Inflammation shows signs of brain damage in obese adolescents

Researchers using MRI reveals brain damage in obese teens.

 There is a positive correlation between brain changes and hormones such as leptin and insulin.

According to a study being presented at the annual meeting of the Radiological Society of North America, Researchers using MRI have found signs of damage that may be related to inflammation in the brains of obese adolescents.

Obesity in young people has become a significant public health problem. In the US, the percentage of children and adolescents affected by obesity has more than tripled since the 1970s, according to the Centers for Disease Control and Prevention. Data from the World Health Organization indicates that the number of overweight or obese infants and young children ages five years or younger increased from 32 million globally in 1990 to 41 million in 2016.

While obesity is primarily associated with weight gain, recent evidence suggests that the disease triggers inflammation in the nervous system that could damage important regions of the brain. Developments in MRI like diffusion tensor imaging (DTI), a technique that tracks the diffusion of water along the brain's signal-carrying white matter tracts, have enabled researchers to study this damage directly.

For the new study, researchers compared DTI results in 59 obese adolescence. Scientists present students and 61 healthy adolescents, ages 12 to 16 years. From DTI, the researchers derived a measure called fractional anisotropy (FA), which correlates with the condition of the brain's white matter. A reduction in FA is indicative of increasing damage in the white matter.

The results showed a reduction of FA values in the obese adolescents in regions located in the corpus callosum, a bundle of nerve fibres that connects the left and right hemispheres of the brain. Decrease of FA was also found in the middle orbit ofrontal gyrus, a brain region related to emotional control and the reward circuit. None of the brain regions in obese patients had increased FA.

"Brain changes found in obese adolescents related to important regions responsible for the control of appetite, emotions and cognitive functions," said study co-author .

This pattern of damage correlated with some inflammatory markers like leptin, a hormone made by fat cells that helps regulate energy levels and fat stores. In some obese people, the brain does not respond to leptin, causing them to keep eating despite adequate or excessive fat stores. This condition, known as leptin resistance, makes the fat cells produce even more leptin.

The worsening condition of the white matter was also associated with levels of insulin, a hormone produced in the pancreas that helps regulate blood sugar levels. Obese people often suffer from insulin resistance, a state in which the body is resistant to the effects of the hormone.

"Our maps showed a positive correlation between brain changes and hormones such as leptin and insulin," the Dr. said. "Furthermore, we found a positive association with inflammatory markers, which leads us to believe in a process of neuroinflammation besides insulin and leptin resistance."

Dr.  noted that additional studies are needed to determine if this inflammation in young people with obesity is a consequence of the structural changes in the brain.

"In the future, we would like to repeat brain MRI in these adolescents after multi-professional treatment for weight loss to assess if the brain changes are reversible or not," she added.

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Stressed Pregnancy Might Hinder Infants’ Brain Development

While stress is at no time considered healthy, maternal stress during or even before pregnancy can affect the infant’s brain development, found a new study. The study looked at the relationship between maternal stress and brain development in 251 premature kids. Researchers found evidence for the impaired development of a white matter tract, the uncinate fasciculus, in babies whose mothers experience more stress in the prenatal period. These findings were published in the Journal Biological Psychiatry.

The mothers completed a questionnaire that asked them about their experiences of stressful events, ranging from everyday stress such as moving house or taking an exam to more severe stressors like experiencing bereavement, separation or divorce.

A score of severity of stress was calculated based on how many stressors they experienced as well as how severe those stressors were. This is what was related to the baby’s brain.
Researchers used a medical imaging technique called diffusion tensor imaging that was specifically developed to look at the structure of the white matter, which has previously been implicated in anxiety disorders – adults that have an anxiety disorder may show changes in the tract.

We found that in the mums that were more stressed during pregnancy and the period before birth, white matter was altered in the babies, said lead researcher.

Clinicians have an important role to play when speaking with expectant mothers. While questions are asked about depressive symptoms, few questions are asked about general stress and anxiety. Women who deal with stressful life events during pregnancy are not picked up by their GPs or by their health care providers very often.

It is not diagnosed as often as it should be during pregnancy and we are trying to emphasise that maternal mental health during pregnancy can impact the baby’s brain development which may impact on their outcomes later in life, researcher added.
Antenatal services need to be aware that it is important to think about stress of the mums and we need to have some kind of support there for the mums who identify that they are stressed, the researcher opined.

There is some evidence to suggest that if mothers experience poor mental health during pregnancy that leads to adverse outcomes in the baby – obstetric outcomes, lower birth weight or premature birth.
A mother’s poor mental health may also lead to altered early behavior such as more frequent crying.

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'Pied Piper' Device That Lures Tumors From The Brain Awarded Breakthrough Status By FDA

Brain tumors are notoriously difficult to treat, often growing quickly and spreading through the brain. But what if we could trick the cancerous cells to proliferate in a new direction, essentially luring them out of the brain and outside the skull? Well, researchers are attempting to do just that, and their work has been awarded “ breakthrough status” by the government.

Called the Tumor Monorail, the device has been described as a “pied piper”, thanks to its ability to trick and lure cells away from a tumor, just as the Pied Piper lured rats, and then children, away from the town of Hamelin in the well-known fairy tale.

The Tumor Monorail is essentially a long, thin tube with a small reservoir at one end. The reservoir sits on top of the skull, just under the scalp, and tricks tumor cells into migrating up the tube and out of the brain where they can be removed by a surgeon. It does this by mimicking the brain’s white matter, where the tumor would normally grow. The cancerous cells spread up the tube, thinking they are growing further into the brain and expanding the tumor. Gotcha.

So far, the Tumor Monorail has only been tested successfully in rats. The researchers now need to work on testing its safety and efficacy in humans. That’s why its new breakthrough status is so important. Developing new treatments and proving they are fit for clinical use is a long, ardous process, but the FDA breakthrough initiative helps to fast-track the development and review of new treatments for serious or life-threatening illnesses.

Glioblastoma – an aggressive type of brain tumor with a poor survival rate – is one of these conditions. Innovative new ways to tackle it, like the Tumor Monorail, could have a hugely positive impact, so speeding up its development is key. Still, it’s important to note that the new allocation doesn’t mean the device has been approved for clinical use by the FDA. The researchers behind it will have to prove it's both safe and effective in people first.

“The tumor monorail device is a true game-changer in how we think about treating brain tumors,” said  a neurosurgeon in a statement. “There are many tumors that are considered inoperable due to the location of the tumor or the frailty of the patient. This device affords clinicians the ability to surgically treat these tumors with a minimal approach.”

Back in 2014, the researchers successfully managed to get their device to work in rats. The rats’ brain tumors shrank by more than 90 percent and spread more slowly. Since then, the researchers have tweaked the device, and repeatedly shown its effectiveness in rats.

“This was the first demonstration that you can engineer migration inside the body and move a tumor from point A to point B by design,” explained  one of the researcher. “It was also the first demonstration of bringing the tumor to your drug rather than your drug going into the brain and killing valuable cells.”

Five years on and the device has breakthrough status. “The most exciting part about this designation is that it gives us the opportunity to look at the FDA as a partner rather than a reviewer,” said project leader. “With direct access to the FDA reviewers, we can get more efficient, faster feedback on our experimental ideas to make sure we’re addressing all of their concerns from the very start.”

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MRI brain scans can predict MRI dementia risk before symptoms appear

MRI brain scans can help predict whether a person will develop dementia in the next three years, before the symptoms of the disorder appear, scientists have found. In a study, researchers  used magnetic resonance imaging (MRI) brain scans to predict dementia with 89 per cent accuracy.
 
The findings suggest that doctors may one day be able to use widely available tests to tell people their risk of developing dementia before symptoms arise.

"Right now it's hard to say whether an older person with normal cognition or mild cognitive impairment is likely to develop dementia," said  an assistant professor.

"We showed that a single MRI scan can predict dementia on average 2.6 years before memory loss is clinically detectable, which could help doctors advise and care for their patients," said the Prof.

Although there are no drugs available yet to prevent or delay the onset of Alzheimer's disease, identifying those at high risk of developing dementia within the next few years could still be beneficial, the researchers said. People could make decisions on their financial and living arrangements while they are still in full control of their faculties.

Researchers analysed MRI scans for physical signs of impending cognitive decline. They used a technique called diffusion tensor imaging to assess the health of the brain's white matter, which encompasses the cables that enable different parts of the brain to talk to one another.

"Diffusion tensor imaging is a way of measuring the movement of water molecules along white matter tracts," the Prof. said.

"If water molecules are not moving normally it suggests underlying damage to white tracts that can underlie problems with cognition," he said.

Using information from the Alzheimer's Disease Neuroimaging Initiative -- a multisite collaboration that pools data, funding and expertise to improve clinical trials for Alzheimer's disease -- researchers identified 10 people whose cognitive skills declined over a two-year period and matched them by age and sex with 10 people whose thinking skills held steady.

The average age of people in both groups was 73. Then, the researchers analysed diffusion tensor MRI scans taken just before the two-year period for all 20 people. The researchers found that people who went on to experience cognitive decline had significantly more signs of damage to their white matter.

The researchers repeated their analysis in a separate sample of 61 people, using a more refined measure of white matter integrity. With this new analysis, they were able to predict cognitive decline with 89 per cent accuracy when looking at the whole brain. When the researchers focused on specific parts of the brain most likely to show damage, the accuracy rose to 95 per cent.

"We could tell that the individuals who went on to develop dementia have these differences on diffusion MRI, compared with scans of cognitively normal people whose memory and thinking skills remained intact,"the Prof. said. 

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Child Abuse May Alter Neurons in Brain

Adults who were victims of child abuse tend to have thinner layers of myelin coating in the brain, according to a new study.

Myelin is the protective fatty coating that covers the long thread-like parts of nerve cells called axons and helps them conduct electrical signals more efficiently. Myelin builds up progressively (in a process known as myelination) primarily during childhood, and then continues to mature until early adulthood.

Earlier research has shown significant white matter abnormalities in the brains of people who had experienced child abuse. (White matter is mostly made up of billions of myelinated nerve fibers stacked together.)

However, because these observations were made in the brains of living people through MRI (magnetic resonance imaging), it was impossible to gain a clear picture of the affected white matter cells and molecules.

To better study the microscopic changes which occur in the brains of adults who have experienced child abuse, the researchers compared post-mortem brain samples from three different groups of adults: people who had committed suicide who suffered from depression and had a history of severe childhood abuse (27 individuals); people with depression who had committed suicide but who had no history of being abused as children (25 individuals); and brain tissue from a third group of people who had neither psychiatric illnesses nor a history of child abuse (26 people).

The findings reveal that the thickness of the myelin coating in a significant proportion of the nerve fibers was reduced only in the brains of those who had suffered abuse as children. The researchers also found underlying molecular changes that selectively affect the cells responsible for myelin generation and maintenance. In addition, increases were found in the diameters of some of the largest axons among only this group.

The researchers speculate that together, these changes may alter functional coupling between the cingulate cortex and subcortical structures such as the amygdala and nucleus accumbens (areas of the brain linked respectively to emotional regulation and to reward and satisfaction). These changes may also contribute to altered emotional processing in adult victims of child abuse.

The researchers conclude that early life abuse may result in long-term disruption of a range of neural functions in the anterior cingulate cortex. They are planning to conduct more research that will help determine exactly how these effects impact the regulation of emotions and attachment.

Severe childhood abuse is tied to an increased risk of psychiatric disorders such as depression, as well as high levels of impulsivity, aggressiveness, anxiety, more frequent substance abuse, and suicide.

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Problem with arithmetic? Blame it on white matter

If you are not able to add or multiply quickly and accurately, that's not exactly your fault - it's the quality of the white matter in your brain that decides it. 

A study led by Bert De Smedt, a professor from University of Leuven in Belgium, has discovered that healthy 12-year-olds - who score well in addition and multiplication - have higher-quality white matter. 

But this correlation does not appear to apply to subtraction and division. 

Neural pathways are comparable to a bundle of cables. These cables are surrounded by an isolating sheath - myelin or 'white matter'. 

"The thicker the isolating sheath and the more cables there are, the more white matter. And the more white matter, the faster the signals are transferred," explained Bert de Smedt. 

In this study, the researchers asked 25 children to solve a series of different arithmetic operations while undergoing a brain scan. 

They then compared the quality of the children's white matter tracts with their arithmetic test performance. 

"We found that a better quality of the arcuate fasciculus anterior - a white matter tract that connects brain regions often used for arithmetic - corresponds to better performance in adding and multiplying, while there is no correlation for subtracting and dividing," they said. 

The arcuate fasciculus anterior (green) is a neural pathway connecting brain regions often used for arithmetic. 

'Grey' cells process information in the brain and are connected via neural pathways, the tracts through which signals are transferred. 

A possible explanation for this is that this white matter bundle is involved in rote memorisation, whereas when we subtract and divide, such memorisation plays less of a role. 

"When subtracting and dividing, we are more likely to use intermediary steps to calculate the solution, even as adults," added Bert de Smedt. 

These findings also add insight into the link between reading and arithmetic, said De Smedt. 

"Reading proficiency and arithmetic proficiency often go hand-in-hand. This also might explain why we often see arithmetic problems in children with dyslexia," stressed de Smedt. 

Next step would be to investigate how white matter tracts can be strengthened through extra arithmetic training. 

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