Adaptable Decision Making In The Brain 

ScienceDaily (June 19, 2012) — Researchers at the University of Iowa, together with colleagues from the California Institute of Technology and New York University, have discovered how a part of the brain helps predict future events from past experiences. The work sheds light on the function of the front-most part of the frontal lobe, known as the frontopolar cortex, an area of the cortex uniquely well developed in humans in comparison with apes and other primates.

Making the best possible decisions in a changing and unpredictable environment is an enormous challenge. Not only does it require learning from past experience, but it also demands anticipating what might happen under previously unencountered circumstances. Past research from the UI Department of Neurology was among the first to show that damage to certain parts of the frontal lobe can cause severe deficits in decision making in rapidly changing environments. The new study from the same department on a rare group of patients with damage to the very frontal part of their brains reveals a critical aspect of how this area contributes to decision making. The findings were published June 19 in the Journal of Neuroscience.

"We gave the patients four slot machines from which to pick in order to win money. Unbeknownst to the patients, the probability of getting money from a particular slot machine gradually and unpredictably changed during the experiment. Finding the strategy that pays the most in the long run is a surprisingly difficult problem to solve, and one we hypothesized would require the frontopolar cortex," explains Christopher Kovach, Ph.D., a UI post-doctoral fellow in neurosurgery and first author of the study.

Contrary to the authors' initial expectation, the patients actually did quite well on the task, winning as much money, on average, as healthy control participants.

"But when we compared their behavior to that of subjects with intact frontal lobe, we found they used a different set of assumptions about how the payoffs changed over time," Kovach says. "Both groups based their decisions on how much they had recently won from each slot machine, but healthy comparison subjects pursued a more elaborate strategy, which involved predicting the direction that payoffs were moving based on recent trends. This points towards a specific role for the frontopolar cortex in extrapolating recent trends."



Kovach's colleague and study author Ralph Adolphs, Ph.D., professor of neuroscience and psychology at the California Institute of Technology, adds that the study results "argue that the frontopolar cortex helps us to make short-term predictions about what will happen next, a strategy particularly useful in environments that change rapidly -- such as the stock market or most social settings."



Adolphs also hold an adjunct appointment in the UI Department of Neurology.



The study's innovative approach to understanding the function of this part of the brain uses model-based analyses of behavior of patients with specific and precisely characterized areas of brain damage. These patients are members of the UI's world-renowned Iowa Neurological Patient Registry, which was established in 1982 and has more than 500 active members with selective forms of damage, or lesions, to one or two defined regions in the brain.



"The University of Iowa is one of the few places in the world where you could carry out this kind of study, since it requires carefully assessed patients with damage to specific parts of their brain," says study author Daniel Tranel, Ph.D., UI professor of neurology and psychology and director of the UI Division of Behavioral Neurology and Cognitive Neuroscience.



In a final twist to the finding, the strategy taken by lesion patients was actually slightly better than the one used by comparison subjects. It happened that the task was designed so that the trends in the payoffs were, in fact, random and uninformative.


"The healthy comparison subjects seemed to perceive trends in what was just random noise," Kovach says.



This implies that the functions of the frontopolar cortex, which support more complex and detailed models of the environment, at times come with a downside: setting up mistaken assumptions.



"To the best of my knowledge this is the first study which links a normal tendency to see a nonexistent pattern in random noise, a type of cognitive bias, to a particular brain region," Kovach notes.



The researchers next want to investigate other parts of the frontal cortex in the brain, and have also begun to record activity directly from the brains of neurosurgical patients to see how single cells respond while making decisions. The work is also important to understand difficulties in decision making seen in disorders such as addiction.



The study, "Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends," also included authors David Rudrauf from the University of Iowa, John O'Doherty from the California Institute of Technology, and Nathaniel Daw from New York University.

Breaking Point: When Does Head Trauma in Sports Lead to Memory Loss?

ScienceDaily (Apr. 18, 2012) — A new study suggests there may be a starting point at which blows to the head or other head trauma suffered in combat sports start to affect memory and thinking abilities and can lead to chronic traumatic encephalopathy, or CTE, in the brain.



The research was released April 18 and will be presented as part of the Emerging Science program at the American Academy of Neurology's 64th Annual Meeting in New Orleans April 21 to April 28, 2012.

"While we already know that boxing and other combat sports are linked to brain damage, little is known about how this process develops and who may be on the path to developing CTE, which is a degenerative brain disease found in athletes and others with a history of multiple concussions and brain damage," said study author Charles Bernick, MD, of the Cleveland Clinic in Cleveland and a member of the American Academy of Neurology. CTE is only diagnosed through autopsy after death, but symptoms include memory loss, aggression and difficulty thinking.

The study involved 35 boxers and 43 mixed martial arts athletes with an average age of 29 who were part of the ongoing Professional Fighters Brain Health Study. The fighters were given computer tests that measured memory and thinking skills and underwent MRI brain scans. Years of fighting and number of fights were recorded based on self-reporting and published records. The fighters were then split into two groups: those who fought for nine or fewer years and those with more than nine years of fighting history.

In both groups, those with more years of fighting and more fights per year were more likely to have lower brain volumes in three areas of the brain. In those with fewer than nine years of fighting, there was no relationship between the years of fighting or the number of fights per year and the results on memory and thinking tests. But for those who had fought for nine or more years, those with more fights per year performed worse on the thinking and memory tests than those with fewer fights per year.

"Our study shows there appears to be a threshold at which continued repetitive blows to the brain begin to cause measurable changes in memory and thinking, despite brain volume changes that can be found earlier," said Bernick.

The study was supported by the Lincy Foundation.

Physical Activity May Reduce Alzheimer’s Disease Risk at Any Age

ScienceDaily (Apr. 18, 2012) — Daily physical activity may reduce the risk of Alzheimer's disease and cognitive decline, even in people over the age of 80, according to a new study by neurological researchers from Rush University Medical Center that will be published in the online issue of Neurology, the medical journal of the American Academy of Neurology on April 18.


"The results of our study indicate that all physical activities including exercise as well as other activities such as cooking, washing the dishes, and cleaning are associated with a reduced risk of Alzheimer's disease," said Dr. Aron S. Buchman, lead author of the study and associate professor of neurological sciences at Rush. "These results provide support for efforts to encourage all types of physical activity even in very old adults who might not be able to participate in formal exercise, but can still benefit from a more active lifestyle."

"This is the first study to use an objective measurement of physical activity in addition to self-reporting," said Dr. Aron S. Buchman, lead author of the study and associate professor of neurological sciences at Rush. "This is important because people may not be able to remember the details correctly."

To measure total daily exercise and non-exercise physical activity, researchers from Rush asked 716 older individuals without dementia with an average age of 82 to wear a device called an actigraph, which monitors activity, on their non-dominant wrist continuously for 10 days.

All exercise and non-exercise physical activity was recorded. Study participants also were given annual cognitive tests during this ongoing study to measure memory and thinking abilities. Participants also self-reported their physical and social activities. Study participants were individuals from the Rush Memory and Aging Project, an ongoing, longitudinal community study of common chronic conditions of old age.

Over a mean of 3.5 years of follow-up, 71 participants developed Alzheimer's disease The research found that people in the bottom 10 percent of daily physical activity were more than twice as likely (2.3 times) to develop Alzheimer's disease as people in the top 10 percent of daily activity.

The study also showed that those individuals in the bottom 10 percent of intensity of physical activity were almost three times (2.8 times) as likely to develop Alzheimer's disease as people in the top percent of the intensity of physical activity.

"Since the actigraph was attached to the wrist, activities like cooking, washing the dishes, playing cards and even moving a wheelchair with a person's arms were beneficial," said Buchman. "These are low-cost, easily accessible and side-effect free activities people can do at any age, including very old age, to possibly prevent Alzheimer's."

The number of Americans older than 65 years of age will double to 80 million by 2030. "Our study shows that physical activity, which is an easily modifiable risk factor, is associated with cognitive decline and Alzheimer's disease. This has important public health consequences," said Buchman.

Co-authors of the study from Rush are Patricia Boyle, PhD; Li Yu, PhD; Dr. Raj C. Shah; Robert S. Wilson, PhD; and Dr. David A. Bennett.

The National Institutes of Health, National Institute on Aging, the Illinois Department of Public Health and the Robert C. Borwell Endowment Fund helped fund the study.

New Medication Offers Hope to Patients With Frequent, Uncontrollable Seizures

ScienceDaily (Apr. 18, 2012) — A new type of anti-epilepsy medication that selectively targets proteins in the brain that control excitability may significantly reduce seizure frequency in people whose recurrent seizures have been resistant to even the latest medications, new Johns Hopkins-led research suggests. "Many other drugs to treat frequent seizures have been released in the last 10 years and for many people, they just don't work," says study leader Gregory L. Krauss, M.D., a professor of neurology at the Johns Hopkins University School of Medicine. "For a drug-resistant population that has run out of options, this study is good news. These are patients who are tough to treat and are fairly desperate."


Perampanel is the first in a new class of drugs that appears to blunt an excitatory response in the brain by inhibiting a specific form of glutamate receptor called an AMPA receptor and therefore reducing seizures without causing major side effects. Other drugs targeting all three forms of glutamate receptors in the brain have tended to make patients too sleepy to function, even putting them in comas, Krauss says. But this new medication, he says, may potentially offer relief not only to people with epilepsy, but to those struggling with drug addiction problems or the neurodegenerative disorder ALS.

"For years, people have been trying to modify glutamate receptors to cure disease," he says. "It's been a very difficult area to develop new drugs in."

In a multinational, blinded, placebo-controlled trial of more than 700 people with uncontrolled partial-onset seizures, roughly one-third of participants saw the frequency of their seizures fall by more than 50 percent when they were given 8 milligrams a day of perampanel. Partial-onset seizures -- the most common form in epilepsy -- begin in one part of the brain, occurring when there is an injury or abnormality in one of the brain's electrical networks. They can involve anything from the twitching of a limb to confusion to convulsions. Those in this trial typically had roughly 10 seizures a day at baseline.

One in 200 Americans have epilepsy and more than half have partial-onset seizures.

The participants in the study, being reported this week in the journal Neurology, were all taking one to three anti-epileptic drugs before adding perampanel (or a placebo) to their regimen. Krauss and his colleagues assigned each to receive a placebo, two milligrams, four milligrams or eight milligrams per day of the drug. The lowest effective dose was four milligrams per day and the higher the dose, they found, the better the results. Another trial is currently looking at a 12 milligram per day dose. The most common side effect was dizziness, Krauss says.

The study was paid for by Eisai Inc., a New Jersey-based pharmaceutical firm. Krauss says he believes the U.S. Food and Drug Administration will review perampanel in the next year.

Training Can Improve Memory and Increase Brain Activity in Mild Cognitive Impairment

Science Daily (Mar. 1, 2012) — If someone has trouble remembering where the car keys or the cheese grater are, new research shows that a memory training strategy can help. Memory training can even re-engage the hippocampus, part of the brain critical for memory formation, the results suggest.



Researchers at Emory University School of Medicine and Atlanta Veterans Affairs Medical Center have been investigating memory-building strategies for people with MCI (mild cognitive impairment). The techniques used in the study were known to be effective for healthy people, but it has been uncertain how they could affect brain function in people with MCI.

The results are published online in the journal Hippocampus.


"Our results suggest that these strategies can help patients remember specific information, such as the locations of objects, " says lead author Benjamin Hampstead, PhD, assistant professor of rehabilitation medicine at Emory University School of Medicine. "This is the first randomized controlled trial to show that these techniques are not only effective in MCI patients, but that they can also re-engage the hippocampus, which is a brain region that is critical for forming new memories."

Hampstead is a clinical neuropsychologist at the Atlanta VA Rehabilitation, Research and Development Center of Excellence. Study co-authors included Krish Sathian, MD, PhD, professor of neurology, rehabilitation medicine, and psychology, and director of the Rehabilitation R&D Center of Excellence at the Atlanta VAMC; and Anthony Stringer, PhD, professor of rehabilitation medicine and psychology.

MCI is a diagnosis meant to identify those at increased risk of eventually converting to Alzheimer's disease. People with MCI have difficulty forming new memories but are still able to handle tasks of daily living. The difficulty learning and remembering new information is because of impaired function in parts of the brain including the hippocampus.

The study focused on how well participants could remember the locations of common household objects. The memory-building strategy involves three steps. First, participants focused on a feature of the room that stood out and was close to the object, then they learned a short explanation for why the object was in that location. Finally, they created a mental picture to tie the information together.

In several sessions, study participants were shown household objects one at a time, each object followed by its location in a computer-simulated room. An hour later, they were asked to identify the location of each object from among three choices.

After the first visit, participants returned to the laboratory for three training sessions. On a fifth visit two weeks later, they were evaluated on how well they could remember the objects' locations. A control group received the same amount of exposure to the objects and their locations, but was not given explicit training.

As expected, at the start of the study MCI patients had more difficulty remembering where objects were and showed less brain activity in the hippocampus (measured through functional magnetic resonance imaging) when compared with healthy people.

Both people with MCI and healthy controls benefited significantly more from using memory strategies than from mere exposure. In addition, MCI patients in the memory strategy-training group showed increased activity in the hippocampus as they learned and remembered the location of the objects. Participants in the training group showed increases in hippocampal activity, even when trying to remember the locations of new objects.

"This is an initial, albeit encouraging, step in determining methods that can help these patients function better in their everyday lives," says Stringer, who originally developed the strategies on which training in this study was based.

"These techniques may hold particular promise given that they appear to promote neuroplastic changes in key brain regions," Sathian says.

The Emory/VA team has also tested the effectiveness of the memory-building techniques for associating faces and names, in another set of studies. They are continuing the study of the memory-building techniques, with the aim of determining how long the benefits of training last, and whether participants can use the strategies independently outside the laboratory.

The research was supported by the Department of Veterans Affairs and the National Institute on Aging, part of the National Institutes of Health.