Neuroscience

Articles and news from the latest research reports.

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Modelling how neurons work together A newly-developed, highly accurate representation of the way in which neurons behave when performing movements such as reaching could not only enhance understanding of the complex dynamics at work in the brain, but aid in the development of robotic limbs which are capable of more complex and natural movements. Researchers from the University of Cambridge, working in collaboration with the University of Oxford and the Ecole Polytechnique Fédérale de Lausanne (EPFL), have developed a new model of a neural network, offering a novel theory of how neurons work together when performing complex movements. The results are published in the 18 June edition of the journal Neuron. While an action such as reaching for a cup of coffee may seem straightforward, the millions of neurons in the brain’s motor cortex must work together to prepare and execute the movement before the coffee ever reaches our lips. When we reach for the much-needed cup of coffee, the neurons spring into action, sending a series of signals from the brain to the hand. These signals are transmitted across synapses – the junctions between neurons. Determining exactly how the neurons work together to execute these movements is difficult, however. The new theory was inspired by recent experiments carried out at Stanford University, which had uncovered some key aspects of the signals that neurons emit before, during and after the movement. “There is a remarkable synergy in the activity recorded simultaneously in hundreds of neurons,” said Dr Guillaume Hennequin of the University’s Department of Engineering, who led the research. “In contrast, previous models of cortical circuit dynamics predict a lot of redundancy, and therefore poorly explain what happens in the motor cortex during movements.” Better models of how neurons behave will not only aid in our understanding of the brain, but could also be used to design prosthetic limbs controlled via electrodes implanted in the brain. “Our theory could provide a more accurate guess of how neurons would want to signal both movement intention and execution to the robotic limb,” said Dr Hennequin. The behaviour of neurons in the motor cortex can be likened to a mousetrap or a spring-loaded box, in which the springs are waiting to be released and are let go once the lid is opened or the mouse takes the bait. As we plan a movement, the ‘neural springs’ are progressively flexed and compressed. When released, they orchestrate a series of neural activity bursts, all of which takes place in the blink of an eye. The signals transmitted by the synapses in the motor cortex during complex movements can be either excitatory or inhibitory, which are in essence mirror reflections of each other. The signals cancel each other out for the most part, leaving occasional bursts of activity. Using control theory, a branch of mathematics well-suited to the study of complex interacting systems such as the brain, the researchers devised a model of neural behaviour which achieves a balance between the excitatory and inhibitory synaptic signals. The model can accurately reproduce a range of multidimensional movement patterns. The researchers found that neurons in the motor cortex might not be wired together with nearly as much randomness as had been previously thought. “Our model shows that the inhibitory synapses might be tuned to stabilise the dynamics of these brain networks,” said Dr Hennequin. “We think that accurate models like these can really aid in the understanding of the incredibly complex dynamics at work in the human brain.” Future directions for the research include building a more realistic, ‘closed-loop’ model of movement generation in which feedback from the limbs is actively used by the brain to correct for small errors in movement execution. This will expose the new theory to the more thorough scrutiny of physiological and behavioural validation, potentially leading to a more complete mechanistic understanding of complex movements.

Modelling how neurons work together

A newly-developed, highly accurate representation of the way in which neurons behave when performing movements such as reaching could not only enhance understanding of the complex dynamics at work in the brain, but aid in the development of robotic limbs which are capable of more complex and natural movements.

Researchers from the University of Cambridge, working in collaboration with the University of Oxford and the Ecole Polytechnique Fédérale de Lausanne (EPFL), have developed a new model of a neural network, offering a novel theory of how neurons work together when performing complex movements. The results are published in the 18 June edition of the journal Neuron.

While an action such as reaching for a cup of coffee may seem straightforward, the millions of neurons in the brain’s motor cortex must work together to prepare and execute the movement before the coffee ever reaches our lips. When we reach for the much-needed cup of coffee, the neurons spring into action, sending a series of signals from the brain to the hand. These signals are transmitted across synapses – the junctions between neurons.

Determining exactly how the neurons work together to execute these movements is difficult, however. The new theory was inspired by recent experiments carried out at Stanford University, which had uncovered some key aspects of the signals that neurons emit before, during and after the movement. “There is a remarkable synergy in the activity recorded simultaneously in hundreds of neurons,” said Dr Guillaume Hennequin of the University’s Department of Engineering, who led the research. “In contrast, previous models of cortical circuit dynamics predict a lot of redundancy, and therefore poorly explain what happens in the motor cortex during movements.”

Better models of how neurons behave will not only aid in our understanding of the brain, but could also be used to design prosthetic limbs controlled via electrodes implanted in the brain. “Our theory could provide a more accurate guess of how neurons would want to signal both movement intention and execution to the robotic limb,” said Dr Hennequin.

The behaviour of neurons in the motor cortex can be likened to a mousetrap or a spring-loaded box, in which the springs are waiting to be released and are let go once the lid is opened or the mouse takes the bait. As we plan a movement, the ‘neural springs’ are progressively flexed and compressed. When released, they orchestrate a series of neural activity bursts, all of which takes place in the blink of an eye.

The signals transmitted by the synapses in the motor cortex during complex movements can be either excitatory or inhibitory, which are in essence mirror reflections of each other. The signals cancel each other out for the most part, leaving occasional bursts of activity.

Using control theory, a branch of mathematics well-suited to the study of complex interacting systems such as the brain, the researchers devised a model of neural behaviour which achieves a balance between the excitatory and inhibitory synaptic signals. The model can accurately reproduce a range of multidimensional movement patterns.

The researchers found that neurons in the motor cortex might not be wired together with nearly as much randomness as had been previously thought. “Our model shows that the inhibitory synapses might be tuned to stabilise the dynamics of these brain networks,” said Dr Hennequin. “We think that accurate models like these can really aid in the understanding of the incredibly complex dynamics at work in the human brain.”

Future directions for the research include building a more realistic, ‘closed-loop’ model of movement generation in which feedback from the limbs is actively used by the brain to correct for small errors in movement execution. This will expose the new theory to the more thorough scrutiny of physiological and behavioural validation, potentially leading to a more complete mechanistic understanding of complex movements.

Filed under neurons neural networks motor cortex motor movements prosthetic limbs robotics neuroscience science

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ucsdhealthsciences: Single Dose Reverses Autism-like Symptoms in MiceOld drug used for sleeping sickness may point to new treatment in humans In a further test of a novel theory that suggests autism is the consequence of abnormal cell communication, researchers at the University of California, San Diego School of Medicine report that an almost century-old drug approved for treating sleeping sickness also restores normal cellular signaling in a mouse model of autism, reversing symptoms of the neurological disorder in animals that were the human biological age equivalent of 30 years old. The findings, published in the June 17, 2014 online issue of Translational Psychiatry, follow up on similar research published last year by senior author Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology, and colleagues. Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: “Twenty percent of the known factors associated with autism are genetic, but most are not. It’s wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact.  The net result of this interaction is metabolism.” Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, said one of the universal symptoms of autism is metabolic disturbances. “Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them. These create a sort of chemical glow that broadcasts the state of health of the cell.” Cells threatened or damaged by microbes, such as viruses or bacteria, or by physical forces or by chemicals, such as pollutants, react defensively, a part of the normal immune response, Naviaux said. Their membranes stiffen. Internal metabolic processes are altered, most notably mitochondria – the cells’ critical “power plants.” And communications between cells are dramatically reduced. This is the “cell danger response,” said Naviaux, and if it persists, the result can be lasting, diverse impairment. If it occurs during childhood, for example, neurodevelopment is delayed. “Cells behave like countries at war,” said Naviaux. “When a threat begins, they harden their borders. They don’t trust their neighbors. But without constant communication with the outside, cells begin to function differently. In the case of neurons, it might be by making fewer or too many connections. One way to look at this related to autism is this: When cells stop talking to each other, children stop talking.” Naviaux and colleagues have focused on a cellular signaling system linked to both mitochondrial function and to the cell’s innate immune function. Specifically, they have zeroed in on the role of nucleotides like adenosine triphosphate (ATP) and other signaling mitokines – molecules generated by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body. Nineteen types of so-called purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism, such as impaired language and social skills. In their latest work, Naviaux again tested the effect of suramin, a well-known inhibitor of purinergic signaling that was first synthesized in 1916 and is used to treat trypanosomiasis or African sleeping sickness, a parasitic disease. They found that suramin blocked the extracellular signaling pathway used by ATP and other mitokines in a mouse model of autism spectrum disorder (ASD), ending the cell danger response and related inflammation. Cells subsequently began behaving normally and autism-like behaviors and metabolism in the mice were corrected.  However, the biological and behavioral benefits of suramin were not permanent, nor preventive. A single dose remained effective in the mice for about five weeks, and then washed out. Moreover, suramin cannot be taken long-term since it can result in anemia and adrenal gland dysfunction. Still, Naviaux said these and earlier findings are sufficiently encouraging to soon launch a small phase 1 clinical trial with children who have ASD. He expects the trial to begin later this year.  “Obviously correcting abnormalities in a mouse is a long way from a cure in humans, but we think this approach – antipurinergic therapy – is a new and fresh way to think about and address the challenge of autism. “Our work doesn’t contradict what others have discovered or done. It’s another perspective. Our idea is that this kind of treatment – eliminating a basic, underlying metabolic dysfunction – removes a hurdle that might make other non-drug behavioral and developmental therapies of autism more effective.  The discovery that a single dose of medicine can fundamentally reset metabolism for weeks means that newer and safer drugs might not need to be given chronically.  Members of this new class of medicines might need to be given only intermittently during sensitive developmental windows to unblock metabolism and permit improved development in response to many kinds of behavioral and occupational therapies, and to natural play.” Pictured: Transmission electron micrograph of cell mitochondrion. Thomas Deerinck, NCMIR, UC San Diego.

ucsdhealthsciences:

Single Dose Reverses Autism-like Symptoms in Mice
Old drug used for sleeping sickness may point to new treatment in humans

In a further test of a novel theory that suggests autism is the consequence of abnormal cell communication, researchers at the University of California, San Diego School of Medicine report that an almost century-old drug approved for treating sleeping sickness also restores normal cellular signaling in a mouse model of autism, reversing symptoms of the neurological disorder in animals that were the human biological age equivalent of 30 years old.

The findings, published in the June 17, 2014 online issue of Translational Psychiatry, follow up on similar research published last year by senior author Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology, and colleagues.

Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: “Twenty percent of the known factors associated with autism are genetic, but most are not. It’s wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact.  The net result of this interaction is metabolism.”

Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, said one of the universal symptoms of autism is metabolic disturbances. “Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them. These create a sort of chemical glow that broadcasts the state of health of the cell.”

Cells threatened or damaged by microbes, such as viruses or bacteria, or by physical forces or by chemicals, such as pollutants, react defensively, a part of the normal immune response, Naviaux said. Their membranes stiffen. Internal metabolic processes are altered, most notably mitochondria – the cells’ critical “power plants.” And communications between cells are dramatically reduced. This is the “cell danger response,” said Naviaux, and if it persists, the result can be lasting, diverse impairment. If it occurs during childhood, for example, neurodevelopment is delayed.

“Cells behave like countries at war,” said Naviaux. “When a threat begins, they harden their borders. They don’t trust their neighbors. But without constant communication with the outside, cells begin to function differently. In the case of neurons, it might be by making fewer or too many connections. One way to look at this related to autism is this: When cells stop talking to each other, children stop talking.”

Naviaux and colleagues have focused on a cellular signaling system linked to both mitochondrial function and to the cell’s innate immune function. Specifically, they have zeroed in on the role of nucleotides like adenosine triphosphate (ATP) and other signaling mitokines – molecules generated by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body. Nineteen types of so-called purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism, such as impaired language and social skills.

In their latest work, Naviaux again tested the effect of suramin, a well-known inhibitor of purinergic signaling that was first synthesized in 1916 and is used to treat trypanosomiasis or African sleeping sickness, a parasitic disease. They found that suramin blocked the extracellular signaling pathway used by ATP and other mitokines in a mouse model of autism spectrum disorder (ASD), ending the cell danger response and related inflammation. Cells subsequently began behaving normally and autism-like behaviors and metabolism in the mice were corrected. 

However, the biological and behavioral benefits of suramin were not permanent, nor preventive. A single dose remained effective in the mice for about five weeks, and then washed out. Moreover, suramin cannot be taken long-term since it can result in anemia and adrenal gland dysfunction.

Still, Naviaux said these and earlier findings are sufficiently encouraging to soon launch a small phase 1 clinical trial with children who have ASD. He expects the trial to begin later this year. 

“Obviously correcting abnormalities in a mouse is a long way from a cure in humans, but we think this approach – antipurinergic therapy – is a new and fresh way to think about and address the challenge of autism.

“Our work doesn’t contradict what others have discovered or done. It’s another perspective. Our idea is that this kind of treatment – eliminating a basic, underlying metabolic dysfunction – removes a hurdle that might make other non-drug behavioral and developmental therapies of autism more effective.  The discovery that a single dose of medicine can fundamentally reset metabolism for weeks means that newer and safer drugs might not need to be given chronically.  Members of this new class of medicines might need to be given only intermittently during sensitive developmental windows to unblock metabolism and permit improved development in response to many kinds of behavioral and occupational therapies, and to natural play.”

Pictured: Transmission electron micrograph of cell mitochondrion. Thomas Deerinck, NCMIR, UC San Diego.

131 notes

Hearing protein required to convert sound into brain signals A specific protein found in the bridge-like structures that make up part of the auditory machinery of the inner ear is essential for hearing. The absence of this protein or impairment of the gene that codes for this protein leads to profound deafness in mice and humans, respectively, reports a team of researchers in the journal EMBO Molecular Medicine. “The goal of our study was to identify which isoform of protocadherin-15 forms the tip-links, the essential connections of the auditory mechanotransduction machinery within mature hair cells that are needed to convert sound into electrical signals,” remarks Christine Petit, the lead author of the study and Professor at the Institut Pasteur in Paris and at Collège de France. Three types of protocadherin-15 are known to exist in auditory sensory cells of the inner ear but it was not clear which of these protein isoforms was essential for hearing. “Our work pinpoints the CD2 isoform of protocadherin-15 as an essential component of the tip-link and reveals that the absence of protocadherin-15 CD2 in mouse hair cells results in profound deafness.” Within the hair bundle, the sensory antenna of auditory sensory cells, the tip-link is a bridge-like structure that when stretched can activate the ion channel responsible for generating electrical signals from sound. Tension in the tip-link created by sound stimulation opens this channel of unknown molecular composition thus generating electrical signals and, ultimately, the perception of sound. The researchers engineered mice that lack only the CD2 isoform of protocadherin-15 exclusively during adulthood. While the absence of this isoform led to profound deafness, the lack of the other protocadherin-15 isoforms in mice did not affect their hearing. Patients who carry a mutation in the gene encoding protocadherin-15 are affected by a rare devastating disorder, Usher syndrome, which is characterized by profound deafness, balance problems and gradual visual loss due to retinitis pigmentosa. In a separate approach, the scientists also sequenced the genes of 60 patients who had profound deafness without balance and visual impairment. Three of these patients were shown to have mutations specifically affecting protocadherin-15 CD2. “The demonstration of a requirement for protocadherin-15 CD2 for hearing not only in mice but also in humans constitutes a major step in the objective of deciphering the components of the auditory mechanotransduction machinery. This isoform can be used as a starting point to identify the other components of the auditory machinery. By focusing our attention on the CD2 isoform of protocadherin-15, we can now consider developing gene therapy strategies for deafness caused by defects in this gene,” says EMBO Member Christine Petit.

Hearing protein required to convert sound into brain signals

A specific protein found in the bridge-like structures that make up part of the auditory machinery of the inner ear is essential for hearing. The absence of this protein or impairment of the gene that codes for this protein leads to profound deafness in mice and humans, respectively, reports a team of researchers in the journal EMBO Molecular Medicine.

“The goal of our study was to identify which isoform of protocadherin-15 forms the tip-links, the essential connections of the auditory mechanotransduction machinery within mature hair cells that are needed to convert sound into electrical signals,” remarks Christine Petit, the lead author of the study and Professor at the Institut Pasteur in Paris and at Collège de France.

Three types of protocadherin-15 are known to exist in auditory sensory cells of the inner ear but it was not clear which of these protein isoforms was essential for hearing. “Our work pinpoints the CD2 isoform of protocadherin-15 as an essential component of the tip-link and reveals that the absence of protocadherin-15 CD2 in mouse hair cells results in profound deafness.”

Within the hair bundle, the sensory antenna of auditory sensory cells, the tip-link is a bridge-like structure that when stretched can activate the ion channel responsible for generating electrical signals from sound. Tension in the tip-link created by sound stimulation opens this channel of unknown molecular composition thus generating electrical signals and, ultimately, the perception of sound.

The researchers engineered mice that lack only the CD2 isoform of protocadherin-15 exclusively during adulthood. While the absence of this isoform led to profound deafness, the lack of the other protocadherin-15 isoforms in mice did not affect their hearing.

Patients who carry a mutation in the gene encoding protocadherin-15 are affected by a rare devastating disorder, Usher syndrome, which is characterized by profound deafness, balance problems and gradual visual loss due to retinitis pigmentosa. In a separate approach, the scientists also sequenced the genes of 60 patients who had profound deafness without balance and visual impairment. Three of these patients were shown to have mutations specifically affecting protocadherin-15 CD2. “The demonstration of a requirement for protocadherin-15 CD2 for hearing not only in mice but also in humans constitutes a major step in the objective of deciphering the components of the auditory mechanotransduction machinery. This isoform can be used as a starting point to identify the other components of the auditory machinery. By focusing our attention on the CD2 isoform of protocadherin-15, we can now consider developing gene therapy strategies for deafness caused by defects in this gene,” says EMBO Member Christine Petit.

Filed under hair cells inner ear usher syndrome hearing protocadherin-15 medicine science

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Boost for dopamine packaging protects brain in Parkinson’s model

Researchers from Emory’s Rollins School of Public Health discovered that an increase in the protein that helps store dopamine, a critical brain chemical, led to enhanced dopamine neurotransmission and protection from a Parkinson’s disease-related neurotoxin in mice.

Dopamine and related neurotransmitters are stored in small storage packages called vesicles by the vesicular monoamine transporter (VMAT2). When released from these packages dopamine can help regulate movement, pleasure and emotional response. Low dopamine levels are associated with neurodegenerative diseases such as Parkinson’s disease and recent research has shown that VMAT2 function is impaired in people with the disease.

Lead researcher Gary W. Miller, PhD professor and associate dean for research at the Rollins School of Public Health and his team generated transgenic mice with increased levels of VMAT2 and found it led to an increase in dopamine release. In addition, the group found improved outcomes on anxiety and depressive behaviors, increased movement, and protection from MPTP, the chemical that can cause Parkinson’s disease-related damage in the brain.

The complete study is available in the June 17, 2014 edition of Proceedings of the National Academy of Sciences (PNAS).

According to Miller, “This work suggests that enhanced vesicular filling can be sustained over time and may be a viable
 therapeutic approach for a variety of central nervous system disorders that involve the storage and release of dopamine, serotonin or norepinephrine.”

(Source: news.emory.edu)

Filed under parkinson's disease dopamine VMAT2 neurotransmitters neuroscience science

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Stress hormone linked to short-term memory loss as we age A new study at the University of Iowa reports a potential link between stress hormones and short-term memory loss in older adults. The study, published in the Journal of Neuroscience, reveals that having high levels of cortisol—a natural hormone in our body whose levels surge when we are stressed—can lead to memory lapses as we age. Short-term increases in cortisol are critical for survival. They promote coping and help us respond to life’s challenges by making us more alert and able to think on our feet. But abnormally high or prolonged spikes in cortisol—like what happens when we are dealing with long-term stress—can lead to negative consequences that numerous bodies of research have shown to include digestion problems, anxiety, weight gain, and high blood pressure. In this study, the UI researchers linked elevated amounts of cortisol to the gradual loss of synapses in the prefrontal cortex, the region of the brain that houses short-term memory. Synapses are the connections that help us process, store, and recall information. And when we get older, repeated and long-term exposure to cortisol can cause them to shrink and disappear. “Stress hormones are one mechanism that we believe leads to weathering of the brain,” says Jason Radley, assistant professor in psychology at the UI and corresponding author on the paper. Like a rock on the shoreline, after years and years it will eventually break down and disappear. While previous studies have shown cortisol to produce similar effects in other regions of the aging brain, this was the first study to examine its impact on the prefrontal cortex. And although preliminary, the findings raise the possibility that short-memory decline in aging adults may be slowed or prevented by treatments that decrease levels of cortisol in susceptible individuals, says Radley. That could mean treating people who have naturally high levels of cortisol—such as those who are depressed—or those who experience repeated, long-term stress due to traumatic life events like the death of a loved one. According to Radley and Rachel Anderson, the paper’s lead author and a second year-graduate student in psychology at the UI, short-term memory lapses related to cortisol start around age 65. That’s about the equivalent of 21 month-old rats, which the pair studied to make their discovery. The UI scientists compared the elderly rats to four-month old rats, which are roughly the same age as a 20 year-old person. The young and elderly groups were then separated further according to whether the rats had naturally high or naturally low levels of corticosterone—the hormone comparable to cortisol in humans. The researchers subsequently placed the rats in a T-shaped maze that required them to use their short-term memory. In order to receive a treat, they needed to recall which direction they had turned at the top of the T just 30, 60, or 120 seconds ago and then turn the opposite way each time they ran the maze. Though memory declined across all groups as the time rats waited before running the maze again increased, older rats with high corticosterone levels consistently performed the worst. They chose the correct direction only 58 percent of the time, compared to their older peers with low corticosterone levels who chose it 80 percent of the time. When researchers took tissue samples from the rats’ prefrontal cortexes and examined them under a microscope, they found the poor performers had smaller and 20 percent fewer synapses than all other groups, indicating memory loss. In contrast, older rats with low corticosterone levels showed little memory loss and ran the maze nearly as well as the younger rats, who were not affected by any level of corticosterone—low or high. Still, researchers say it’s important to remember that stress hormones are only one of a host of factors when it comes to mental decline and memory loss as we age.

Stress hormone linked to short-term memory loss as we age

A new study at the University of Iowa reports a potential link between stress hormones and short-term memory loss in older adults.

The study, published in the Journal of Neuroscience, reveals that having high levels of cortisol—a natural hormone in our body whose levels surge when we are stressed—can lead to memory lapses as we age.

Short-term increases in cortisol are critical for survival. They promote coping and help us respond to life’s challenges by making us more alert and able to think on our feet. But abnormally high or prolonged spikes in cortisol—like what happens when we are dealing with long-term stress—can lead to negative consequences that numerous bodies of research have shown to include digestion problems, anxiety, weight gain, and high blood pressure.

In this study, the UI researchers linked elevated amounts of cortisol to the gradual loss of synapses in the prefrontal cortex, the region of the brain that houses short-term memory. Synapses are the connections that help us process, store, and recall information. And when we get older, repeated and long-term exposure to cortisol can cause them to shrink and disappear.

“Stress hormones are one mechanism that we believe leads to weathering of the brain,” says Jason Radley, assistant professor in psychology at the UI and corresponding author on the paper. Like a rock on the shoreline, after years and years it will eventually break down and disappear.

While previous studies have shown cortisol to produce similar effects in other regions of the aging brain, this was the first study to examine its impact on the prefrontal cortex.

And although preliminary, the findings raise the possibility that short-memory decline in aging adults may be slowed or prevented by treatments that decrease levels of cortisol in susceptible individuals, says Radley. That could mean treating people who have naturally high levels of cortisol—such as those who are depressed—or those who experience repeated, long-term stress due to traumatic life events like the death of a loved one.

According to Radley and Rachel Anderson, the paper’s lead author and a second year-graduate student in psychology at the UI, short-term memory lapses related to cortisol start around age 65. That’s about the equivalent of 21 month-old rats, which the pair studied to make their discovery.

The UI scientists compared the elderly rats to four-month old rats, which are roughly the same age as a 20 year-old person. The young and elderly groups were then separated further according to whether the rats had naturally high or naturally low levels of corticosterone—the hormone comparable to cortisol in humans.

The researchers subsequently placed the rats in a T-shaped maze that required them to use their short-term memory. In order to receive a treat, they needed to recall which direction they had turned at the top of the T just 30, 60, or 120 seconds ago and then turn the opposite way each time they ran the maze.

Though memory declined across all groups as the time rats waited before running the maze again increased, older rats with high corticosterone levels consistently performed the worst. They chose the correct direction only 58 percent of the time, compared to their older peers with low corticosterone levels who chose it 80 percent of the time.

When researchers took tissue samples from the rats’ prefrontal cortexes and examined them under a microscope, they found the poor performers had smaller and 20 percent fewer synapses than all other groups, indicating memory loss.

In contrast, older rats with low corticosterone levels showed little memory loss and ran the maze nearly as well as the younger rats, who were not affected by any level of corticosterone—low or high.

Still, researchers say it’s important to remember that stress hormones are only one of a host of factors when it comes to mental decline and memory loss as we age.

Filed under stress memory cortisol STM prefrontal cortex synapses aging neuroscience science

354 notes

Researchers identify new compound to treat depression There is new hope for people suffering from depression. Researchers have identified a compound, hydroxynorketamine (HNK), that may treat symptoms of depression just as effectively and rapidly as ketamine, without the unwanted side effects associated with the psychoactive drug, according to a study in the July issue of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®).  Interestingly, use of HNK may also serve as a future therapeutic approach for treating neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, the authors note. “The clinical use of ketamine therapy for depression is limited because the drug is administered intravenously and may produce adverse effects such as hallucinations and sedation to the point of anesthesia,” said Irving Wainer, Ph.D., senior investigator with the Intramural Research Program at the National Institute on Aging, Baltimore. “We found that the HNK compound significantly contributes to the anti-depressive effects of ketamine in animals, but doesn’t produce the sedation or anesthesia, which makes HNK an attractive alternative as an antidepressant in humans.” HNK is one of several different compounds produced when ketamine, an anesthesia medicine-turned-antidepressant, is broken down (metabolized) in the body. Using a rat model, researchers tested HNK to see if the compound alone could produce the same beneficial effects attributed to ketamine without ketamine’s unwanted side effects.  In the study, rats were given intravenous doses of ketamine, HNK and another compound produced by ketamine metabolism known as norketamine. The effect each had on stimulating certain cellular pathways of the rats’ brains was examined after 20, 30 and 60 minutes.  Brain tissue from drug-free rats was used as a control. Researchers found the compound HNK, like ketamine, not only produced potent and rapid antidepressant effects, but also stimulated neuro-regenerative pathways and initiated the regrowth of neurons in rats’ brains. HNK also appears to have several advantages over ketamine in that it is 1,000 times more potent, does not act as an anesthetic agent, and can be taken by mouth, the authors report.  Surprisingly, HNK was also found to reduce the production of D-serine, a chemical found in the body, overproduction of which is associated with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. HNK’s ability to reduce the production of D-serine, while stimulating the regeneration of neuron connections in the brain, may present a potential new therapeutic approach to the treatment of these disorders.  “HNK’s unique properties increase the possibility of the development of a self-administered, daily treatment that works quickly and can be taken at home for a variety of central nervous system diseases,” said Dr. Wainer.  “This is a very exciting discovery and we hope that the results of this study will enable future investigations into this potentially therapeutic and important compound.” Dr. Wainer and several of the study’s authors are listed as co-inventors on a patent application for the use of ketamine compounds in the treatment of bipolar disorder and major depression. 

Researchers identify new compound to treat depression

There is new hope for people suffering from depression. Researchers have identified a compound, hydroxynorketamine (HNK), that may treat symptoms of depression just as effectively and rapidly as ketamine, without the unwanted side effects associated with the psychoactive drug, according to a study in the July issue of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®).  Interestingly, use of HNK may also serve as a future therapeutic approach for treating neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, the authors note.

“The clinical use of ketamine therapy for depression is limited because the drug is administered intravenously and may produce adverse effects such as hallucinations and sedation to the point of anesthesia,” said Irving Wainer, Ph.D., senior investigator with the Intramural Research Program at the National Institute on Aging, Baltimore. “We found that the HNK compound significantly contributes to the anti-depressive effects of ketamine in animals, but doesn’t produce the sedation or anesthesia, which makes HNK an attractive alternative as an antidepressant in humans.”

HNK is one of several different compounds produced when ketamine, an anesthesia medicine-turned-antidepressant, is broken down (metabolized) in the body. Using a rat model, researchers tested HNK to see if the compound alone could produce the same beneficial effects attributed to ketamine without ketamine’s unwanted side effects. 

In the study, rats were given intravenous doses of ketamine, HNK and another compound produced by ketamine metabolism known as norketamine. The effect each had on stimulating certain cellular pathways of the rats’ brains was examined after 20, 30 and 60 minutes.  Brain tissue from drug-free rats was used as a control.

Researchers found the compound HNK, like ketamine, not only produced potent and rapid antidepressant effects, but also stimulated neuro-regenerative pathways and initiated the regrowth of neurons in rats’ brains. HNK also appears to have several advantages over ketamine in that it is 1,000 times more potent, does not act as an anesthetic agent, and can be taken by mouth, the authors report. 

Surprisingly, HNK was also found to reduce the production of D-serine, a chemical found in the body, overproduction of which is associated with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. HNK’s ability to reduce the production of D-serine, while stimulating the regeneration of neuron connections in the brain, may present a potential new therapeutic approach to the treatment of these disorders. 

“HNK’s unique properties increase the possibility of the development of a self-administered, daily treatment that works quickly and can be taken at home for a variety of central nervous system diseases,” said Dr. Wainer.  “This is a very exciting discovery and we hope that the results of this study will enable future investigations into this potentially therapeutic and important compound.”

Dr. Wainer and several of the study’s authors are listed as co-inventors on a patent application for the use of ketamine compounds in the treatment of bipolar disorder and major depression. 

Filed under hydroxynorketamine ketamine depression neurodegenerative diseases norketamine medicine science

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Does the moon affect our sleep? Popular beliefs about the influence of the moon on humans widely exist. Many people report sleeplessness around the time of full moon. In contrast to earlier studies, scientists from the Max Planck Institute of Psychiatry in Munich did not observe any correlation between human sleep and the lunar phases. The researchers analyzed preexisting data of a large cohort of volunteers and their sleep nights. Further identification of mostly unpublished null findings suggests that the conflicting results of previous studies might be due to a publication bias. For centuries, people have believed that the moon cycle influences human health, behavior and physiology. Folklore mainly links the full moon with sleeplessness. But what about the scientific background? Several studies searched in re-analyses of pre-existing datasets on human sleep for a lunar effect, although the results were quite varying and the effects on sleep have rarely been assessed with objective measures, such as a sleep EEG. In some studies women appeared more affected by the moon phase, in others men. Two analyses of datasets from 2013 and 2014, each including between 30 and 50 volunteers, agreed on shorter total sleep duration in the nights around full moon. However, both studies came to conflicting results in other variables. For example, in one analysis the beginning of the REM-sleep phase in which we mainly dream was delayed around new moon, whereas the other study observed the longest delay around full moon. To overcome the problem of possible chance findings in small study samples, scientists now analyzed the sleep data of overall 1,265 volunteers during 2,097 nights. “Investigating this large cohort of test persons and sleep nights, we were unable to replicate previous findings,” states Martin Dresler, neuroscientist at the Max Planck Institute of Psychiatry in Munich, Germany, and the Donders Institute for Brain, Cognition and Behaviour in Nijmegen, Netherlands. “We could not observe a statistical relevant correlation between human sleep and the lunar phases.” Further, his team identified several unpublished null findings including cumulative analyses of more than 20,000 sleep nights, which suggest that the conflicting results might be an example of a publication bias (i.e. the file drawer problem). The file drawer problem describes the phenomenon, that many studies may be conducted but never reported – they remain in the file drawer. One much-discussed publication bias in science, medicine and pharmacy is the tendency to report experimental results that are positive or show a significant finding and to omit results that are negative or inconclusive. Up to now, the influence of the lunar cycle on human sleep was investigated in re-analyses of earlier studies which originally followed different purposes. “To overcome the obvious limitations of retrospective data analysis, carefully controlled studies specifically designed for the test of lunar cycle effects on sleep in large samples are required for a definite answer,” comments Dresler.

Does the moon affect our sleep?

Popular beliefs about the influence of the moon on humans widely exist. Many people report sleeplessness around the time of full moon. In contrast to earlier studies, scientists from the Max Planck Institute of Psychiatry in Munich did not observe any correlation between human sleep and the lunar phases. The researchers analyzed preexisting data of a large cohort of volunteers and their sleep nights. Further identification of mostly unpublished null findings suggests that the conflicting results of previous studies might be due to a publication bias.

For centuries, people have believed that the moon cycle influences human health, behavior and physiology. Folklore mainly links the full moon with sleeplessness. But what about the scientific background?

Several studies searched in re-analyses of pre-existing datasets on human sleep for a lunar effect, although the results were quite varying and the effects on sleep have rarely been assessed with objective measures, such as a sleep EEG. In some studies women appeared more affected by the moon phase, in others men. Two analyses of datasets from 2013 and 2014, each including between 30 and 50 volunteers, agreed on shorter total sleep duration in the nights around full moon. However, both studies came to conflicting results in other variables. For example, in one analysis the beginning of the REM-sleep phase in which we mainly dream was delayed around new moon, whereas the other study observed the longest delay around full moon.

To overcome the problem of possible chance findings in small study samples, scientists now analyzed the sleep data of overall 1,265 volunteers during 2,097 nights. “Investigating this large cohort of test persons and sleep nights, we were unable to replicate previous findings,” states Martin Dresler, neuroscientist at the Max Planck Institute of Psychiatry in Munich, Germany, and the Donders Institute for Brain, Cognition and Behaviour in Nijmegen, Netherlands. “We could not observe a statistical relevant correlation between human sleep and the lunar phases.” Further, his team identified several unpublished null findings including cumulative analyses of more than 20,000 sleep nights, which suggest that the conflicting results might be an example of a publication bias (i.e. the file drawer problem).

The file drawer problem describes the phenomenon, that many studies may be conducted but never reported – they remain in the file drawer. One much-discussed publication bias in science, medicine and pharmacy is the tendency to report experimental results that are positive or show a significant finding and to omit results that are negative or inconclusive.

Up to now, the influence of the lunar cycle on human sleep was investigated in re-analyses of earlier studies which originally followed different purposes. “To overcome the obvious limitations of retrospective data analysis, carefully controlled studies specifically designed for the test of lunar cycle effects on sleep in large samples are required for a definite answer,” comments Dresler.

Filed under sleep lunar phases EEG moon cycle psychology neuroscience science

119 notes

New Study Shows Limited Motor Skills In Early Infancy May Be Trait of Autism Researchers from Kennedy Krieger Institute in Baltimore, Md., announced findings that provide evidence for reduced grasping and fine motor activity among six-month-old infants with an increased familial risk for autism spectrum disorders (ASD). The research, which was published in Child Development, has important implications for our overall understanding of ASDs. Furthermore, the results suggest that subtle lags in object exploration-related motor skills in early infancy may present an ASD endophenotype - a heritable characteristic that may have genetic relation to ASD without predicting a full diagnosis- and further our understanding of the genes involved in the disorder. “Among the infants with familial history of ASD, many were shown to have reduced fine motor skills regardless of eventual ASD diagnosis,” says Dr. Rebecca Landa, lead author and director of Kennedy Krieger’s Center for Autism and Related Disorders. “This means that reduced fine motor skills could be an ASD endophenotype without predicting full diagnosis. Identifying potential endophenotypes has important implications for future research and may improve our understanding of the neurobiology and genetics of ASDs.” Researchers conducted two experiments examining the correlation of early motor development and object exploration in children with low risk (LR) or high risk (HR) of developing an ASD. Researchers measured key early learning skills, such as object manipulation and grasping activity, in infants at six months of age and again at 10 months. While all infants scored within the expected range and showed no difference in terms of their object manipulation, there were subtle signs that showed reduced grasping activity in HR infants as compared to their LR age-peers. These findings demonstrate that regardless of developmental outcomes, early motor skill differences in HR infants may represent an endophenotype that can be linked to ASD. About Experiment 1 In experiment 1, participants included 129 infants, largely consisting of infant siblings of children with confirmed ASD diagnoses. During the testing period, most participants were six months old and were then followed longitudinally to the age of 36 months. Infants completed an assessment using the Mullen Scales of Early Learning (MSEL), which is a standardized assessment tool providing scores in five categories: Gross Motor (GM); Fine Motor (FM); Visual Reception (VR); Receptive Language (RL); and Expressive Language (EL). Based on the results of this assessment, infants were then divided into four groups : low-risk (LR) infants without ASD; high-risk (HR) infants without ASD, language, or social delays; HR infants showing language or social delays but not ASD; and HR infants with autism or ASD diagnosis. All children in the HR ASD group met DSM-IV diagnostic criteria for the disorder. All four groups in Experiment 1 scored within the typical range on the MSEL subtests, meaning that none exhibited a clinical delay in their overall fine motor development at age six months. Subtle differences between HR and LR infants emerged even in HR infants who did not receive a diagnosis of ASD or other delays by age 36 months, which suggests that lower fine motor scores on the MSEL are characteristic of infants at high familial risk for ASD. In order to examine whether the HR infants would catch up to the LR infants in time, researchers conducted a second experiment with new participants. About Experiment 2 Experiment 2 focused on a new group of six-month-old infants in both LR and HR categories and examined only their grasping behaviors in a naturalistic, free-play context, which was an important factor that emerged in Experiment 1. Participants included 42 infants who were siblings of children with ASD. The infants were observed in an unstructured play session. The results of Experiment 2 showed reduced grasping and object exploration activity in six-month-old infants at HR for ASD. Overall, the MSEL FM T-score results observed in Experiment 2 show a similar pattern as in Experiment 1, but statistical results are somewhat weakened by an effect of gender in the LR sample. Unique to Experiment 2, was the sole focus on object manipulation-related items of the MSEL, which offered a consistent measure to identify differences between HR and LR infants. Reduced grasping activity in HR infants at age 6 months was also observed during an unstructured free-play task in Experiment 2, which provides additional evidence for the findings observed in Experiment 1. However, the HR infants caught up to the LR group in grasping, as measured in this study, by 10 months of age. Future studies are needed to examine these preliminary findings more closely to specifically assess grasping ability in infants that receive an ASD diagnosis later in life. (Image: Bigstock)

New Study Shows Limited Motor Skills In Early Infancy May Be Trait of Autism

Researchers from Kennedy Krieger Institute in Baltimore, Md., announced findings that provide evidence for reduced grasping and fine motor activity among six-month-old infants with an increased familial risk for autism spectrum disorders (ASD). The research, which was published in Child Development, has important implications for our overall understanding of ASDs. Furthermore, the results suggest that subtle lags in object exploration-related motor skills in early infancy may present an ASD endophenotype - a heritable characteristic that may have genetic relation to ASD without predicting a full diagnosis- and further our understanding of the genes involved in the disorder.

“Among the infants with familial history of ASD, many were shown to have reduced fine motor skills regardless of eventual ASD diagnosis,” says Dr. Rebecca Landa, lead author and director of Kennedy Krieger’s Center for Autism and Related Disorders. “This means that reduced fine motor skills could be an ASD endophenotype without predicting full diagnosis. Identifying potential endophenotypes has important implications for future research and may improve our understanding of the neurobiology and genetics of ASDs.”

Researchers conducted two experiments examining the correlation of early motor development and object exploration in children with low risk (LR) or high risk (HR) of developing an ASD. Researchers measured key early learning skills, such as object manipulation and grasping activity, in infants at six months of age and again at 10 months. While all infants scored within the expected range and showed no difference in terms of their object manipulation, there were subtle signs that showed reduced grasping activity in HR infants as compared to their LR age-peers. These findings demonstrate that regardless of developmental outcomes, early motor skill differences in HR infants may represent an endophenotype that can be linked to ASD.

About Experiment 1

In experiment 1, participants included 129 infants, largely consisting of infant siblings of children with confirmed ASD diagnoses. During the testing period, most participants were six months old and were then followed longitudinally to the age of 36 months. Infants completed an assessment using the Mullen Scales of Early Learning (MSEL), which is a standardized assessment tool providing scores in five categories: Gross Motor (GM); Fine Motor (FM); Visual Reception (VR); Receptive Language (RL); and Expressive Language (EL). Based on the results of this assessment, infants were then divided into four groups : low-risk (LR) infants without ASD; high-risk (HR) infants without ASD, language, or social delays; HR infants showing language or social delays but not ASD; and HR infants with autism or ASD diagnosis. All children in the HR ASD group met DSM-IV diagnostic criteria for the disorder.

All four groups in Experiment 1 scored within the typical range on the MSEL subtests, meaning that none exhibited a clinical delay in their overall fine motor development at age six months. Subtle differences between HR and LR infants emerged even in HR infants who did not receive a diagnosis of ASD or other delays by age 36 months, which suggests that lower fine motor scores on the MSEL are characteristic of infants at high familial risk for ASD. In order to examine whether the HR infants would catch up to the LR infants in time, researchers conducted a second experiment with new participants.

About Experiment 2

Experiment 2 focused on a new group of six-month-old infants in both LR and HR categories and examined only their grasping behaviors in a naturalistic, free-play context, which was an important factor that emerged in Experiment 1. Participants included 42 infants who were siblings of children with ASD. The infants were observed in an unstructured play session.

The results of Experiment 2 showed reduced grasping and object exploration activity in six-month-old infants at HR for ASD. Overall, the MSEL FM T-score results observed in Experiment 2 show a similar pattern as in Experiment 1, but statistical results are somewhat weakened by an effect of gender in the LR sample. Unique to Experiment 2, was the sole focus on object manipulation-related items of the MSEL, which offered a consistent measure to identify differences between HR and LR infants. Reduced grasping activity in HR infants at age 6 months was also observed during an unstructured free-play task in Experiment 2, which provides additional evidence for the findings observed in Experiment 1. However, the HR infants caught up to the LR group in grasping, as measured in this study, by 10 months of age.

Future studies are needed to examine these preliminary findings more closely to specifically assess grasping ability in infants that receive an ASD diagnosis later in life.

(Image: Bigstock)

Filed under ASD autism motor control motor activity infants psychology neuroscience science

117 notes

Distracted minds still see blurred lines

From animated ads on Main Street to downtown intersections packed with pedestrians, the eyes of urban drivers have much to see.

But while city streets have become increasingly crowded with distractions, our ability to process visual information has remained unchanged for millions of years. Can modern eyes keep up?

Encouragingly, a new study suggests that even as we’re processing a million things at once, we are still sensitive to certain kinds of changes in our visual environment — even while performing a difficult task.

In a paper published in Visual Cognition, researchers from Concordia University, Kansas State University, the University of Findlay, the University of Central Florida and the University of Illinois prove that we can automatically detect changes in blur across our field of view.

To investigate, the research team focused on the common problem of blurred sight, which can be caused by factors like changes in distance between objects, as well as vision disorders like near-sightedness, far-sightedness and astigmatism.

“Blur is normally compensated for by adjusting the lens of the eye to bring the image back into focus,” says study co-author Aaron Johnson, a professor in the Department of Psychology at Concordia.

“We wanted to know if the detection of this blur by the brain happens automatically, because previous research had resulted in two conflicting views.”

Those views suggest:

  1. Blur-detection requires mental effort: By focusing your attention on a blurry object in your peripheral vision, you can bring the object into focus — as though you were focusing a camera manually.
  2. Blur-detection is automatic: When the brain encounters blurred vision, it automatically compensates — as though you were using a camera with a permanent autofocus function.

“If blur is detected automatically and doesn’t require attention, then performing another cognitive task  — driving, say — at the same time shouldn’t change our ability to detect the blur,” Johnson says.

To determine which of these two theories was correct, he and his colleagues used a new technique that presented different amounts of blur to various regions of the eye.

The researchers showed study participants (individuals with normal, or corrected-to-normal, vision) 1,296 distinct images — pictures of things ranging from forests to building interiors — and used a window that moved based on the their eye movements to give the pictures two levels of resolution.

As they changed the resolution from blurry to sharp, the researchers gave participants mental tasks of varying degree of difficulty. Regardless of the difficulty levels, though, the subjects’ ability to detect blur in these pictures was unchanged.

“Our study proves that, much like other simple visual features such as colour and size, blur in an image doesn’t seem to require mental effort to detect,” Johnson says.

“The process may be what we call ‘pre-attentive’ — that is, little or no attention is required to detect it. As such, this research provides insight into a key task, compensating for blur, that the visual system must perform on a daily basis. In the future, I hope to study how blur detection changes with age.”

(Source: concordia.ca)

Filed under object recognition visual system categorization blurred vision psychology neuroscience science

323 notes

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."

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."

Filed under ADHD dopamine psychostimulants iron neuroscience science

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