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.

Pitt/UPMC Team Describes Technology that Lets Spinal Cord-Injured Man Control Robot Arm with Thoughts

Researchers at the University of Pittsburgh School of Medicine and UPMC describe in PLoS ONE how an electrode array sitting on top of the brain enabled a 30-year-old paralyzed man to control the movement of a character on a computer screen in three dimensions with just his thoughts. It also enabled him to move a robot arm to touch a friend’s hand for the first time in the seven years since he was injured in a motorcycle accident.

With brain-computer interface (BCI) technology, the thoughts of Tim Hemmes, who sustained a spinal cord injury that left him unable to move his body below the shoulders, were interpreted by computer algorithms and translated into intended movement of a computer cursor and, later, a robot arm, explained lead investigator Wei Wang, Ph.D., assistant professor, Department of Physical Medicine and Rehabilitation, Pitt School of Medicine.

“When Tim reached out to high-five me with the robotic arm, we knew this technology had the potential to help people who cannot move their own arms achieve greater independence,” said Dr. Wang, reflecting on a memorable scene from September 2011 that was re-told in stories around the world. “It’s very important that we continue this effort to fulfill the promise we saw that day.”

Six weeks before the implantation surgery, the team conducted functional magnetic resonance imaging (fMRI) of Mr. Hemmes’ brain while he watched videos of arm movement. They used that information to place a postage stamp-size electrocortigraphy (ECoG) grid of 28 recording electrodes on the surface of the brain region that fMRI showed controlled right arm and hand movement. Wires from the device were tunneled under the skin of his neck to emerge from his chest where they could be connected to computer cables as necessary.

For 12 days at his home and nine days in the research lab, Mr. Hemmes began the testing protocol by watching a virtual arm move, which triggered neural signals that were sensed by the electrodes. Distinct signal patterns for particular observed movements were used to guide the up and down motion of a ball on a computer screen. Soon after mastering movement of the ball in two dimensions, namely up/down and right/left, he was able to also move it in/out with accuracy on a 3-dimensional display.

“During the learning process, the computer helped Tim hit his target smoothly by restricting how far off course the ball could wander,” Dr. Wang said. “We gradually took off the ‘training wheels,’ as we called it, and he was soon doing the tasks by himself with 100 percent brain control.”

The robot arm was developed by Johns Hopkins University’s Applied Physics Laboratory. Currently, Jan Scheuermann, of Whitehall, Pa., is testing another BCI technology at Pitt/UPMC.

Fluctuations in the size of brain waves contribute to information processing

Cyclical variations in the size of brain wave rhythms may participate in the encoding of information by the brain, according to a new study led by Colin Molter of the Neuroinformatics Japan Center, RIKEN Brain Science Institute, Wako.

Brain waves are produced by the synchronized activity of large populations of neurons. Low frequency brain waves called theta oscillations are known to support memory formation. Researchers typically examine the frequency of oscillations in a given part of the brain and the timing of oscillations in different brain regions, but know very little about how variations in the size of these oscillations contribute to information processing.

Molter and his colleagues used electrode arrays to record brain waves from the rat hippocampus, a structure known to be critical for memory formation and spatial navigation, while the animals performed various behaviors, such as exploring open spaces, running through a maze and in a wheel, and sleeping. They observed fluctuations in the size of theta oscillations during all the behaviors—the brain waves did not remain the same size, but rather waxed and waned second by second.

During spatial navigation for example, individual hippocampal neurons called place cells become more active when the animal is in one or a few specific locations compared to the rest of the explored environment. The researchers found that the time of firing of many of the place cells correlated with the fluctuations in the size of the theta waves. During sleep, the activity of most of the cells was timed with the largest theta oscillations.

Even though the size of theta waves is correlated with motor behavior, their cyclic fluctuations at this time scale, observed while the rats ran and explored, were not correlated with the animals’ speed or acceleration. The fluctuations are instead likely to be generated by the brain itself, as their presence during sleep also suggests they are intrinsic.

The researchers speculate that this phenomenon could be helpful for the neuronal representation of space, resolving the ambiguity of space coding by place cells that become active in multiple preferred locations. “We are currently working on several new experiments to understand how the spatial location may affect the slow modulation and how the timing of the slow modulation affects behavior,” says Molter. “We are also trying to provide a model that incorporates the theta slow modulation to help propagation of activity between cell assemblies.”

Turning repulsive feelings into desires

Hunger, thirst, stress and drugs can create a change in the brain that transforms a repulsive feeling into a strong positive “wanting,” a new University of Michigan study indicates.

The research used salt appetite to show how powerful natural mechanisms of brain desires can instantly transform a cue that always predicted a repulsive Dead Sea Salt solution into an eagerly wanted beacon or motivational magnet.

Mike Robinson, a research fellow in the U-M Department of Psychology and the study’s lead author, said the findings help explain how related brain activations in people could cause them to avidly want something that has been always disliked.

This instant transformation of motivation, he said, lies in the ability of events to activate particular brain circuitry—a structure called the nucleus accumbens, which sits near the base of the front of the brain and is also activated by addictive drugs.

Cues for rewards often trigger intense motivation. The smell of food can make a person suddenly feel hungry when this wasn’t the case earlier. Drug cues may prompt relapse in addicts trying to quit. In some cases, desires may be triggered even for a relatively unpleasant event.

Researchers studied how rats responded to metal objects that represented either pleasant sugar or disgustingly intense Dead Sea saltiness. The rats quickly learned to jump on and nibble the sweetness cue, but turned away from and avoided the saltiness cue.

But one day the rats suddenly woke up in a new state of sodium appetite induced by drugs given the night before. On their first re-encounter with the saltiness cue in the new appetite state, their brain systems became activated and the rats instantly jumped on and nibbled the saltiness cue as though it were the sugar cue.

"The cue becomes avidly ‘wanted’ despite knowledge the salt always tasted disgusting," Robinson said.

The sudden brain changes help explain how an event, such as taking an addictive drug, could become “wanted” despite a person’s knowledge of the negative and unpleasant consequences of the drug.

"Our findings highlight what it means to say that drugs hijack our natural reward system," said Robinson, who authored the new study with Kent Berridge, James Olds Collegiate Professor of Psychology and Neuroscience.

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.

Hopkins Researchers Uncover Key to Antidepressant Response

Through a series of investigations in mice and humans, Johns Hopkins researchers have identified a protein that appears to be the target of both antidepressant drugs and electroconvulsive therapy. Results of their experiments explain how these therapies likely work to relieve depression by stimulating stem cells in the brain to grow and mature. In addition, the researchers say, these experiments raise the possibility of predicting individual people’s response to depression therapy, and fine-tuning treatment accordingly. Reports on separate aspects of the research were published in December on the Molecular Psychiatry website, and will also appear in the Feb. 7 issue of Cell Stem Cell.

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.