Neuroscience

Inattention, hyperactivity, and impulsive behavior in children with ADHD can result in social problems and they tend to be excluded from peer activities. They have been found to have impaired recognition of emotional expression from other faces. The research group of Professor Ryusuke Kakigi of the National Institute for Physiological Sciences, National Institutes of Natural Sciences, in collaboration with Professor Masami K. Yamaguchi and Assistant Professor Hiroko Ichikawa of Chuo University first identified the characteristics of facial expression recognition of children with ADHD by measuring hemodynamic response in the brain and showed the possibility that the neural basis for the recognition of facial expression is different from that of typically developing children. The findings are discussed in Neuropsychologia (available online on Aug. 23, 2014).

The research group showed images of a happy expression or an angry expression to 13 children with ADHD and 13 typically developing children and identified the location of the brain activated at that time. They used non-invasive near-infrared spectroscopy to measure brain activity. Near-infrared light, which is likely to go through the body, was projected through the skull and the absorbed or scattered light was measured. The strength of the light depends on the concentration in “oxyhemoglobin” which gives the oxygen to the nerve cells working actively. The result was that typically developing children showed significant hemodynamic response to both the happy expression and angry expression in the right hemisphere of the brain. On the other hand, children with ADHD showed significant hemodynamic response only to the happy expression but brain activity specific for the angry expression was not observed. This difference in the neural basis for the recognition of facial expression might be responsible for impairment in social recognition and the establishment of peer-relationships.

The first animal model for ALS dementia, a form of ALS that also damages the brain, has been developed by Northwestern Medicine scientists. The advance will allow researchers to directly see the brains of living mice, under anesthesia, at the microscopic level. This will allow direct monitoring of test drugs to determine if they work.

This is one of the latest research findings since the ALS Ice Bucket Challenge heightened interest in the disease and the need for expanded research and funding.

“This new model will allow rapid testing and direct monitoring of drugs in real time,” said Northwestern scientist and study senior author Teepu Siddique, MD. “This will allow scientists to move quickly and accelerate the testing of drug therapies.”

The new mouse model has the pathological hallmarks of the disease in humans with mutations in the genes for UBQLN2 (ubliqulin 2) and SQSTM1 (P62) that Siddique and colleagues identified in 2011. That pathology was linked to all forms of ALS and ALS/dementia.

Dr. Siddique and Han-Xiang Deng, MD, the corresponding authors on the paper, said they have reproduced behavioral, neurophysiological and pathological changes in a mouse that mimic this form of dementia associated with ALS (amyotrophic lateral sclerosis). 

Dr. Siddique is the Les Turner ALS Foundation/Herbert C. Wenske Professor of Neurology at Northwestern University Feinberg School of Medicine and a neurologist at Northwestern Memorial Hospital. Dr. Deng is a research professor in Neurology at Feinberg.

The study was published Sept. 22 in the Proceedings of the National Academy of Sciences.

It’s been difficult for scientists to reproduce the genetic mutations of ALS, especially ALS/dementia in animal models, Dr. Siddique noted, which has hampered drug therapy testing.

Five percent or more of ALS cases, also known as Lou Gherig’s disease, also have ALS/dementia.

“ALS with dementia is an even more vicious disease than ALS alone because it attacks the brain causing changes in behavior and language well as causing paralysis,” Dr. Siddique said.

ALS affects an estimated 350,000 people worldwide, with an average survival of three years. In this progressive neurological disorder, the degeneration of neurons leads to muscle weakness and impaired speaking, swallowing and breathing, eventually causing paralysis and death. The associated dementia affects behavior and may affect decision-making, judgment, insight and language.

Simultaneously using mobile phones, laptops and other media devices could be changing the structure of our brains, according to new University of Sussex research.

A study published today (24 September) in PLOS ONE reveals that people who frequently use several media devices at the same time have lower grey-matter density in one particular region of the brain compared to those who use just one device occasionally.

The research supports earlier studies showing connections between high media-multitasking activity and poor attention in the face of distractions, along with emotional problems such as depression and anxiety.

But neuroscientists Kep Kee Loh and Dr Ryota Kanai point out that their study reveals a link rather than causality and that a long-term study needs to be carried out to understand whether high concurrent media usage leads to changes in the brain structure, or whether those with less-dense grey matter are more attracted to media multitasking.

The researchers at the University of Sussex’s Sackler Centre for Consciousness Science used functional magnetic resonance imaging (fMRI) to look at the brain structures of 75 adults, who had all answered a questionnaire regarding their use and consumption of media devices, including mobile phones and computers, as well as television and print media.

They found that, independent of individual personality traits, people who used a higher number of media devices concurrently also had smaller grey matter density in the part of the brain known as the anterior cingulate cortex (ACC), the region notably responsible for cognitive and emotional control functions.

Kep Kee Loh says: “Media multitasking is becoming more prevalent in our lives today and there is increasing concern about its impacts on our cognition and social-emotional well-being. Our study was the first to reveal links between media multitasking and brain structure.”

Scientists have previously demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. The neural pathways and synapses can change based on our behaviours, environment, emotions, and can happen at the cellular level (in the case of learning and memory) or cortical re-mapping, which is how specific functions of a damaged brain region could be re-mapped to a remaining intact region.

Other studies have shown  that training (such as learning to juggle, or taxi drivers learning the map of London) can increase grey-matter densities in certain parts of the brain.

“The exact mechanisms of these changes are still unclear,” says Kep Kee Loh. “Although it is conceivable that individuals with small ACC are more susceptible to multitasking situations due to weaker ability in cognitive control or socio-emotional regulation, it is equally plausible that higher levels of exposure to multitasking situations leads to structural changes in the ACC. A longitudinal study is required to unambiguously determine the direction of causation.”

New research by scientists at the University of Kentucky’s Sanders-Brown Center on Aging suggests that people who notice their memory is slipping may be on to something.

The research, led by Richard Kryscio, Ph.D., chair of the Department of of Biostatistics and associate director of the Alzheimer’s Disease Center at UK, appears to confirm that self-reported memory complaints are strong predictors of clinical memory impairment later in life.

Kryscio and his group asked 531 people with an average age of 73 and free of dementia if they had noticed any changes in their memory in the prior year. The participants were also given annual memory and thinking tests for an average of 10 years. After death, participants’ brains were examined for evidence of Alzheimer’s disease.

During the study, 56 percent of the participants reported changes in their memory, at an average age of 82. The study found that participants who reported changes in their memory were nearly three times more likely to develop memory and thinking problems. About one in six participants developed dementia during the study, and 80 percent of those first reported memory changes.

"What’s notable about our study is the time it took for the transition from self-reported memory complaint to dementia or clinical impairment — about 12 years for dementia and nine years for clinical impairment — after the memory complaints began," Kryscio said. "That suggests that there may be a significant window of opportunity for intervention before a diagnosable problem shows up."

Kryscio points out that while these findings add to a growing body of evidence that self-reported memory complaints can be predictive of cognitive impairment later in life, there isn’t cause for immediate alarm if you can’t remember where you left your keys.

"Certainly, someone with memory issues should report it to their doctor so they can be followed. Unfortunately, however, we do not yet have preventative therapies for Alzheimer’s disease or other illnesses that cause memory problems."

The research, which was supported by grants from the National Institutes of Health, the National Institute on Aging, and the National Center for Advancing Translational Sciences, was published in the Sept. 24, 2014, online issue of Neurology.

A new, easy-to-use EEG electrode set for the measurement of the electrical activity of the brain was developed in a recent study completed at the University of Eastern Finland. The solutions developed in the PhD study of Pasi Lepola, MSc, make it possible to attach the electrode set on the patient quickly, resulting in reliable results without any special treatment of the skin. As EEG measurements in emergency care are often performed in challenging conditions, the design of the electrode set pays particular attention to the reduction of electromagnetic interference from external sources.

EEG measurements can be used to detect such abnormalities in the electrical activity of the brain that require immediate treatment. These abnormalities are often indications of severe brain damage, cerebral infarction, cerebral haemorrhage, poisoning, or unspecified disturbed levels of consciousness. One of the most serious brain function abnormalities is a prolonged epileptic seizure, status epilepticus, which is impossible to diagnose without an EEG measurement. In many cases, a rapidly performed EEG measurement and the start of a proper treatment significantly reduces the need for aftercare and rehabilitation. This, in turn, drastically improves the cost-effectiveness of the treatment chain.

Although the benefits of EEG measurements are indisputable, they remain underused in acute and emergency care. A significant reason for this is the fact that the electrode sets available on the markets are difficult to attach on the patient, and their use requires special skills and constant training. This new type of an electrode set is expected to provide solutions for making EEG measurements feasible at as an early stage as possible.

The EEG electrode set was produced using screen printing technology, in which silver ink was used to print the conductors and measurement electrodes on a flexible polyester film. The EEG electrode set consists of 16 hydrogel-coated electrodes which, unlike in the traditional method, are placed on the hair-free areas of the patient’s head, making it easy to attach. The new EEG electrode set significantly speeds up the measurement process because there is no need to scrape the patient’s skin or to use any separate gels. As the electrode set is flexible and solid, the electrodes get automatically placed in their correct places. Furthermore, there is no need to move the patient’s head when putting on the EEG electrode set, which is especially important in patients possibly suffering from a neck or skull injury. Due to the fact that the disposable electrode set is easy and fast to use, it is particularly well-suited to be used in emergency care, in ambulances and even in field conditions. Thanks to the materials used, the electrode set does not interfere with any magnetic resonance or computed tomography imaging the patient may undergo.

The performance of the electrode set was tested by using various electrical tests, on several volunteers, and in real patient cases. The results were compared to those obtained by traditional EEG methods.

The PhD study also focused on the use of screen printing technology solutions to protect electrodes against electromagnetic interference. The silver or graphite shielding layer printed to the outer edge of the electrode set was discovered to significantly reduce external interference on the EEG signal. This shielding layer can be easily and cost-efficiently introduced to all measurement electrodes produced with similar methods. Protecting the electrode with a shielding layer is beneficial when measuring weak signals in conditions that contain external interference.

Areas of the brain that respond to reward and pleasure are linked to the ability of a drug known as butorphanol to relieve itch, according to new research led by Gil Yosipovitch, MD, Professor and Chair of the Department of Dermatology at Temple University School of Medicine (TUSM), and Director of the Temple Itch Center. The findings point to the involvement of the brain’s opioid receptors—widely known for their roles in pain, reward, and addiction—in itch relief, potentially opening up new avenues to the development of treatments for chronic itch.

The article, published online September 11, in the Journal of Investigative Dermatology, is the first to show precisely where in the brain butorphanol works to relieve itch. In identifying those areas, the study helps to explain why butorphanol works better for chronic itching mediated by histamine, a small molecule involved in allergic reactions, than for nonhistamine-related types of itch.

"The research allows us to assess butorphanol’s effects," Dr. Yosipovitch said. "We can now identify better targets in the brain that drugs can work on to relieve itch."

The research marks an important step toward the development of itch-specific agents. As Dr. Yosipovitch explained, chronic itching, which affects roughly 12 percent of the population, comprises not just one disease, but many—ranging from atopic eczema and psoriasis to systemic diseases such as lymphoma and chronic liver failure. Biochemically, each of those diseases induces itching via one of two main pathways: one that is mediated by histamine and one that is not. Most pathological itching originates along nonhistaminergic pathways.

Working with Alexandru D. P. Papoiu, MD, PhD, at Wake Forest University School of Medicine, Dr. Yosipovitch experimentally induced itch in human volunteers using either histamine or cowhage, which incites nonhistaminergic itching. Study volunteers were then treated with either butorphanol or a placebo and subjected to functional magnetic resonance imaging (fMRI) to analyze brain activity and assess the effects of butorphanol (or placebo). When volunteers returned seven days later, they received the other treatment and again underwent fMRI.

Butorphanol suppressed histamine itching in all cases and reduced cowhage itching in 35 percent of subjects. The drug’s suppression of histamine itching was associated specifically with the activation of brain areas known as the nucleus accumbens and septal nuclei—areas located deep at the base of the forebrain. The regions are notably rich in so-called kappa (κ)-opioid receptors, on which butorphanol acts. By contrast, the relief of cowhage itch by butorphanol was linked to effects in other brain areas.

The findings suggest that butorphanol works primarily on κ-opioid receptors to suppress the itch sensation induced by histamine. But the drug also has important effects on an itch pathway that does not involve histamine, where the demand for new treatments is greatest.

How nonhistaminergic itching is reduced through the involvement of opioid receptors remains unclear. Opioid receptors modulate the transmission of information about itch in the brain and occur in high levels in the areas of the brain that house neural pathways associated with reward. Reward pathways are known particularly for their response to pleasurable stimuli. Dr. Yosipovitch and Dr. Papoiu have shown in previous work that the activation of reward circuits is correlated with pleasurability and the degree of itch relief derived from self-scratching.

The new study, which Yosipovitch carried out at Wake Forest University prior to joining the TUSM faculty in 2013, further illustrates the power of applying imaging technologies to basic questions in itch research. At Temple’s Itch Center, Yosipovitch is continuing to explore those applications.

"We are in a position now to better understand the itch-scratch cycle," he said. "To break the cycle from the top down, knowing where to target receptors in the brain, would be a major achievement."

Xanthohumol, a type of flavonoid found in hops and beer, has been shown in a new study to improve cognitive function in young mice, but not in older animals.

The research was just published in Behavioral Brain Research by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University. It’s another step toward understanding, and ultimately reducing the degradation of memory that happens with age in many mammalian species, including humans.

Flavonoids are compounds found in plants that often give them their color. The study of them – whether in blueberries, dark chocolate or red wine - has increased in recent years due to their apparent nutritional benefits, on issues ranging from cancer to inflammation or cardiovascular disease. Several have also been shown to be important in cognition.

Xanthohumol has been of particular interest because of possible value in treating metabolic syndrome, a condition associated with obesity, high blood pressure and other concerns, including age-related deficits in memory. The compound has been used successfully to lower body weight and blood sugar in a rat model of obesity.

The new research studied use of xanthohumol in high dosages, far beyond what could be obtained just by diet. At least in young animals, it appeared to enhance their ability to adapt to changes in the environment. This cognitive flexibility was tested with a special type of maze designed for that purpose.

“Our goal was to determine whether xanthohumol could affect a process we call palmitoylation, which is a normal biological process but in older animals may become harmful,” said Daniel Zamzow, a former OSU doctoral student and now a lecturer at the University of Wisconsin/Rock County.

“Xanthohumol can speed the metabolism, reduce fatty acids in the liver and, at least with young mice, appeared to improve their cognitive flexibility, or higher level thinking,” Zamzow said. “Unfortunately it did not reduce palmitoylation in older mice, or improve their learning or cognitive performance, at least in the amounts of the compound we gave them.”

Kathy Magnusson, a professor in the OSU Department of Biomedical Sciences, principal investigator with the Linus Pauling Institute and corresponding author on this study, said that xanthohumol continues to be of significant interest for its biological properties, as are many other flavonoids.

“This flavonoid and others may have a function in the optimal ability to form memories,” Magnusson said. “Part of what this study seems to be suggesting is that it’s important to begin early in life to gain the full benefits of healthy nutrition.”

It’s also important to note, Magnusson said, that the levels of xanthohumol used in this study were only possible with supplements. As a fairly rare micronutrient, the only normal dietary source of it would be through the hops used in making beer, and “a human would have to drink 2000 liters of beer a day to reach the xanthohumol levels we used in this research.”

In this and other research, Magnusson’s research has primarily focused on two subunits of the NMDA receptor, called GluN1 and GluN2B. Their decline with age appears to be related to the decreased ability to form and quickly recall memories.

In humans, many adults start to experience deficits in memory around the age of 50, and some aspects of cognition begin to decline around age 40, the researchers noted in their report.

Brain activity can be used to tell whether someone recognizes details they encountered in normal, daily life, which may have implications for criminal investigations and use in courtrooms, new research shows.

The findings, published in Psychological Science, a journal of the Association for Psychological Science, suggest that a particular brain wave, known as P300, could serve as a marker that identifies places, objects, or other details that a person has seen and recognizes from everyday life.

Research using EEG recordings of brain activity has shown that the P300 brain wave tends to be large when a person recognizes a meaningful item among a list of nonmeaningful items. Using P300, researchers can give a subject a test called the Concealed Information Test (CIT) to try to determine whether they recognize information that is related to a crime or other event.

Most studies investigating P300 and recognition have been conducted in lab settings that are far removed from the kinds of information a real witness or suspect might be exposed to. This new study marks an important advance, says lead research John B. Meixner of Northwestern University, because it draws on details from activities in participants’ normal, daily lives.

“Much like a real crime, our participants made their own decisions and were exposed to all of the distracting information in the world,” he explains.

“Perhaps the most surprising finding was the extent to which we could detect very trivial details from a subject’s day, such as the color of umbrella that the participant had used,” says Meixner. “This precision is exciting for the future because it indicates that relatively peripheral crime details, such as physical features of the crime scene, might be usable in a real-world CIT — though we still need to do much more work to learn about this.”

To achieve a more realistic CIT, Meixner and co-author J. Peter Rosenfeld outfitted 24 college student participants with small cameras that recorded both video and sound — the students wore the cameras clipped to their clothes for 4 hours as they went about their day.

For half of the students, the researchers used the recordings to identify details specific to each person’s day, which became “probe” items for that person. The researchers also came up with corresponding, “irrelevant” items that the student had not encountered — if the probe item was a specific grocery store, for example, the irrelevant items might include other grocery stores.

For the other half of the students, the “probe” items related to details or items they had not encountered, but which were instead drawn from the recordings of other participants. The researchers wanted to simulate a real investigation, in which a suspect with knowledge of a crime would be shown the same crime-related details as a suspect who may have no crime-related knowledge.

The next day, all of the students returned to the lab and were shown a series of words that described different details or items (i.e., the probe and irrelevant items), while their brain activity was recorded via EEG.

The results showed that the P300 was larger for probe items than for irrelevant items, but only for the students who had actually seen or encountered the probe.

Further analyses revealed that P300 responses effectively distinguished probe items from irrelevant items on the level of each individual participant, suggesting that it is a robust and reliable marker of recognition.

These findings have implications for memory research, but they may also have real-world application in the domain of criminal law given that some countries, like Japan and Israel, use the CIT in criminal investigations.

“One reason that the CIT has not been used in the US is that the test may not meet the criteria to be admissible in a courtroom,” says Meixner. “Our work may help move the P300-based CIT one step closer to admissibility by demonstrating the test’s validity and reliability in a more realistic context.”

Meixner, Rosenfeld, and colleagues plan on investigating additional factors that may impact detection, including whether images from the recordings may be even more effective at eliciting recognition than descriptive words – preliminary data suggest this may be the case.

Have you ever eaten something totally new and it made you sick? Don’t give up; if you try the same food in a different place, your brain will be more “forgiving” of the new attempt. In a new study conducted by the Sagol Department of Neurobiology at the University of Haifa, researchers found for the first time that there is a link between the areas of the brain responsible for taste memory in a negative context and those areas in the brain responsible for processing the memory of the time and location of the sensory experience. When we experience a new taste without a negative context, this link doesn’t exist.

The area of the brain responsible for storing memories of new tastes is the taste cortex, found in a relatively insulated area of the human brain known as the insular cortex. The area responsible for formulating a memory of the place and time of the experience (the episode) is the hippocampus. Until now, researchers assumed that there was no direct connection between these areas – i.e., the processing of information about a taste is not related to the time or the place one experiences the taste. The accepted thinking was that a negative experience – for example, being exposed to a bad taste – would be negative in the same way anywhere, and the brain would create a memory of the taste itself, divorced from the time or place.

But in this new study, conducted by doctoral student Adaikkan Chinnakkaruppan in the laboratory of Prof. Kobi Rosenblum of the Sagol Department of Neurobiology at the University of Haifa, in cooperation with the Riken Institute, the leading brain research institute in Tokyo, the researchers demonstrate for the first time that there is a functional link between the two brain regions.

In the study the researchers sought to examine the relationship between the taste cortex (which is responsible for taste memory), and three different areas in the hippocampus: CA1, which is responsible for encoding the concept of space (where we are located); DG, the area responsible for encoding the time relationship between events; and CA3, responsible for filling in missing information. To do this the researchers took ordinary mice and mice that were genetically engineered by their Japanese colleagues such that these three areas of the brain functioned normally but were lacking plasticity, which did not allow new memories reliant on them to be created.

“In brain research, the manipulation we do must be very delicate and precise, otherwise the changes can make the entire experiment irrelevant to proving or refuting the research hypothesis,” said Prof. Rosenblum.

The mice were exposed to two new tastes, one that caused stomach pains (to mimic exposure to toxic food) and another that didn’t cause that feeling. By comparing the two groups it emerged that when the new taste was not accompanied by an association with toxic food, there was no difference between the normal mice and those whose various functional areas in the hippocampus didn’t allow plasticity. But when the taste caused a negative feeling, there was clear involvement of the CA1 area, which is responsible for encoding the space.

“The significance of this is that the moment we go back to the same place at which we experienced the taste associated with a bad feeling, subconsciously the negative memory will be much stronger than if we come to taste the same taste in a totally different place,” explained Prof. Rosenblum. Similarly, the DG area, which is responsible for encoding the time between incidents, was involved the more time that passed between the new taste and the stomach discomfort. “This means that even during a simple associative taste, the brain operates the hippocampus to produce an integrated experience that includes general information about the time between events and their location,” he said.

The findings, which were recently published in the Journal of Neuroscience, expose the complexity and richness of the simple sensory experiences that are engraved in our brains and that in most cases we aren’t even aware of. Moreover, the study can help explain behavioral results and the difficulty in producing memories when certain areas of the brain become dysfunctional following and illness or accident. The better we understand the encoding of simple sensory experiences in the brain and the link between the feeling, time and place of the experiences; we will better understand the complex process of creating memories and storing them in our brains.

Patients who were treated with a statin in the hospital after suffering from a hemorrhagic stroke were significantly more likely to survive than those who were not, according to a study published today in JAMA Neurology. This study was conducted by the same researchers who recently discovered that the use of cholesterol-lowering statins can improve survival in victims of ischemic stroke.

Ischemic stroke is caused by a constriction or obstruction of a blood vessel that blocks blood from reaching areas of the brain, while hemorrhagic stroke, also known as intracerebral hemorrhage, is bleeding in the brain.

“Some previous research has suggested that treating patients with statins after they suffer hemorrhagic stroke may increase their long-term risk of continued bleeding,” said lead author Alexander Flint, MD, PhD, of the Kaiser Permanente Department of Neuroscience in Redwood City, Calif. “Yet the findings of our study suggest that stopping statin treatments for these patients may carry substantial risks.”

The study included 3,481 individuals who were admitted to any of 20 Kaiser Permanente hospitals in Northern California with a hemorrhagic stroke over a 10-year period. Researchers looked at patient survival and discharge 30 days after the stroke.

Patients treated with a statin while in the hospital were more likely to be alive 30 days after suffering a hemorrhagic stroke than those who were not treated with a statin — 81.6 percent versus 61.3 percent. Patients treated with a statin while in the hospital were also more likely to be discharged to home or an acute rehabilitation facility than those who were not — 51.1 percent compared to 35.0 percent.

Patients whose statin therapy was discontinued — that is, patients taking a statin as an outpatient prior to experiencing a hemorrhagic stroke who did not receive a statin as an inpatient — had a mortality rate of 57.8 percent compared with a mortality rate of 18.9 percent for patients using a statin before and during hospitalization.

The researchers concluded that statin use is strongly associated with improved outcomes after hemorrhagic stroke, and that discontinuing statin use is strongly associated with worsened outcomes after hemorrhagic stroke.

Available research evidence supports the use of deep brain stimulation (DBS) for patients with obsessive-compulsive disorder (OCD) who don’t respond to other treatments, concludes a review in the October issue of Neurosurgery, official journal of the Congress of Neurological Surgeons (CNS). The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Based on evidence, two specific bilateral DBS techniques are recommended for treatment of carefully selected patients with OCD, according to a new clinical practice guideline endorsed by the CNS and the American Association of Neurological Surgeons. While calling for further research in key areas, Dr. Clement Hamani of Toronto Western Hospital and coauthors emphasize that patients with OCD symptoms that don’t respond to other treatments should continue to have access to DBS.

Deep Brain Stimulation for OCD—What’s the Evidence?

Dr. Hamani led a multispecialty expert group in performing a systematic review of research on the effectiveness of DBS for OCD. Deep brain stimulation—placement of electrodes in specific areas of the brain, followed by electrical stimulation of those areas—has become an important treatment for patients with Parkinson’s disease and other movement disorders.

Although many patients with OCD respond well to medications and/or psychotherapy, 40 to 60 percent continue to experience symptoms despite treatment. Over the past decade, a growing number of reports have suggested that DBS may be an effective alternative in these “medically refractory” cases.

Dr. Hamani and colleagues were tasked with analyzing the supporting evidence and developing an initial clinical practice guideline for the use of DBS for patients with OCD. The review and guideline development process was sponsored by the American Society of Stereotactic and Functional Neurosurgery and the CNS. Out of more than 350 papers, the reviewers identified seven high-quality studies evaluating DBS for OCD.

Based on that evidence, they conclude that bilateral stimulation (on both sides of the brain) of two brain “targets”—areas called the subthalamic nucleus and the nucleus accumbens—can be regarded as effective treatments for OCD. In controlled clinical trials, both techniques improved OCD symptoms by around 30 percent on a standard rating scale.

While Research Proceeds, well-selected treatment-resistant severe OCD Patients Should Have Access to DBS

That evidence forms the basis for a clinical guideline stating that bilateral DBS is a “reasonable therapeutic option” for patients with severe OCD that does not respond to other treatments. The guideline also notes that there is “insufficient evidence” supporting the use of any type of unilateral DBS target (one side of the brain) for OCD.

The review highlights the difficulties of studying the effectiveness of DBS for OCD—because most patients respond to medical treatment, studies of this highly specialized treatment typically include only small numbers of patients. Dr. Hamani and coauthors identify some priorities for future research: particularly to identify the most effective brain targets and the subgroups of patients most likely to benefit.

Despite the limited evidence base, DBS therapy for OCD has been approved by the Food and Drug Administration under a humanitarian device exemption. Dr. Hamani and coauthors note that various safeguards are in place to ensure appropriate use, and prevent overuse, of DBS for OCD.

While research continues, they believe that functional neurosurgeons should continue to work with other specialists to ensure that patients with severe, medically refractory OCD continue to have access to potentially beneficial DBS therapy.

An international, interdisciplinary group of researchers led by Gabor G. Kovacs from the Clinical Institute of Neurology at the MedUni Vienna has demonstrated, through the use of a new antibody, how Parkinson’s disease spreads from cell to cell in the human brain. Until now, this mechanism has only been observed in experimental models, but has now been demonstrated for the first time in humans too.

At the focus of the study, recently published in the highly respected journal “Neurobiology of Disease”, is the protein α-synuclein. This protein is present in the human brain but develops into a pathologically modified form in the presence of Parkinson’s disease and a common type of age-related dementia (known as Lewy body dementia, responsible for up to a quarter of all dementia-related diseases).

This study, which was carried out by a team from the MedUni Vienna in collaboration with researchers from the USA, Germany and Hungary, demonstrates for the first time that human nerve cells take up the pathological α-synuclein and thereby transfer the disease from one cell to the next. “This explains why patients with Parkinson’s disease deteriorate more and more from a clinical perspective and develop new symptoms, because the disease is able to spread to other parts of the brain through this infection process,” says Gabor G Kovacs, commenting on the central finding of the study.

New antibody achieved major breakthrough
The researchers demonstrated this mechanism using an antibody that scientists from the MedUni Vienna played a key role in helping to develop in collaboration with the German biotech firm Roboscreen. As the study shows, this antibody is the first to distinguish between the physiologically present and disease-associated form of α-synuclein and reacts exclusively with the pathological form.

Mechanism of spread demonstrated for the first time could provide a basis for new treatments for Parkinson’s
"For patients with Parkinson’s disease, this means that α-synuclein’s mechanism of spread from cell to cell could serve as a point of therapeutic attack if we are able to block this cell-to-cell transfer mechanism", continues Kovacs. In diagnostic terms, this antibody also represents a major breakthrough, since the antibodies used previously were unable to distinguish between the physiological and disease-associated form, which meant that they could not be used as easily for diagnostic purposes, e.g. in body fluids.

New antibody improves diagnosis
The fact that this is now possible for the first time has been demonstrated by a further study, also recently published in the specialist publication “Clinical Neuropathology”. According to this study, the new antibody can be used to detect disease-associated α-synuclein in the cerebrospinal fluid of patients with brain disease associated with α-synuclein. This is of major importance for clinical practice, because it means it will be possible to clinically determine whether the dementia is caused by Lewy bodies or not. This study arose through close collaboration between the Clinical Institute of Neurology (Gabor G. Kovacs) and the University Department of Neurology (Walter Pirker) at the MedUni Vienna.

While dialysis can cause blood pressure changes that damage the brain, cooling dialysis fluids can protect against such effects. The findings come from a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The cooling intervention can be delivered without additional cost and is simple to perform.

While dialysis is an essential treatment for many patients with kidney disease, it can cause damage to multiple organs, including the brain and heart, due to the sudden removal of bodily fluids.

To characterize dialysis-induced brain injury and to see whether cooled dialysis fluids (called dialysate) might help reduce such injury, Christopher McIntyre, DM, and his colleagues randomized 73 new dialysis patients to dialyze with body temperature dialysate or dialysate cooled to 0.5◦C below body temperature for 1 year.

The study demonstrated that dialysis drives progressive white matter brain injury due to blood pressure instability; however, patients who dialyzed at 0.5◦C below body temperature were completely protected against such white matter changes.

“This study demonstrates that paying attention to improving the tolerability of dialysis treatment—in this case by the simple and safe intervention of reducing the temperature of dialysate—does not just make patients feel better, but also can completely protect the brain from progressive damage,” said Dr. McIntyre.

The link between a protein typically associated with Alzheimer’s disease and its impact on memory and cognition may not be as clear as once thought, according to a new study from the University of Wisconsin-Madison’s Waisman Center. The findings are revealing more information about the earliest stages of the neurodegenerative disease.

The researchers — including lead study author Sigan Hartley, UW-Madison assistant professor of human development and family studies, and Brad Christian, UW-Madison associate professor of medical physics and psychiatry and director of PET Physics in the Waisman Laboratory for Brain Imaging and Behavior — looked at the role of the brain protein amyloid-β in adults living with Down syndrome, a genetic condition that leaves people more susceptible to developing Alzheimer’s. They published their findings in the September issue of the journal Brain.

"Our hope is to better understand the role of this protein in memory and cognitive function," says Hartley. "With this information we hope to better understand the earliest stages in the development of this disease and gain information to guide prevention and treatment efforts."

However, the findings of their study not only may help scientists better understand the condition as it impacts those living with Down syndrome, but they are also relevant to adults without the genetic syndrome.

"There are many unanswered questions about at what point amyloid-β, together with other brain changes, begins to take a toll on memory and cognition and why certain individuals may be more resistant than others," says Hartley.

The UW-Madison scientists, along with collaborators at the University of Pittsburgh, studied 63 healthy adults with Down syndrome, aged 30 to 53, who did not exhibit clinical signs of Alzheimer’s or other forms of dementia. They found that many adults with Down syndrome had high levels of amyloid-β protein but did not suffer the expected negative consequences of the elevated protein.

Alzheimer’s disease is the sixth leading cause of death in the U.S. People with Down syndrome are born with an extra copy of the 21st chromosome, where the gene that codes for the amyloid-β protein resides.

For the study, which was conducted over the course of two days, researchers used magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to capture images of the participants’ brains. Twenty-two of the 63 participants had elevated levels of amyloid-β but showed no evidence of diminished memory or cognitive function when compared to those without elevated levels of the protein. The researchers controlled for differences in age and intellectual level.

Similarly, when assessed as a continuous measure, amyloid-β levels were not tied to differences in memory or cognitive ability, such as changes in visual and verbal memory, attention and language.

Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons – a phenomenon strongly linked to autism.

(Image caption: A comparison of a dendrite with the protein NrCAM (top) and a dendrite without the protein (bottom), which has a greater density of spines that neurons use to form synaptic connections.)

The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.

“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.

Maness’s finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.

It is too early to tell if NrCAM and MTOR are linked, but Maness is now studying if the decreased amount of the NrCAM protein could trigger activation of MTOR. If so, then NrCAM, which is an accessible membrane-bound protein, might be a preferred therapeutic target for certain autism-related conditions.

In their study, Maness and her colleagues found that the NrCAM protein forms a complex with two other molecules to create a receptor on the membrane of excitatory pyramidal neurons. Maness’s team found that this receptor allows dendritic spines to retract, allowing for proper neuron pruning during maturation of the cortex. As a result, excitatory and inhibitory synapses between neurons develop in a balanced ratio necessary for brain circuits to function properly. 

Maness, a member of the UNC Neuroscience Center and the Carolina Institute for Developmental Disabilities, also said that there are likely many other proteins downstream of NrCAM that depend on the protein to maintain the proper amount of dendritic spines. Decreasing NrCAM could allow for an increase in the levels of some of these proteins, thus kick starting the creation of dendritic spines.

“Basic science in autism is converging in really exciting ways,” Maness said. “Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.”

New research from the Copenhagen Centre for Social Evolution and Yale University offers compelling support for the general evolutionary theory that birth weight and -length can partially predict the likelihood of being diagnosed with mental health disorders such as autism and schizophrenia later in life. The study analyzed medical records of 1.75 million Danish births, and subsequent hospital diagnoses for up to 30 years, and adjusted for almost all other known risk factors. The study is published today in the Proceedings of the Royal Society, London B.

The number of people diagnosed with mental health disorders is on the rise in most affluent countries, but we do not yet have a comprehensive understanding of the factors that make people vulnerable to these disorders.

A new analysis of the extensive Danish public health database suggests that part of the answer may reside in genetic imprints established at conception that influence both size at birth and mental health during childhood and early adolescence.

The study tests predictions of the evolutionary theory of genomic imprinting – the idea that during fetal development some genes inherited from the mother are expressed differently to those inherited from the father. The potential consequence of this asymmetry is that maternal and paternal genes in a fetus will not cooperate fully during this period, even though they subsequently have shared interests due to their lifetime commitment to the same body.

Opposite forces balance each other

The reason for the conflict is that some of the genes known to be expressed in the placenta and the brain carry imprints that affect resource provisioning of the unborn child. When such genes come from the father, they favor investment of more of the mother’s resources in the developing fetus, whereas the maternally-imprinted genes will normally compensate for such paternally-influenced manipulative effects to lessen the drain on maternal resources. These opposite forces balance each other in most pregnancies, with the result that most children are born with close to average length and weight and with a high likelihood of balanced mental health development.

Small deviations may well be favorable in human populations, when somewhat heavier babies are more likely to develop abstract talents and somewhat lighter babies above average social talents, for instance. However, this incurs the risk of increasing the frequency of autistic- and schizophrenic-spectrum disorders in the rare cases where imprinting imbalances are larger. The theory may explain why natural selection has not removed this portion of the burden of mental disease from our ancestors.

The new study tests these predictions and its results are remarkably consistent. They show that the change to the risk of developing mental disorders when born smaller or larger than average are relatively small, but very consistent, clearly diametrical, and part of the single continuum that the theory predicts.

“When we started this large scale analysis four years ago, we hoped to find evidence that genetic imprinting happens, but we did not expect that the results would match the predictions as consistently as we found”, explains Professor Jacobus Boomsma, Director of the Centre for Social Evolution, University of Copenhagen, who coordinated the work.

Boomsma adds: “Our study confirms that larger babies have a higher risk for incurring autism-spectrum diagnoses later in life and lower risk for schizophrenia-spectrum disorders. For example, Danish newborns are on average 52 cm long and being born at 54 cm increases the autism risk by 20%. However, these are relative risks and these disorders remain rare: in this example the absolute risk increases from 0.65% to 0.78%. Risk patterns are opposite in smaller newborns, who have higher risks for schizophrenia and lower risks for autism. Only for the smallest, prematurely-born babies does this diametric pattern disappear, because they have elevated risks for almost all disease categories”.

Evolutionary conflicts

Boomsma also underlines that focused genomic studies will be needed to find out which genes are involved and how they affect brain function: ”Our Centre’s main objective is to develop and test evolutionary theory about the ways in which gene-level conflicts can corrupt even the most sophisticated forms of naturally evolved cooperation. It is no surprise that humans are vulnerable to such deep evolutionary conflicts, as are other mammals, and it is both useful and interesting to be aware of this part of our biological heritage”, says Professor Boomsma.

New research shows that patients with fibromyalgia have hypersensitivity to non-painful events based on images of the patients’ brains, which show reduced activation in primary sensory regions and increased activation in sensory integration areas. Findings published in Arthritis & Rheumatology, a journal of the American College of Rheumatology (ACR), suggest that brain abnormalities in response to non-painful sensory stimulation may cause the increased unpleasantness that patients experience in response to daily visual, auditory and tactile stimulation.

Fibromyalgia is a chronic, musculoskeletal syndrome characterized by widespread pain, affecting roughly two percent of the world population, say experts. According to the ACR, five million people in the U.S. have fibromyalgia, which is more prevalent among women. In previous studies fibromyalgia patients report reduced tolerance to normal sensory (auditory, visual, olfactory, and tactile) stimulation in addition to greater sensitivity to pain.

For the present study, researchers used functional magnetic resonance imaging (fMRI) to assess brain response to sensory stimulation in 35 women with fibromyalgia and 25 healthy, age-matched controls. Patients had an average disease duration of 7 years and a mean age of 47.

According to the study, patients reported increased unpleasantness in response to multisensory stimulation in daily life activities. Furthermore, fMRI displayed reduced activation of both the primary and secondary visual and auditory areas of the brain, and increased activation in sensory integration regions. These brain abnormalities mediated the increased unpleasantness to visual, auditory and tactile stimulation that patients reported to experience in daily life.

Lead study author, Dr. Marina López-Solà from the Institute of Cognitive Science, University of Colorado Boulder said, “Our study provides new evidence that fibromyalgia patients display altered central processing in response to multisensory stimulation, which are linked to core fibromyalgia symptoms and may be part of the disease pathology. The finding of reduced cortical activation in the visual and auditory brain areas that were associated with patient pain complaints may offer novel targets for neurostimulation treatments in fibromyalgia patients.”

Using advanced computer models, neuroscience researchers at the University of Copenhagen have gained new knowledge about the complex processes that cause Parkinson’s disease. The findings have recently been published in the prestigious Journal of Neuroscience.

The defining symptoms of Parkinson’s disease are slow movements, muscular stiffness and shaking. There is currently no cure for the condition, so it is essential to conduct innovative research with the potential to shed some light on this terrible disruption to the central nervous system that affects one person in a thousand in Denmark.

Dopamine is an important neurotransmitter which affects physical and psychological functions such as motor control, learning and memory. Levels of this substance are regulated by special dopamine cells. When the level of dopamine drops, nerve cells that constitute part of the brain’s ‘stop signal’ are activated.

“This stop signal is rather like the safety lever on a motorised lawn mower: if you take your hand off the lever, the mower’s motor stops. Similarly, dopamine must always be present in the system to block the stop signal. Parkinson’s disease arises because for some reason the dopamine cells in the brain are lost, and it is known that the stop signal is being over-activated somehow or other. Many researchers have therefore considered it obvious that long-term lack of dopamine must be the cause of the distinctive symptoms that accompanies the disease. However, we can now use advanced computer simulations to challenge the existing paradigm and put forward a different theory about what actually takes place in the brain when the dopamine cells gradually die,” explains Jakob Kisbye Dreyer, Postdoc at the Department of Neuroscience and Pharmacology, University of Copenhagen.

A thorn in the side

Scanning the brain of a patient suffering from Parkinson’s disease reveals that in spite of dopamine cell death, there are no signs of a lack of dopamine – even at a comparatively late stage in the process.

“The inability to establish a lack of dopamine until advanced cases of Parkinson’s disease has been a thorn in the side of researchers for many years. On the one hand, the symptoms indicate that the stop signal is over-activated, and patients are treated accordingly with a fair degree of success. On the other hand, data prove that they are not lacking dopamine,” says Postdoc Jakob Kisbye Dreyer.

Computer models predict the progress of the disease

“Our calculations indicate that cell death only affects the level of dopamine very late in the process, but that symptoms can arise long before the level of the neurotransmitter starts to decline. The reason for this is that the fluctuations that normally make up a signal become weaker. In the computer model, the brain compensates for the shortage of signals by creating additional dopamine receptors. This has a positive effect initially, but as cell death progresses further, the correct signal may almost disappear. At this stage, the compensation becomes so overwhelming that even small variations in the level of dopamine trigger the stop signal – which can therefore cause the patient to develop the disease.”

The new research findings may pave the way for earlier diagnosis of Parkinson’s disease.