MRI Technique May Help Prevent ADHD Misdiagnosis

Brain iron levels offer a potential biomarker in the diagnosis of attention deficit hyperactivity disorder (ADHD) and may help physicians and parents make better informed treatment decisions, according to new research published online in the journal Radiology.

ADHD is a common disorder in children and adolescents that can continue into adulthood. Symptoms include hyperactivity and difficulty staying focused, paying attention and controlling behavior. The American Psychiatric Association reports that ADHD affects 3 to 7 percent of school-age children.

Psychostimulant medications such as Ritalin are among the drugs commonly used to reduce ADHD symptoms. Psychostimulants affect levels of dopamine, a neurotransmitter in the brain associated with addiction.

"Much debate and concern has emerged regarding the continual rise of ADHD diagnosis in the U.S. given that two-thirds of those diagnosed receive psychostimulant medications," said Vitria Adisetiyo, Ph.D., postdoctoral research fellow at the Medical University of South Carolina in Charleston, S.C. "We wanted to see if we could identify brain iron as a potential noninvasive biomarker for medication-naïve ADHD to prevent misdiagnosis."

For the study, the research team measured brain iron levels in 22 children and adolescents with ADHD, 12 of whom had never been on medication for their condition (medication naïve), and 27 healthy control children and adolescents using a magnetic resonance imaging (MRI) technique called magnetic field correlation imaging. The technique was introduced in 2006 by study co-authors and faculty members Joseph A. Helpern, Ph.D., and Jens H. Jensen, Ph.D. No contrast agents were used, and blood iron levels in the body were measured using a blood draw.

The results showed that the 12 ADHD medication-naïve patients had significantly lower brain iron levels than the 10 ADHD patients who had been on psychostimulant medication and the 27 children and adolescents in the control group. In contrast, ADHD patients with a history of psychostimulant medication treatment had brain iron levels comparable to controls, suggesting that brain iron may increase to normal levels with psychostimulant treatment.

"Our research suggests that iron absorption into the brain may be abnormal in ADHD given that atypical brain iron levels are found even when blood iron levels in the body are normal," Dr. Adisetiyo said. "We found no differences in blood iron measures between controls, medication-naïve ADHD patients or pscyhostimulant-medicated ADHD patients."

Magnetic field correlation imaging’s ability to noninvasively detect the low iron levels may help improve ADHD diagnosis and guide optimal treatment. Currently, ADHD diagnosis is based only on subjective clinical interviews and questionnaires. Having a biological biomarker may help inform clinical diagnosis, particularly in borderline cases, Dr. Adisetiyo noted.

If the results can be replicated in larger studies, magnetic field correlation might have a future role in determining which patients would benefit from psychostimulants—an important consideration because the drugs can become addictive if taken inappropriately and lead to abuse of other drugs like cocaine.

"We want the public to know that progress is being made in identifying potential noninvasive biological biomarkers of ADHD which may help to prevent misdiagnosis," Dr. Adisetiyo said. "We are currently testing our findings in a larger cohort to confirm that measuring brain iron levels in ADHD is indeed a reliable and clinically feasible biomarker."

Brain imaging shows enhanced executive brain function in people with musical training

A controlled study using functional MRI brain imaging reveals a possible biological link between early musical training and improved executive functioning in both children and adults, report researchers at Boston Children’s Hospital. The study, appearing online June 17 in the journal PLOS ONE, uses functional MRI of brain areas associated with executive function, adjusting for socioeconomic factors.

Executive functions are the high-level cognitive processes that enable people to quickly process and retain information, regulate their behaviors, make good choices, solve problems, plan and adjust to changing mental demands.

"Since executive functioning is a strong predictor of academic achievement, even more than IQ, we think our findings have strong educational implications," says study senior investigator Nadine Gaab, PhD, of the Laboratories of Cognitive Neuroscience at Boston Children’s. "While many schools are cutting music programs and spending more and more time on test preparation, our findings suggest that musical training may actually help to set up children for a better academic future."

While it’s already clear that musical training relates to cognitive abilities, few previous studies have looked at its effects on executive functions specifically. Among these studies, results have been mixed and limited by a lack of objective brain measurements, examination of only a few aspects of executive function, lack of well-defined musical training and control groups, and inadequate adjustment for factors like socioeconomic status.

Gaab and colleagues compared 15 musically trained children, 9 to 12, with a control group of 12 untrained children of the same age. Musically trained children had to have played an instrument for at least two years in regular private music lessons. (On average, the children had played for 5.2 years and practiced 3.7 hours per week, starting at the age of 5.9.) The researchers similarly compared 15 adults who were active professional musicians with 15 non-musicians. Both control groups had no musical training beyond general school requirements.

Since family demographic factors can influence whether a child gets private music lessons, the researchers matched the musician/non-musician groups for parental education, job status (parental or their own) and family income. The groups, also matched for IQ, underwent a battery of cognitive tests, and the children also had functional MRI imaging (fMRI) of their brains during testing.

On cognitive testing, adult musicians and musically trained children showed enhanced performance on several aspects of executive functioning. On fMRI, the children with musical training showed enhanced activation of specific areas of the prefrontal cortex during a test that made them switch between mental tasks. These areas, the supplementary motor area, the pre-supplementary area and the right ventrolateral prefrontal cortex, are known to be linked to executive function.

"Our results may also have implications for children and adults who are struggling with executive functioning, such as children with ADHD or [the] elderly," says Gaab. "Future studies have to determine whether music may be utilized as a therapeutic intervention tools for these children and adults."

The researchers note that children who study music may already have executive functioning abilities that somehow attract them to music and predispose them to stick with their lessons. To establish that musical training influences executive function, and not the other way around, they hope to perform additional studies that follow children over time, assigning them to musical training at random.

Understanding the unique nature of children’s bodies and brains

With the increase in childhood obesity and the associated increase in type 2 diabetes among children and adolescents, there is growing interest in how children’s bodies process the foods they eat and how obesity and diabetes begin to develop at early ages. Two studies presented at the American Diabetes Association’s 74th Scientific Sessions® help to shed light on this topic.

One study, by researchers at the Yale School of Medicine, compared how the brains of adolescents and adults differed in their response to ingestion of a glucose drink. It found that in adolescents, glucose increased the blood flow in the regions of the brain implicated in reward-motivation and decision-making, whereas in adults, it decreased the blood flow in these regions.

"While we cannot speculate directly about how glucose ingestion may influence behavior, certainly we have shown that there are differences in how adults and adolescents respond to glucose," said lead researcher Ania Jastreboff, MD, PhD, an Assistant Professor of Medicine and Pediatrics at the Yale School of Medicine. "This is important because adolescents are the highest consumers of dietary added sugars. This is just the first step in understanding what is happening in the adolescent brain in response to consumption of sugary drinks. Ultimately, it will be important to investigate whether such exposure to sugar during adolescence impacts food and drink consumption, and whether it relates to the development of obesity."

Another study, by researchers in Germany at the University Children’s Hospital in Leipzig, compared fat cell composition and biology in lean and obese children and adolescents. They found that when children become obese, beginning as early as age six, there was an increase in the number of adipose cells, and that they are larger in size than the cells found in the bodies of lean children. The researchers also found evidence of dysfunction of the fat cells of obese children, including signs of inflammation, which can lead to insulin resistance, diabetes and other problems, such as high blood pressure.

"Our research shows that obese children start to have not only more but also larger adipocytes, or fat cells, at a very young age and that this is associated with increased inflammation and is linked to impaired metabolic function," said lead researcher Antje Körner, MD, Professor of Pediatrics and Pediatric Researcher at the Pediatric Research Center, University Children’s Hospital, Leipzig. "What we were interested in was seeing whether something was already going on with the adipose tissue itself if the children become obese at an early age, and it appears that there is. It’s important because this can contribute to the development of comorbidities of obesity in children, such as diabetes."

Strokefinder quickly differentiates bleeding strokes from clot-induced strokes

The results from the initial clinical studies involving the microwave helmet Strokefinder confirm the usefulness of microwaves for rapid and accurate diagnosis of stroke patients. This is shown in a scientific article published on Monday. Strokefinder enables earlier diagnosis than current methods, which improves the possibility to counteract brain damage.

In the article, researchers from Chalmers University of Technology, Sahlgrenska Academy and Sahlgrenska University Hospital present results from the initial patient studies completed last year. The study included 45 patients, and the results show that the technique can with great certainty differentiate bleeding strokes from clot-induced strokes in patients with acute symptoms.

Strokefinder is placed on the patient’s head where it examines the brain tissue by using microwaves. The signals are interpreted by the system to determine if the stroke is caused by a blood clot or bleeding.

“The results of this study show that we will be able to increase the number of stroke patients who receive optimal treatment when the instrument makes a diagnosis already in the ambulance,” says Mikael Persson, professor of biomedical engineering at Chalmers University of Technology. “The possibility to rule out bleeding already in the ambulance is a major achievement that will be of great benefit in acute stroke care. Equally exciting is the potential application in trauma care.

Diagnosis and treatment already in the ambulance

The initial patient studies have been performed inside hospitals, and this autumn the research groups at Chalmers and Sahlgrenska Academy will test a mobile stroke helmet on patients in ambulances.

“Our goal with Strokefinder is to diagnose and initiate treatment of stroke patients already in the ambulance,” says Mikael Elam, professor of clinical neurophysiology at Sahlgrenska University Hospital. “Since time is a critical factor for stroke treatment, the use of the instrument leads to patients suffering less extensive injury. This in turn can shorten the length of stay at hospitals and reduce the need for rehabilitation, thus providing a number of other positive consequences for both the patient and the health care system.”

Studies involving Strokefinder are currently being conducted at Sahlgrenska University Hospital and Södra Älvsborg Hospital in Borås. The research is being conducted in close collaboration between Chalmers University of Technology, Sahlgrenska Academy, Sahlgrenska University Hospital, Södra Älvsborg Hospital and MedTech West, which is a platform for collaboration in medical device R&D, with premises at Sahlgrenska University Hospital.

A new product, based on the results of the present study, has been developed, and further studies will be conducted in several countries in preparation for the CE approval that Medfield Diagnostics, a spin-off from Chalmers, expects to obtain later this year.

(Illustration: Boid)

How Strokefinder differentiates bleeding strokes from clot-induced strokes

The antennas of the helmet sequentially transmit weak microwave signals into the brain. At the same time, the receiving antennas listen for reflected signals. The brain’s different structures and substances affect the microwave scattering and reflections in different ways. The received signals give a complex pattern, which is interpreted with the help of advanced algorithms. Based on these data, the system can diagnose bleeding or a clot. Bleeding is particularly pronounced, but an area with a clot and oxygen deficiency can also be distinguished. (Watch the video).

(Image caption: Brain scans show high activity in the medial prefrontal cortex (top) and striatum (bottom) while playing a competitive game. UC Berkeley and UIUC researchers have now found genetic variations in dopamine-regulating genes in the prefrontal cortex and striatum associated with differences in belief learning and reinforcement learning, respectively. Credit: Ming Hsu)

Your genes affect your betting behavior

Investors and gamblers take note: your betting decisions and strategy are determined, in part, by your genes.

Researchers from the University of California, Berkeley, National University of Singapore and University of Illinois at Urbana-Champaign (UIUC) have shown that betting decisions in a simple competitive game are influenced by the specific variants of dopamine-regulating genes in a person’s brain.

Dopamine is a neurotransmitter – a chemical released by brain cells to signal other brain cells – that is a key part of the brain’s reward and pleasure-seeking system. Dopamine deficiency leads to Parkinson’s disease, while disruption of the dopamine network is linked to numerous psychiatric and neurodegenerative disorders, including schizophrenia, depression and dementia.

While previous studies have shown the important role of the neurotransmitter dopamine in social interactions, this is the first study tying these interactions to specific genes that govern dopamine functioning.

“This study shows that genes influence complex social behavior, in this case strategic behavior,” said study leader Ming Hsu, an assistant professor of marketing in UC Berkeley’s Haas School of Business and a member of the Helen Wills Neuroscience Institute. “We now have some clues about the neural mechanisms through which our genes affect behavior.”

The implications for business are potentially vast but unclear, Hsu said, though one possibility is training workforces to be more strategic. But the findings could significantly affect our understanding of diseases involving dopamine, such as schizophrenia, as well as disorders of social interaction, such as autism.

“When people talk about dopamine dysfunction, schizophrenia is one of the first diseases that come to mind,” Hsu said, noting that the disease involves a very complex pattern of social and decision making deficits. “To the degree that we can better understand ubiquitous social interactions in strategic settings, it may help us understand how to characterize and eventually treat the social deficits that are symptoms of diseases like schizophrenia.”

Hsu, UIUC graduate student Eric Set and their colleagues, including Richard P. Ebstein and Soo Hong Chew from the National University of Singapore, will publish their findings the week of June 16 in the online early edition of the Proceedings of the National Academy of Sciences.

Two brain areas involved in competition

Hsu established two years ago that when people engage in competitive social interactions, such as betting games, they primarily call upon two areas of the brain: the medial prefrontal cortex, which is the executive part of the brain, and the striatum, which deals with motivation and is crucial for learning to acquire rewards. Functional magnetic resonance imaging (fMRI) scans showed that people playing these games displayed intense activity in these areas.

“If you think of the brain as a computing machine, these are areas that take inputs, crank them through an algorithm, and translate them into behavioral outputs,” Hsu said. “What is really interesting about these areas is that both are innervated by neurons that use dopamine.”

Hsu and Set of UIUC’s Department of Economics wanted to determine which genes involved in regulating dopamine concentrations in these brain areas were associated with strategic thinking, so they enlisted as subjects a group of 217 undergraduates at the National University of Singapore, all of whom had had their genomes scanned for some 700,000 genetic variants. The researchers focused on only 143 variants within 12 genes involved in regulating dopamine. Some of the 12 are primarily involved in regulating dopamine in the prefrontal cortex, while others primarily regulate dopamine in the striatum.

The competition was a game called patent race, commonly used by social scientists to study social interactions. It involves one person betting, via computer, with an anonymous opponent.

“We know from brain imaging studies that when people compete against one another, they actually engage in two distinct types of learning processes,” Set said, referring to Hsu’s 2012 study. “One type involves learning purely from the consequences of your own actions, called reinforcement learning. The other is a bit more sophisticated, called belief learning, where people try to make a mental model of the other players, in order to anticipate and respond to their actions.”

Trial-and-error learning vs belief learning

Using a mathematical model of brain function during competitive social interactions, Hsu and Set correlated performance in reinforcement learning and belief learning with different variants or mutations of the 12 dopamine-related genes, and discovered a distinct difference.

They found that differences in belief learning – the degree to which players were able to anticipate and respond to the actions of others, or to imagine what their competitor is thinking and respond strategically – was associated with variation in three genes which primarily affect dopamine functioning in the medial prefrontal cortex.

In contrast, differences in trial-and-error reinforcement learning – how quickly they forget past experiences and how quickly they change strategy – was associated with variation in two genes that primarily affect striatal dopamine.

Hsu said that the findings correlate well with previous brain studies showing that the prefrontal cortex is involved in belief learning, while the striatum is involved in reinforcement learning.

“We were surprised by the degree of overlap, but it hints at the power of studying the neural and genetic levels under a single mathematical framework, which is only beginning in this area,” he said.

Hsu is currently collaborating with other scientists to correlate career achievements in older adults with genes and performance on competitive games, to see which brain regions and types of learning are most important for different kinds of success in life.