A new study reveals that when it comes to pain control, the "placebo effect" involves evolutionarily old pain control pathways in the human brainstem, the part of the brain that is continuous with the spinal cord. The research, published by Cell Press in the August 27th issue of the journal Neuron, provides fascinating mechanistic insight into how and why simply expecting that a treatment will reduce pain can act as an effective analgesic.

Placebo analgesia refers to an individual's relief from pain following administration of a chemically inert substance and is thought to be due to a person's belief that a potent pain medication was administered. Endogenous opioids, which are naturally produced by the brain in small amounts and play a key role in the relief of pain and anxiety, have been implicated in placebo analgesia. Brain imaging studies have shown that placebo analgesia stimulates release of endogenous opioids from higher brain regions associated with pain modulation and is associated with a decrease in signals from pain-sensitive areas.

"It has been hypothesized that placebo analgesia also recruits the opioidergic descending pain control system, which inhibits pain processing in the spinal cord and, therefore, subsequently reduces pain-related responses in the brain, leading to a decreased pain experience," explains lead study author Falk Eippert from the University Medical Center Hamburg-Eppendorf in Germany. However, thus far this has not been demonstrated experimentally.

Eippert and colleagues employed sophisticated brain imaging techniques to examine both higher cortical and lower brainstem responses in two groups of subjects: one receiving a drug called naloxone, which blocks opioid signaling, and one group with a natural opioid state. Expectations of pain relief were induced in both groups using an established placebo analgesia paradigm.

The researchers found that naloxone reduced behavioral placebo effects as well as placebo-induced decreases in pain-related brain responses. Most importantly, they also observed that, under placebo, cortical areas interacted with brainstem structures implicated in pain control and that these interactions were dependent on endogenous opioids and were related to the strength of experienced placebo effects.

"Taken together, our findings show that opioid signaling in pain-modulating areas and the projections to downstream effectors of the descending pain control system are crucially important for placebo analgesia," concludes Eippert. "It will be interesting to see whether opioid-dependent activation of the descending pain control system is a common feature of different forms of pain modulation, such as hypnosis and attentional distraction, which share some common neuroanatomical features."

In a finding that sheds new light on the neural mechanisms involved in social behavior, neuroscientists at the California Institute of Technology (Caltech) have pinpointed the brain structure responsible for our sense of personal space.

Patient SM, a woman with complete bilateral amygdala lesions (red), preferred to stand close to the experimenter (black). On average, control participants (blue) preferred to stand nearly twice as far away from the same experimenter. Images drawn to scale.

The structure, the amygdala—a pair of almond-shaped regions located in the medial temporal lobes—was previously known to process strong negative emotions, such as anger and fear, and is considered the seat of emotion in the brain. However, it had never been linked rigorously to real-life human social interaction.

The scientists, led by Ralph Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology and postdoctoral scholar Daniel P. Kennedy, were able to make this link with the help of a unique patient, a 42-year-old woman known as SM, who has extensive damage to the amygdala on both sides of her brain.

"SM is unique, because she is one of only a handful of individuals in the world with such a clear bilateral lesion of the amygdala, which gives us an opportunity to study the role of the amygdala in humans," says Kennedy, the lead author of the new report.

SM has difficulty recognizing fear in the faces of others, and in judging the trustworthiness of someone, two consequences of amygdala lesions that Adolphs and colleagues published in prior studies.

During his years of studying her, Adolphs also noticed that the very outgoing SM is almost too friendly, to the point of "violating" what others might perceive as their own personal space. "She is extremely friendly, and she wants to approach people more than normal. It's something that immediately becomes apparent as you interact with her," says Kennedy.

Previous studies of humans never had revealed an association between the amygdala and personal space. From their knowledge of the literature, however, the researchers knew that monkeys with amygdala lesions preferred to stay in closer proximity to other monkeys and humans than did healthy monkeys.

Intrigued by SM's unusual social behavior, Adolphs, Kennedy, and their colleagues devised a simple experiment to quantify and compare her sense of personal space with that of healthy volunteers.

The experiment used what is known as the stop-distance technique. Briefly, the subject (SM or one of 20 other volunteers, representing a cross-section of ages, ethnicities, educations, and genders) stands a predetermined distance from an experimenter, then walks toward the experimenter and stops at the point where they feel most comfortable. The chin-to-chin distance between the subject and the experimenter is determined with a digital laser measurer.

Among the 20 other subjects, the average preferred distance was .64 meters—roughly two feet. SM's preferred distance was just .34 meters, or about one foot. Unlike other subjects, who reported feelings of discomfort when the experimenter went closer than their preferred distance, there was no point at which SM became uncomfortable; even nose-to-nose, she was at ease. Furthermore, her preferred distance didn't change based on who the experimenter was and how well she knew them.

"Respecting someone's space is a critical aspect of human social interaction, and something we do automatically and effortlessly," Kennedy says. "These findings suggest that the amygdala, because it is necessary for the strong feelings of discomfort that help to repel people from one another, plays a central role in this process. They also help to expand our understanding of the role of the amygdala in real-world social interactions."

Adolphs and colleagues then used a functional magnetic resonance imaging (fMRI) scanner to examine the activation of the amygdala in a separate group of healthy subjects who were told when an experimenter was either in close proximity or far away from them. When in the fMRI scanner, subjects could not see, feel, or hear the experimenter; nevertheless, their amygdalae lit up when they believed the experimenter to be close by. No activity was detected when subjects thought the experimenter was on the other side of the room.

"It was just the idea of another person being there, or not, that triggered the amygdala," Kennedy says. The study shows, he says, that "the amygdala is involved in regulating social distance, independent of the specific sensory cues that are typically present when someone is standing close, like sounds, sights, and smells."

The researchers believe that interpersonal distance is not something we consciously think about, although, unlike SM, we become acutely aware when our space is violated. Kennedy recounts his own experience with having his personal space violated during a wedding: "I felt really uncomfortable, and almost fell over a chair while backing up to get some space."

Across cultures, accepted interpersonal distances can vary dramatically, with individuals who live in cultures where space is at a premium (say, China or Japan) seemingly tolerant of much closer distances than individuals in, say, the United States. (Meanwhile, our preferred personal distance can vary depending on our situation, making us far more willing to accept less space in a crowded subway car than we would be at the office.)

One explanation for this variation, Kennedy says, is that cultural preferences and experiences affect the brain over time and how it responds in particular situations. "If you're in a culture where standing close to someone is the norm, you'd learn that was acceptable and your personal space would vary accordingly," he says. "Even then, if you violate the accepted cultural distance, it will make people uncomfortable, and the amygdala will drive that feeling."

The findings may have relevance to studies of autism, a complex neurodevelopmental disorder that affects an individual's ability to interact socially and communicate with others. "We are really interested in looking at personal space in people with autism, especially given findings of amygdala dysfunction in autism. We know that some people with autism do have problems with personal space and have to be taught what it is and why it's important," Kennedy says.

He also adds a word of caution: "It's clear that amygdala dysfunction cannot account for all the social impairments in autism, but likely contributes to some of them and is definitely something that needs to be studied further."

---

Journal reference:

1. Kennedy et al. Personal space regulation by the human amygdala. Nature Neuroscience, 2009; DOI: 10.1038/nn.2381

Adapted from materials provided by California Institute of Technology.

California Institute of Technology (2009, August 31). Neuroscientists Find Brain Region Responsible For Our Sense Of Personal Space. ScienceDaily. Retrieved August 31, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090830192041.htm

I didn't realise the area had been investigated and apparently there is a small literature on these most sublime of experiences.

The paper is brief, accessible and is available online as a pdf but the abstract gives a great summary:

Chills as an indicator of individual emotional peaks

Ann N Y Acad Sci. 2009 Jul;1169:351-4.

Grewe O, Kopiez R, Altenmüller E.

Chills (goose bumps) have been repeatedly associated with positive emotional peaks. Chills seem to be related to distinct musical structures and the reward system in the brain. A new approach that uses chills as indicators of individual emotional peaks is discussed. Chill reactions of 95 participants in response to seven music pieces were recorded. Subjective intensity as well as physiological arousal (skin conductance response, heart rate) revealed peaks during chill episodes. This review suggests that chills are a reliable indicator of individual emotional peaks, combining reports of subjective feelings with physiological arousal.

pdf of scientific paper.
Link to PubMed entry for same.

via mindhacks.com

Psychologists at the University of Edinburgh found a link between facial symmetry and mental performance between the ages of 79 and 83.

The researchers analysed results of the 1932 Scottish Mental Survey and mapped the faces of subjects from photographs.

They said it could show a link between physical condition and mental decline.

Facial symmetry, the researchers argued, may indicate a man has experienced fewer genetic and environmental disturbances such as diseases, toxins, malnutrition or genetic mutations during his development.

Dr Lars Penke, who led the study, said: "Previous research has suggested that cognitive decline is an aspect of body-wide ageing. This link could show that facial symmetry can be used as a marker which could predict this decline."

The team was unable to find comparable results in women.

One explanation suggested by the researchers was that DNA has a different effect on ageing among women. Another theory was that mental decline is delayed in women because, on average, they live longer.

The results of the study have been published in the journal Evolution and Human Behaviour.

Worried you'll blink and miss a crucial piece of the action? Then you can relax. While watching a film, we subconsciously control the timing of blinks to make sure we don't miss anything important. And because we tend to watch films in a similar way, moviegoers often blink in unison, researchers find.

The flow of visual information to the brain is halted by up to 450 milliseconds with every blink, and we lose up to 6 seconds of information every minute, says Tamani Nakano at the University of Tokyo in Japan. This means moviegoers who sit through a 150-minute film have their eyes shut for up to 15 minutes.

Nakano and colleagues worked out how we cope with such extreme information loss. They monitored the eye blinks of volunteers as they watched a clip of a silent comedy with a strong narrative, or a movie of an aquarium with no narrative, or listened to an audio book with a narrative, but not a visual one.

Hidden pattern

Using the timing of those blinks as a reference, the researchers then played the volunteers the same clip again and measured whether the eye blinks occurred at the same time as the reference blinks.

For all three kinds of clip, there was a strong correlation between the timing of blinks in the repeat viewing and the reference blinks. That is because we blink so often that the chances of a repeat blink matching a reference one are high, says Nakano.

But after statistically filtering out that strong signal, the researchers found that between 23 and 31 per cent of blinks were synchronised when watching the silent movie, while the aquarium movie and the audio book had no such synchronisation. So for at least some of the time, individuals will blink in unison while watching the same film.

"This is the first study to demonstrate that blinks are excellently coordinated during video playback," says Nakano.

Window on the mind

The synchronised blinks occurred at "non-critical" points during the silent movie – at the conclusion of an action sequence or when the main character had disappeared from view. "We all commonly find implicit breaks for blinking while viewing a video story," Nakano says.

Geraint Rees at University College London thinks it is an interesting study. This synchronisation between individuals "implies that there's something common to everyone that is triggering the blinks," he says.

He points out that other studies have shown that brain activity across individuals can become synchronised when watching a movie. "The blinks may form one external manifestation of that, which may provide a window into understanding what people are thinking when they watch a movie."

In the current online edition of the journal Human Brain Mapping, Paul Thompson, senior author and a UCLA professor of neurology, and lead author Cyrus A. Raji, a medical student at the University of Pittsburgh School of Medicine, and colleagues compared the brains of people who were obese, overweight, and of normal weight, to see if they had differences in brain structure; that is, did their brains look equally healthy.

They found that obese people had 8 percent less brain tissue than people with normal weight, while overweight people had 4 percent less tissue. According to Thompson, who is also a member of UCLA's Laboratory of Neuro Imaging, this is the first time anyone has established a link between being overweight and having what he describes as "severe brain degeneration."

"That's a big loss of tissue and it depletes your cognitive reserves, putting you at much greater risk of Alzheimer's and other diseases that attack the brain," said Thompson. "But you can greatly reduce your risk for Alzheimer's, if you can eat healthily and keep your weight under control."

The researchers used brain images from an earlier study called the Cardiovascular Health Study Cognition Study. Scans were selected of 94 elderly people in their 70s who were healthy not cognitively impaired - five years after the scan was taken. To define the weight categories, they used the Body Mass Index (BMI), the most widely used measurement for obesity. Normal weight people were defined as having a BMI between 18.5-25; overweight people between 25-30, and obese people greater than 30. The researchers then converted the scans into detailed three-dimensional images using tensor-based morphometry, a neuroimaging method that offers high resolution mapping of anatomical differences in the brain.

BACKGROUND: At the university of Pittsburgh Medical Center, a scanning device which measures the brain's magnetic field in real time is allowing clinicians to more accurately pinpoint those areas of the brain causing epileptic seizures.

The scanner also can aid in the diagnosis and study of disorders such as Parkinson's disease, multiple sclerosis, dementia, and schizophrenia. Currently, researchers are using the device to determine the location of seizures in epileptic patients and identify the functional centers of the brain responsible for language, vision, motor and sensory information.

HOW IT WORKS: Real-time brain mapping and monitoring is considered to be one of the most exciting areas of neuroscience today. Magnetoencephalography (MEG) measures the magnetic fields produced by electrical activity in the brain via extremely sensitive superconducting sensors. Any electrical current will produce a magnetic field, and MEG measures the field generated by the brain's electrical currents. Traditionally, brain activity has been measured using electroencephalography (EEG), in which the electrical signals are recorded from electrodes placed on the scalp.

BENEFITS: With MEG, clinicians can now map nerve cell activity in the brain non-invasivelyto see the brain in action, rather than analyzing a series of still images. The system simultaneously produces 306 separate recordings of magnetic activity and determines where it originates and which parts of the brain undertake various tasks. An MEG scan can also determine how the brain functions both normally and in cases of illness. The graphical representations produced by the system can be sent directly into a navigational system used by neurosurgeons in the operating room to help guide them to the area of the brain that should be taken out, while at the same time marking vital centers and abnormalities -- thereby improving surgical outcomes.

The research group investigated how neural circuits rearrange themselves after cerebral strokes by using two-photon laser microscopy in vivo. In a specific period after strokes in the right side of the moue brain, namely one to two weeks after strokes, the left side of the brain rearranged its neural circuits actively. After three to four weeks, the left side of the brain became to receive sensory information from the left leg that is usually received by the right side of the brain. In conclusion, the stroke in the right side of the brain activated the rearrangement of the neural circuits in the left side of the brain, and then these rearrangements helped to recuperate from stroke-induced damaged neural function.

"We found that the active rearrangement of the neural circuits in the opposite side of the brain happens only in the specific period after strokes. Our findings can be applied to rehabilitative programs for stroke survivors", said Professor Nabekura.

Source:
Junichi Nabekura
National Institute for Physiological Sciences

Scientists in Bristol claim results from a research project into multiple sclerosis (MS) could lead to treatment to reduce the severity of the disease.

Professor Wynick set up research into the effects of galanin on MS

The team carried out tests on mice and then on human brain tissue and found galanin, a protein within brain nerve cells, was resistant to MS.

Professor David Wraith at the University of Bristol said the results were "extremely promising".

The team said it could be at least 10 years before a drug is developed.

Professor David Wynick, who works on the function of galanin, set up the project with a group of other scientists working on the development of a vaccine for the treatment of multiple sclerosis.

He said: "It has been known for some time that galanin plays a protective role in both the central and peripheral nerve systems - when a nerve is injured levels of galanin increase dramatically in an attempt to limit cell death."

The team discovered that mice with high levels of galanin were completely resistant to the MS-like disease, experimental autoimmune encephalomyelitis (EAE). Transgenic mice that contained no galanin at all developed a more severe form of the disease.

MS is a neurological condition that affects the transfer of messages from the central nervous system to the rest of the body.

It is the most common neurological disorder among young adults, affecting 85,000 people in the UK with 2,500 newly diagnosed each year.

There is no cure for MS, but drugs can be used to reduce the number and severity of relapses, and to reduce the number of new attacks.

Dr Doug Brown, research manager at the MS Society, said: "This is an early study and there's a long way to go before we understand what this means for people with MS, but any insight into how MS might be treated is valuable to researchers.

Clinically depressed individuals are less capable of finding pleasure in activities they previously enjoyed, a recent study has proven. Research featured in the August 26 issue of the NeuroReport shows reduced brain function in the reward center of the brain in depressed individuals, when compared to healthy subjects.

To investigate the effects of depression on brain activity, Dr. Osuch and her team asked 15 healthy subjects and 16 recently depressed subjects to provide a list of their favourite music as well as identify music that they neither liked nor disliked (neutral music). The subjects then listened to their musical selections for three minutes while a functional magnetic resonance imaging (fMRI) scanner measured the neural activity in their brain.

The researchers found that the healthy subjects showed more brain activity in specific regions when they listed to their favourite music compared to the depressed subjects. More specifically, several regions of the brain that are associated with reward processing were shown to be less activated in the depressed individuals, suggesting that even the most basic capacity of enjoyment seems to be malfunctioning in this area of the brain in those who have depression. This was true in spite of no difference in how enjoyable the two groups rated listening to the music in the scanner.

"Our results revealed significant responses within the areas of the brain that are associated with reward processing in healthy individuals. They also showed significant deficits in these neurophysiological responses in recently depressed subjects compared to the healthy subjects,” explains Dr. Osuch. “It is known that depressed individuals experience anhedonia—a loss of enjoyment in previously pleasurable activities. The study results show that for recently depressed individuals this loss of enjoyment is linked to very specific parts of the brain which are involved with experiencing pleasure. If we can target these areas of the brain through treatment, we have the potential to treat depression earlier, right at the source.”

---

Journal reference:

1. Osuch, Elizabeth A; Bluhm, Robyn L; et al. Brain activation to favorite music in healthy controls and depressed patients. Neuroreport, 2009; 20 (13): 1204 DOI: 10.1097/WNR.0b013e32832f4da3