Mysterious Disease Discovered Locally, Strikes Mainly Young Women

It’s a mysterious, newly discovered disease that strikes mainly young women, and it’s often misdiagnosed. Doctors who discovered it, here in Philadelphia, say it’s like your brain is on fire. 3 On Your Side Health Reporter Stephanie Stahl says it starts with personality changes.

Young women dazed, restrained in hospital beds, acting possessed and then becoming catatonic. They’d been so normal, when suddenly their lives went haywire.

“One minute I’d be sobbing, crying hysterically, and the next minute I’d be laughing, said Susannah Cahalan, of New Jersey.

“I was very paranoid and manic. There was something wrong. I thought trucks were following me,” said Emily Gavigan, of Pennsylvania.

And it got worse for Emily Gavigan, who was a sophomore at the University of Scranton. Hospitalized, and out of it, she couldn’t control her arm movements. Then there were seizures, and she needed a ventilator. Her parents were watching their only child slip away.

"It was life and death for weeks," said Grace Gavigan, Emily’s mom.

"We were losing her. This is something that I couldn’t control," said Bill Gavigan, Emily’s dad.

Doctors also couldn’t figure out what was wrong with Susannah.

"I had bizarre abnormal movements, would leave my arms out extended, you know, in front of me. I was a relatively normal person, then the next minute I’m hallucinating and insisting that my father had kidnapped me," said Susannah.

Turns out, Susannah and Emily weren’t mentally ill. They both had an auto immune disease called Anti-NMDA Receptor Encephalitis, when antibodies attack the brain, causing swelling.

Susannah says this is how doctors explained it to her parents, “He told them her brain is on fire. He used those words: ‘Her brain is on fire.’”

New brain-test app

Two years ago, researcher Josef Bless was listening to music on his phone when he suddenly had an idea.

"I noticed that the sounds of the different instruments were distributed differently between the ears, and it struck me that this was very similar to the tests we routinely use in our laboratory to measure brain function. In dichotic listening, each ear is presented with a different syllable at the same time (one to the left and one to the right ear) and the listener has to say which syllable seems clearest. The test indicates which side of the brain is most active during language processing," Bless explains.

Josef Bless is working on a PhD in psychology at the University of Bergen. He is a member of the Bergen fMRI Group, an interdisciplinary research group headed by Professor Kenneth Hugdahl, who has received a European Research Council (ERC) Advanced Grant for his brain research.

The iPhone app for dichotic listening is called iDichotic and was launched on the App Store in 2011, where it can be downloaded for free. Some one year later, more than 1,000 people have downloaded the app, and roughly half have sent their test results to the researchers’ database.

The researchers analysed the first 167 results they received and compared them with the results of 76 individuals tested in laboratories in Norway and Australia. The results have been published in the journal Frontiers in Psychology.

"We found that the results from the app were as reliable as those of the controlled laboratory tests. This means that smartphones can be used as a tool for psychological testing, opening up a wealth of exciting new possibilities," says Bless.

"The app makes it possible to gather large volumes of data easily and inexpensively. I think we will see more and more psychological tests coming to smartphones," he adds.

The researchers have also developed a special version of iDichotic for patients with schizophrenia who suffer from auditory hallucinations (i.e. hear “voices”). The app helps in training patients to improve their focus, so that when they hear voices, they are better able to shut them out.

"Using a mobile app, patients can be tested and receive training at home, instead of having to come to our laboratory," says Bless.

The app iDichotic has been developed in collaboration with Professor Kenneth Hugdahl, Doctor René Westerhausen, and Magne Gudmundsen.

Veterans with mild traumatic brain injury have brain abnormalities

Mild traumatic brain injury (TBI), including concussion, is one of the most common types of neurological disorder, affecting approximately 1.3 million Americans annually.

It has received more attention recently because of its frequency and impact among two groups of patients: professional athletes, especially football players; and soldiers returning from mid-east conflicts with blast-related TBI. An estimated 10 to 20 percent of the more than 2 million U.S. soldiers deployed in Iraq or Afghanistan have experienced TBI.

A recent study by psychiatrists from the Iowa City VA Medical Center and University of Iowa Health Care finds that soldiers returning from Iraq and Afghanistan with mild TBI have measurable abnormalities in the white matter of their brains when compared to returning veterans who have not experienced TBI. These abnormalities appear to be related to the severity of the injury and are related to cognitive deficits. The findings were published online in December in the American Journal of Psychiatry.

In the brain, broken down ‘motors’ cause anxiety

When motors break down, getting where you want to go becomes a struggle. Problems arise in much the same way for critical brain receptors when the molecular motors they depend on fail to operate. Now, researchers reporting in Cell Reports, a Cell Press publication, on February 7, have shown these broken motors induce stress and anxiety in mice. The discovery may point the way to new kinds of drugs to treat anxiety and other disorders.

The study in mice focuses on one motor in particular, known as KIF13A, which, according to the new evidence, is responsible for ferrying serotonin receptors. Without proper transportation, those receptors fail to reach the surface of neurons and, as a result, animals show signs of heightened anxiety.

In addition to their implications for understanding anxiety, the findings also suggest that defective molecular motors may be a more common and underappreciated cause of disease.

"Most proteins are transported in vesicles or as protein complexes by molecular motors," said Nobutaka Hirokawa of the University of Tokyo. "As shown in this study, defective motors could cause many diseases."

Scientists know that serotonin and serotonin receptors are involved in anxiety, aggression, and mood. But not much is known about how those players get around within cells. When Hirokawa’s team discovered KIF13A at high levels in the brain, they wondered what it did.

The researchers discovered that mice lacking KIF13A show greater anxiety in both open-field and maze tests and suggest that this anxious behavior may stem from an underlying loss of serotonin receptor transport, which leads to a lower level of expression of those receptors in critical parts of the brain.

"Collectively, our results suggest a role for this molecular motor in anxiety control," the researchers wrote. Hirokawa says the search should now be on for anti-anxiety drug candidates aimed at restoring the brain’s serotonin receptor transport service.

The brain circuit that makes it hard for obese people to lose weight

Imagine you are driving a car, and the harder you press on the accelerator, the harder an invisible foot presses on the brake. That’s what happens when obese people diet – the less food they eat, the less energy they burn, and the less weight they lose.

While this phenomenon is known, scientists at Sydney’s Garvan Institute of Medical Research and the University of NSW have pinpointed the exact brain circuitry behind it and have published their findings in the prestigious international journal Cell Metabolism, now online.

Dr Shu Lin, Dr Yanchuan Shi and Professor Herbert Herzog and his team have been studying the complex processes behind energy balance using various mouse models. They have shown that the neurotransmitter Neuropeptide Y (NPY), known for stimulating appetite, also plays a major role in controlling whether the body burns or conserves energy.

The researchers found that NPY produced in a particular region of the brain – the arcuate nucleus (Arc) of the hypothalamus – inhibits the activation of ‘brown fat’, one of the primary tissues where the body generates heat.

“This study is the first to identify the neurotransmitters and neural pathways that carry signals generated by NPY in the brain to brown fat cells in the body. It is also the first to show a direct connection between Arc NPY, the sympathetic nervous system and the control of energy expenditure.” said Professor Herzog.

“We know that NPY also influences other aspects of the sympathetic nervous system – such as heart rate and gut function – but its control of heat generation through brown fat seems to be the most critical factor in the control of energy expenditure.”

“When you don’t eat, or dramatically curtail your calorie intake, levels of NPY rise sharply. High levels of NPY signal to the body that it is in ‘starvation mode’ and should try to replenish and conserve as much energy as possible. As a result, the body reduces processes that are not absolutely necessary for survival.”

“Evolution has provided us with these mechanisms to help us survive famine, and they are strictly controlled. When people had to survive by finding food or hunting game, they could not afford to run out of energy and die of exhaustion, so their bodies evolved to cope.”

“Until the twentieth century, there were no fast food chains and people did not have ready access to high fat, high sugar, foods. So in evolutionary terms, it was unlikely that people were going to get very fat and mechanisms were only put in place to prevent you losing weight.”

“Obesity is a modern epidemic, and the challenge will be to find ways of tricking the body into losing weight – and that will mean somehow circumventing or manipulating this NPY circuit, probably with drugs.”

Brain research provides clues to what makes people think and behave differently

Differences in the physical connections of the brain are at the root of what make people think and behave differently from one another. Researchers reporting in the February 6 issue of the Cell Press journal Neuron shed new light on the details of this phenomenon, mapping the exact brain regions where individual differences occur. Their findings reveal that individuals’ brain connectivity varies more in areas that relate to integrating information than in areas for initial perception of the world.

"Understanding the normal range of individual variability in the human brain will help us identify and potentially treat regions likely to form abnormal circuitry, as manifested in neuropsychiatric disorders," says senior author Dr. Hesheng Liu, of the Massachusetts General Hospital.

Dr. Liu and his colleagues used an imaging technique called resting-state functional magnetic resonance imaging to examine person-to-person variability of brain connectivity in 23 healthy individuals five times over the course of six months.

The researchers discovered that the brain regions devoted to control and attention displayed a greater difference in connectivity across individuals than the regions dedicated to our senses like touch and sight. When they looked at other published studies, the investigators found that brain regions previously shown to relate to individual differences in cognition and behavior overlap with the regions identified in this study to have high variability among individuals. The researchers were therefore able to pinpoint the areas of the brain where variable connectivity causes people to think and behave differently from one another.

Higher rates of variability across individuals were also displayed in regions of the brain that have undergone greater expansion during evolution. “Our findings have potential implications for understanding brain evolution and development,” says Dr. Liu. “This study provides a possible linkage between the diversity of human abilities and evolutionary expansion of specific brain regions,” he adds.

Human memory study adds to global debate

An international study involving researchers from the University of Adelaide has made a major contribution to the ongoing scientific debate about how processes in the human brain support memory and recognition.

The study used a rare technique in which data was obtained from within the brain itself, using electrodes placed inside the brains of surgery patients.

Obtained in Germany, the data was sent to the University of Adelaide’s School of Psychology for further analysis using new techniques developed there. The results are published today in the Proceedings of the National Academy of Sciences (PNAS).

"Being able to understand how human memory works is important because there is a range of conditions that affect memory, such as Alzheimer’s disease, head injury, and ageing," says Professor John Dunn, Head of the School of Psychology at the University of Adelaide and a co-author of the study, which was led by researchers at the universities of Cambridge, UK, and Bonn, Germany.

"Scientists know a lot about memory from years of study, but there is an ongoing debate about how certain mechanisms in the brain process memory, and how those mechanisms work together.

"What we’re looking at is how the human brain processes ‘recognition memory’, which is our ability to recognise people, objects or events that we’ve encountered in the past."

The debate has centered on two key regions in the brain:

• the hippocampus, which is very important to memory and is one of the first regions of the brain to suffer damage from Alzheimer’s disease; and
• the perirhinal cortex, which receives sensory information from all of the body’s sensory regions.

"The debate is whether or not these two regions work in the same or different ways to support memory and recognition Studies over the years have led to both conclusions," Professor Dunn says.

He says this new study, which uses data from inside the brain instead of from electrodes on the scalp, far from the critical regions, revealed that different processes are at work in the hippocampus and the perirhinal cortex.

"Our analysis shows that these regions are responding to and processing memory in two very different ways. The activity levels in those regions changed in different ways according to the amount of information that could be remembered," Professor Dunn says.

"This study won’t settle the debate once and for all, but it does add weight to those scientists who believe that these two distinct parts of the brain respond to memory in different ways," he says.