Posts tagged brain

April 25, 2012

Can one feel too attached? Does one need to let go to mature? Neural stem cells have this problem, too.

As immature cells, neural stem cells must stick together in a protected environment called a niche in order to divide so they can make all of the cells that populate the nervous system. But when it’s time to mature, or differentiate, the neural stem cells must stop dividing, detach from their neighbors and migrate to where they are needed to form the circuits necessary for humans to think, feel and interact with the world.

Now, stem cell researchers at UCLA have identified new components of the genetic pathway that controls the adhesive properties and proliferation of neural stem cells and the formation of neurons in early development.

The finding by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA could be important because errors in this pathway can lead to a variety of birth defects that affect the structure of the nervous system, as well as more subtle changes that impair cognitive and motor functions associated with disorders such as autism.

The results of the four-year study are published April 26, 2012 in the peer-reviewed journal Neuron.

The UCLA team found that a delicate balance of gene expression enables the pool of neural stem and progenitor cells in early development to initially increase and then quickly stop dividing to form neurons at defined times.

"One of the greatest mysteries in developmental biology is what constitutes the switch between stem cell proliferation and differentiation. In our studies of the formation of motor neurons, the cells that are essential for movement, we were able to uncover what controls the early expansion of neural stem and progenitor cells, and more importantly what stops their proliferation when there are enough precursors built up," said Bennett G. Novitch, an assistant professor of neurobiology, a Broad Stem Cell Research Center scientist and senior author of the study. "If the neurons don’t form at the proper time, it could lead to deficits in their numbers and to catastrophic, potentially fatal neurological defects." 

During the first trimester of development, the neural stem and progenitor cells form a niche, or safe zone, within the nervous system. The neural stem and precursor cells adhere to each other in a way that allows them to expand their numbers and keep from differentiating. A protein called N-cadherin facilitates this adhesion, Novitch said.

When it is time for the neural precursors to become motor neurons, two proteins that repress gene expression, called Foxp2 and Foxp4, become elevated and then silence N-cadherin expression, causing the clustered neural stem and precursor cells to break apart and begin differentiating.

"We have these cells in a dividing state, making more of themselves, and to make neurons that process has to be stopped and those contacts between the cells disassembled," Novitch said. "Until now, it has not been clear how the cells are pulled apart."

Novitch and his team showed that if you eliminate Foxp protein function, motor neurons and other mature cells in the nervous system are not properly formed because the N-cadherin gene is not silenced, confirming the delicate balancing act that must be achieved for normal development of both the stem and precursor cells and their neuronal progeny.

"It’s a fundamental discovery. Most studies have focused on defining what promotes the adhesiveness and self-renewal of neural stem cells, rather than what breaks these contacts," Novitch said. "We were also surprised to see how small changes in the degree of cell adhesion can markedly alter the development and structure of the nervous system. It’s all about balance, if you have too many or too few stem and precursor cells, the result could be disastrous."

Going forward, Novitch and his team will examine whether the functions of Foxp2 and Foxp4 in regulating cell adhesion may be important for the maintenance and differentiation of neural stem cells in the adult brain, and whether the loss of their activity may contribute to the formation and growth of brain tumors. In addition, Novitch’s group plans to examine whether their findings are relevant for investigating the function of Foxp2 and Foxp4 in other aspects of neural development, as mutations in Foxp proteins have previously been associated with a range of intellectual disabilities and speech-language disorders.

"It is tempting to speculate that these loss-of-function phenotypes might result from abnormal cell adhesion associated with dysregulated N-cadherin expression or function," the study states. "If true, these findings could provide a molecular explanation for the association of Foxp mutations with developmental human language and motor disorders, including autism."

Provided by University of California - Los Angeles Health Sciences

Source: medicalxpress.com

April 25, 2012 By Allison Flynn

McGill physiology research team sheds light on how the brain processes what we sense.

We rely on our senses in all aspects of our lives. Unfortunately, many people suffer from some kind of impaired sensory function. In Canada alone, 600,000 people are visually impaired while almost three million suffer from partial or total hearing loss. In a paper published this week in The Journal of Neuroscience, researchers from McGill University have demonstrated for the first time that there are specific neurons that respond selectively to first and second order sensory attributes. In the visual system, for example, luminance is a first-order attribute, whereas contrast is second-order. These findings could pave the way to the development of novel therapies and improved prosthetics for those with sensory deficiencies.

The research team, led by physiology student Patrick McGillivray, recorded the responses to stimuli of midbrain electro-sensory neurons in the weakly electric fish. Based on these responses, the researchers were able to demonstrate that there are specific neurons that respond selectively to different attributes at the same time. Moreover, they uncovered the simple and generic neural circuits that enable this selectivity. These findings provide important clues about how the brain processes first and second order sensory attributes in audition (like pitch and timbre) and vision (like luminance and contrast).

"Uncovering these clues relies on identifying the attributes that we use to perceive stimuli, the computations performed by the brain, and the actual neural networks that implement these," explained Dr. Maurice Chacron, lead author and principal investigator at McGill’s Computational Systems Neuroscience Lab. "Stimuli like speech and music are characterized by multiple attributes. For example, when listening to music, we can perceive both frequency (how low or high an instrument is playing), as well as timbre (the type of instrument playing)."

Provided by McGill University

Source: medicalxpress.com

April 24th, 2012

Researchers at the University of Sydney have thrown new light on the tricks the brain plays as it struggles to make sense of the visual and other sensory signals it constantly receives.

In this tilt illusion, the lines in the centre of the image appear tilted counterclockwise, but they are actually vertical. Image adapted from University of Sydney image.

The research has implications for understanding how the brain interprets the world visually and how the brain itself works.

People rely on their eyes for most tasks – yet the information provided by our visual sensing system is often distorted, unreliable and subject to illusion.

In a just published article in Proceedings of the National Academy of Science, Dr Isabelle Mareschal and Professor Colin Clifford, from the University’s School of Psychology and The Vision Centre, report a series of groundbreaking experiments tracing the origins of the tilt illusion to the cells of the primary visual cortex. This is where the first stage of vision processing takes place before the conscious mind takes over.

“We tend to regard what we see as the real world,” said Dr Mareschal.

“In fact a lot of it is distortion, and it is occurring in the early processing of the brain, before consciousness takes over. Our work shows that the cells of the primary visual cortex create small distortions, which then pass on to the higher levels of the brain, to interpret as best it can.”

A common example of this that is often exploited by artists and designers is known as the tilt illusion where perfectly vertical lines appear tilted because they are placed on an oriented background.

“We wanted to test at what level the illusion occurs in the brain, unconscious or conscious – and also to see if the higher brain is aware of the illusions it is receiving and how it tries to correct for them,” she explains.

“The answer is that the brain seeks more contextual information from the background to try to work out the alignment of the object it is seeing.”

The team subjected volunteers to a complex test in which they indicated the orientation of a vertical line, perceived as constantly tilting from side to side, against a fuzzy background that was also changing.

“These illusions happen very fast, perhaps in milliseconds,” Dr Mareschal says. “And we found that even the higher brain cannot always correct for them, as it doesn’t in fact know they are illusions.”

This is one reason why people’s eyes sometimes mislead them when looking at objects in their visual landscape.

Normally, Dr Mareschal explains, it doesn’t matter all that much – but in the case of a person driving a car fast in traffic, an athlete performing complex acrobatic feats, a pilot landing an aircraft or other high-speed uses of sight, the illusion may be of vital importance by causing them to misinterpret the objects they ‘see’.

The brain uses context, or background, to interpret a host of other visual signals besides the orientation of objects. For example, it uses context to tell colour, motion, texture and contrast. The research will help study how the brain understands these visual cues adding to our overall understanding of brain function.

Source: Neuroscience News

By Brian Alexander

Good news for all those who ever had a teacher or a parent say “If you would just apply yourself you could learn anything! You’re only using 10 percent of your brain!”

All those people were wrong. If we did use only 10 percent of our brains we’d be close to dead, according to Eric Chudler, director of the Center for Sensorimotor Neural Engineering at the University of Washington, who maintains an entertaining brain science website for kids. “When recordings are made from brain EEGs, or PET scans, or any type of brain scan, there’s no part of the brain just sitting there unused,” he said. 

Larry Squire, a research neuroscientist with the Veterans Administration hospital in San Diego, and at the University of California San Diego, pointed out that “any place the brain is damaged there is a consequence.”

Damaged brains may have been where this myth originated. During the first half of the last century, a pioneering neuroscientist named Karl Lashley experimented on rodents by excising portions of their brains to see what happened. When he put these rodents in mazes they’d been trained to navigate, he found that animals with missing bits of brain often successfully navigated the mazes.

This wound up being transmuted into the idea humans must be wasting vast brain potential. With the rise of the human potential movement in the 1960s, some preached that all sorts of powers, including bending spoons and psychic abilities, were laying dormant in our heads and that all we had to do was get off our duffs and activate them.

“That’s a case of something one often sees, of taking something from the world of psychology and in trying to make the idea concrete, bringing in the mechanisms of biology,” Squire explained. “It’s fair to say we can all do better, and we have room for improvement through practice and developing skills, but that has nothing to do with the idea that we use only 10 percent of our brains.”

The brain, Chudler said, isn’t like a disc drive with some set amount of capacity. It’s a dynamic maze of wiring where new connections can be created in response to new stimuli, or lost with disuse. And much of it is constantly occupied not with intellectual thinking, but running our systems.

“That’s why the brain is such an expensive organ,” he explained. “It requires 20 percent of our blood supply, and it’s a real energy hog.” If we used only 10 percent of it, the brain wouldn’t require such high maintenance.

“Besides,” he pointed out, “why would our brains have gotten bigger through evolution if so much of it were going unused?”

Source: The Body Odd

April 24, 2012

Older animals show cellular changes in the brain “clock” that sets sleep and wakeful periods, according to new research in the April 25 issue of The Journal of Neuroscience. The findings may help explain why elderly people often experience trouble sleeping at night and are drowsy during the day.

Like humans, mice experience shifts in daily activities and sleep patterns as they age. To find out why, researchers directed by Johanna Meijer, PhD, at the Leiden University Medical Center in the Netherlands studied the electrical activity of cells in the suprachiasmatic nucleus (SCN), an area of the brain responsible for setting sleep-wake cycles.

Consistent with previous studies, the researchers found aged mice showed disrupted sleep behavior and weakened brain network activity in the SCN. But Meijer and colleagues also found changes occurring in individual SCN cells, not just in their networks.

"In fact, the changes at the single-cell level were more severe than the changes at the network level," said Meijer. This represents a shift in understanding of aging’s effects on the brain.

The researchers made electrophysiological recordings from isolated SCN neurons, a difficult experiment given the advanced age of the animals and the small size of this type of neuron. They found aged SCN neurons lack day-night rhythms in some membrane properties. In addition, the team identified age-related reductions of certain potassium currents that are important to the neurons’ rhythmic firing.

Because potassium and other ion channels can be manipulated with drugs, “This work provides a new target for potential therapeutic interventions that can mitigate the age-related decline in the sleep-wake cycle,” said Christopher Colwell, PhD, an expert in circadian clock function at the University of California, Los Angeles, who was not involved in the study.

Provided by Society for Neuroscience

Source: medicalxpress.com

April 24, 2012

A history of binge eating — consuming large amounts of food in a short period of time — may make an individual more likely to show other addiction-like behaviors, including substance abuse, according to Penn State College of Medicine researchers. In the short term, this finding may shed light on the factors that promote substance abuse, addiction, and relapse. In the long term, may help clinicians treat individuals suffering from this devastating disease.

"Drug addiction persists as a major problem in the United States," said Patricia Sue Grigson, Ph.D., professor, Department of Neural and Behavioral Sciences. "Likewise, excessive food intake, like binge eating, has become problematic. Substance-abuse and binge eating are both characterized by a loss of control over consumption. Given the common characteristics of these two types of disorders, it is not surprising that the co-occurrence of eating disorders and substance abuse disorders is high. It is unknown, however, whether loss of control in one disorder predisposes an individual to loss of control in another."

Grigson and her colleagues found a link between bingeing on fat and the development of cocaine-seeking and -taking behaviors in rats, suggesting that conditions promoting excessive behavior toward one substance can increase the probability of excessive behavior toward another. They report their results in Behavioral Neuroscience.

The researchers used rats to test whether a history of binge eating on fat would augment addiction-like behavior toward cocaine by giving four groups of rats four different diets: normal rat chow; continuous ad lib access to an optional source of dietary fat; one hour of access to optional dietary fat daily; and one hour of access to dietary fat on Mondays, Wednesdays, and Fridays. All four groups also had unrestricted access to nutritionally complete chow and water. The researchers then assessed the cocaine-seeking and -taking behaviors.

"Fat bingeing behaviors developed in the rats with access to dietary fat on Mondays, Wednesdays, and Fridays — the group with the most restricted access to the optional fat," Grigson said. 

This group tended to take more cocaine late in training, continued to try to get cocaine when signaled it was not available, and worked harder for cocaine as work requirements increased.

"While the underlying mechanisms are not known, one point is clear from behavioral data: A history of bingeing on fat changed the brain, physiology, or both in a manner that made these rats more likely to seek and take a drug when tested more than a month later," Grigson said. "We must identify these predisposing neurophysiological changes."

While the consumption of fat in and of itself did not increase the likelihood of subsequent addiction-like behavior for cocaine, the irregular binge-type manner in which the fat was eaten proved critical. Rats that had continuous access to fat consumed more fat than any other group, but were three times less likely to exhibit addiction-like behavior for cocaine than the group with access only on Mondays, Wednesdays and Fridays.

"Indeed, while about 20 percent of those rats and humans exposed to cocaine will develop addiction-like behavior for the drug under normal circumstances, in our study, the probability of addiction to cocaine increased to approximately 50 (percent) for subjects with a history of having binged on fat," Grigson said.

Future studies will look more closely at how bingeing can lead to addiction-like behaviors — whether bingeing on sugar or a mixture of sugar and fat also promotes cocaine or heroin addiction, for example, and whether bingeing on a drug, in turn, increases the likelihood of bingeing on fat.

Provided by Pennsylvania State University

Source: medicalxpress.com

ScienceDaily (Apr. 24, 2012) — Scientists at The Scripps Research Institute have found clinical evidence that the drug gabapentin, currently on the market to treat neuropathic pain and epilepsy, helps people to quit smoking marijuana (cannabis). Unlike traditional addiction treatments, gabapentin targets stress systems in the brain that are activated by drug withdrawal.

In a 12-week trial of 50 treatment-seeking cannabis users, those who took gabapentin used less cannabis, experienced fewer withdrawal symptoms such as sleeplessness, and scored higher on tests of attention, impulse-control, and other cognitive skills, compared to patients who received a placebo. If these results are confirmed by ongoing larger trials, gabapentin could become the first FDA-approved pharmaceutical treatment for cannabis dependence.

"A lot of other drugs have been tested for their ability to decrease cannabis use and withdrawal, but this is the first to show these key effects in a controlled treatment study," said Barbara J. Mason, the Pearson Family Chair and Co-Director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research. "The other nice thing about gabapentin is that it is already widely prescribed, so its safety is less likely to be an issue."

Mason led the new gabapentin study, recently published online ahead of print by the journal Neuropsychopharmacology.

Stress Circuits

Addiction researchers have long known that recreational drugs hook users by disrupting the normal tuning of their brains’ reward and motivation circuitry. But as scientists at Scripps Research and other institutions have shown in animal studies, cannabis withdrawal after prolonged heavy use also leads to the long-term activation of basic stress circuits. “In human cannabis users who try to quit, this stress response is reflected in reports of drug craving, sleep disturbances, anxiety, irritability, and dysphoria, any one of which can motivate a person to return to using, because cannabis will quiet these symptoms,” said Mason.

A 2008 study by Pearson Center Co-Director George Koob and his colleagues found that gabapentin, an FDA-approved anticonvulsant drug that resembles the neurotransmitter GABA, can quiet this withdrawal-related activation in stress circuitry in alcohol-dependent rats. That finding motivated Mason to set up a pilot trial of gabapentin in cannabis-dependent individuals, whose withdrawal syndrome features a similar over-activation of stress circuits.

She and her colleagues recruited cannabis users with local newspaper and web ads headlined: “Smoking too much pot? We want to help you stop.” "We needed only 50 subjects, but we quickly got more than 700 queries from cannabis users who were eager to quit," Mason said. "Some people deny that cannabis can be addictive, but surveys show that between 16 and 25 percent of substance use treatment admissions around the world every year involve people with primary cannabis dependence."

Twice as Many Abstinent from Cannabis Use

The trial was based at Mason’s laboratory at The Scripps Research Institute. Half of the 50 recruits were randomly assigned to take 1,200 mg/day of gabapentin; the rest were given identical-looking placebo capsules. Over 12 weeks, Mason and her colleagues, including a medical team from the nearby Scripps Clinic, monitored the subjects with tests. Using standard behavioral therapy techniques, they also counseled the patients to stay off cannabis.

The subjects’ self-reports and more objective urine tests revealed that gabapentin, compared to placebo, significantly reduced their continuing cannabis use. “Urine metabolite readings indicate about twice as many of the gabapentin subjects had no new cannabis use during the entire study, and, in the last four weeks of the study, all of the gabapentin subjects who completed the study stayed abstinent,” Mason said.

Gabapentin also clearly reduced the reported symptoms of withdrawal such as sleep disturbances, drug cravings, and dysphoria. And even though gabapentin normally is thought of as a brain-quieting drug that can cause sleepiness as a side effect, there was some evidence that it sharpened cognition among the cannabis users. Seven gabapentin and ten placebo patients sat for tests of attention, impulse-control, and other executive functions just before the start of the trial and at week four. While the placebo patients tended to score lower after four weeks of attempted abstinence, the gabapentin patients generally scored higher.

Help Resisting Cravings

Addiction researchers now recognize that one of the effects of repeated drug use is the weakening of executive functions — which can happen through the over-activation of reward circuitry as well as by withdrawal-related stress. “That weakening of self-control-related circuits makes it even harder for people to resist drug cravings when they’re trying to quit, but gabapentin may help restore those circuits, by reducing stress and enabling patients to sleep better, so that they function better while awake,” Mason said.

She is now conducting a larger, confirmatory study of gabapentin in cannabis users, as well as a new study of a novel drug that targets the same stress circuitry.

"People in the treatment community have told me that they’re eager for these trial results to come out, because until now nothing has been shown to work against both relapse and withdrawal symptoms," Mason said.

Source: Science Daily

ScienceDaily (Apr. 24, 2012) — Stanford University School of Medicine neuroscientists have demonstrated, in a study published online April 24 in Stroke, that a compound mimicking a key activity of a hefty, brain-based protein is capable of increasing the generation of new nerve cells, or neurons, in the brains of mice that have had strokes. The mice also exhibited a speedier recovery of their athletic ability.

These results are promising, because the compound wasn’t administered to the animals until a full three days after they had suffered strokes, said the study’s senior author, Marion Buckwalter, MD, PhD, an assistant professor of neurology and neurological sciences. This means that the compound works not by limiting a stroke’s initial damage to the brain, but by enhancing recovery.

This is of critical significance, said Buckwalter, a practicing clinical neurologist who often treats recently arrived stroke patients in Stanford Hospital’s intensive care unit.

"No existing therapeutic agents today enhance recovery from stroke," Buckwalter said. "The only approved stroke drug, tissue plasminogen activator, can bust up clots that initially caused the stroke but does nothing to stimulate the restoration of brain function later." Furthermore, to be effective, tPA has to be given within four and a half hours after a stroke has occurred, she added. "In real life, many people don’t get to the hospital that quickly. They may live alone or have their stroke while sleeping, or they and the people close to them didn’t recognize the stroke’s symptoms well enough to realize they’d just had one."

Looking for an alternative, Buckwalter chose to focus on a compound called LM22A-4, which had shown promise in previous research. LM22A-4 is a small molecule whose bulk is less than one-seventieth that of the brain protein it mimics: brain-derived neurotrophic factor, a powerful and long-studied nerve growth factor. BDNF is critical during the development of the nervous system and known to be involved in important brain functions including memory and learning.

Stem-cell therapy, while an exciting prospect, is a relatively invasive and expensive way to replace lost or damaged tissue. A drug that could achieve similar results in such a delicate and complex organ as the brain would be a welcome development.

Read more …

ScienceDaily (Apr. 24, 2012) — In an important test of one of the first drugs to target core symptoms of autism, researchers at Mount Sinai School of Medicine are undertaking a pilot clinical trial to evaluate insulin-like growth factor (IGF-1) in children who have SHANK3 deficiency (also known as 22q13 Deletion Syndrome or Phelan-McDermid Syndrome), a known cause of autism spectrum disorder (ASD).

This study builds on findings announced by the researchers in 2010, which showed that after two weeks of treatment with IGF-1 in a mouse model, deficits in nerve cell communication were reversed and deficiencies in adaptation of nerve cells to stimulation, a key part of learning and memory, were restored.

"This clinical trial is part of a paradigm shift to develop medications specifically to treat the core symptoms of autism, as opposed to medications that were developed for other purposes but were found to be beneficial for autism patients as well," said Joseph Buxbaum, PhD, Director of the Seaver Autism Center at Mount Sinai. "Our study will evaluate the impact of IGF-1 vs. placebo on autism-specific impairments in socialization and associated symptoms of language and motor disability."

The seven-month study, which begins this month, will be conducted under the leadership of the Seaver Autism Center Clinical Director Alex Kolevzon, MD, and will utilize a double-blind, placebo-controlled crossover design in children ages 5 to 17 years old with SHANK3 deletions or mutations. Patients will receive three months of treatment with active medication or placebo, separated by a four-week washout period. Future trials are planned to explore the utility of IGF-1 in ASD without SHANK3 deficiency.

The primary aim of the study is to target core features of ASD, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. If preliminary results are promising, the goal is to expand the studies into larger, multi-centered efforts to include as many children as possible affected by this disorder.

IGF-1 is a US Food and Drug Administration-approved, commercially available compound that is known to promote neuronal cell survival as well as synaptic maturation and plasticity. Side effects of IGF-1 administration include low blood sugar, liver function abnormalities, and increased cholesterol and triglyceride levels. Study subjects will undergo rigorous safety screening before they are enrolled in the trial, and will be carefully monitored every two to four weeks with safety and efficacy assessments.

"We are excited that the researchers at the Seaver Autism Center are undertaking this pilot study to evaluate a possible treatment for SHANK3 deficiency, which may also help everyone with ASD," said Geraldine Bliss, Research Support Chair of the Phelan-McDermid Foundation. "This will be the first clinical trial in Phelan-McDermid Syndrome to emerge from convincing preclinical evidence in a model system."

The cause of autism has been debated for many years. Currently the best scientific evidence indicates that genetic mutations are the most likely culprits, acting either directly or indirectly, in upwards of 80 to 90 percent of individuals with ASDs. In the past few years, gene mutations and gene copy number variations have been identified that cause approximately 15 percent of cases of ASD. However, it is thought that hundreds of genes may be involved in causing autism.

One copy of the q13 portion of chromosome 22 is either missing or otherwise mutated in SHANK3 deficiency, also known as Phelan-McDermid Syndrome or 22q13 Deletion Syndrome (22q13DS). The area in question contains the gene SHANK3, and there is overwhelming evidence that it is the loss of one copy of SHANK3 that produces the neurological and behavioral aspects of the syndrome. The SHANK3 gene is key to the development of the human nervous system, and loss of SHANK3 can impair the ability of neurons to communicate with one another.

Source: Science Daily

ScienceDaily (Apr. 24, 2012) — Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study. Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question. In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient’s measured level of fatigue. The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation. Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue,” will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

More Fatigue, Less Activation

Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue. Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy. Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS. Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward. The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

Results Suggest Role of Inflammation

Unger notes that the findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome. “Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future, she adds. Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. Similarly, the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

Estimates from the CDC suggest that annual medical costs associated with chronic fatigue syndrome total about $14 billion in the United States. Annual losses to productivity because of lost work time range between $9 and $37 billion, with costs to individual households ranging between $8,000 and $20,000 per year.

Source: Science Daily