Out of Sight, Out of Mind? How the brain codes its surroundings beyond the field of view

Even when they are not directly in sight, we are aware of our surroundings: so it is that when our eyes are fixed on an interesting book, for example, we know that the door is to the right, the bookshelf is to the left and the window is behind us. However, research into the brain has so far concerned itself predominantly with how information from our field of vision is coded in the visual cortex. To date it has not been known how the brain codes our surroundings beyond the field of view from an egocentric perspective (that is, from the point of view of the observer).

In the latest issue of the renowned journal Current Biology, Andreas Schindler und Andreas Bartels, scientists at the Werner Reichardt Center for Integrative Neuroscience (CIN) of the University of Tübingen, present for the first time direct evidence of this kind of spatial information in the brain.

The participants in their study found themselves in the center of a virtual octagonal room, with a unique object in each corner. As the brain’s activity was monitored by means of functional magnetic resonance imaging, the participants stood in front of one corner and looked at its object. Now they were instructed to determine the position of a second randomly chosen object within the room relative to their current perspective (for example, the object behind them). After a few trials the participant turned around so that the next object was brought into the field of view and the task was set up again. The whole procedure was repeated until every object had been looked at once.

The scientists discovered that patterns of activity in the parietal cortex code the participant’s egocentric position, that is, the relative position to his or her surroundings. The spatial information discovered there proved to be independent of the particular object, its absolute position in the room or that of the observer – i.e. it encoded egocentric spatial information of the three-dimensional surroundings. This result turns out to be particularly interesting because damage to the brain in the parietal cortex can lead to serious disruption of egocentric spatial awareness. Hence it is difficult for patients suffering from optical ataxia to carry out coordinated grasping movements. Lesions in the parietal cortex can also lead to a symptom called spatial neglect where patients have difficulties in perceiving their surroundings on the side opposite to the lesion. The brain areas identified in the present study coincided precisely with the areas of brain damage in such patients and provide for the first time insights regarding their function in the healthy brain.

Botox may help stroke patients

Injecting botox into the arm muscles of stroke survivors, with severe spasticity, changes electrical activity in the brain and may assist with longer-term recovery, according to new research.

Researchers at NeuRA (Neuroscience Research Australia) monitored nerve activity in the arms and brains of stroke survivors before and after botulinum toxin (botox) injections in rigid and stiff muscles in the arm.

They found that botox indeed improved arm muscles, but also altered brain activity in the cortex – the brain region responsible for movement, memory, learning and thinking.

“Botulinum toxin is used to treat a range of muscular and neurological conditions and our data shows that this treatment results in electrical and functional changes within the brain itself”, says Dr William Huynh, lead author of the study and a research neurologist at NeuRA.

“This effect of botox on the brain may arise because the toxin travels to the central nervous system directly, or because muscles treated with botox are sending different signals back to the brain”.

“Either way, we found that botox treatment in affected muscles not only improves muscle disorders in stroke patients, but also normalises electrical activity in the brain, particularly in the half of the brain not damaged by stroke”.

“Restoring normal activity in the unaffected side of the brain is particularly important because we suspect that abnormal information sent from affected muscles to the brain may be disrupting patients’ long-term recovery”, Dr Huynh concluded.

This paper is published in the journal Muscle and Nerve.

Imaging Study Examines Effect of Fructose on Brain Regions That Regulate Appetite

In a study examining possible factors regarding the associations between fructose consumption and weight gain, brain magnetic resonance imaging of study participants indicated that ingestion of glucose but not fructose reduced cerebral blood flow and activity in brain regions that regulate appetite, and ingestion of glucose but not fructose produced increased ratings of satiety and fullness, according to a preliminary study published in the January 2 issue of JAMA.

“Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety,” according to background information in the article. “Thus, fructose possibly increases food-seeking behavior and increases food intake.” How brain regions associated with fructose- and glucose-mediated changes in animal feeding behaviors translates to humans is not completely understood.

Kathleen A. Page, M.D., of Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to examine neurophysiological factors that might underlie associations between fructose consumption and weight gain. The study included 20 healthy adult volunteers who underwent two magnetic resonance imaging sessions in conjunction with fructose or glucose drink ingestion. The primary outcome measure for the study was the relative changes in hypothalamic (a region of the brain) regional cerebral blood flow (CBF) after glucose or fructose ingestion.

The researchers found that there was a significantly greater reduction in hypothalamic CBF after glucose vs. fructose ingestion. “Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula, and striatum—brain regions that regulate appetite, motivation, and reward processing; glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety.”

“The disparate responses to fructose were associated with reduced systemic levels of the satiety-signaling hormone insulin and were not likely attributable to an inability of fructose to cross the blood-brain barrier into the hypothalamus or to a lack of hypothalamic expression of genes necessary for fructose metabolism.”

(Image: iStockphoto)

Why overlearned sequences are special: distinct neural networks for ordinal sequences

Several observations suggest that overlearned ordinal categories (e.g., letters, numbers, weekdays, months) are processed differently than non-ordinal categories in the brain. In synesthesia, for example, anomalous perceptual experiences are most often triggered by members of ordinal categories (Rich et al., 2005; Eagleman, 2009). In semantic dementia (SD), the processing of ordinal stimuli appears to be preserved relative to non-ordinal ones (Cappelletti et al., 2001). Moreover, ordinal stimuli often map onto unconscious spatial representations, as observed in the SNARC effect (Dehaene et al., 1993; Fias, 1996). At present, little is known about the neural representation of ordinal categories. Using functional neuroimaging, we show that words in ordinal categories are processed in a fronto-temporo-parietal network biased toward the right hemisphere. This differs from words in non-ordinal categories (such as names of furniture, animals, cars, and fruit), which show an expected bias toward the left hemisphere. Further, we find that increased predictability of stimulus order correlates with smaller regions of BOLD activation, a phenomenon we term prediction suppression. Our results provide new insights into the processing of ordinal stimuli, and suggest a new anatomical framework for understanding the patterns seen in synesthesia, unconscious spatial representation, and SD.

Brain imaging insight into cannabis as a pain killer

The pain relief offered by cannabis varies greatly between individuals, a brain imaging study carried out at the University of Oxford suggests.

The researchers found that an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.

MRI brain imaging showed reduced activity in key areas of the brain that substantiated the pain relief the study participants experienced. 

'We have revealed new information about the neural basis of cannabis-induced pain relief,' says lead researcher Dr Michael Lee of Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB). 

'Cannabis does not seem to act like a conventional pain medicine. Some people respond really well, others not at all, or even poorly,' he says. 'Brain imaging shows little reduction in the brain regions that code for the sensation of pain, which is what we tend to see with drugs like opiates. Instead cannabis appears to mainly affect the emotional reaction to pain in a highly variable way.'

Long-term pain, often without clear cause, is a complex healthcare problem. Different approaches are often needed to help patient manage pain, and can include medications, physiotherapy and other forms of physical therapy, and psychological support. 

For a few patients, cannabis or cannabis-based medications remain effective when other drugs have failed to control pain, while others report very little effect of the drug on their pain but experience side-effects.

'We know little about cannabis and what aspects of pain it affects, or which people might see benefits over the side-effects or potential harms in the long term. We carried out this study to try and get at what is happening when someone experiences pain relief using cannabis,' says Dr Lee.

He adds: ‘Our small-scale study, in a controlled setting, involved 12 healthy men and only one of many compounds that can be derived from cannabis. That’s quite different from doing a study with patients.

'My view is the findings are of interest scientifically but it remains to see how they impact the debate about use of cannabis-based medicines. Understanding cannabis' effects on clinical outcomes, or the quality of life of those suffering chronic pain, would need research in patients over long time periods.'

(The paper ‘Amygdala activity contributes to the dissociative effect of cannabis on pain perception' by Michael C. Lee, Markus Ploner, Katja Wiech, Ulrike Bingel, Vishvarani Wanigasekera, Jonathan Brooks, David K. Menon, Irene Tracey (DOI: 10.1016/j.pain.2012.09.017) will appear in PAIN®, Volume 154, Issue 1 (January 2013) published by Elsevier)

Study reveals how the brain categorizes thousands of objects and actions

Humans perceive numerous categories of objects and actions, but where are these categories represented spatially in the brain?

Researchers reporting in the December 20 issue of the Cell Press journal Neuron present their study that undertook the remarkable task of determining how the brain maps over a thousand object and action categories when subjects watched natural movie clips. The results demonstrate that the brain efficiently represents the diversity of categories in a compact space. Instead of having a distinct brain area devoted to each category, as previous work had identified, for some but not all types of stimuli, the researchers uncovered that brain activity is organized by the relationship between categories.

"Humans can recognize thousands of categories. Given the limited size of the human brain, it seems unreasonable to expect that every category is represented in a distinct brain area," says first author Alex Huth, a graduate student working in Dr. Jack Gallant’s laboratory at the University of California, Berkeley. The authors proposed that perhaps a more efficient way for the brain to represent object and action categories would be to organize them into a continuous space that reflects the similarity between categories.

To test this hypothesis, they used blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) to measure human brain activity evoked by natural movies in five people. They then mapped out how 1,705 distinct object and action categories are represented across the surface of the cortex of the brain. Their results show that categories are organized as smooth gradients that cover much of the surface of the visual as well as nonvisual cortex, such that similar categories are located next to each other, and notably, this organization was shared across the individuals imaged.

"Discovering the feature space that the brain uses to represent information helps us to recover functional maps across the cortical surface. The brain probably uses similar mechanisms to map other kinds of information across the cortical surface, so our approach should be widely applicable to other areas of cognitive neuroscience," says Dr. Gallant.

Brain imaging identifies bipolar risk

Researchers from the Black Dog Institute and University of NSW have used brain imaging technology to show that young people with a known genetic risk of bipolar but no clinical signs of the condition have clear and quantifiable differences in brain activity when compared to controls.

“We found that the young people who had a parent or sibling with bipolar disorder had reduced brain responses to emotive faces, particularly a fearful face. This is an extremely promising breakthrough,” says study leader Professor Philip Mitchell.

Affecting around 1 in 75 Australians, bipolar disorder involves extreme and often unpredictable fluctuations in mood. The mood swings and associated behaviours such as disinhibited behaviour, aggression and severe depression, have a significant impact on day-to-day life, careers and relationships. Bipolar has the highest suicide rate of all psychiatric disorders.

“We know that bipolar is primarily a biological illness with a strong genetic influence but triggers are yet to be understood. Being able to identify young people at risk will enable implementation of early intervention programs, giving them the best chance for a long and happy life,” says Prof Mitchell.

Researchers used functional MRI to visualise brain activity when participants were shown pictures of happy, fearful or calm (neutral) human faces. Results showed that those with a genetic risk of bipolar displayed significantly reduced brain activity in a specific part of the brain known to regulate emotional responses.

“Our results show that bipolar disorder may be linked to a dysfunction in emotional regulation and this is something we will continue to explore,” Professor Mitchell said.

“And we now have an extremely promising method of identifying children and young people at risk of bipolar disorder.”

 “We expect that early identification will significantly improve outcomes for people that go on to develop bipolar disorder, and possibly even prevent onset in some people.”

Results are published this week in Biological Psychiatry and come from the NHMRC-funded ‘Kids and Sibs study’, the biggest research study in the world focusing on genetic and environmental aspects of bipolar disorder. Based at the Black Dog Institute, the trial is still recruiting.

Stress-Resilience/Susceptibility Traced to Neurons in Reward Circuit

A specific pattern of neuronal firing in a brain reward circuit instantly rendered mice vulnerable to depression-like behavior induced by acute severe stress, a study supported by the National Institutes of Health has found. When researchers used a high-tech method to mimic the pattern, previously resilient mice instantly succumbed to a depression-like syndrome of social withdrawal and reduced pleasure-seeking – they avoided other animals and lost their sweet tooth. When the firing pattern was inhibited in vulnerable mice, they instantly became resilient.

“For the first time, we have shown that split-second control of specific brain circuitry can switch depression-related behavior on and off with flashes of an LED light,” explained Ming-Hu Han, Ph.D., of the Mount Sinai School of Medicine, New York City, a grantee of NIH’s National Institute of Mental Health (NIMH). “These results add to mounting clues about the mechanism of fast-acting antidepressant responses.” Han, Eric Nestler, M.D., Ph.D., of Mount Sinai, and colleagues, report on their study online, Dec. 12, 2012, in the journal Nature.

In a companion article, NIMH grantees Kay Tye, Ph.D., of the Massachusetts Institute of Technology, Cambridge, Mass., and Karl Deisseroth, M.D., Ph.D., of Stanford University, Stanford, Calif., used the same cutting-edge technique to control mouse brain activity in real time. Their study reveals that the same reward circuit neuronal activity pattern had the opposite effect when the depression-like behavior was induced by daily presentations of chronic, unpredictable mild physical stressors, instead of by shorter-term exposure to severe social stress.

Prior to the new studies, Han’s team suspected that a telltale pattern – rapid firing of neurons that secrete the chemical messenger dopamine in a key circuit hub – makes an animal vulnerable to the depression-like effects of acute severe stress, and that slower firing supports resilience. But they lacked direct, real-time evidence.

To pinpoint cause-and-effect, they turned to a research technology pioneered by Deisseroth, called optogenetics. It melds fiber optics and genetic engineering to precisely control the activity of a specific brain circuit in a living, behaving animal. Genetically modified viruses are used to inject light-reactive proteins, borrowed from primitive organisms like algae, to make the circuitry similarly light-responsive.

New Research on How the Brain Makes Decisions

Neuroscience researchers at Trinity College Dublin have opened a new avenue for research on how the brain enables us to make decisions about our environment. By observing the gradual formation of a decision in brain activity before the particular decision was actually reported, the findings also have the potential to contribute to improved understanding and diagnosis of numerous brain disorders that are associated with impaired perceptual decision making. The discovery was recently published in Nature Neuroscience.

When interacting with our environment, we need to be sure about what we’re seeing, feeling or hearing in order to decide how to act. What does that road sign ahead say? Is that a train I hear approaching? Is it too dark for me to cycle home without a light? Somehow the brain enables us to make concrete decisions about the vast and often unreliable array of information it continually receives through the senses. One influential theory about how this might be achieved proposes that the brain allows information from the senses to accumulate over time and only commits to a particular decision once a reliable quantity has been gathered. While this theory has existed for several decades Assistant Professor, Redmond O’Connell at the Trinity College Institute of Neuroscience and colleagues are the first to have identified exactly how this occurs in the human brain.

The researchers designed a new test which required participants to detect a gradual change in a visual display or an auditory tone. The gradual change occurred over several seconds and was undetectable at first but eventually became obvious. This allowed the researchers to pinpoint the precise moment at which participants decided that a change had occurred. At the same time, the researchers recorded brain activity using electrodes placed on the scalp. Using this method the authors succeeded in isolating a brain signal that increased in parallel with the visual or auditory change and continued to increase thereafter. Most importantly, the authors found that participants only reported perceiving the change once this signal had reached a certain level. As a result, it was possible to precisely predict both the timing and accuracy of the participant’s decisions simply by monitoring this brain signal. In other words, it was possible to observe the gradual formation of a decision in the participant’s brain activity before that decision was actually reported.