Scary Faces Terrify Woman with Unusual Condition

When the 67-year-old woman came to the hospital, she was deeply afraid of two things — the visions of odd-looking faces that appeared hovering before her, and that the hallucinations might mean she was losing her mind.

But this retired teacher wasn’t going crazy, and laboratory tests also ruled out two common culprits of hallucinations — infection and drug interactions.

"She was absolutely terrified by what she was seeing," said Dr. Bharat Kumar, an internal medicine resident at the University of Kentucky who treated the woman. In fact, the patient and her family were so concerned in the days before she came to the hospital, they asked a priest about performing an exorcism, Kumar said.

The woman drew a picture of what she saw. The faces had large teeth, eyes and ears, and a horizontally elongated shape, like a football.

That peculiar shape and the fact that the patient recognized that she was hallucinating (rather than believing the visions to be real) provided two important clues in making a diagnosis, Kumar said. He determined that the woman had condition called Charles Bonnet syndrome.

Patients with the syndrome may see small people and animals, bright moving shapes or distorted faces. These hallucinations are purely visual; no sounds accompany them.

In the woman’s case, the condition developed because she had macular degeneration. Tissue within the retinas of her eyes was deteriorating, and her ability to see was declining.

Charles Bonnet syndrome results from the absence of such sensory input to the brain. “When it expects sensory input and receives nothing, it often creates its own input,” Kumar explained.

The brain isn’t a sophisticated computer that processes information objectively and efficiently, he said. “It’s more of a wibbly-wobbly, messy-guessy ball of goo.”

There is no treatment for the condition, but in many cases the hallucinations stop happening as the brain becomes used to vision loss. Patients who are very frightened might be given anti-psychotic medications, but these drugs have serious side effects and aren’t appropriate for everyone.

The woman was grateful to receive her diagnosis and learn that she was not losing her mind, Kumar said. When he followed up with her three months later, she was still having the hallucinations, but they were happening less often.

A 2010 study showed that 10 to 40 percent of elderly patients with visual impairments may have Charles Bonnet syndrome.

Kumar had never before seen a patient with the condition, although he noted that it may occur more commonly than it is diagnosed. “Patients are often hesitant to say that they see things because they are afraid that they will be called crazy,” he said.

The case report was published online Feb. 25 in the journal Age and Aging.

New Hope for Reversing the Effects of Spinal Cord Injury

Walking is the obvious goal for individuals who have a chronic spinal cord injury, but it is not the only one. Regaining sensation and continence control also are important goals that can positively impact an individual’s quality of life. New hope for reversing the effects of spinal cord injury may be found in a combination of stem cell therapy and physical therapy as reported in Cell Transplantation by scientists at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

“Our phase one/two clinical trial had one goal: to give patients who have no other treatment options some hope,” said Hatem E. Sabaawy, MD, PhD, an assistant professor of medicine in the molecular and regenerative medicine program at Robert Wood Johnson Medical School. “Early findings have concluded that we have met our goal and can improve the quality of life for individuals with spinal cord injuries by providing a safe treatment that restores some neurological function.”

Dr. Sabaawy led a clinical trial that included 70 patients who had cervical or thoracic spinal cord injuries and were previously treated for at least six months without response. The patients were randomized into two groups, both of which were given physical therapy treatment. One of the groups also received stem cells derived from their own bone marrow injected near the injury site. Using the American Spinal Injury Association Impairment (AIS) Scale, patients received neurological and physical evaluations monthly for 18 months to determine if sensory and motor functions improved.

“Of primary importance, there was a notable absence of side effects in patients treated with stem cells during the course of our investigation,” added Dr. Sabaawy, who also is a resident member of The Cancer Institute of New Jersey at Robert Wood Johnson Medical School.

None of the patients in the control group who received only physical therapy showed any improvement in sensory or motor function during the same time frame. Although the scale of injuries differed, all patients who were treated with a combination of bone-marrow derived stem cells and physical therapy responded to tactile and sensory stimuli as early as 4 weeks into the study. After 12 weeks, they experienced improvements in sensation and muscle strength, which was associated with enhanced potency and improved bladder and bowel control that eventually allowed patients to live catheter-free. Patients who showed improvement based on the AIS scale also were able to sit up and turn in their beds.

“Since the emergence of stem cells as a potential therapy for spinal cord injury, scientists have diligently sought the best application for using their regenerating properties to improve a patient’s mobility,” said Joseph R. Bertino, MD, University Professor of medicine and pharmacology, interim director, Stem Cell Institute of New Jersey and chief scientific officer at The Cancer Institute of New Jersey. “Dr. Sabaawy’s discovery that treatment is more successful when stem cell therapy is combined with physical therapy could provide a remarkable, and hopefully sustainable, improvement in the overall quality of life for patients with spinal cord injury.”

At the end of 18 months, 23 of the 50 patients who received both physical therapy and stem cell therapy showed a significant improvement of at least 10 points on the AIS scale. Several were able to walk with assistance. In addition, more gains were made in motor skill control by patients with thoracic spinal cord injuries, suggesting that patients with thoracic spinal cord injuries may respond better to the combined treatment.

Dr. Sabaawy however cautioned that more studies are needed with a larger number of patients to test different cell dose levels and intervals at which stem cell therapy should be delivered.

“Although a cure for spinal cord injury does not yet exist, it is clear that the regenerative and secretory properties of bone-marrow derived stem cells can improve symptoms of paralysis in some patients when coupled with the current standard of care that physical therapy provides,” said Dr. Sabaawy. “We will continue monitoring our patients for long-term safety effects of stem cell therapy and work to expand our research through a phase two clinical trial that can be conducted at multiple centers nationwide and internationally.”

(Image courtesy: University of Alberta, Faculty of Rehabilitation Medicine)

'I don't want to pick!' Preschoolers know when they aren't sure

Children as young as 3 years old know when they are not sure about a decision, and can use that uncertainty to guide decision making, according to new research from the Center for Mind and Brain at the University of California, Davis.

"There is behavioral evidence that they can do this, but the literature has assumed that until late preschool, children cannot introspect and make a decision based on that introspection," said Simona Ghetti, professor of psychology at UC Davis and co-author of the study with graduate student Kristen Lyons, now an assistant professor at Metropolitan State University of Denver. [Preschoolers Use Introspection to Make Decisions]

The findings are published online by the journal Child Development and will appear in print in an upcoming issue.

Ghetti studies how reasoning, memory and cognition emerge during childhood. It is known that children get better at introspection through elementary school, she said. Lyons and Ghetti wanted to see whether this ability to ponder exists in younger children.

Previous studies have used open-ended questions to find out how children feel about a decision, but that approach is limited by younger children’s ability to report on the content of their mental activity. Instead, Lyons and Ghetti showed 3-, 4- and 5-year-olds ambiguous drawings of objects and asked them to point to a particular object, such as a cup, a car or the sun. Then they asked the children to point to one of two pictures of faces, one looking confident and one doubtful, to rate whether they were confident or not confident about a decision.

In one of the tests, children had to choose a drawing even if unsure. In a second set of tests they had a “don’t want to pick” option.

Across the age range, children were more likely to say they were not confident about their decision when they had in fact made a wrong choice. When they had a “don’t know” option, they were most likely to take it if they had been unsure of their choice in the “either/or” test.

By opting not to choose when uncertain, the children could improve their overall accuracy on the test.

"Children as young as 3 years of age are aware of when they are making a mistake, they experience uncertainty that they can introspect on, and then they can use that introspection to drive their decision making," Ghetti said.

The researchers hope to extend their studies to younger children to examine the emergence of introspection and reasoning.

(Image: Jupiter Images)

Neuro-magic: Magician uses magic tricks to study the brain’s powers of perception and memory

A magician is using his knowledge of magic theory and practice to investigate the brain’s powers of observation.

Hugo Caffaratti, engineer and semi-professional magician from Barcelona, Spain, has embarked on a PhD with the University of Leicester’s Centre for Systems Neuroscience.

Hugo has 12 years of experience working with magic – specialising in card tricks – and is a member of the Spanish Society of Illusionism (SEI-ACAI).

The engineer also has a longstanding interest in neuroscience and bioengineering, having taken a Master’s degree in Biomedical Engineering at University of Barcelona.

He hopes to combine his two interests in his PhD thesis project, which covers a new field of Cognitive Neuroscience: Neuro-Magic.

As part of his work, he will investigate how our brains perceive what actually happens before our eyes – and how our attention can be drawn away from important details.

He also plans to study “forced choice” - a tool often used by magicians where we are fooled into thinking we have made a free choice.

Among other experiments, Hugo will ask participants to watch videos of card trick performances, while sitting in front of an eye-tracker device.

This will allow him to monitor where our attention is focused during illusions – and how our brain can be deceived when our eyes miss the whole picture.

Hugo said: “I have always been interested in the study of the brain. It is amazing to be involved in the process of combining the disciplines of neuroscience and magic.

“I am really interested in the fields of decision making and forced-choice. It is incredible that many times a day we make a decision and feel free. We do not realise that we have been forced to make that decision.

“I am constructing an experiment to study what happens when we make forced decisions – to try and find the reasons for it. I am thinking about which kinds of tricks I know could be useful to give more insights about brain function.”

He will work under the tutelage of Professor Rodrigo Quian Quiroga, director of the Centre for Systems Neuroscience.

Professor Quian Quiroga’s recent work on memory formation was the topic of his recent book “Borges and memory” (MIT Press) and was also featured on the front page of the international science publication Scientific American.

Professor Rodrigo Quian Quiroga said: “I am very interested in connections between science and the arts. Last year, for example, we organized an art and science exhibition as a result of a 1-year rotation in my lab of visual artist Mariano Molina. Hugo’s PhD will look at decision-making and attention – and although he is doing his first steps in neuroscience, I think he already has a lot of expertise in this area based on his training as a magician.

“Magic theory has thousands of years of experience. Magicians have been answering similar questions that we have in the lab, and they have an intuitive knowledge of how the mind works. Hugo will likely bring a fresh new view on how to address questions we deal with in neuroscience.”

Hugo is also keen to carry on with his work in magic while studying for his PhD, and is hoping to perform in bars in Leicester while staying here.

He has also applied for membership with The Magic Circle – a prestigious magic society of London. He will have to sit exams to prove his magical mettle in order to join the exclusive club.

Using Fat to Fight Brain Cancer

In laboratory studies, Johns Hopkins researchers say they have found that stem cells from a patient’s own fat may have the potential to deliver new treatments directly into the brain after the surgical removal of a glioblastoma, the most common and aggressive form of brain tumor.

The investigators say so-called mesenchymal stem cells (MSCs) have an unexplained ability to seek out damaged cells, such as those involved in cancer, and may provide clinicians a new tool for accessing difficult-to-reach parts of the brain where cancer cells can hide and proliferate anew. The researchers say harvesting MSCs from fat is less invasive and less expensive than getting them from bone marrow, a more commonly studied method.

Results of the Johns Hopkins proof-of-principle study are described online in the journal PLOS ONE.

“The biggest challenge in brain cancer is the migration of cancer cells. Even when we remove the tumor, some of the cells have already slipped away and are causing damage somewhere else,” says study leader Alfredo Quinones-Hinojosa, M.D., a professor of neurosurgery, oncology and neuroscience at the Johns Hopkins University School of Medicine. “Building off our findings, we may be able to find a way to arm a patient’s own healthy cells with the treatment needed to chase down those cancer cells and destroy them. It’s truly personalized medicine.”

For their test-tube experiments, Quinones-Hinojosa and his colleagues bought human MSCs derived from both fat and bone marrow, and also isolated and grew their own stem cell lines from fat removed from two patients. Comparing the three cell lines, they discovered that all proliferated, migrated, stayed alive and kept their potential as stem cells equally well.

This was an important finding, Quinones-Hinojosa says, because it suggests that a patient’s own fat cells might work as well as any to create cancer-fighting cells. The MSCs, with their ability to home in on cancer cells, might be able to act as a delivery mechanism, bringing drugs, nanoparticles or some other treatment directly to the cells. Quinones-Hinojosa cautions that while further studies are under way, it will be years before human trials of MSC delivery systems can begin.

Ideally, he says, if MSCs work, a patient with a glioblastoma would have some adipose tissue (fat) removed — from any number of locations in the body — a short time before surgery. The MSCs in the fat would be drawn out and manipulated in the lab to carry drugs or other treatments. Then, after surgeons removed the brain tumor, they could deposit these treatment-armed cells into the brain in the hopes that they would seek out and destroy the cancer cells.

Currently, standard treatments for glioblastoma are chemotherapy, radiation and surgery, but even a combination of all three rarely leads to more than 18 months of survival after diagnosis. Glioblastoma tumor cells are particularly nimble, migrating across the entire brain and establishing new tumors. This migratory capability is thought to be a key reason for the low cure rate of this tumor type.

“Essentially these MSCs are like a ‘smart’ device that can track cancer cells,” Quinones-Hinojosa says.

Quinones-Hinojosa says it’s unclear why MSCs are attracted to glioblastoma cells, but they appear to have a natural affinity for sites of damage in the body, such as a wound. MSCs, whether derived from bone marrow or fat, have been studied in animal models to treat trauma, Parkinson’s disease, ALS and other diseases.

Single Concussion May Cause Lasting Brain Damage

A single concussion may cause lasting structural damage to the brain, according to a new study published online in the journal Radiology.

"This is the first study that shows brain areas undergo measureable volume loss after concussion," said Yvonne W. Lui, M.D., Neuroradiology section chief and assistant professor of radiology at NYU Langone School of Medicine. "In some patients, there are structural changes to the brain after a single concussive episode."

According to the Centers for Disease Control and Prevention, each year in the U.S., 1.7 million people sustain traumatic brain injuries, resulting from sudden trauma to the brain. Mild traumatic brain injury (MTBI), or concussion, accounts for at least 75 percent of all traumatic brain injuries.

Following a concussion, some patients experience a brief loss of consciousness. Other symptoms include headache, dizziness, memory loss, attention deficit, depression and anxiety. Some of these conditions may persist for months or even years.

Studies show that 10 to 20 percent of MTBI patients continue to experience neurological and psychological symptoms more than one year following trauma. Brain atrophy has long been known to occur after moderate and severe head trauma, but less is known about the lasting effects of a single concussion.

Dr. Lui and colleagues set out to investigate changes in global and regional brain volume in patients one year after MTBI. Twenty-eight MTBI patients (with 19 followed at one year) with post-traumatic symptoms after injury and 22 matched controls (with 12 followed at one year) were enrolled in the study. The researchers used three-dimensional magnetic resonance imaging (MRI) to determine regional gray matter and white matter volumes and correlated these findings with other clinical and cognitive measurements.

The researchers found that at one year after concussion, there was measurable global and regional brain atrophy in the MTBI patients. These findings show that brain atrophy is not exclusive to more severe brain injuries but can occur after a single concussion.

"This study confirms what we have long suspected," Dr. Lui said. "After MTBI, there is true structural injury to the brain, even though we don’t see much on routine clinical imaging. This means that patients who are symptomatic in the long-term after a concussion may have a biologic underpinning of their symptoms."

Certain brain regions showed a significant decrease in regional volume in patients with MTBI over the first year after injury, compared to controls. These volume changes correlated with cognitive changes in memory, attention and anxiety.

"Two of the brain regions affected were the anterior cingulate and the precuneal region," Dr. Lui said. "The anterior cingulate has been implicated in mood disorders including depression, and the precuneal region has a lot of different connections to areas of the brain responsible for executive function or higher order thinking."

According to Dr. Lui, researchers are still investigating the long-term effects of concussion, and she advises caution in generalizing the results of this study to any particular individual.

"It is important for patients who have had a concussion to be evaluated by a physician," she said. "If patients continue to have symptoms after concussion, they should follow-up with their physician before engaging in high-risk activities such as contact sports."

Neural “Synchrony” May be Key to Understanding How the Human Brain Perceives

Despite many remarkable discoveries in the field of neuroscience during the past several decades, researchers have not been able to fully crack the brain’s “neural code.” The neural code details how the brain’s roughly 100 billion neurons turn raw sensory inputs into information we can use to see, hear and feel things in our environment.

In a perspective article published in the journal Nature Neuroscience on Feb. 25, 2013, biomedical engineering professor Garrett Stanley detailed research progress toward “reading and writing the neural code.” This encompasses the ability to observe the spiking activity of neurons in response to outside stimuli and make clear predictions about what is being seen, heard, or felt, and the ability to artificially introduce activity within the brain that enables someone to see, hear, or feel something that is not experienced naturally through sensory organs.

Stanley also described challenges that remain to read and write the neural code and asserted that the specific timing of electrical pulses is crucial to interpreting the code. He wrote the article with support from the National Science Foundation (NSF) and the National Institutes of Health (NIH). Stanley has been developing approaches to better understand and control the neural code since 1997 and has published about 40 journal articles in this area.

“Neuroscientists have made great progress toward reading the neural code since the 1990s, but the recent development of improved tools for measuring and activating neuronal circuits has finally put us in a position to start writing the neural code and controlling neuronal circuits in a physiological and meaningful way,” said Stanley, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

With recent reports that the Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, progress toward breaking the neural code could begin to accelerate.

The potential rewards for cracking the neural code are immense. In addition to understanding how brains generate and manage information, neuroscientists may be able to control neurons in individuals with epilepsy and Parkinson’s disease or restore lost function following a brain injury. Researchers may also be able to supply artificial brain signals that provide tactile sensation to amputees wearing a prosthetic device.

Stanley’s paper highlighted a major challenge neuroscientists face: selecting a viable code for conveying information through neural pathways. A longstanding debate exists in the neuroscience community over whether the neural code is a “rate code,” where neurons simply spike faster than their background spiking rate when they are coding for something, or a “timing code,” where the pattern of the spikes matters. Stanley expanded the debate by suggesting the neural code is a “synchrony code,” where the synchronization of spiking across neurons is important.

A synchrony code argues the need for precise millisecond timing coordination across groups of neighboring neurons to truly control the circuit. When a neuron receives an incoming stimulus, an electric pulse travels the neuron’s length and triggers the cell to dump neurotransmitters that can spark a new impulse in a neighboring neuron. In this way, the signal gets passed around the brain and then the body, enabling individuals to see, touch, and hear things in the environment. Depending on the signals it receives, a neuron can spike with hundreds of these impulses every second.

“Eavesdropping on neurons in the brain is like listening to a bunch of people talk—a lot of the noise is just filler, but you still have to determine what the important messages are,” explained Stanley. “My perspective is that information is relevant only if it is going to propagate downstream, a process that requires the synchronization of neurons.”

Neuronal synchrony is naturally modulated by the brain. In a study published in Nature Neuroscience in 2010, Stanley reported finding that a change in the degree of synchronous firing of neurons in the thalamus altered the nature of information as it traveled through the pathway and enhanced the brain’s ability to discriminate between different sensations. The thalamus serves as a relay station between the outside world and the brain’s cortex.

Synchrony induced through artificial stimulation poses a real challenge for creating a wide range of neural representations. Recent technological advances have provided researchers with new methods of activating and silencing neurons via artificial means. Electrical microstimulation had been used for decades to activate neurons, but the technique activated a large volume of neurons at a time and could not be used to silence them or separately activate excitatory and inhibitory neurons. Stanley compared the technique with driving a car that has the gas and brake pedals welded together.

New research methods, such as optogenetics, enable activation and silencing of neurons in close proximity and provide control unavailable with electrical microstimulation. Through genetic expression or viral transfection, different cell types can be targeted to express specific proteins that can be activated with light.

“Moving forward, new technologies need to be used to stimulate neural activity in more realistic and natural scenarios and their effects on the synchronization of neurons need to be thoroughly examined,” said Stanley. “Further work also needs to be completed to determine whether synchrony is crucial in different contexts and across brain regions.”

Study Explains Why Fainting Can Result From Blood Pressure Drug Used In Conjunction With Other Disorders

A new study led by a Canadian research team has identified the reason why prazosin, a drug commonly used to reduce high blood pressure, may cause lightheadedness and possible fainting upon standing in patients with normal blood pressure who take the drug for other reasons, such as the treatment of PTSD and anxiety.

According to University of British Columbia researcher and study team leader Dr. Nia Lewis, the body is in constant motion leading to changes in blood pressure with every activity. For example, when standing, the body copes with the sudden drop in blood pressure by constricting peripheral vessels to concentrate the blood in the areas that help stabilize the body.

This study found that prazosin prevents this process by blocking the α1-adrenoreceptor, a critical pathway that allows the vessels to constrict. This physiological response is dangerous for individuals with normal blood pressure who take prazosin to treat the symptoms of PTSD and anxiety, for the act of standing up can cause light-headedness and/or fainting.

The study, entitled “Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity,” is published in the American Journal of Physiology–Regulatory, Integrative and Comparative Physiology.

Methodology

Eight males and four females, with an average age of 25, and all of whom had normal blood pressure, were enrolled in the cross-over trial.  On day one of the study, participants were weighed, measured, and familiarized with the blood pressure monitoring equipment and procedures that would be used.

On the next visit, participants stayed overnight at the research facility in order to control for activity and diet. The following morning they were given either prazosin (1mg/20kg body weight) or a placebo, and instructed to lie down.  After 20 minutes, they were told to rise in one smooth motion from the lying-down position to standing, and their blood pressure and cerebral blood flow was continuously monitored. They were required to remain standing for three minutes or until they felt severe lightheadedness and dizziness, or felt as if they were about to faint.

On their third and final visit the participants underwent the same procedure as on the second visit. At this visit, however, they received the placebo if they had previously been given the medication, and vice versa.

Results

The investigators found that:

• All but one of the 12 participants who took the medication experienced temporary dizziness or lightheadedness upon standing.
• All participants who took the placebo were able to complete the three-minute standing test. By contrast, only 2 of the 12 were able to complete the standing test after taking prazosin.
• After taking prazosin, none of the participants were able to attain normal blood pressure levels after standing. As a result, blood flow to the brain was reduced and subjects were unable to stand for 3 minutes as they began to experience the onset of fainting.
• When the participants had taken prazosin, mean arterial blood pressure and systolic blood pressure was significantly lower—by 15 percent— when lying down compared to when they took the placebo. Mean arterial blood pressure also fell for a longer period (11 seconds versus eight for placebo) after participants stood up following consumption of the medication, resulting in a lower arterial pressure levels.
• Blood flow to the brain, as measured by cerebral blood flow velocity, was not different when lying down. However, brain blood flow in the prazosin trial was reduced by 33 percent more than in than compared with the placebo trial.

Conclusions

“We were able to determine that, because prazosin shuts down a pathway that is critical to regulate blood pressure, the capacity to safely control blood flow to the brain was also reduced to a level that could induce fainting,” said Dr. Lewis. “No study has examined the effects of prazosin on the interaction between blood pressure and blood flow to the brain. The findings derived from this study show a mechanism of how prazosin causes fainting,” she explained.

Importance of the Findings

“This study highlights the importance of a key pathway in the body’s blood pressure system, known as the α1-adrenergic sympathetic pathway, in ensuring the recovery of blood pressure following standing and how important this pathway is in ensuring blood flow to the brain is not reduced to a level where fainting may occur,” said Dr. Lewis.

Additionally, this study provides a cautionary alert to those who are prescribed prazosin, for other conditions besides hypertension.