Your Brain On--and Off--Caffeine

Ever miss your daily cup of coffee and subsequently get a pounding headache? According to reports from consumers of coffee and other caffeinated products, caffeine withdrawal is often characterized by a headache, fatigue, feeling less alert, less energetic and experiencing difficulty concentrating. Researchers from the University of Vermont College of Medicine and Johns Hopkins School of Medicine sought to investigate the biological mechanisms of caffeine withdrawal in a paper published recently in the online edition of the scientific journal Psychopharmacology. They looked at brain electrical activity and blood flow during caffeine withdrawal to examine what was taking place physiologically during acute caffeine abstinence, including the likely mechanism underlying the common "caffeine withdrawal headache."

The group examined caffeine's effects in a double-blind study, which involved the administration of caffeine and placebo capsules. Each participant's response to the caffeine or placebo was measured using three different measures -- brain electrical activity via electroencephalogram (EEG); blood flow velocity in the brain via ultrasound; and participants' self-reports of subjective effects via questionnaires. The team demonstrated that stopping daily caffeine consumption produces changes in cerebral blood flow velocity and quantitative EEG that are likely related to the classic caffeine withdrawal symptoms of headache, drowsiness and decreased alertness. More specifically, acute caffeine abstinence increased brain blood flow, an effect that may account for commonly reported withdrawal headaches. Acute caffeine abstinence also produced changes in EEG (increased theta rhythm) that has previously been linked to the common withdrawal symptom of fatigue. Consistent with this, volunteers reported increases in measures of "tired," "fatigue," "sluggish" and "weary." Overall, these findings provide the most rigorous demonstration to date of physiological effects of caffeine withdrawal.

The researchers also discovered a provocative and somewhat unexpected finding -- that there were no net benefits associated with chronic caffeine administration.
"In addition to looking at caffeine withdrawal, this rigorous design also permitted comparison of chronic caffeine maintenance with chronic placebo maintenance, which provides unique information about the extent to which there are net beneficial effects of daily caffeine administration," said Stacey Sigmon, Ph.D., research associate professor of psychiatry at the University of Vermont and first author on the study. "In contrast to what most of us coffee lovers would think, our study showed no difference between when the participant was maintained on chronic placebo and when the participant was stabilized on chronic caffeine administration. What this means is that consuming caffeine regularly does not appear to produce any net beneficial effects, based on the measures we examined."

Co-authors on the study, which was a collaboration between Sigmon and Roland Griffiths, Ph.D., at the Johns Hopkins University School of Medicine, include Griffiths, as well as Ronald Herning, Warren Better and Jean Cadet of the National Institute on Drug Abuse's Molecular Neuropsychiatry section.

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Most Emailed: Weighing the Options after Life-Altering Stroke

After a catastrophic stroke, it's always painful and difficult to decide whether aggressive surgery is worth it. Even under the best circumstances after a severe infarction, patients could experience paralysis, loss of speech, breathing problems, and at the very least they could require help bathing, cooking, and taking care of themselves. But recent research findings may make the decision over surgery a little bit easier.

The research done by neurologists Adam G. Kelly and Robert Holloway shows that aggressive brain surgery after a severe stroke does improve the patients' quality of life and increases their life expectancy.

From the article:

Choosing to have aggressive brain surgery after suffering a severe stroke generally improves the patients' lives and allows them to live longer, according to research by neurologists at the University of Rochester Medical Center.

The findings should help patients and families put into perspective a decision that is nearly always painful and difficult to make - whether putting a patient through aggressive surgery after a catastrophic stroke is worth it. "For families facing this difficult choice, the more information we can provide, the better for their decision-making," said neurologist Adam G. Kelly, M.D., who has helped hundreds of families chart a course after severe stroke. Kelly presented the findings last month at the International Stroke Conference in San Diego.

Kelly and colleague Robert Holloway, M.D., studied three separate analyses of patients who had had a serious type of stroke known as a malignant middle cerebral artery infarction, in which blood flow to a large part of the brain is cut off. Further damage occurs when the damaged brain swells in the days immediately following the initial stroke, as delicate brain tissue is pushed up against the hard inner skull. Increased swelling and pressure in the brain diminish blood flow even further.

Even under the best circumstances, patients who have suffered such strokes face at least moderate disability, and often their challenges are severe, no matter what type of treatment is chosen. A patient might be paralyzed on one side of the body. They may have lost their ability to speak or even to comprehend what is said to them. They may need a breathing or feeding tube. At the very least, they'll likely need help each day with tasks like bathing, cooking, and taking care of themselves.

Kelly and Holloway looked at patients who were treated with medical options alone and compared their outcomes to those of patients who had a surgical procedure known as a hemicraniectomy. In that procedure, doctors remove a piece of the skull temporarily, limiting further damage by giving the brain room to swell. The portion of the skull that is removed is put back in place a few months later.

Typically the decision whether or not to go ahead with the surgery is made by families grappling with the catastrophic effects of severe stroke on their loved one. In the face of great uncertainty and under great duress and time pressures, families have to make the decision.

"There is no reliable early predictor of how most people will do after a stroke," said Kelly, an instructor and fellow in the Department of Neurology.

"Some people have a small stroke, with few effects, and we can predict that outcome fairly well. Others have strokes that are immediately catastrophic. But the vast majority of patients are in the middle, and we have a hard time predicting what the outcome will be. There is a lot we don't know about how the brain responds to injury, and how it recovers," Kelly said.

Kelly and Holloway studied data from three studies in Europe that looked at the outcomes of 93 people after stroke. The studies demonstrated that patients who didn't have the surgery were about three times more likely to die within a year than patients who did have the surgery, though many of the surgical patients were left with considerable disability.

Using a technique called decision analysis, Kelly and Holloway re-evaluated the outcomes of these trials to incorporate quality-of-life ratings for surviving patients. The authors found that even in the face of significant stroke-related disability, as a whole, patients who had undergone the surgical procedure had an improvement in their quality of life. The physicians then used a related method called sensitivity analysis to determine situations in which surgery might not be the preferred treatment. Only under circumstances where patients valued the outcome after stroke extremely poorly - almost as a fate worse than death - was surgery not the preferred option.

"There has been debate for a long time about the effects of this surgery for patients. It definitely saves lives, but we're asking whether the surgery really paid off for these patients. Did the patients value their health state? Was it worth it to them?" asks Kelly. "The answer most often is 'yes.'"

The authors say there are several types of patients for whom surgery clearly isn't a good option. These include people who were already in poor health before the stroke, people whose chances of surviving the surgery are questionable, and patients who have clearly stated that they would not want such measures to be taken.

For those who do opt for surgery, Kelly and Holloway found that living longer due to the surgery was only part of the benefit. Those patients also valued their health. That might seem difficult to understand for people who are healthy, but it does not surprise Holloway, who has worked with hundreds of patients severely limited by stroke.

"For years I've witnessed families wrestle with these decisions," said Holloway. "If the families make the decision based on what they imagine the future to be, they may decide it's a surgery the patient wouldn't want. But nearly always, when they've made the decision to go ahead with the surgery, the families are subsequently happy they made that decision.

"People who survive devastating stroke often do much better than people think they will do. People who haven't experienced a health condition, such as stroke, almost always provide a lower estimate of their quality of life compared to people who are actually living with that condition or disease," Holloway added.

Kelly has witnessed the same dynamics himself.

"People have a remarkable ability to compensate for whatever problems they face," said Kelly, whose fellowship is supported by the National Institute of Neurological Disorders and Stroke. "Oftentimes, the fear of the unknown, and the anxiety it causes, is worse than the actual situation. Over time, people adapt to their deficits, and as they do, they value their quality of life more highly."

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Playing, and Even Watching, Sports Improves Brain Function

Newswise — Being an athlete or merely a fan improves language skills when it comes to discussing their sport because parts of the brain usually involved in playing sports are instead used to understand sport language, new research at the University of Chicago shows.

The research was conducted on hockey players, fans, and people who’d never seen or played the game. It shows, for the first time, that a region of the brain usually associated with planning and controlling actions is activated when players and fans listen to conversations about their sport. The brain boost helps athletes and fans understanding of information about their sport, even though at the time when people are listening to this sport language they have no intention to act.

The study shows that the brain may be more flexible in adulthood than previously thought. “We show that non-language related activities, such as playing or watching a sport, enhance one’s ability to understand language about their sport precisely because brain areas normally used to act become highly involved in language understanding,” said Sian Beilock, Associate Professor in Psychology at the University of Chicago. “Personality of older fathers has been suggested to explain the association between mental disorders and advancing paternal age,” the authors write. “However, the mental disorders associated with increasing paternal age are under considerable genetic influence.” Therefore, there may be a genetic link between advancing age of the father and bipolar and other disorders in offspring.

“As men age, successive germ cell replications occur, and de novo [new, not passed from parent to offspring] mutations accumulate monotonously as a result of DNA copy errors,” the authors continue. “Women are born with their full supply of eggs that have gone through only 23 replications, a number that does not change as they age. Therefore, DNA copy errors should not increase in number with maternal age. Consistent with this notion, we found smaller effects of increased maternal age on the risk of bipolar disorder in the offspring.”

(Arch Gen Psychiatry. 2008;65[9]:1034-1040. Available pre-embargo to the media at http://www.jamamedia.org.)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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