Functional brain imaging reliably predicts which vegetative patients have potential to recover consciousness

A functional brain imaging technique known as positron emission tomography (PET) is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover consciousness, according to new research published in The Lancet.

It is the first time that researchers have tested the diagnostic accuracy of functional brain imaging techniques in clinical practice.

“Our findings suggest that PET imaging can reveal cognitive processes that aren’t visible through traditional bedside tests, and could substantially complement standard behavioural assessments to identify unresponsive or “vegetative” patients who have the potential for long-term recovery”, says study leader Professor Steven Laureys from the University of Liége in Belgium.

In severely brain-damaged individuals, judging the level of consciousness has proved challenging. Traditionally, bedside clinical examinations have been used to decide whether patients are in a minimally conscious state (MCS), in which there is some evidence of awareness and response to stimuli, or are in a vegetative state (VS) also known as unresponsive wakefulness syndrome, where there is neither, and the chance of recovery is much lower. But up to 40% of patients are misdiagnosed using these examinations.

“In patients with substantial cerebral oedema [swelling of the brain], prediction of outcome on the basis of standard clinical examination and structural brain imaging is probably little better than flipping a coin,” writes Jamie Sleigh from the University of Auckland, New Zealand, and Catherine Warnaby from the University of Oxford, UK, in a linked Comment.

The study assessed whether two new functional brain imaging techniques—PET with the imaging agent fluorodeoxyglucose (FDG) and functional MRI (fMRI) during mental imagery tasks—could distinguish between vegetative and MCS in 126 patients with severe brain injury (81 in a MCS, 41 in a VS, and four with locked-in syndrome—a behaviourally unresponsive but conscious control group) referred to the University Hospital of Liége, in Belgium, from across Europe. The researchers then compared their results with the well-established standardised Coma Recovery Scale–Revised (CSR-R) behavioural test, considered the most validated and sensitive method for discriminating very low awareness.

Overall, FDG-PET was better than fMRI in distinguishing conscious from unconscious patients. Mental imagery fMRI was less sensitive at diagnosis of a MCS than FDG-PET (45% vs 93%), and had less agreement with behavioural CRS-R scores than FDG-PET (63% vs 85%). FDG-PET was about 74% accurate in predicting the extent of recovery within the next year, compared with 56% for fMRI.

Importantly, a third of the 36 patients diagnosed as behaviourally unresponsive on the CSR-R test who were scanned with FDG-PET showed brain activity consistent with the presence of some consciousness. Nine patients in this group subsequently recovered a reasonable level of consciousness.

According to Professor Laureys, “We confirm that a small but substantial proportion of behaviourally unresponsive patients retain brain activity compatible with awareness. Repeated testing with the CRS–R complemented with a cerebral FDG-PET examination provides a simple and reliable diagnostic tool with high sensitivity towards unresponsive but aware patients. fMRI during mental tasks might complement the assessment with information about preserved cognitive capability, but should not be the main or sole diagnostic imaging method.”

The authors point out that the study was done in a specialist unit focusing on the diagnostic neuroimaging of disorders of consciousness and therefore roll out might be more challenging in less specialist units.

Commenting on the study Jamie Sleigh and Catherine Warnaby add, “From these data, it would be hard to sustain a confident diagnosis of unresponsive wakefulness syndrome solely on behavioural grounds, without PET imaging for confirmation…[This] work serves as a signpost for future studies. Functional brain imaging is expensive and technically challenging, but it will almost certainly become cheaper and easier. In the future, we will probably look back in amazement at how we were ever able to practise without it.”

Better memory at ideal temperature

People’s working memory functions better if they are working in an ambient temperature where they feel most comfortable. That is what Leiden psychologists Lorenza Colzato and Roberta Sellaro conclude after having conducted research. They are publishing their findings in Psychological Research.

Studied for the first time
Everyone knows from experience that climate and temperature influence how you feel. But what about our ability to think? Does ambient temperature affect that too? The little research that has been done on this question shows that cooler environments promote cognitive performance when performing complex thinking tasks. Colzato and Sellaro are the first to investigate whether a person’s working memory works better when the ambient temperature perfectly matches his or her preference.

N-back test
To study the influence ambient temperature has on cognitive skills, Colzato and Sellaro performed tests on two groups of participants. One group had a preference for a cool environment, the other group preferred a warm one. The test subjects had to carry out thinking tasks in three different spaces. In the first the temperature was 25 degrees Celsius (77 Fahrenheit), in the second it was 15 degrees (59 Fahrenheit), and in the third the thermostat was set to 20 (68 Fahrenheit). The thinking task that the subjects had to perform was the so-called N-back task. Different letters would appear one after the other on the computer screen. Subjects had to indicate whether the letter that they saw was the same as the one they had seen two steps earlier.

Idea confirmed
Test subjects proved to perform better in a room with their preferred temperature. The conjecture is that working in one’s preferred temperature counteracts ‘ego depletion’: sources of energy necessary to be able to carry out mental tasks get used up less quickly. ‘The results confirm the idea that temperature influences cognitive ability. Working in one’s ideal temperature can promote efficiency and productivity,’ according to Colzato and Sellaro.

Neuroscientists disprove idea about brain-eye coordination

By predicting our eye movements, our brain creates a stable world for us. Researchers used to think that those predictions had so much influence that they could cause us to make errors in estimating the position of objects. Neuroscientists at Radboud University have shown this to be incorrect. The Journal of Neuroscience published their findings – which challenge fundamental knowledge regarding coordination between brain and eyes – on 15 April.

You continually move your eyes all day long, yet your perception of the world remains stable. That is because the brain processes predictions about your eye movements while you look around. Without these predictions, the image would shoot back and forth constantly.

Errors of estimation
People sometimes make mistakes in estimating the positions of objects – missing the ball completely during a game of tennis, for example. Predictions on eye movements were long held responsible for such localization errors: if the prediction does not correspond to the eventual eye movement, a mismatch between what you expect to see and what you actually see could be the result. Jeroen Atsma, a PhD candidate at the Donders Institute of Radboud University, wanted to know how that worked. ‘If localization errors really are caused by predictions, you would also expect those errors to occur if an eye movement, which has already been predicted in your brain, fails to take place at the very last moment.’ Atsma investigated this by means of an ingenious experiment.

Localizing flashes of light
Atsma asked test subjects to look at a computer screen where a single small ball appeared at various positions at random. The subjects followed the balls with their eyes while an eye-tracker registered their eye movements. The experiment ended with one last ball on the screen, followed by a short flash of light near that ball. The person had to look at the last, stationary ball while using the computer mouse to indicate the position of the flash of light. However, in some cases, a signal was sent around the time the last ball appeared, indicating that the subject was NOT allowed to look at the ball. In other words, the eye movement was cancelled at the last moment. The person being tested still had to indicate where the flash was visible.

Remarkable findings
Even when test subjects heard at very short notice that they should not look at the ball – in other words when the brain had already predicted the eye movement – they did not make any mistakes in localizing the flash of light. ‘That demonstrates you don’t make localization errors solely on the basis of predictions’, Atsma explained. ‘So far, literature has pretty much suggested the exact opposite. That is why we repeated the experiment several times to be sure.’

The findings of the neuroscientists in Nijmegen are remarkable because they challenge much of the existing knowledge about eye-brain coordination. Atsma: ‘This has been an issue ever since we started studying how the eyes function. For the first time ever our experiment offered the opportunity to research brain predictions when the actual eye movement is aborted. Therefore I expect our publication to lead to some lively discussions among fellow researchers.’

(Image credit)

(Image caption: A cross-section of mouse brain in the nucleus accumbens, a region of the brain known to be involved in reward and motivation, taken by a fluorescence microscope. Blue corresponds to cell nuclei, and green to fluorescence emitted by a green-fluorescent protein (NdT: the original incorrectly states “green fluorescente protein”) that identifies neurons having received the virus that can genetically abolish the expression of lipoprotein lipase protein. Credit: ©Serge Luquet, CNRS/Université Paris Diderot)

Obesity: are lipids hard drugs for the brain?

Why can we get up for a piece of chocolate, but never because we fancy a carrot? Serge Luquet’s team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) has demonstrated part of the answer: triglycerides, fatty substances from food, may act in our brains directly on the reward circuit, the same circuit that is involved in drug addiction. These results, published on April 15, 2014 in Molecular Psychiatry, show a strong link in mice between fluctuations in triglyceride concentration and brain reward development. Identifying the action of nutritional lipids on motivation and the search for pleasure in dietary intake will help us better understand the causes of some compulsive behaviors and obesity.

Though the act of eating responds to a biological need, it is also an essential cultural and social function in our modern societies. Meals are generally associated with a strong notion of pleasure, a feeling that pushes us towards food. Sometimes this is dangerous: 2.8 million people worldwide die from the consequences of obesity each year. Fundamentally, obesity is caused by imbalance between calories consumed and expended. A sedentary life combined with an abundance of sugary, fatty foods provides fertile ground for this disease.

The body uses sugars and fats as energy sources. The brain only consumes glucose. So why do we find an enzyme that can decompose triglycerides, lipids that come in particular from food, at its core, at the heart of the reward mechanism? A team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) led by Serge Luquet, a CNRS researcher, has tackled this fundamental question.

If they have the choice, normal behavior in mice is to prefer a high-fat diet to simpler foods. To simulate the action of a good meal, researchers have developed an approach that allows small quantities of lipids to be injected directly into the brains of mice. They observed that an infusion of triglycerides in the brain reduces the animal’s motivation to press a lever to obtain a food reward. It also reduces physical activity by half. What is more, an “infused” mouse balances its diet between the two food sources offered (high-fat foods and simpler foods).

To ensure that it is indeed the lipids injected that change the mice’s behavior, these Parisian scientists made sure that the lipids could not be detected by the animal’s brain any longer. They managed to remove the specific enzyme for triglycerides by silencing its coding gene, but only at the heart of the reward mechanism. The animal then shows increased motivation to obtain a reward, and if given the choice, consumes much richer food than average. This work echoes the previous work by their colleagues: reducing this enzyme in the hippocampus causes obesity.

Paradoxically, with obesity, blood (and therefore brain) triglyceride levels are higher than average. So obesity is often associated with overconsumption of sugary, fatty foods. The researchers explain this: with long-lasting high exposure to triglycerides, mice always display lower locomotor activity. By contrast, food rewards are still attractive! The ideal conditions for weight gain are therefore in place. At high triglyceride contents, the brain adapts to obtain its reward, similar to the mechanisms observed when people consume drugs.

This work, financed in particular by CNRS and ANR, indicate for the first time that triglycerides from food may act as hard drugs in the brain, on the reward system, controlling the motivational and pleasureseeking component of food intake.

Long-term study supports detrimental effects of television viewing on sleep in young children

A study following more than 1,800 children from ages 6 months to nearly 8 years found a small but consistent association between increased television viewing and shorter sleep duration. The presence of a television in the room where a child sleeps also was associated with less sleep, particularly in minority children. Investigators from MassGeneral Hospital for Children (MGHfC) and Harvard School of Public Health (HSPH) report their results – the first to examine the connection between television and sleep duration over several years – in the May issue of Pediatrics.

The study participants, children and their mothers, were enrolled in Project Viva, a long-term investigation of the health effects of several factors during pregnancy and after birth. This study analyzed information – reported by mothers when the children were around 6 months old and then annually for the next seven years – regarding how much time each day infants were in a room where a television was on, how much time older children watched television daily, whether children ages 4 to 7 slept in a room where a TV was present and their child’s average daily amount of sleep.

The study revealed that, over the course of the study, each additional hour of television viewing was associated with 7 fewer minutes of sleep daily, with the effects appearing to be stronger in boys than in girls. Racial and ethnic minority children were much more likely to sleep in a room where a television was present, and among those children, the presence of a bedroom television reduced average sleep around a half-hour per day.

The study authors note their results support previous short-term studies finding that both television viewing and sleeping in a room with a television decrease total sleep time, which can have negative effects on both mental and physical health.

Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

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Transplanting interneurons: Getting the right mix

Despite early optimistic studies, the promise of curing neurological conditions using transplants remains unfulfilled. While researchers have exhaustively cataloged different types of cells in the brain, and also the largely biochemical issues underlying common diseases, neural repair shops are still a ways off. Fortunately, significant progress is being made towards identifying the broader operant principles that might bear on any one disease work-around. A review just published in Science focuses on recent work on transplanting interneurons—a diverse family of cells united by their mutual love of inhibition and their local loyalty. The UCLA-based authors, reach the conclusion that the fate of transplanted neurons ultimately depends less on the influences of the new host environment, and more on the early upbringing of the cells within the donor embryo.

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