the central amygdala. These changes in the strength of neuronal connections are known as synaptic plasticity.

Particularly important in this process, the team discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevent the activation of SOM+ neurons.

SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. Thus, instead of being a passive relay for the signals driving fear learning and responses in mice, the team’s work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected.

“We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action — or what we call the fear response,” explains Li.

In the future Li’s group will try to obtain a better understanding of how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One important goal is to develop pharmacological interventions for such disorders.

Li says more research is needed, but is hopeful that with the discovery of specific cellular markers and techniques such as optogenetics, a breakthrough can be made.

Autism severity may stem from fear

Most people know when to be afraid and when it’s ok to calm down.

But new research on autism shows that children with the diagnosis struggle to let go of old, outdated fears. Even more significantly, the Brigham Young University study found that this rigid fearfulness is linked to the severity of classic symptoms of autism, such as repeated movements and resistance to change.

For parents and others who work with children diagnosed with autism, the new research highlights the need to help children make emotional transitions – particularly when dealing with their fears.

“People with autism likely don’t experience or understand their world in the same way we do,” said Mikle South, a psychology professor at BYU and lead author of the study. “Since they can’t change the rules in their brain, and often don’t know what to expect from their environment, we need to help them plan ahead for what to expect.”

The complete study appears in the journal Autism Research.