Neuroscience

A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year follow-up study compared to men who were not diagnosed with the condition. The study appears in the May 20 online edition of Pediatrics.

“Few studies have focused on long-term outcomes for patients diagnosed with ADHD in childhood. In this study, we wanted to assess the health outcomes of children diagnosed with ADHD, focusing on obesity rates and Body Mass Index,” said lead author Francisco Xavier Castellanos, MD, Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry, Child Study Center at NYU Langone. “Our results found that even when you control for other factors often associated with increased obesity rates such as socioeconomic status, men diagnosed with ADHD were at a significantly higher risk to suffer from high BMI and obesity as adults.”

According to the Centers for Disease Control and Prevention, ADHD is one of the most common neurobehavioral disorders, often diagnosed in childhood and lasting into adulthood. People with ADHD typically have trouble paying attention, controlling impulsive behaviors and tend to be overly active. ADHD has an estimated worldwide prevalence of five percent, with men more likely to be diagnosed than women.

The prospective study included 207 white men diagnosed with ADHD at an average age of 8 and a comparison group of 178 men not diagnosed with childhood ADHD, who were matched for race, age, residence and social class. The average age at follow up was 41 years old. The study was designed to compare Body Mass Index (BMI) and obesity rates in grown men with and without childhood ADHD.

Results showed that, on average, men with childhood ADHD had significantly higher BMI (30.1 vs. 27.6) and obesity rates (41.1 percent vs. 21.6 percent) than men without childhood ADHD.

“The results of the study are concerning but not surprising to those who treat patients with ADHD. Lack of impulse control and poor planning skills are symptoms often associated with the condition and can lead to poor food choices and irregular eating habits,” noted Dr. Castellanos. “This study emphasizes that children diagnosed with ADHD need to be monitored for long-term risk of obesity and taught healthy eating habits as they become teenagers and adults.”

Imaging technique shows premature birth interrupts vital brain development processes, leading to reduced cognitive abilities in infants

Researchers from King’s College London have for the first time used a novel form of MRI to identify crucial developmental processes in the brain that are vulnerable to the effects of premature birth. This new study, published today in the Proceedings of the National Academy of Sciences (PNAS), shows that disruption of these specific processes can have an impact on cognitive function.

The researchers say the new techniques developed here will enable them to explore how the disruption of key processes can also cause conditions such as autism, and will be used in future studies to test possible treatments to prevent brain damage.

Scientists from King’s College London and Imperial College London used diffusion MRI – a type of imaging which looks at the natural diffusion of water – to observe the maturation of the cerebral cortex where much of the brain’s computing power resides. By analysing the diffusion of water in the cerebral cortex of 55 premature infants and 10 babies born at full term they mapped the growing complexity and density of nerve cells across the whole of the cortex in the months before the normal time of birth.

They found that during this period maturation was most rapid in areas of the brain relating to social and emotional processing, decision making, working memory and visual-spatial processing. These functions are often impaired after premature birth, and the researchers found that cortical development was reduced in preterm compared to full term infants, with the greatest effect in the most premature infants. When they re-examined the infants at two years of age, the preterm infants with the slowest cortical development performed less well on neurodevelopmental testing, demonstrating the longer-term impact of prematurity on cortical maturation.

Professor David Edwards, Director of the Centre for the Developing Brain at King’s, based at the Evelina Children’s Hospital, said: ‘The number of babies born prematurely is increasing, so it has never been more important to improve our understanding of how preterm birth affects brain development and causes brain damage. We know that prematurity is extremely stressful for an infant, but by using a new technique we are able to track brain maturation in babies to pinpoint the exact processes that might be affected by premature birth. Here we have used innovative ways to understand how the development of the cerebral cortex is affected.

‘These findings highlight a key stage of brain development where the neurons branch out to create a complex, mature structure. We can now see that this happens in the latter stages of development that would usually take place in healthy babies when they are still in the womb. This suggests that premature birth can interrupt this vital developmental process. It may explain why we sometimes see adverse effects on brain development in those born only slightly prematurely as we now know that this process is happening right up to the normal time of birth. With this study we found that the earlier a baby is born, the less mature the cortex structure. The weeks a baby loses in the womb really matter.

‘These new techniques we’ve developed to identify these crucial processes will allow us to examine how disruption caused by premature birth can lead to conditions such as autism and learning difficulties. We will also use the technique in future studies to test new treatments to prevent brain damage. It’s an extremely exciting step forward.’

While Huntington’s disease (HD) is currently incurable, the HD research community anticipates that new disease-modifying therapies in development may slow or minimize disease progression. The success of HD research depends upon the identification of reliable and sensitive biomarkers to track disease and evaluate therapies, and these biomarkers may eventually be used as outcome measures in clinical trials. Biomarkers could be especially helpful to monitor changes during the time prior to diagnosis and appearance of overt symptomatology. Three reports in the current issue of the Journal of Huntington’s Disease explore the potential of neuroimaging, proteomic analysis of brain tissue, and plasma inflammatory markers as biomarkers for Huntington’s disease.

"Characteristics of an ideal biomarker include quantification which is reliable, reproducible across sites, minimally invasive and widely available. The biomarker should show low variability in the normal population and change linearly with disease progression, ideally over short time intervals. Finally, the biomarker should respond predictably to an intervention which modifies the disease," says Elin Rees, researcher at UCL Institute of Neurology, London.

In the first report, Rees and colleagues explore the use of neuroimaging biomarkers. She says they are strong candidates as outcome measures in future clinical trials because of their clear relevance to the neuropathology of disease and their increased precision and sensitivity compared with some standard functional measures. This review looks at results from longitudinal imaging studies, focusing on the most widely available imaging modalities: structural MRI (volumetric and diffusion), functional MRI, and PET.

"All imaging modalities are logistically complicated and expensive compared with standard clinical or cognitive end-points and their sensitivity is generally reduced in individuals with later stage HD due to movement," says Rees. "Nevertheless, imaging has several advantages including the ability to track progression in the pre-manifest stage before any detectable clinical or cognitive change."

Current evidence suggests that the best neuroimaging biomarkers are structural MRI and PET using [11C] raclopride (RACLO-PET) as the tracer, in order to assess changes in the basal ganglia, especially the caudate.

A study led by Garth J.S. Cooper, PhD, professor of Biochemistry and Clinical Biochemistry at the School of Biological Sciences and the Department of Medicine at the University of Auckland, used comparative proteome analysis to identify how protein expression might correlate with Huntington’s neurodegeneration in two regions of human brain: the middle frontal gyrus (MFG) and the visual cortex (VC). The investigators studied post mortem human brain tissue from seven HD brains and eight matched controls. They found that the MFG of HD brains differentially expressed 22 proteins compared to controls, while only seven were different in the VC. Several of these proteins had not been linked to HD previous. Investigators categorized these proteins into six general functional categories: stress response, apoptosis, glycolysis, vesicular trafficking, and endocytosis. They determined that there is a common thread in the degenerative processes associated with HD, Alzheimer’s disease, and diabetes.

The third report explores the possibility that inflammatory markers in plasma can be used to track HD, noting that immune changes are apparent even during the preclinical stage. “The innate immune system orchestrates an inflammatory response involving complex interactions between cytokines, chemokines and acute phase proteins and is thus a rich source of potential biomarkers,” says Maria Björkqvist, PhD, head of the Brain Disease Biomarker Unit, Department of Experimental Science of Lund University, Sweden.

The authors compare plasma levels of several markers involved in inflammation and innate immunity of healthy controls and HD patients at different stages of disease. Two methods were used to analyze plasma: antibody-based technologies and multiple reaction monitoring (MRM).

None of the measures were significantly altered in both HD cohorts tested and none correlated with HD disease stage. Only one substance, C-reactive protein (CRP), was decreased in early HD – but this was found in only one of the two cohorts, so the finding may not be reliable. The investigators were unable to confirm other studies that had found HD-related changes in other inflammatory markers, including components of the complement system.

Some markers correlated with clinical measures. For instance, ApoE was positively correlated with depression and irritability scores, suggesting an association between ApoE and mood changes.

Even though recent data suggest that the immune system is likely to be a modifier of HD disease, inflammatory proteins do not seem to be likely candidates to be biomarkers for HD. “Many proteomic studies designed to provide potential biomarkers of disease have generated significant findings, however, often these biomarkers fail to replicate during the validation process,” says Björkqvist.

In 1979 China instituted the one-child policy, which limited every family to just one offspring in a controversial attempt to reduce the country’s burgeoning population. The strictly enforced law had the desired effects: in 2011 researchers estimated that the policy prevented 400 million births. In a new study in Science, researchers find that it has also caused China’s so-called little emperors to be more pessimistic, neurotic and selfish than their peers who have siblings.

Psychologist Xin Meng of the Australian National University in Canberra and her colleagues recruited 421 Chinese young adults born between 1975 and 1983 from around Beijing for a series of surveys and tests that evaluated a variety of psychological traits, such as trustworthiness and optimism. Almost all the participants born after 1979 were only children compared with about one fifth of those born before 1979. The study participants born after the policy went into effect were found to be both less trusting and less trustworthy, less inclined to take risks, less conscientious and optimistic, and less competitive than those born a few years earlier.

“Because of the one-child policy, parents are less likely to teach their child to be imaginative, trusting and unselfish,” Meng says. Without siblings, she notes, the need to share may not be emphasized, which could help explain these findings.

Only children in other parts of the world, however, do not show such striking differences from their peers. Toni Falbo, a social psychologist at the University of Texas at Austin, who was not involved in the study, suggests that larger social forces in China also probably contributed to these results. “There’s a lot of pressure being placed on [Chinese] parents to make their kid the best possible because they only had one,” Falbo says. These types of pressures could harm anyone, even if they had siblings, she says.

Whatever its cause, the personality profile of China’s little emperors may be troubling to a nation hoping to continue its ascent in economic prosperity. The traits marred by the one-child policy, the study authors point out, are exactly those needed in leaders and entrepreneurs.

The mental fuzziness induced by cancer treatment could be eased by cognitive exercises performed online, say researchers.

Cancer survivors sometimes suffer from a condition known as “chemo fog”—a cognitive impairment caused by repeated chemotherapy. A study hints at a controversial idea: that brain-training software might help lift this cognitive cloud.

Various studies have concluded that cognitive training can improve brain function in both healthy people and those with medical conditions, but the broader applicability of these results remains controversial in the field.

In a study published in the journal Clinical Breast Cancer, investigators report that those who used a brain-training program for 12 weeks were more cognitively flexible, more verbally fluent, and faster-thinking than survivors who did not train.

Patients treated with chemotherapy show changes in brain structure and function in line with diffuse brain injury, and they often report long-term cognitive effects, says Shelli Kesler, a Stanford University clinical neuropsychologist who led the research. The new study “suggests that cognitive training could be one possible avenue for helping to improve cognitive function in breast cancer survivors treated with chemotherapy,” she says.

The results may not convince everyone. “One of the biggest challenges in the cognitive training world is to show an effect that generalizes to real-world functioning,” says Susan Landau, a neuroscientist at the University of California, Berkeley. Several companies offer commercial cognitive training programs that promise improvements in memory, attention, mental agility, and problem-solving skills. The appeal is clear, says Zach Hambrick, a psychologist at Michigan State University in East Lansing, but whether they have lasting general effects is not.

The fact that companies are marketing these training programs to customers before their value has been rigorously proved has caused some skepticism in the field, say experts. “The field is still growing,” says Suzanne Jaeggi, a neuropsychologist at the University of Maryland. While studies have shown that there are cognitive benefits to the training, it’s very hard to detect an impact on daily life, she says. However, some work, including research by her own group, has shown that working memory exercises can improve reading abilities in schoolchildren.

In the study conducted by Kesler and colleagues, the participants trained at home on Lumosity, a collection of gamelike cognitive exercises developed by Lumos Labs in San Francisco. (Lumos Labs did not fund the study.)

Kesler’s project is one of around two dozen efforts using Lumosity software to study human cognition. With 35 million customers worldwide, Lumosity is collecting what it says is the world’s largest database of human cognition, which could be queried for connections between lifestyle and cognitive ability. “Our technology collects a lot of data and makes it easy to run experiments to learn more generally about human cognitive performance,” says Mike Scanlon, cofounder of Lumos Labs. “We track all of the results from the cognitive testing and training, and we can combine that with demographic information to learn about how people’s cognitive performance changes and develops over the years.”

One such finding, he says, is a correlation between outside weather temperature and cognitive performance: “It turned out that the colder it is, the higher people’s performance is, even though generally they are inside doing this on a computer.”

Most of the scientific projects involving Lumosity’s software are exploring the effectiveness of brain training in different populations, from schoolchildren to stroke patients. For the study on breast cancer survivors, 41 women aged 40 and older, who were at least a year and half past their last chemotherapy treatment, were tested on several cognitive tasks at the beginning of the study. Then half the women used Lumosity training modules for 20 to 30 minutes four times a week for 12 weeks, and all were tested again.

When the investigators tested the participants in verbal memory, processing speed, and cognitive function, they found that the women who had used the brain training program improved in three of five objective measures.

“This is a well-done study—they had not just one transfer test but several,” says Hambrick, who notes that many studies of cognitive training depend on a single test to measure results. “But an issue is the lack of activity within the control group.” Better would be to have the control group do another demanding cognitive task in lieu of Lumosity training—something analogous to a placebo, he says: “The issue is that maybe the improvement in the group that did the cognitive training doesn’t reflect enhancement of basic cognitive processes per se, but could be a motivational phenomenon.”

Even if the effects are due to motivation or some other benefit not related to mental agility, that’s still useful, says Landau. “If [cognitive training] is something that makes people feel good and improves their confidence in their own skills, that’s not trivial at all,” she says. “That could be a big part of the effect that’s observed.”

Working with lab mice models of multiple sclerosis (MS), UC Davis scientists have detected a novel molecular target for the design of drugs that could be safer and more effective than current FDA-approved medications against MS.

The findings of the research study, published online today in the journal EMBO Molecular Medicine could have therapeutic applications for MS as well as cerebral palsy and leukodystrophies, all disorders associated with loss of white matter, which is the brain tissue that carries information between nerve cells in the brain and the spinal cord.

The target, a protein referred to as mitochondrial translocator protein (TSPO), had been previously identified but not linked to MS, an autoimmune disease that strips the protective fatty coating off nerve fibers of the brain and spinal cord. The mitrochronical TSPO is located on the outer surface of mitochondria, cellular structures that supply energy to the cells. Damage to the fatty coating, or myelin, slows the transmission of the nerve signals that enable body movement as well as sensory and cognitive functioning.

The scientists identified mitochondrial TSPO as a potential therapeutic target when mice that had symptoms of MS improved after being treated with the anti-anxiety drug etifoxine, which interacts with mitochondrial TSPO. When etifoxine, a drug clinically available in Europe, was administered to the MS mice before they had clinical signs of disease, the severity of the disease was reduced when compared to the untreated lab animals. When treated at the peak of disease severity, the animals’ MS symptoms improved.

“Etifoxine has a novel protective effect against the loss of the sheath that insulates the nerve fibers that transmit the signals from brain cells,” said Wenbin Deng, principal investigator of the study and associate professor of biochemistry and molecular medicine at UC Davis.

“Our discovery of etifoxine’s effects on an MS animal model suggests that mitochondrial TSPO represents a potential therapeutic target for MS drug development,” said Deng.

“Drugs designed to more precisely bind to mitochondrial TSPO may help repair the myelin sheath of MS patients and thereby even help restore the transmission of signals in the central nervous system that enable normal motor, sensory and cognitive functions,” he said.

Deng added that better treatments for MS and other demyelinating diseases are needed, especially since current FDA-approved therapies do not repair the damage of immune attacks on the myelin sheath. 

The UC Davis research team hopes to further investigate the therapeutic applications of mitochondrial TSPO in drug development for MS and other autoimmune diseases. To identify more efficacious and safer drug candidates, they plan to pursue research grants that will enable them to test a variety of pharmacological compounds that bind to mitochondrial TSPO and other molecular targets in experimental models of MS and other myelin diseases.

In the first successful experiment with humans using a treatment known as sensory-motor or environmental enrichment, researchers documented marked improvement in young autistic boys when compared to boys treated with traditional behavioral therapies, according to research published by the American Psychological Association.

The rationale for the new treatment is rooted in the fact that autistic children typically have sensory problems, the most common involving smell and touch sensitivity. Building on decades of work in animals documenting the profound effects of environmental enrichment on behavioral and neurological outcomes, the authors of the study predicted that similar enrichment in autistic children would have beneficial effects.

“Because parents can give their child sensory enrichment using items typically available in their home, this therapy provides a low-cost option for enhancing their child’s progress,” said study co-author Cynthia C. Woo, PhD, a project scientist at the University of California Irvine.

The study, which was published online in the APA journal Behavioral Neuroscience, involved 28 autistic boys, ages 3 to 12. Researchers placed the boys in two groups based on their age and autism severity. For six months, both groups participated in standard behavioral therapy but boys in one of the groups also underwent daily environmental enrichment exercises.

Parents of each of the 13 boys in the enrichment group received a kit that contained essential oil fragrances such as apple, lavender, lemon and vanilla to stimulate sense of smell. For touch, the kit contained squares of plastic doormat, smooth foam, a rubber sink mat, aluminum, fine sandpaper, felt and sponges. The kit also included pieces of carpet, hard flooring, pillows, cardboard and bubble wrap that parents laid on the floor to create a multi-textured walking path. Items for the children to manipulate included a piggy bank with plastic coins, miniature plastic fruits and a small fishing pole with a magnetic hook. Many household items were also used, such as bowls for holding water at different temperatures for the child to dip in a hand or foot and metal spoons that parents would warm or cool and touch to the child’s skin.

Researchers instructed the parents of children in the enrichment group to conduct two sessions a day of four to seven exercises involving different combinations of sensory stimuli for touch, temperature, sight and movement. Each session took 15 to 30 minutes to complete. The children also listened to classical music once a day.

Following six months of therapy, 42 percent of the children in the enrichment group significantly improved in behaviors such as relating to people and responding to sights and sounds, compared to 7 percent of the standard care group, according to the study. The children in the enrichment group also improved on scores for cognitive function, which covers aspects of perception and reasoning, whereas the average scores for the children in the standard care group decreased. In addition, 69 percent of parents in the enrichment group reported improvement in their child’s overall autism symptoms, compared to 31 percent of parents of the standard care group, the authors wrote.

“Sensory enrichment may well be an effective therapy for the treatment of autism, particularly in children much past the toddler stage,” said study co-author Michael Leon, PhD, a professor of neurobiology and behavior with the University of California Irvine.

“This is an exciting study for several reasons,” said Mark Blumberg, PhD, editor of Behavioral Neuroscience. “It is well designed, it builds on established findings from numerous experiments using non-human animals and it addresses the critical need to find effective treatments for autism. The obvious next step has to be replication of these results in a larger-scale study.”

Before the experiment, most of the children in both groups were undergoing the standard treatment for autism, applied behavior analysis, which typically involves 25 to 40 hours a week with a trained professional for a number of years, the study said. Some children in both groups were also undergoing speech therapy, social skills therapy, physical therapy for fine motor skills or occupational therapy with different types of exercises. Most current therapies for autism must be started at a very young age to be effective, whereas environmental enrichment worked for boys at least to age 12, the study said.

The researchers are now conducting a larger randomized clinical trial that includes girls. Another important next step will be to test environmental enrichment therapy when a child is not also receiving other standard treatments, the authors noted.

A study led by researchers from Plymouth University Peninsula Schools of Medicine and Dentistry has for the first time revealed how the loss of a particular tumour suppressing protein leads to the abnormal growth of tumours of the brain and nervous system.

The study is published in Brain: A Journal of Neurology.

Tumour suppressors exist in cells to prevent abnormal cell division in our bodies. The loss of a tumour suppressor called Merlin leads to tumours in many cell types within our nervous systems. There are two copies of a tumour suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin can be caused by random loss of both copies in a single cell, causing sporadic tumours, or by inheriting one abnormal copy and losing the second copy throughout our lifetime as is seen in the inherited condition of neurofibromatosis type 2 (NF2).

With either sporadic loss or inherited NF2, these tumours lacking the Merlin protein develop in the Schwann cells that form the sheaths that surround and electrically insulate neurons. These tumours are called schwannomas, but tumours can also arise in the cells that form the membrane around the brain and spinal cord, and the cells that line the ventricles of the brain.

Although the schwannomas are slow-growing and benign, they are frequent and come in numbers. The sheer number of tumours caused by this gene defect can overwhelm a patient, often leading to hearing loss, disability and eventually death. Patients can suffer from 20 to 30 tumours at any one time, and the condition typically manifests in the teenage years and through into adulthood.

No effective therapy for these tumours exists, other than repeated invasive surgery or radiotherapy aiming at a single tumour at a time and which is unlikely to eradicate the full extent of the tumours.

The Brain study investigated how loss of a protein called Sox10 functions in causing these tumours. Sox10 is known to play a major role in the development of Schwann cells, but this is the first time it has been shown to be involved in the growth of schwannoma tumour cells. By understanding the mechanism, the research team has opened the way for new therapies to be developed that will provide a viable to alternative to surgery or radiotherapy.

The study, undertaken by researchers from Plymouth University Peninsula Schools of Medicine and Dentistry with colleagues from the State University of New York and Universitat Erlangen-Nurmberg, was led by Professor David Parkinson.

He said: “We have for the first time shown that human schwannoma cells have reduced expression of Sox10 protein and messenger RNA. By identifying this correlation and gaining an understanding of the mechanism of this process, we hope that drug-based therapies may in time be created and introduced that will reduce or negate the need for multiple surgery or radiotherapy.”

Investigation by researchers from the University of Exeter and ETH Zurich has shed new light on a protein which is linked to a common neurological disorder called Charcot-Marie-Tooth disease.

Peroxisomes (green) and mitochondria (red) in a mammalian cell. The nucleus (blue) contains the cellular DNA.

The team has discovered that a protein previously identified on mitochondria - the energy factories of the cell - is also found on the fat-metabolising organelles peroxisomes, suggesting a closer link between the two organelles.

Charcot-Marie-Tooth disease is currently incurable and affects around one in every 2,500 people in the UK, meaning that it is one of the most common inherited neurological disorders, thus understanding the molecular basis of the disease is of great importance. Symptoms can range from tremors and loss of touch sensation in the feet and legs to difficulties with breathing, swallowing, speaking, hearing and vision.

The research published online in EMBO Reports combines work from University of Exeter Biosciences researcher Dr Michael Schrader and PhD student Sofia Guimaraes. The major finding of the study is that the protein GDAP1, originally thought to only be involved in fragmentation of mitochondria, also contributes to the regulation of peroxisome number through their division.

Peroxisomes are small organelles occurring in nearly all cells, from yeast to crop plants to humans, and are essential for cell viability due to their important role in the metabolism of fatty acids and reactive oxygen species. Peroxisomes are also of particular interest as they play a key role in ageing.

This current study shows that the division of both mitochondria and peroxisomes follows a similar mechanism, although many of the disease-causing mutations occur in a region of the gene that is more critical for mitochondrial than peroxisomal division.

Dr Michael Schrader said of this project: “This study supports our hypothesis of a closer connection between mitochondria and peroxisomes. We have identified several membrane proteins, which are shared by both organelles, particularly key components of the division machinery, meaning there must be coordinated biogenesis and cross-talk.”

As numerous diseases have been linked to problems in the mitochondria, Dr Schrader proposes that this connection could have far-reaching medical implications.

This work contributes to the research being addressed through the prestigious Marie Curie Initial Training Network PERFUME programme (PERoxisome, FUnction, and MEtabolism), recently awarded to Michael Schrader along with several other top European research groups which focus on peroxisome biology.

Our researchers have found a previously undiscovered link between epileptic seizures and the signs of autism in adults.

Dr SallyAnn Wakeford from the Department of Psychology revealed that adults with epilepsy were more likely to have higher traits of autism and Asperger syndrome.

Characteristics of autism, which include impairment in social interaction and communication as well as restricted and repetitive interests, can be severe and go unnoticed for many years, having tremendous impact on the lives of those who have them.

The research found that epileptic seizures disrupt the neurological function that affects social functioning in the brain resulting in the same traits seen in autism.

Dr Wakeford said: “The social difficulties in epilepsy have been so far under-diagnosed and research has not uncovered any underlying theory to explain them. This new research links social difficulties to a deficit in somatic markers in the brain, explaining these characteristics in adults with epilepsy.”

Dr Wakeford and her colleagues discovered that having increased autistic traits was common to all epilepsy types, however, this was more pronounced for adults with Temporal Lobe Epilepsy (TLE).

The researchers suggest that one explanation may be because anti-epileptic drugs are often less effective for TLE. The reason why they suspect these drugs are implicated is because they were strongly related to the severity of autistic characteristics.

Dr Wakeford carried out a comprehensive range of studies with volunteers with epilepsy and discovered that all of the adults with epilepsy showed autism traits.

She said: “It is unknown whether these adults had a typical developmental period during childhood or whether they were predisposed to having autistic traits before the onset of their epilepsy. However what is known is that the social components of autistic characteristics in adults with epilepsy may be explained by social cognitive differences, which have largely been unrecognised until now.”

Dr Wakeford said the findings could lead to improved treatment for people with epilepsy and autism. She said: “Epilepsy has a history of cultural stigma, however the more we understand about the psychological consequences of epilepsy the more we can remove the stigma and mystique of this condition.

“These findings could mean that adults with epilepsy get access to better services, as there is a wider range of treatments available for those with autism condition.”

Margaret Rawnsley, research administration officer at Epilepsy Action welcomed the findings.

She said: “We welcome any research that could further our understanding of epilepsy and ultimately improve the lives of those with the condition. This research has the potential to tell us more about the links between epilepsy and other conditions, such as autism spectrum disorders.”

Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.

Ultrasound consists of mechanical vibrations, like sound, but with frequencies far greater than the upper limit of human hearing, around 20 thousand to 20 million cycles per second (20 kilohertz to 20 megahertz). Ultrasound vibrations penetrate bodily tissue including bone, and are widely used to image anatomical structures via echo effects, e.g. visualizing unborn babies in mothers’ wombs, and organs, blood vessels, nerves and other structures in medical procedures. Virtually every part of the body, including the brain, has been safely imaged with low to moderate intensity ultrasound.

High intensity, focused ultrasound can damage tissue by heating and cavitation, and has been used to ablate tumors and other lesions. ‘Sub-thermal’ ultrasound can safely stimulate neural tissue. In 2002 a UCLA group led by Alexander Bystritsky noticed beneficial side effects in psychiatric patients whose brains were imaged by TUS. A team led by Virginia Tech’s W. Jamie Tyler has shown TUS-induced behavioral and electrophysiological changes in animals. A Harvard group led by S-S Yoo has used focused ultrasound aimed at mouse motor cortex to wag the mouse’s tail. But clinical trials of TUS aimed at human mental states have been lacking.

Now, in an article in the journal Brain Stimulation, a group from the Departments of Anesthesiology and Radiology at the University of Arizona Medical Center in Tucson, Arizona has investigated TUS for modulating mental states in a pilot study in human volunteers suffering from chronic pain. A clinical ultrasound imaging device (General Electric LOGIQe) was used, with the ultrasound probe applied at the scalp overlying the brain’s temporal and frontal cortex (visible on the imaging screen). In random order, each subject received two 15 second exposures: sham/placebo, and 8 megahertz ultrasound (undetectable to subjects). Following exposure, subjects reported (by visual analog scales) significant improvement in mood both 10 minutes and 40 minutes after TUS, but not after sham/placebo. In a followup study (led by University of Arizona psychologists Jay Sanguineti and John JB Allen) preliminary results suggest 2 megahertz TUS (which traverses skull more readily) may be more effective in mood enhancement than 8 megahertz TUS.

The mechanism by which TUS can affect mental states is unknown (as is the mechanism by which the brain produces mental states). Tyler proposed TUS acts by vibrational stretching of neuronal membranes and/or extracellular matrix, but two recent papers from the group of Anirban Bandyopadhyay at National Institute of Material Sciences (NIMS) in Tsukuba, Japan (Sahu et al. [2013] Appl. Phys. Letts.; Sahu et al [2013] Biosensors and Bioelectronics) have suggested another possibility. The NIMS group used nanotechnology to study conductive properties of individual microtubules, protein polymers of tubulin (the brain’s most prevalent protein). Major components of the neuronal cytoskeleton, microtubules grow and extend neurons, form and regulate synapses, are disrupted in Alzheimer’s disease, and theoretically linked to information processing, memory encoding and mental states. Bandyopadhyay’s NIMS group found that microtubules have remarkable electronic conductive properties when excited at certain specific resonant frequencies, e.g. in the low megahertz, precisely the range of TUS.

Dr. Stuart Hameroff, lead author on the new TUS study, said: “This suggests TUS may stimulate natural megahertz resonances in brain microtubules, enhancing not only mood and conscious mental states, but perhaps also microtubule functions in synaptic plasticity, nerve growth and repair. We plan further studies of TUS on traumatic brain injury, Alzheimer’s disease and post-traumatic stress disorders. ‘Tuning the tubules’ may help a variety of mental states and cognitive disorders.”

The instability of “white matter” in humans may contribute to greater cognitive decline during the aging of humans compared with chimpanzees, scientists from Yerkes National Primate Research Center, Emory University have found.

Yerkes scientists have discovered that white matter — the wires connecting the computing centers of the brain — begins to deteriorate earlier in the human lifespan than in the lives of aging chimpanzees.

This was the first examination of white matter integrity in aging chimpanzees. The results were published April 24 and are available online before print in the journal Neurobiology of Aging.

"Our study demonstrates that the price we pay for greater longevity than other primates may be the unique vulnerability of humans to neurodegenerative disease," says research associate Xu (Jerry) Chen, first author of the paper. “The breakdown of white matter in later life could be part of that vulnerability.” 

Both humans’ longer life spans and distinctive metabolism could lie behind the differences in the patterns of brain aging, says co-author Todd Preuss, PhD, associate research professor in Yerkes’ Division of Neuropharmacology and Neurologic Diseases.

“White matter integrity actually peaks around the same absolute age in both chimpanzees and humans, but humans may experience more degradation because they live longer. Perhaps the need to retain brain capacity late in life is one reason increased brain size was selected for in human evolution,” Preuss says.  

The senior author is James Rilling, PhD, Yerkes researcher, associate professor of anthropology at Emory and director of the Laboratory for Darwinian Neuroscience. Collaborators at the University of Oslo also contributed to the paper.

In the brain, gray matter represents information processing centers, while white matter represents wires connecting these centers. White matter looks white because it is made up of myelin, a fatty electrical insulator that coats the axons of neurons.

If myelin deteriorates, neurons’ electrical signals are not transmitted as effectively, which contributes to cognitive decline. Myelin breakdown has been linked with cognitive decline both in healthy aging and in the context of Alzheimer’s disease.

The team’s data show that white matter integrity, as measured through a form of magnetic resonance imaging (MRI), peaks at age 31 in chimpanzees and at age 30 in humans. The average lifespan of chimpanzees is between 40 to 45 years, although in zoos or research facilities some have lived until 60. For comparison, human life expectancy in some developed countries is more than 80 years.

"The human equivalent of a 31 year old chimpanzee is about 47 years," Rilling says. "Extrapolating from chimpanzees, we could expect that human white matter integrity would peak at age 47, but instead it peaks and begins to decline at age 30."

The researchers collected MRI scans from 32 female chimpanzees and 20 female rhesus macaques and compared them with a pre-existing set of scans from human females. They used diffusion-weighted imaging (a form of MRI) to examine age-related changes in white matter integrity.

Diffusion-weighted imaging picks up microscopic changes in white matter by detecting directional differences in the ability of water molecules to diffuse. When the myelin coating of axons breaks down, water molecules in the brain can diffuse more freely, especially in directions perpendicular to axon bundles, Chen says.

Scientists at Washington University School of Medicine in St. Louis have helped identify many of the biomarkers for Alzheimer’s disease that could potentially predict which patients will develop the disorder later in life. Now, studying spinal fluid samples and health data from 201 research participants at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, the researchers have shown the markers are accurate predictors of Alzheimer’s years before symptoms develop.

“We wanted to see if one marker was better than the other in predicting which of our participants would get cognitive impairment and when they would get it,” said Catherine Roe, PhD, research assistant professor of neurology. “We found no differences in the accuracy of the biomarkers.”

The study, supported in part by the National Institute on Aging, appears in Neurology.

The researchers evaluated markers such as the buildup of amyloid plaques in the brain, newly visible thanks to an imaging agent developed in the last decade; levels of various proteins in the cerebrospinal fluid, such as the amyloid fragments that are the principal ingredient of brain plaques; and the ratios of one protein to another in the cerebrospinal fluid, such as different forms of the brain cell structural protein tau.

The markers were studied in volunteers whose ages ranged from 45 to 88. On average, the data available on study participants spanned four years, with the longest recorded over 7.5 years.

The researchers found that all of the markers were equally good at identifying subjects who were likely to develop cognitive problems and at predicting how soon they would become noticeably impaired.

Next, the scientists paired the biomarkers data with demographic information, testing to see if sex, age, race, education and other factors could improve their predictions.

“Sex, age and race all helped to predict who would develop cognitive impairment,” Roe said. “Older participants, men and African Americans were more likely to become cognitively impaired than those who were younger, female and Caucasian.”

Roe described the findings as providing more evidence that scientists can detect Alzheimer’s disease years before memory loss and cognitive decline become apparent.

“We can better predict future cognitive impairment when we combine biomarkers with patient characteristics,” she said. “Knowing how accurate biomarkers are is important if we are going to some day be able to treat Alzheimer’s before symptoms and slow or prevent the disease.”

Clinical trials are already underway at Washington University and elsewhere to determine if treatments prior to symptoms can prevent or delay inherited forms of Alzheimer’s disease. Reliable biomarkers for Alzheimer’s should one day make it possible to test the most successful treatments in the much more common sporadic forms of Alzheimer’s.