Neuroscience

An imaging study by Stanford University School of Medicine investigators has found distinct differences between the brains of patients with chronic fatigue syndrome and those of healthy people.

The findings could lead to more definitive diagnoses of the syndrome and may also point to an underlying mechanism in the disease process.

It’s not uncommon for CFS patients to face several mischaracterizations of their condition, or even suspicions of hypochondria, before receiving a diagnosis of CFS. The abnormalities identified in the study, published Oct. 29 in Radiology, may help to resolve those ambiguities, said lead author Michael Zeineh, MD, PhD, assistant professor of radiology.

“Using a trio of sophisticated imaging methodologies, we found that CFS patients’ brains diverge from those of healthy subjects in at least three distinct ways,” Zeineh said.

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

Scientific challenge

“CFS is one of the greatest scientific and medical challenges of our time,” said the study’s senior author, Jose Montoya, MD, professor of infectious diseases and geographic medicine. “Its symptoms often include not only overwhelming fatigue but also joint and muscle pain, incapacitating headaches, food intolerance, sore throat, enlargement of the lymph nodes, gastrointestinal problems, abnormal blood-pressure and heart-rate events, and hypersensitivity to light, noise or other sensations.”

The combination of symptoms can devastate a patient’s life for 10, 20 or even 30 years, said Montoya, who has been following 200 CFS patients for several years in an effort to identify the syndrome’s underlying mechanisms. He hopes to accelerate the development of more-effective treatments than now exist.

“In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” Montoya said.

“If you don’t understand the disease, you’re throwing darts blindfolded,” said Zeineh. “We asked ourselves whether brain imaging could turn up something concrete that differs between CFS patients’ and healthy people’s brains. And, interestingly, it did.”

The Stanford investigators compared brain images of 15 CFS patients chosen from the group Montoya has been following to those of 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing symptoms similar to those of CFS.

Three key findings

The analysis yielded three noteworthy results, the researchers said. First, an MRI showed that overall white-matter content of CFS patients’ brains, compared with that of healthy subjects’ brains, was reduced. The term “white matter” largely denotes the long, cablelike nerve tracts carrying signals among broadly dispersed concentrations of “gray matter.” The latter areas specialize in processing information, and the former in conveying the information from one part of the brain to another.

That finding wasn’t entirely unexpected, Zeineh said. CFS is thought to involve chronic inflammation, quite possibly as a protracted immunological response to an as-yet unspecified viral infection. Inflammation, meanwhile, is known to take a particular toll on white matter.

But a second finding was entirely unexpected. Using an advanced imaging technique — diffusion-tensor imaging, which is especially suited to assessing the integrity of white matter — Zeineh and his colleagues identified a consistent abnormality in a particular part of a nerve tract in the right hemisphere of CFS patients’ brains. This tract, which connects two parts of the brain called the frontal lobe and temporal lobe, is called the right arcuate fasciculus, and in CFS patients it assumed an abnormal appearance.

Furthermore, there was a fairly strong correlation between the degree of abnormality in a CFS patient’s right arcuate fasciculus and the severity of the patient’s condition, as assessed by performance on a standard psychometric test used to evaluate fatigue.

Right vs. left

Although the right arcuate fasciculus’s function is still somewhat mysterious, its counterpart in the brain’s left hemisphere has been extensively explored. The left arcuate fasciculus connects two critical language areas of the left side of the brain termed Wernicke’s and Broca’s areas, which are gray-matter structures several centimeters apart. These two structures are important to understanding and generating speech, respectively. Right-handed people almost always have language organized in this fashion exclusively in the left side of the brain, but the precise side (left or right) and location of speech production and comprehension are not so clear-cut in left-handed people. (It’s sometimes said that every left-hander’s brain is a natural experiment.) So, pooling left- and right-handed people’s brain images can be misleading.  And, sure enough, the finding of an abnormality in the right arcuate fasciculus, pronounced among right-handers, was murky until the two left-handed patients and four left-handed control subjects’ images were exempted from the analysis.

Bolstering these observations was the third finding: a thickening of the gray matter at the two areas of the brain connected by the right arcuate fasciculus in CFS patients, compared with controls. Its correspondence with the observed abnormality in the white matter joining them makes it unlikely that the two were chance findings, Zeineh said.

Although these results were quite robust, he said, they will need to be confirmed. “This study was a start,” he said. “It shows us where to look.” The Stanford scientists are in the planning stages of a substantially larger study.

The effect that genes have on our brain depends on our age. These are the findings of a group of researchers from the MedUni Vienna. It has been known for a number of years that particular genetic variations are of importance for the functioning of neural circuits in the brain. Just how these effects differ in the various stages of life has until recently not been fully understood. This international study has been able to demonstrate that genetic variations at different times in our lives can actually have opposite effects on the brain, which provides an explanation for the differences that clinicians observe in the psychiatric symptoms and response to medications of adolescents and adults.

The group of researchers from Vienna, in collaboration with international cooperation partners, has shown that the effect of a psychiatric risk gene on a resting state network in the forebrain depends greatly on the patient’s age.

The human forebrain is crucial for planning and action, which are closely interwoven with concentration, attention and memory functions. The nerve transmitter substance dopamine orchestrates the activity of neurons in the forebrain in order to ensure an ideal level of functioning. The amount of dopamine in the brain is not constant for life, however. Instead, it rises until adolescence and then falls by the time the individual reaches early adulthood to a much lower level. When the dopaminergic control function collapses, serious mental illnesses such as schizophrenia, depression or attention deficit / hyperactivity disorder (ADHD) can result that usually start around the period of transition to adulthood.

For a number of years, doctors have known that a risk gene involved in dopamine metabolism (COMT) can affect neuronal regulation of the forebrain in adults. Carriers of risk gene variants are more prone to dopaminergic mental illness.

The interaction of genes and stages of development

As part of the study, carried out at the MedUni Vienna’s University Department of Psychiatry and Psychotherapy (led by Siegfried Kasper), the study team used magnetic resonance imaging data from a large random sample of over 200 test subjects to analyse the complex interaction between stages of development and genetic variations in the COMT gene and how it affects the resting state network of the forebrain.
Some of the magnetic resonance scans were performed in Vienna (Centre of Excellent, High-Field MR, Department of MR Physics, Head: Ewald Moser) and some as part of an EU project (Institute of Psychiatry, London, Head: Gunther Schumann). Gene analyses (COMT Val158Met) were carried out in Vienna (Univ. Dept. of Laboratory Medicine, Harald Esterbauer and colleagues) or as part of the EU project.

"Our age has a crucial influence on the effects of psychiatric risk genes. A gene that has positive effects during puberty can be bad for us in adulthood," says study leader Lukas Pezawas, describing the results. In the study, adolescents exhibited contrary gene effects on the brain compared to adults.

The study highlights the dynamism of gene effects on brain function throughout the various stages of life such as adolescence or adulthood. “These results are important for understanding the onset of illness in conditions such as schizophrenia, depression or ADHD, which mostly occur at the threshold of adulthood. Our results also show that there are fundamental differences in the dopamine system between adolescents and adults, which we need to take into account in future treatments”, explains Pezawas.

Future prevention and treatment strategies for vascular diseases may lie in the evaluation of early brain imaging tests long before heart attacks or strokes occur, according to a systematic review conducted by a team of cardiologists, neuroscientists, and psychiatrists from Icahn School of Medicine at Mount Sinai and published in the October issue of JACC Cardiovascular Imaging.

For the review, Mount Sinai researchers examined all relevant brain imaging studies conducted over the last 33 years. They looked at studies that used every available brain imaging modality in patients with vascular disease risk factors but no symptoms that would lead to a diagnosis of diseased blood vessels (vascular disease) in the  heart or brain, or periphery (e.g. arms and legs).

The review demonstrates that patients with high blood pressure, diabetes, obesity, high cholesterol, smoking, or metabolic syndrome, but no symptoms, still had visible signs on their neuroimaging scans of structural and functional brain changes long before the development of any events related to vascular diseases of the heart (heart attack) or brain (stroke).

"This is the first time we have been able to disentangle the brain effects of vascular disease risk factors from the brain effects of cardiovascular and cerebrovascular disease and/or events after they develop," says the article’s lead author, Joseph I. Friedman, MD, Associate Professor in the Departments of Psychiatry and Neuroscience at Icahn School of Medicine at Mount Sinai. "Moreover, subtle cognitive impairment is an important clinical manifestation of these vascular disease risk factor-related brain imaging changes in these otherwise healthy persons."

Dr. Friedman added that, because diminished cognitive capacity adversely impacts a person’s ability to benefit from treatment for these medical conditions, early identification of these brain changes may “present a new window of opportunity” for doctors to intervene early and improve prevention of advancement from vascular disease risk factors to established cardiovascular and cerebrovascular diseases. His team is currently testing these hypotheses in ongoing studies at Mount Sinai.

"Patients need to start today to control their vascular risk factors, otherwise their brains may forever harbor physical changes leading to devastating heart and vascular conditions impacting their future overall health and even cognitive decline causing diseases like dementia or when it exists it can accelerate Alzheimer’s," says study author, Valentin Fuster, MD, PhD, Director of Mount Sinai Heart, Physician-in-Chief of The Mount Sinai Hospital, and Chief of the Division of Cardiology at Icahn School of Medicine at Mount Sinai. "Our publication raises the possibility that these early brain changes are major warning signs of what the future may hold for these asymptomatic patients. These high risk patients, along with their doctors, hold the power to modify their daily vascular risk factors to help halt the future course of the manifestation of their potentially looming cardiovascular diseases."

"We hope our publication serves as a primer for cardiologists and other doctors interpreting the early neuroimaging data of their patients who may be high risk for vascular disease," says senior article author Jagat Narula, MD, PhD, Director of Cardiovascular Imaging, Professor of Medicine and Philip J. and Harriet L. Goodhart Chair in Cardiology at Icahn School of Medicine at Mount Sinai. "These subtle brain changes are clues to us physicians that our patients need to start to lower their vascular risk factors always and way before symptoms or a cardiac or brain event happens. This simple step to lower vascular risk factors can have huge impacts on global prevention efforts of cardiovascular diseases."  

Researchers identified the following impact of key vascular risk factors on the structural and functional brain health of asymptomatic patients:

• Hypertension is associated with globally appreciable brain volume reductions,
  connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions.
• Diabetes is associated with connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions.
• Obesity is associated with brain volume reductions, reduced brain blood flow and metabolism.
• High total cholesterol and LDL cholesterol are associated with brain volume reductions, and connecting brain fiber abnormalities. In addition, high triglycerides is associated with reduced brain blood flow, and high total cholesterol is associated with reduced brain metabolism.
• Smoking is associated with brain volume reductions, and alterations of the normal pattern of blood flow. In addition, it causes reduced MAO B (Monoamine Oxidase B) which metabolizes dopamine, the neurotransmitter chemical that controls the brain’s reward and pleasure zones.
• Metabolic Syndrome is associated with a greater burden of silent brain infarcts (SBIs), visible only on MRI, which represents subclinical cerebrovascular disease. In addition, it is associated with connecting brain fiber abnormalities, and alterations in the normal pattern of synchronized brain activity between different regions.

Scientists have described a way to convert human skin cells directly into a specific type of brain cell affected by Huntington’s disease, an ultimately fatal neurodegenerative disorder. Unlike other techniques that turn one cell type into another, this new process does not pass through a stem cell phase, avoiding the production of multiple cell types, the study’s authors report.

(Image caption: Human skin cells (top) can be converted into medium spiny neurons (bottom) with exposure to the right combination of microRNAs and transcription factors, according to work by Andrew Yoo and his research team)

The researchers, at Washington University School of Medicine in St. Louis, demonstrated that these converted cells survived at least six months after injection into the brains of mice and behaved similarly to native cells in the brain.

“Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells,” said senior author Andrew S. Yoo, PhD, assistant professor of developmental biology. “These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. That’s a landmark point about this paper.”

The work appears Oct. 22 in the journal Neuron.

The investigators produced a specific type of brain cell called medium spiny neurons, which are important for controlling movement. They are the primary cells affected in Huntington’s disease, an inherited genetic disorder that causes involuntary muscle movements and cognitive decline usually beginning in middle-adulthood. Patients with the condition live about 20 years following the onset of symptoms, which steadily worsen over time.

The research involved adult human skin cells, rather than more commonly studied mouse cells or even human cells at an earlier stage of development. In regard to potential future therapies, the ability to convert adult human cells presents the possibility of using a patient’s own skin cells, which are easily accessible and won’t be rejected by the immune system.

To reprogram these cells, Yoo and his colleagues put the skin cells in an environment that closely mimics the environment of brain cells. They knew from past work that exposure to two small molecules of RNA, a close chemical cousin of DNA, could turn skin cells into a mix of different types of neurons.

In a skin cell, the DNA instructions for how to be a brain cell, or any other type of cell, is neatly packed away, unused. In past research published in Nature, Yoo and his colleagues showed that exposure to two microRNAs called miR-9 and miR-124 altered the machinery that governs packaging of DNA. Though the investigators still are unraveling the details of this complex process, these microRNAs appear to be opening up the tightly packaged sections of DNA important for brain cells, allowing expression of genes governing development and function of neurons.

Knowing exposure to these microRNAs alone could change skin cells into a mix of neurons, the researchers then started to fine tune the chemical signals, exposing the cells to additional molecules called transcription factors that they knew were present in the part of the brain where medium spiny neurons are common.

“We think that the microRNAs are really doing the heavy lifting,” said co-first author Matheus B. Victor, a graduate student in neuroscience. “They are priming the skin cells to become neurons. The transcription factors we add then guide the skin cells to become a specific subtype, in this case medium spiny neurons. We think we could produce different types of neurons by switching out different transcription factors.”

Yoo also explained that the microRNAs, but not the transcription factors, are important components for the general reprogramming of human skin cells directly to neurons. His team, including co-first author Michelle C. Richner, senior research technician, showed that when the skin cells were exposed to the transcription factors alone, without the microRNAs, the conversion into neurons wasn’t successful.

The researchers performed extensive tests to demonstrate that these newly converted brain cells did indeed look and behave like native medium spiny neurons. The converted cells expressed genes specific to native human medium spiny neurons and did not express genes for other types of neurons. When transplanted into the mouse brain, the converted cells showed morphological and functional properties similar to native neurons.

To study the cellular properties associated with the disease, the investigators now are taking skin cells from patients with Huntington’s disease and reprogramming them into medium spiny neurons using the approach described in the new paper. They also plan to inject healthy reprogrammed human cells into mice with a model of Huntington’s disease to see if this has any effect on the symptoms.

A nano-sized discovery by Northwestern Medicine® scientists helps explain how bipolar disorder affects the brain and could one day lead to new drug therapies to treat the mental illness. 

Scientists used a new super-resolution imaging method — the same method recognized with the 2014 Nobel Prize in chemistry — to peer deep into brain tissue from mice with bipolar-like behaviors. In the synapses (where communication between brain cells occurs), they discovered tiny “nanodomain” structures with concentrated levels of ANK3 — the gene most strongly associated with bipolar disorder risk. ANK3 is coding for the protein ankyrin-G. 

“We knew that ankyrin-G played an important role in bipolar disease, but we didn’t know how,” said Northwestern Medicine scientist Peter Penzes, corresponding author of the paper. “Through this imaging method we found the gene formed in nanodomain structures in the synapses, and we determined that these structures control or regulate the behavior of synapses.” 

Penzes is a professor in physiology and psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. The results were published Oct. 22 in the journal Neuron. 

High-profile cases, including actress Catherine Zeta-Jones and politician Jesse Jackson, Jr., have brought attention to bipolar disorder. The illness causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. About 3 percent of Americans experience bipolar disorder symptoms, and there is no cure. 

Recent large-scale human genetic studies have shown that genes can contribute to disease risk along with stress and other environmental factors. However, how these risk genes affect the brain is not known. 

This is the first time any psychiatric risk gene has been analyzed at such a detailed level of resolution. As explained in the paper, Penzes used the Nikon Structured Illumination Super-resolution Microscope to study a mouse model of bipolar disorder. The microscope realizes resolution of up to 115 nanometers. To put that size in perspective, a nanometer is one-tenth of a micron, and there are 25,400 microns in one inch. Very few of these microscopes exist worldwide.

“There is important information about genes and diseases that can only been seen at this level of resolution,” Penzes said. “We provide a neurobiological explanation of the function of the leading risk gene, and this might provide insight into the abnormalities in bipolar disorder.”

The biological framework presented in this paper could be used in human studies of bipolar disorder in the future, with the goal of developing therapeutic approaches to target these genes.

As you glance over a menu or peruse the shelves in a supermarket, you may be thinking about how each food will taste and whether it’s nutritious, or you may be trying to decide what you’re in the mood for. A new neuroimaging study suggests that while you’re thinking all these things, an internal calorie counter of sorts is also evaluating each food based on its caloric density.

The findings are published in Psychological Science, a journal of the Association for Psychological Science.

“Earlier studies found that children and adults tend to choose high-calorie food,” says study author Alain Dagher, neurologist at the Montreal Neurological Institute and Hospital. “The easy availability and low cost of high-calorie food has been blamed for the rise in obesity. Their consumption is largely governed by the anticipated effects of these foods, which are likely learned through experience.”

“Our study sought to determine how people’s awareness of caloric content influenced the brain areas known to be implicated in evaluating food options,” says Dagher. “We found that brain activity tracked the true caloric content of foods.”

For the study, 29 healthy participants were asked to examine pictures of 50 familiar foods. The participants rated how much they liked each food (on a scale from 1 to 20) and were asked to estimate the calorie content of each food. Surprisingly, they were poor at accurately judging the number of calories in the various foods, and yet, the amount participants were willing to bid on the food in a simulated auction matched up with the foods that actually had higher caloric content.

Results of functional brain scans acquired while participants looked at the food images showed that activity in the ventromedial prefrontal cortex, an area known to encode the value of stimuli and predict immediate consumption, was also correlated with the foods’ true caloric content.

Participants’ explicit ratings of how much they liked a food, on the other hand, were associated with activity in the insula, an area of the brain that has been linked to processing the sensory properties of food.

According to Dagher, understanding the reasons for people’s food choices could help to control the factors that lead to obesity, a condition that is linked to many health problems, including high blood pressure, heart disease, and Type 2 diabetes.

A drug being studied as a fast-acting mood-lifter restored pleasure-seeking behavior independent of – and ahead of – its other antidepressant effects, in a National Institutes of Health trial. Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom – loss of interest in pleasurable activities – which lasted up to 14 days. Brain scans traced the agent’s action to boosted activity in areas at the front and deep in the right hemisphere of the brain.

“Our findings help to deconstruct what has traditionally been lumped together as depression,” explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health. “We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants – and link that response to different circuitry than other depression symptoms.”

This approach is consistent with the NIMH’s Research Domain Criteria project, which calls for the study of functions – such as the ability to seek out and experience rewards – and their related brain systems that may identify subgroups of patients in one or multiple disorder categories.

Zarate and colleagues reported on their findings Oct. 14, 2014 in the journal Translational Psychiatry.

Although it’s considered one of two cardinal symptoms of both depression and bipolar disorder, effective treatments have been lacking for loss of the ability to look forward to pleasurable activities, or anhedonia. Long used as an anesthetic and sometimes club drug , ketamine and its mechanism-of-action have lately been the focus of research into a potential new class of rapid-acting antidepressants that can lift mood within hours instead of weeks.

Based on their previous studies, NIMH researchers expected ketamine’s therapeutic action against anhedonia would be traceable – like that for other depression symptoms – to effects on a mid-brain area linked to reward-seeking and that it would follow a similar pattern and time course.

To find out, the researchers infused the drug or a placebo into 36 patients in the depressive phase of bipolar disorder. They then detected any resultant mood changes using rating scales for anhedonia and depression. By isolating scores on anhedonia items from scores on other depression symptom items, the researchers discovered that ketamine was triggering a strong anti-anhedonia effect sooner – and independent of – the other effects.

Levels of anhedonia plummeted within 40 minutes in patients who received ketamine, compared with those who received placebo – and the effect was still detectable in some patients two weeks later. Other depressive symptoms improved within 2 hours. The anti-anhedonic effect remained significant even in the absence of other antidepressant effects, suggesting a unique role for the drug.

Next, the researchers scanned a subset of the ketamine-infused patients, using positron emission tomography (PET), which shows what parts of the brain are active by tracing the destinations of radioactively-tagged glucose – the brain’s fuel. The scans showed that ketamine jump-started activity not in the middle brain area they had expected, but rather in the dorsal (upper) anterior cingulate cortex, near the front middle of the brain and putamen, deep in the right hemisphere.

Boosted activity in these areas may reflect increased motivation towards or ability to anticipate pleasurable experiences, according to the researchers. Depressed patients typically experience problems imagining positive, rewarding experiences – which would be consistent with impaired functioning of this dorsal anterior cingulate cortex circuitry, they said. However, confirmation of these imaging findings must await results of a similar NIMH ketamine trial nearing completion in patients with unipolar major depression.

Other evidence suggests that ketamine’s action in this circuitry is mediated by its effects on the brain’s major excitatory neurotransmitter, glutamate, and downstream effects on a key reward-related chemical messenger, dopamine. The findings add to mounting evidence in support of the antidepressant efficacy of targeting this neurochemical pathway. Ongoing research is exploring, for example, potentially more practical delivery methods for ketamine and related experimental antidepressants, such as a nasal spray .

However, ketamine is not approved by the U.S. Food and Drug Administration as a treatment for depression. It is mostly used in veterinary practice, and abuse can lead to hallucinations, delirium and amnesia.

A study led by University of Toronto psychology researchers has found that people who play action video games such as Call of Duty or Assassin’s Creed seem to learn a new sensorimotor skill more quickly than non-gamers do.

A new sensorimotor skill, such as learning to ride a bike or typing, often requires a new pattern of coordination between vision and motor movement. With such skills, an individual generally moves from novice performance, characterized by a low degree of coordination, to expert performance, marked by a high degree of coordination. As a result of successful sensorimotor learning, one comes to perform these tasks efficiently and perhaps even without consciously thinking about them.

“We wanted to understand if chronic video game playing has an effect on sensorimotor control, that is, the coordinated function of vision and hand movement,” said graduate student Davood Gozli, who led the study with supervisor Jay Pratt.

To find out, they set up two experiments. In the first, 18 gamers (those who played a first-person shooter game at least three times per week for at least two hours each time in the previous six months) and 18 non-gamers (who had little or no video game use in the past two years) performed a manual tracking task. Using a computer mouse, they were instructed to keep a small green square cursor at the centre of a white square moving target which moved in a very complicated pattern that repeated itself. The task probes sensorimotor control, because participants see the target movement and try to coordinate their hand movements with what they see.

In the early stages of doing the tasks, the gamers’ performance was not significantly better than non-gamers. “This suggests that while chronically playing action video games requires constant motor control, playing these games does not give gamers a reliable initial advantage in new and unfamiliar sensorimotor tasks,” said Gozli.

By the end of the experiment, all participants performed better as they learned the complex pattern of the target. The gamers, however, were significantly more accurate in following the repetitive motion than the non-gamers. “This is likely due to the gamers’ superior ability in learning a novel sensorimotor pattern, that is, their gaming experience enabled them to learn better than the non-gamers.”

In the next experiment, the researchers wanted to test whether the superior performance of the gamers was indeed a result of learning rather than simply having better sensorimotor control. To eliminate the learning component of the experiment, they required participants to again track a moving dot, but in this case the patterns of motion changed throughout the experiment. The result this time: neither the gamers nor the non-gamers improved as time went by, confirming that learning was playing a key role and the gamers were learning better.

One of the benefits of playing action games may be an enhanced ability to precisely learn the dynamics of new sensorimotor tasks. Such skills are key, for example, in laparoscopic surgery which involves high precision manual control of remote surgery tools through a computer interface.

A researcher at the University of Wisconsin-Milwaukee (UWM) has added to a growing body of evidence that links autism to air pollutants such as those generated by cars and trucks.

Amy Kalkbrenner’s study, published this week online at the journal Epidemiology, showed that pollution’s impact on autism rates in North Carolina is similar to results of pollution-autism studies in California – despite weather and climate differences between the two states.

In addition, the work of Kalkbrenner and her colleagues, building on previous studies, showed that women in the third trimester of pregnancy were more susceptible to the damaging effects of air pollution on their unborn child.

“It adds another piece supporting the hypothesis that environmental chemicals are part of the autism puzzle,” says Kalkbrenner, an assistant professor in UWM’s Joseph J. Zilber School of Public Health. Autism, a spectrum of disorders affecting interpersonal relations and work achievement, now affects some 1 in 68 children in the U.S.

Her research team focused on exposure to coarse and fine particulate matter, known as PM₁₀, which arises in part from traffic-related air pollution. The study evaluated records in the two states, covering pre-conception through the first birthday for 87,000 children in North Carolina and 77,500 in California born in the mid-to-late 1990s. Key regions in each state were selected based on researchers’ ability to simultaneously measure the level of particulate matter present, and know which children had autism in these regions.

Researchers used a new, more exact tool to measure the levels of particulate matter in smaller slices of time, based on pollution at the family’s address during pregnancy. With this method, they were able to compare exposures during specific weeks of pregnancy. The approximately one thousand children who later developed some form of autism spectrum disorders were then compared to all other children.

Kalkbrenner says it was important to look at eastern states because of the differences in climate, seasonal weather patterns and the chemical make-up of the particulate matter that might impact brain development. “Evidence for a link between a chemical exposure and a health impact like autism is stronger when it can be shown in more than one region.” The team found that the concentration of particulate matter was highest among children born in summer months in North Carolina and those born in fall and winter months in California.

Reasons for increased susceptibility in the third trimester of pregnancy are not known at this time. However, Kalkbrenner says this finding is consistent with theories that show links between autism and altered brain network development, specifically synaptic connections that are developing during the final months of pregnancy.

“We’ve now had three solid studies saying the same thing. The evidence is pretty compelling that something is going on with air pollution and autism,” says Kalkbrenner, who adds that further study is needed to determine the neurodevelopmental impacts of specific chemical pollutants during precise developmental windows.