Monday, November 1, 2010

Three-Dimensional Maps Of Brain Wiring

ScienceDaily (Oct. 29, 2010) — A team of researchers at the Eindhoven University of Technology has developed a software tool that physicians can use to easily study the wiring of the brains of their patients. The tool converts MRI scans using special techniques to three-dimensional images. This now makes it possible to view a total picture of the winding roads and their contacts without having to operate. Researcher Vesna Prčkovska defended her PhD thesis on this subject last week.


To know accurately where the main nerve bundles in the brain are located is of immense importance for neurosurgeons, explains Bart ter Haar Romenij (professor of Biomedical Image Analysis, at the Department of Biomedical Engineering). As an example he cites 'deep brain stimulation', with which vibration seizures in patients with Parkinson's disease can be suppressed. "With this new tool, you can determine exactly where to place the stimulation electrode in the brain. The guiding map has been improved: because we now see the roads on the map, we know better where to stick the needle." The technique may also yield many new insights into neurological and psychiatric disorders. And it is important for brain surgeons to know in advance where the critical nerve bundles are, to avoid damaging them.


The accuracy of the tool is a great step forward. Especially intersections of nerve bundles were difficult to identify till now. Ter Haar Romenij: "You can now see for the first time the spaghetti-like structures and their connections." We are far from seeing all brain connections; there are many more smaller compounds in the brains, who are not seen by the new tool. A microscope observed them. "But you cannot, of course, dissect a live patient into slices for under a microscope," the professor smiles.


The tool was developed by TU/e researcher Anna Vilanova, with her PhD students Vesna Prčkovska, Tim Peeters and Paulo Rodrigues. A demonstration of the package can be found on YouTube (see link below). The tool is based on a recently developed technology called HARDI (High Angular Resolution Diffusion Imaging). The MRI measuring technique for HARDI was already there, the research team took care of the processing, interpretation and interactive visualization of these very complex data, so that doctors can get to work.


Bart ter Haar Romenij expects that the tool can be ready at relatively short notice for use in the hospital within a few years. "We need to validate the package. We now need to prove that the images match reality." Also, there is still work to do on the speed of the corresponding MRI scan. For a detailed view, a patient needs to be one hour in the scanner, which is too long. Moreover, the tool is already widely in use by other scientists, says the professor.


The research was supported by NWO (Dutch Organization for Scientific Research). The thesis of Vesna Prčkovska is titled: High Angular Resolution Diffusion Imaging, Processing & Visualization. She graduated on October 20, 2010.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Thursday, October 7, 2010

Neuroscience Research May Help Patients Recover from Brain Injury

ScienceDaily (Oct. 5, 2010) — New neuroscience research by life scientists from UCLA and Australia may potentially help people who have lost their ability to remember due to brain injury or disease.


By examining how we learn and store memories, these scientists have shown that the way the brain first captures and encodes a situation or event is quite different from how it processes subsequent similar events.


The study is published in the Sept. 29 edition of the online journal PLoS ONE, a publication of the Public Library of Science


Memories are formed in the part of the brain known as the hippocampus, a seahorse-shaped structure that plays critical roles in processing, storing and recalling information. The hippocampus is very susceptible to damage through stroke or lack of oxygen and is critically involved in Alzheimer's disease, said study co-author Michael Fanselow, a UCLA professor of psychology and a member of the UCLA Brain Research Institute.


When a memory is first formed, a small protein involved in synaptic transmission -- the NMDA receptor -- is indispensable to the process, said study co-author Bryce Vissel, a group leader of the neuroscience research program at Sydney's Garvan Institute of Medical Research. Activation of the NMDA receptor allows calcium to enter a neuron, and calcium permeability enables a chain of molecular reactions that help encode experience and consolidate memory, Fanselow and Vissel said.


Learning theorists have assumed that learning cannot occur without NMDA receptors. But the new findings show that NMDA receptors are not essential in "second-learning," when the rules of "first-learning" are applied to new yet similar scenarios. Instead, another class of receptors known as AMPA receptors, also calcium permeable, appears to take up the task.


Although the findings are still preliminary, Fanselow is optimistic about what it could mean for people whose memory formation has been impaired. "The system we are working with is one that we know is critically involved in Alzheimer's disease and other kinds of brain deficit memory impairment," he said. "This is just the start. We have uncovered a mechanism that contributes to learning and memory, and we now have to figure out what to do with it. When is it important normally? When can we harness it to take over function when the normal mechanisms aren't working? Can we use it to have some protective effect in conditions like Alzheimer's disease, where neurons are dying? Can we stimulate these pathways and keep them participating in memories?

"We can see that we might now have a target for drugs that are different from the standard class of cognitive enhancers," he added. "We can see the possibilities for different styles of training that better activate this newly discovered mechanism."


If the processes involved in second-stage learning can be mimicked therapeutically, he said, the health benefits potentially could be substantial. Fanselow and Vissel have worked closely over the last six years, along with Thomas O'Dell, a UCLA professor of physiology at the David Geffen School of Medicine at UCLA, to unravel the two different synaptic mechanisms and their meanings.

"When we started this research, we knew that the NMDA receptor was implicated in learning and memory, and we decided to see if we could mimic its process through another receptor system," said Vissel, a molecular neuroscientist. "Instead of having to create a new receptor system, we discovered one already in existence -- one that was NMDA-independent. This amounted to uncovering a whole new mechanism of learning."

Wednesday, August 25, 2010

Human Unbilical Blood Cord Aid Lab Animals Brain Cells Survival After Simulated Stroke

ScienceDaily (Aug. 24, 2010) — Human umbilical cord blood cells (HUCB) used to treat cultured rat brain cells (astrocytes) deprived of oxygen appear to protect astrocytes from cell death after stroke-like damage, reports a team of researchers from the University of South Florida (USF) Department of Neurosurgery and Brain Repair.


Their study was published in the August, 2010 issue of Stem Cell Review and Reports.


The USF study was carried out with astrocytes cultured in the laboratory (in vitro) and then subjected to oxygen deprivation (hypoxia) and glucose deprivation to model what happens in the human brain during a stroke.


Astrocytes, star-shaped cells in the brain and spinal cord, perform several functions, including support of cells that make up the blood-brain barrier separating circulating blood and spinal fluid.

"When we compared survival of astrocytes grown with and without human umbilical cord blood cells during a period of hypoxia and reduced nutrients, we found that the cord blood cells stabilized the brain cell environment and aided astrocyte survival," said lead author and professor Alison Willing, PhD. "However, the cord blood cells also had an impact on cytokines -- small proteins secreted by cells of the immune system -- and also on glial cells that carry signals between cells."


The researchers discovered that the HUCBs changed cytokine "expression" -- sometimes suppressing inflammation and other times enhancing it. "The effects of cord blood cells on astrocytes are not clear and more research is needed to clarify the issue," said Dr. Willing. "HUCBs are composed of different types of immune cells and have the ability to secrete both pro- and anti-inflammatory cytokines. This suggests that the cells may promote recovery following stroke by regulating inflammatory responses and providing support for neural cells, such as astrocytes."


"Our data demonstrated that the different types of HUCBs alone do not enhance astrocyte survival," concluded Dr. Willing. "This result suggests that either another cell component is neuroprotective, or the interaction of all cell types within the entire HUCB population aids protection

Wednesday, July 14, 2010

Amnesia In The Movies

Despite occuring only rarely, amnesia (or memory loss) has featured often in Hollywood films for almost a century. By 1926, at least 10 silent films which used amnesia as a plot device had been made; more recent productions, such as 50 First Dates and Eternal Sunshine of the Spotless Mind, are therefore part of a well established tradition.


In a review published in the British Medical Journal in 2004, clinical neuropsychologist Sallie Baxendale of the Institute of Neurology in London points out that cinematic depictions of amnesia are consistenly inaccurate, and usually "bear no relation whatsoever to any authentic neurological or psychiatric condition".

In her review, Baxendale examines common misconceptions of amnesia found in the cinema, and suggests that knowledge of them can guide clinicians when informing patients and their relatives about diagnoses. She also points out several exceptional films which depict amnesic syndromes accurately.



In the romantic comedy 50 First Dates (2004), Adam Sandler plays veterinarian Henry Roth, who falls for Lucy Whitmore (played by Drew Barrymore) after meeting her in a cafe one morning. The two hit it off, and arrange to meet again. The following day, Roth returns to the café to meet her, but she claims to have no recollection of him. As he leaves, the owner of the café takes him to one side, and explains that Whitmore "lost her short-term memory" after a "terrible car accident". We also learn that she can form new memories during the day, which are then wiped clean during her sleep, so that she wakes up to a "clean slate" every morning.




50 First Dates propagates a number of misconceptions which are common in the films which refer to amnesia. Whitmore's amnesia is the result of a head injury incurred in the car accident; other amnesic characters may lose their memory after being assaulted, or bumping their head in some other way. In reality, memory loss rarely occurs following a head injury; it is most often caused by stroke, brain infection or neurosurgery. The idea that new memories are wiped clean at night is also unrealistic, and unlike any documented amnesic syndrome.

In many cases of cinematic amnesia, head injuries lead to loss of memory of earlier events (retrograde amnesia), but the character usually goes on to lead an otherwise normal life. Real patients who incur brain damage usually suffer from anterograde amnesia - they lose the ability to form new memories, but their memories of events that occured before the amnesia often remain intact. Often they lose memories of many important aspects of their lives - of loved ones and daily routines - and so day-to-day functioning is affected severely.


Amnesic film characters often undergo personality changes or a loss of identity. This confuses amnesia with a poorly-understood condition called dissociative fugue. It also blurs the distinction between the causes of the different amnesic syndromes, as the characters experience psychiatric symptoms, which in reality do not have an organic cause, which are attributed to neurological damage.



Personality changes after a head injury can be seen in the 1987 film Overboard, starring Goldie Hawn and Kurt Russell. Hawn plays a rich and spoilt socialite who loses here memory after bumping her head when falling from her yacht. The character then undergoes a sudden transformation - she becomes warm-hearted and loving and is duped into raising the children of Russel's character as her own. Her memory loss, like that of most other characters, is readly reversible - towards the end of the film, it is cured by another bump on the head. In others, the memories return when they see a familiar object or person. Both of these scenarios are equally implausible.

Memento (2000) is a rare example of a film which depicts amnesia accurately. It is apparently inspired in part by the case of Henry Molaison (H.M.), the famous amnesic who died last December. Guy Pearce plays Leonard, who suffers severe anterograde amnesia after sustaining a head injury in an attack in which his wife is killed. Unlike most amnesic characters, Leonard retains his identity and the memories of events that occurred before the attack, but loses all ability to form new memories. The film's fragmented narrative powerfully depicts how difficult everyday life would be for a severely amnesic patient - Leonard spends much of the film frantically scribbling scraps of information on pieces of paper and, once he has estalished something to be a fact, has it tattooed onto his body.


Another accurate depiction of amnesia is found in the CGI-animated film Finding Nemo (2003). One of the characters, a reef fish called Dory, has a profound memory deficit which, to frustration of her peers, prevents her from learning or retaining any new information, remembering names, or knowing where she is going. As a result, she gets lost when left alone and is often found in a state of confusion. The exact origin of Dory's impairment is not mentioned in the film, but her memory loss accurately reflects the difficulties faced by amnesic patients and those who know them.




Realistic amnesic characters are few and far between in the cinema. Baxendale refers to only one other film, called Se Quien Eres (I Know Who You Are, 2000), containing an accurate depiction of amnesia, in the form of a patient with Korsakoff's Syndrome, the amnesic syndrome condition associated with chronic alcoholism. However, Columbia Pictures announced last month it has acquired the rights to make a film about the life of H.M., based on a book which is to be written by Susanne Corkin, the MIT researcher who worked with him for 4 years.


On a related subject is Rashomon (1950), Akira Kurosawa's masterful examination of the reconstructive nature memory Rashomon depicts a crime as seen from the perspective of four eyewitnesses. As each gives their testimony, the same event is described in four radically different ways. Each of the testimonies contradicts the others, and each of the witnesses initially insists that their version of the event is the right one. Then, as they consider each others' descriptions, something which at first seemed clear becomes utterly confusing, as all the characters and the audience begin to question the accuracy of their own memories.

Thursday, July 8, 2010

Bilingualism Associated With Brain Reorganization Involving Better Efficiency in Executive Functions

ScienceDaily (July 7, 2010) — The research group of Neuropsychology and Functional Neuroimaging at the Universitat Jaume I of Castellón, led by Professor of Basic Psychology, César Ávila Rivera, has reported that bilinguals are faster and more efficient in certain tasks in which executive functions are used due to a different form of cerebral control.


The study, carried out by the research group of the public university of Castellón, in which have also taken part two professors of the Pompeu Fabra University, has shown that bilinguals use the left inferior frontal lobe, the Broca's area, to respond to stimuli where executive functions are performed (such as ordering forms by colour or shape), whereas monolinguals use the right part to respond to the same stimuli.


The left Broca's area, where indeed occurs the response to change the language, is located in the frontal left hemisphere of the brain and is responsible for performing language processing tasks such as speech production and, in the case of bilinguals, control of the language used.

Several behavioural researches had already found this difference in executive functions between bilinguals and monolinguals, but so far there had been developed no neural description. "Findings are very important because they show an unknown aspect of bilingualism, which goes beyond linguistic advantages, and they also show bilinguals are more effective in responding to certain stimuli," explains researcher Cesar Avila, who ensures the research shows that bilingualism does not only have effects on the brain at a linguistic level, but that it also works differently, emphasizing the importance of introducing languages at an early age because it generates cognitive benefits.


To conduct the research, scientists have had the participation of voluntary students from the Universitat Jaume I and the collaboration of the Hospital General of Castellón, where the functional magnetic resonance imagings are done. The sample was composed of two extreme groups. On the one hand, young people who had developed bilingualism (Catalan and Spanish) at an early age and on the other, young Spanish monolinguals from other regions or other Spanish-speaking countries.


The research will be published in short in the prestigious journal NeuroImage, a publication that gathers articles related to brain functions, under the title: "Bridging Language and Attention: Brain basis of the impact of bilingualism on cognitive control."

This research is part of a larger project of the Consolider-Ingenio 2010 program called "Bilingualism and Cognitive Neuroscience," a consortium of four Spanish universities (Universitat Jaume I, Pompeu Fabra University, University of Barcelona and University of the Basque Country) which purpose is to study bilingualism, and specifically its neural basis.

Now, the group continues with the research to get replicas of this pattern with more complex tasks such as using linguistic terms because "if we think the process is evolving and we prove it in similar tasks, we can strongly confirm the results" concludes the Professor of Basic Psychology.

Wednesday, June 16, 2010

Helping The Brain's Messengers Get From A To B

ScienceDaily (June 15, 2010) — In what has been hailed as a breakthrough, scientists from Columbia University Medical Center and Weill Cornell Medical College have outlined the molecular mechanism of membrane transport. The research shows how a protein transforms its shape to transport substances across the cell membrane in order to regulate transmission of the brain's messages across the synaptic gap from one neuron to another.



Because widely used medications for depression modulate this transport process by binding to the transporters, the new findings help explain how the medications work, and the way in which stimulants like cocaine and amphetamine produce their effects. This new understanding should also prove useful in the development of more targeted medication therapies for anxiety, depression, schizophrenia and substance abuse.


The researchers looked at transporter proteins in the family of Na+ symporters, which remove neurotransmitters from the synapse in a process called reuptake that is essential to the proper function of neural transmission. Antidepressants such as Prozac and Zoloft, which are selective serotonin reuptake inhibitors (SSRIs), and cocaine interfere with the reuptake mechanism and alter the normal exchange process between cells.


The paper describing the new findings was published in the May 13 issue of Nature and was lauded as a significant contribution to the understanding of the dynamics of the transport cycle in the journal's News & Views section. The reviewers note that until now biologists have been unable to view transporters on a single-molecule detail, but the new research "lifts the curtain and shines a spotlight onto some of the choreography" of membrane transport. In this spotlight, the new research illuminates the pathway of transported molecules revealing how transporter proteins escort ions and molecules through membranes by forming passageways in a manner the researchers liken to gates opening and closing.


"The study of membrane transport proteins and the genes that encode them offers the opportunity to investigate many aspects of disease processes. The opening and closing of the transporter 'gates' is orchestrated by binding of the transported substances and by inhibitory drugs in ways that could not be determined by previous approaches that were unable to resolve movements in individual proteins," says one senior author, Dr. Jonathan Javitch, who is the Lieber Professor of Experimental Therapeutics in the Departments of Psychiatry and Pharmacology and the Center for Molecular Recognition at Columbia University Medical Center.


Exactly how the gates open and close, and why, is not yet fully understood; however, the results from this research are an important step in that direction.

"Advances in technology have enabled cell biologists to see molecular processes at a level of detail that was not possible even in the last decade. Just as the Hubble telescope and computer-assisted tomography have allowed scientists to view objects in outer space and inside the body more clearly and in greater detail, biologists now have new tools to view what is happening at the cellular level and powerful computational methods to mimic these processes in the computer. This research has brought both advances to bear on a fundamental problem in neural transmission," says study co-author Dr. Harel Weinstein, chairman and Maxwell M. Upson Professor of Physiology and Biophysics, and director of the Institute for Computational Biomedicine (ICB) at Weill Cornell Medical College.


Dr. Weinstein credits the work of his colleague Dr. Scott Blanchard, associate professor of physiology and biophysics at Weill Cornell Medical College, in providing the expertise in a new technology that is crucial to this research. Dr. Blanchard and his team developed this new technology over numerous years and it is now at a place where functional motions of individual proteins can be directly visualized in nearly real time.

"Understanding molecular movements is important because enzyme functions hinge on motion," says Dr. Blanchard, another senior author of the new study. "To observe molecules, we attach reporter molecules called fluorophores that can be directly measured at the single-molecule scale. In so doing, motional information can be obtained about the protein to which they are linked."


In the current study, the investigators used this technique to study the LeuT transporter. They were able to monitor changes of individual molecules and reported observing two distinct states which they believe report on the open and closed states of the gating mechanism.

Dr. Weinstein notes that SSRIs were developed without a real understanding of how they work and only now researchers are beginning to understand how they bind and affect the transporters. "These medications are effective in treating many mental illnesses, including depression, obsessive-compulsive disorder and panic disorder, suggesting that these disorders have some relation to serotonin levels in the brain. Our study is the start of understanding how SSRIs work at a mechanistic level, and why they work in some people and not in others."


The study's equally contributing lead authors are Dr. Yongfang Zhao of the Center for Molecular Recognition at Columbia University Medical Center, and Daniel Terry, a graduate student in the Tri-Institutional Program in Computational Biology and Medicine at WCMC; the study is co-authored by Dr. Lei Shi of the Department of Physiology and Biophysics and the ICB, Weill Cornell Medical College.

Friday, June 11, 2010

Early Alzheimer's Disease

Impaired memory is typically one of the first signs of Alzheimer's
disease, but difficulty recalling the names of friends or recent events is also common among normal elderly persons. The clinician is thus faced
with the difficulty of distinguishing between normal aging and the early stages of Alzheimer's disease. Mild cognitive impairment is an
intermediate state in which persons have more memory problems than would be considered normal for their age, but their symptoms are not as severe as the symptoms of Alzheimer disease and they do not have functional impairment.


Alzheimer's disease develops at a much higher frequency
among persons with mild cognitive impairment than among those with
normal aging. Determining when patients have reached the very early stage of Alzheimer's disease is not easy, particularly because it is likely that a preclinical stage of Alzheimer's disease exists in which senile plaques, neuritic plaques, and neurofibrillary tangles occur in
sufficient numbers to meet standard neuropathological criteria for Alzheimer's disease in the absence of overt symptoms or signs of dementia. Other causes of memory impairment must also be considered, such as cerebrovascular disease, hydrocephalus, hypothyroidism, vitamin B12 deficiency, central nervous system infection, a cognitive disorder related to human immunodeficiency virus infection, adverse effects of
prescribed medications, substance abuse, and cancer.


A substantial decline in verbal memory and executive function (e.g., the ability to perform sequential tasks) typically occurs at the onset of
Alzheimer's disease but may be difficult to document without formal neuropsychological testing.

Reduced independence in daily
activities (often recognized by the patient's family) is one of the strongest predictors of disease.16 Functional status can be measured by the Clinical Dementia Rating (CDR) scale, which evaluates cognitive and
functional performance on a scale ranging from 0 to 3, with higher
scores indicating a greater severity of impairment. This assessment requires a collateral source of information gathering concerning the patient's ability to function independently but can be performed in the primary care setting and is particularly useful for clinicians who do
not have ready access to formal neuropsychological testing.

Formal neuropsychological testing that shows a substantial
decline in verbal memory and executive function supports the diagnosis of Alzheimer's disease1 but requires a trained professional for administration and interpretation.




Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and
the N-methyl-D-aspartate receptor antagonist memantine are the only
treatments for Alzheimer's disease that have been approved by the Food and Drug Administration. Randomized, placebo-controlled clinical trials of cholinesterase inhibitors have included patients with mainly mild-to-moderate Alzheimer's disease and have shown significant but clinically marginal benefits with respect to cognition, daily function, and behavior. The condition of patients who are taking
these drugs remains stable for a year or more and then may decline,
though at a rate that is slower than that among untreated patients.


Although there are few studies directly comparing the three
cholinesterase inhibitors, a systematic review and meta-analysis of data from 27 randomized trials concluded that there were no significant
differences in effects on cognitive performance among these medications.


During the study period (usually, 3 to 6 months), the use of each of
these drugs as prescribed at a standard dose resulted in a mean
improvement of 2 to 3 points on the Alzheimer's Disease Assessment Scale
for cognition (a scale ranging from 0 to 70, with higher scores
indicating better cognition) or a decreased rate of decline, as compared with the placebo group (approximately a 3-point difference, with a minimal clinically important difference of 4 points).


On the basis of 14 studies that measured daily function, donepezil was
modestly but significantly more effective than rivastigmine. Donepezil was likewise modestly but significantly better than rivastigmine and galantamine with regard to behavior, as measured by the Neuropsychiatric
Inventory (on a scale ranging from 1 to 144, with higher scores
indicating a greater severity of disease). Patients receiving donepezil had a mean reduction of 4.3 points in the baseline score, as compared with a reduction of 1.4 for those receiving the other agents. The likelihood of an overall improvement in score was 1.9 times as great with donepezil as with placebo, 1.2 times as great with rivastigmine as
with placebo, and 1.6 times as great with galantamine as with placebo. Adverse effects (including nausea, vomiting, diarrhea, dizziness, and
weight loss) were frequent with all three medications, although slightly less frequent with donepezil than with the other medications.



The author note provides the following contact info: Address reprint
requests to Dr. Mayeux at the Taub Institute for Research on Alzheimer's Disease and the Aging


New England Journal of Medicine (Volume 36Number 23, June 10),
by Richard Mayeux, M.D

Individual Brain Cells Can ID Objects As Dissimilar As Cars and Dogs

ScienceDaily (June 9, 2010) — Researchers at MIT's Picower Institute for Learning and Memory found that single brain cells, if confronted with a difficult task, can identify objects as dissimilar as sports cars and dogs.


Cognitive neuroscience
Functional neuroimaging
Researchers have never been sure exactly how specialized cells in the brain can be. Do different neurons each contribute to unique thoughts or can some neurons be cognitive "generalists" and participate in multiple thoughts? To answer this, MIT researchers examined the prefrontal cortex, the brain's executive in charge of decision-making and planning.


In previous studies, Earl K. Miller, Picower Professor of Neuroscience, found that individual neurons in monkeys' brains can become tuned to the concept of "cat" and others to the concept of "dog."

This time, Miller and colleagues Jason Cromer and Jefferson Roy recorded activity in the monkeys' brains as the animals switched back and forth between distinguishing cats vs. dogs and sports cars vs. sedans. Although they found individual neurons that were more attuned to car images and others to animal images, to their surprise, there were many neurons active in both categories. In fact, these "multitasking" neurons were best at making correct identifications in both categories.


The study suggests that cognitive demands -- how much brainpower is needed for a particular task -- may determine whether neurons in the prefrontal cortex "multitask" or stick to specialized categories.

"This ability to 'multitask' allows the brain to re-utilize the same pool of neurons for different tasks. Without it, storage capacity for critical thought might be severely limited," Miller said. The work could lead to a better understanding of disorders such as autism and schizophrenia in which individuals become overwhelmed by individual stimuli. For instance, a person with autism, when asked to picture a dog, may be flooded with dozens of mental images of all the canines he had ever seen.


Whether or not prefrontal cortex neurons are generalists or specialists had been unresolved because virtually all neurophysiologists train monkeys on a single cognitive problem. In this study, Picower researchers investigated how the prefrontal cortex encodes multiple, independent categories in monkeys trained to randomly alternate between performing two category problems. Wearing devices that allowed researchers to identify activity in individual neurons, the monkeys were presented with morphed images, such as that of a sports car with attributes of a sedan or a cat with attributes of a dog. If the image was more than 50 percent like a sports car or a cat, the monkeys had to identify it as such to get a reward. The monkeys scored correctly 80 percent of the time.


Next steps: Researchers hope to explore further whether individual prefrontal cortex neurons are true "cognitive generalists," able to categorize stimuli across multiple modalities.


Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Massachusetts Institute of Technology. The original article was written by Deborah Halber.

Tuesday, May 25, 2010

Brain Injury May Result In Trouble Sleeping

ScienceDaily (May 24, 2010) — People with brain injuries may produce low amounts of melatonin, which affects their sleep, according to a study published in the May 25, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.


For the study, 23 people who had a severe traumatic brain injury an average of 14 months earlier and 23 healthy people of the same age spent two nights in a sleep laboratory. "We've known that people often have problems with sleep after a brain injury, but we haven't known much about the exact causes of these problems," said study author Shantha Rajaratnam, PhD, of Monash University in Victoria, Australia.


The healthy people produced more melatonin than the people with brain injuries in the evening hours, when melatonin levels are supposed to rise to signal sleep. Melatonin is a hormone that regulates biological rhythms, including sleep. "These results suggest that the brain injury may disrupt the brain structures that regulate sleep, including the production of melatonin," Rajaratnam said. "Future studies should examine whether taking supplemental melatonin can improve sleep in people with brain injuries."


The people with brain injuries had other differences in their sleep patterns. They spent less of their time in bed actually asleep than the healthy participants did, or a "sleep efficiency" percentage of 82 compared to 90 for the healthy group. They also spent more time awake after initially falling asleep, or an average of 62 minutes per night compared to 27 minutes for the healthy group.


In addition, the people with brain injuries spent more time in non-REM sleep, in a stage of sleep called slow-wake sleep or deep sleep. Those with brain injuries spent an average of 24 percent of their time in slow-wake sleep, compared to 20 percent of the time for healthy participants.


Those with brain injuries also had more symptoms of anxiety and depression. However, the researchers calculated the results to control for the anxiety and depression symptoms and still found differences in sleep patterns.


The study was supported by the Australian National Health and Medical Research Council.



Story Source:

Adapted from materials provided by American Academy of Neurology

Friday, April 30, 2010

Prevalence of ADHD Diagnosis and Nonmedical Prescription Stimulant Use in Medical Students

The new issue of *Academic Psychiatry (vol. 34, #3, May-June) includesan article: "Prevalence of ADHD Diagnosis and Nonmedical PrescriptionStimulant Use in Medical Students."The authors are Jeffrey P. Tuttle, M.D., Neil E. Scheurich, M.D. andJohn Ranseen, Ph.D.Here's the

OBJECTIVE: The authors aimed to determine the prevalence of ADHDdiagnosis and the prevalence of nonmedical prescription stimulant useamong a sample of medical students.

METHODS: An anonymous survey was administered to 388 medical students(84.0% return rate) across all 4 years of education at a public medicalcollege.

RESULTS: Eighteen medical students (5.5%) reported being diagnosed withADHD and 72.2% of those students were diagnosed after the age of 18.Thirty-three medical students (10.1%) reported using prescriptionstimulants for nonmedical purposes during their lifetime. The mostcommonly reported motivation for nonmedical prescription stimulant usewas to improve academic performance. There was no significantcorrelation between an ADHD diagnosis and a history of nonmedicalprescription stimulant use (p=0.072).

CONCLUSION: This survey suggests that medical students appear to be arelatively high-risk population for nonmedical prescription stimulant use.The author note provides the following contact info: Jeffrey PaulTuttle, University of Kentucky, Department of Psychiatry, 3470 BlazerParkway, Lexington, KY 40509;

Wednesday, April 21, 2010

Brain Repair After Stroke

Stroke is the second leading cause of death worldwide. A majority of patients survive stroke, however, making this disorder a major source of human disability. Although most patients have some spontaneous behavioral improvements after a stroke, the recovery is generally incomplete. Compounding this burden of disability is the fact that one in four patients who have a stroke is under 65 years of age.


An emerging approach to reducing the degree of disability after a stroke focuses on brain repair. Repair therapies aim to restore the brain, a goal that differs from that of neuroprotection therapies, in which the aim is to limit acute stroke injury. A number of repair-related therapies have been defined in preclinical studies. Such therapies can produce enduring behavioral gains when introduced days to months after the onset of stroke. Several classes of therapy are under study for brain repair, including the use of stem cells, growth factors, small molecules, electromagnetic stimulation, and intensive physiotherapy.1 Many of these therapies, including robot-based physiotherapy,2 are already in human trials.


It is in this context that Lo et al.3 describe a multicenter, randomized, controlled trial to evaluate the effect of robotic therapy on motor status in people with long-term disability after stroke. As reported in this issue of the Journal, the primary study hypothesis was that robotic therapy, when compared with intensive comparison therapy or usual care, would lead to greater improvements in upper-limb function at 12 weeks, as measured by the change in score on the Fugl-Meyer scale. Patients were randomly assigned to one of three types of treatment: robot-assisted therapy, which consisted of high-intensity, repetitive movements of the proximal and distal arm; intensive comparison therapy, which matched the robotic therapy in schedule, form, and intensity but did so with the use of conventional rehabilitation techniques; or usual care, which may have included various types of physical and occupational therapy. Subjects in the two intensive-therapy groups received three sessions (each approximately 1 hour in duration) per week over 12 weeks. Patients in the trial varied widely in the time since the onset of stroke (6 months to 24 years), had multiple coexisting illnesses (including mental health conditions and previous strokes), and were receiving multiple medications.


The investigators' results did not support their study hypothesis. When robot-assisted therapy was compared with either intensive comparison therapy or usual care, no significant differences in the change in the Fugl-Meyer score were seen. There were no safety concerns. In secondary analyses extending to 24 weeks after treatment, robot-based therapy was better than usual care but was not better than intensive comparison therapy. However, since function had improved in patients in the two active treatment groups, these findings reaffirm the idea that motor status can be improved in patients with long-term disability after stroke.
Lo et al. successfully completed a difficult study and achieved a high rate of compliance, a low dropout rate, an extended follow-up period, and careful matching of therapy details across the two active treatment groups. But some basic facts of the chronic phase of stroke can frustrate hypothesis testing in clinical trials. Behavioral gains in the active-treatment groups were smaller than anticipated in power calculations, possibly because the average baseline motor deficits in patients were severe, and severe deficits are harder to improve. Finding a treatment difference between groups also might have been hampered by recruitment of highly motivated patients in all three study groups, since patients who had had a stroke sometimes many years earlier had to agree to leave home for 36 visits to a research laboratory.


Other features of the patients also may have influenced study outcomes. Patients had a substantial number of coexisting illnesses in multiple domains. For example, depression might have influenced results, given that 38% of patients were taking antidepressants. In addition, 73% of all study enrollees were receiving some form of rehabilitation therapy at baseline — a very high rate for patients with long-term disability after stroke4 — and this proportion changed little throughout the study. The high rate of rehabilitation therapy outside study protocol but concomitant with study interventions, as observed by Lo et al., is similar to previous experience in patients months or years after stroke5 and complicates hypothesis testing. What else did subjects practice during the other 165 hours per week? The experience of Lo et al. reminds us that many factors can have a substantial effect on studies involving patients after stroke and prompts conservative power calculations for future repair-based trials.
In the bigger picture, the potential for robotic therapy after stroke remains enormous. Robotic devices can provide therapy in different functional modes, a point that was not examined by Lo et al. Robots work in a consistent and precise manner and over long periods without fatigue.6 They can modulate timing, content, and intensity of training in reproducible ways, with a reduced need for human oversight.2 Robotic devices can also measure the performance of patients during therapy. In addition, robot-based therapy can interface with computers in brain-stimulation treatment or to provide simultaneous cognitive training.
The findings of Lo et al. are of broad value to planning repair-based trials. Movement training, at the heart of the current study, stands on its own as a means of improving behavior in the stroke-injured brain, as shown by Wolf et al. in a phase 3 trial.7 But movement training will also be of critical value as an adjunctive therapy to other treatments that target brain repair, such as the use of growth factors or stimulants. Repair-based therapies drive maximum brain plasticity and achieve best behavioral gains when they are shaped by training and experience.8 Thus, the findings in the active treatment groups in the study by Lo et al. will be instructive in future trials.
These results challenge us to better stratify patients with long-term disabilities after stroke. Such patients are generally selected on the basis of behavioral status. Functional neuroimaging studies have clearly shown that a single behavioral phenotype can arise on the basis of many different brain states. Anatomical and physiological testing might assist in the identification of patients whose brains have sufficient biologic substrate to improve in response to therapy. Toward this end, recent studies suggest that measures of injury to the central nervous system9 or of brain function10 can help predict a patient's capacity for treatment gains after stroke. Many different neurobiologic states can produce a particular behavioral picture, but only some of these states are likely to yield improved behavior in response to a repair-based therapy.
Studies such as that by Lo et al. reinforce the theory that the adult brain has the capacity for clinically relevant plasticity even in the chronic phase after a stroke. The future holds great hope for the development of brain-repair protocols to greatly reduce the degree of disability after stroke.
Source Information
From the Departments of Neurology and Anatomy and Neurobiology, University of California, Irvine. This article (10.1056/NEJMe1003399) was published on April 16, 2010, at NEJM.org.

Psychotropic Medications Overprescribed to Children: Study Suggests

ScienceDaily (Apr. 20, 2010) — A new study from the Journal of Marital & Family Therapy warns of the dramatic rise in the use of psychotropic medications for children. One in every fifty Americans is now considered permanently disabled by mental illness, and up to eight million children take one or more psychotropic drugs.


The authors, James P. Morris, Ph.D. and George Stone, LCSW, state that there is little evidence available to warrant the widespread use of psychotropic drugs for children, and little long term data regarding its long term impact on development.

According to the authors the mental health field is currently designed to treat adults with psychotropic medications, but they are often misused in the case of children and adolescents, "This presents an ethical challenge to marriage and family therapists, who should be very cautious about these medications as an option for children. The long-term research on their safety for children is uncertain."


As an example, the diagnosis of early onset bipolar disorder and attention deficit hyperactivity disorder has climbed drastically in the past decade. Drugs designed to treat the above two disorders show a fair short term risk-benefit ratio, but a poor long-term benefit. Morris and Stone indicate, "If the psychiatric community has been misled by pharmaceutical companies in thinking that these drugs are safe for their children, the parents of these children have been in turn deluded into putting their children in harm's way."


The authors continue that the pharmaceutical industry is largely influenced by the desire for economic profit, and the marketing muscle behind the industry, and leniency of institutions such as the FDA, tout benefits that are not yet properly evaluated for pediatric use. Between 1994 and 2001, psychotropic prescriptions for adolescents rose more than sixty percent; the rise post-1999 was connected to the development and marketing of several new psychotropic drugs and the rebranding of several older ones.


Morris and Stone claim that family health professionals are put in the line of fire when children begin to experience the negative consequences of long-term use of these medications. They are left with the challenge of evaluating the quality of evidence-based care offered to their pediatric clients by the psychiatric community, and the negative effects of the medications without sufficient empirical evidence or information

Tuesday, March 30, 2010

When Memory-Related Neurons Fire in Sinc With Certain Brain Waves, Memories Last

ScienceDaily (Mar. 28, 2010) — They say there's only one chance to make a first impression, but what makes that memory last?


Research scientists at Cedars-Sinai Medical Center and the California Institute of Technology suggest in an article in the March 24, 2010, journal Nature (online) that when memory-related neurons in the brain fire in sync with certain brain waves, the resulting image recognition and memories are stronger than if this synchronization does not occur.


Synchronization is influenced by "theta waves," which are associated with relaxation, daydreaming and drowsiness, but also with learning and memory formation. While it has long been understood that a relaxed mind is one that is ready to receive new information, this study pinpoints a mechanism by which this state of mind allows neurons to work together to improve memory retention. Further exploration of these events could have implications for developing new therapies to treat learning disabilities and some types of dementia, according to the authors.


Brain waves oscillate, with rhythmic highs and lows, and can be measured with electroencephalograms, which use electrodes to record electrical activity. One measure of waves is the frequency of peaks per second, but two waves of the same frequency may not be locked in "phase." Like the sound waves of two musical instruments that are slightly out of tune, two out-of-phase brain waves of the same frequency would be similar but slightly out of sync.
"Theta oscillations are known to be involved in memory formation, and previous studies have identified correlations between memory strength and the activity of certain neurons, but the relationships between these events have not been understood. Our research shows that when memory-related neurons are well coordinated to theta waves during the learning process, memories are stronger," said Adam N. Mamelak, M.D., a neurosurgeon at Cedars-Sinai Medical Center whose areas of expertise include treatment of seizure disorders. Mamelak is one of the article's senior authors, with Erin M. Schuman, Ph.D., professor of biology at the California Institute of Technology.
"We have yet to discover all factors that influence theta oscillations and the coordination of spike timing, but this study establishes a direct relationship between events at the circuit level of the brain -- individual neuron spike timing relative to the local brain wave environment -- and their effects on human behavior," said Ueli Rutishauser, Ph.D., a postdoctoral scholar at the California Institute of Technology, and the article's first author. He noted that the study also found that while the predictability of memory strength was determined by spike timing relative to theta oscillations, it was not influenced by other related factors, such as the neuron firing rate or the amplitude of the theta oscillations.


Subjects in the study were presented with novel stimuli that they had not previously seen. These were in the form of 100 photographs of a wide range of objects, each viewed for one second. Fifteen to 30 minutes later, they were shown a set of 100 photos, 50 that were new and 50 that had been in the first set. They were asked to recall which ones they had seen before and to estimate how confident they were in their answers.
While these activities were in progress, the researchers recorded the activity of single neurons -- 296 in all -- and the "background" local electrical signals in regions of the brain where memories are encoded (the hippocampus and the amygdala). According to the results, image recognition was stronger when learning occurred while neuronal spikes were in sync with local theta waves.


Most studies of theta waves have been conducted in rats, with only a few studies in humans, in part because EEG electrodes need to be placed directly on the brain's surface for highly precise measurements. This study was conducted with eight volunteers who suffer from epilepsy and were undergoing intracranial EEGs. These are often used to pinpoint the source of epileptic seizure activity. The authors note that steps were taken to ensure that the patients' underlying medical condition did not affect the outcome of the study.


Brain wave frequency is measured per second and quantified in hertz (Hz). A wave that cycles 10 times per second is considered a 10 Hz wave. Most brain waves recorded in humans range up to about 40 Hz, although they also go much higher. Theta waves oscillate toward the lower end of the scale, in about the four Hz to seven Hz range.
Neurosurgeon Ian B. Ross, M.D., and the Huntington Memorial Hospital Epilepsy & Brain Mapping Unit also participated in this study.
Funding for the study was provided by the Gordon and Betty Moore Foundation, the William T. Gimbel Discovery Fund, and the Howard Hughes Medical Institute.

Thursday, February 11, 2010

Evidence-Based Steps To Reduce Risk of Dementia by 20%

Your guide to reducing the risk of dementia

The jury is unfortunately still out on whether the crossword can help. You cannot alter your age or the genes you are born with, but there are lifestyle changes you can adopt which may reduce your chance of developing dementia by as much as 20%.


The BBC convened a panel of independent experts, chaired by the Alzheimer's Society, which evaluated more than 70 research papers and articles to come up with a series of tips for reducing your risk.


It may sound young, but the age of 35, they suggest, is high time to start thinking about these recommendations. If more of us acted on these, thousands of cases of dementia could be prevented in the future.
There is very strong evidence for the following:


EXERCISE
Prof Clive Ballard gives his top tips on how to cheat dementia
What is good for the heart is good for the brain. Exercise can have a beneficial effect at any age to help protect against dementia. To help reduce the risk at least 30 minutes of exercise, five times a week is suggested. It does not have to be the gym - a brisk walk is a perfectly acceptable alternative. Whatever form of exercise gets your heart pumping and leaves you somewhat out of breath is doing the trick. Exercise helps maintain a healthy weight and blood pressure, and so is indirectly thought to reduce the risk of dementia.
There is also growing evidence that regular exercise has other health effects such as promoting cell and tissue repair mechanisms including growth of new cells in the brain.


NOT BEING OBESE
Being seriously overweight is deemed a risk factor for developing dementia. This really matters in mid-life - between the ages of 35 and 65. Obesity increases the likelihood of developing Type 2 diabetes - believed to be a risk factor - but whether this causes the disease, or is simply more likely to develop in those who are also more prone to dementia is unclear. Obesity is also associated with higher cholesterol and blood pressure - again, known to be risk factors. You are deemed clinically obese - very overweight - if you have a BMI of 30 and above.


BRING DOWN HIGH BLOOD PRESSURE

The panel evaluated more than 70 research papers
Again, the key here is having consistently raised blood pressure in mid-life - anything above 140/90mmHg. It is thought that this increases the chance of dementia by causing damage to the brain. This may happen as a result of a stroke - in which blood supply to part or all of the brain is cut off - or due to microvascular disease, a condition which slows the flow of blood through the body thereby damaging cells and nerves in the brain. If you are over 40, or have a history of dementia or cardiovascular disease in your family, then get your blood pressure checked regularly.
REDUCE CHOLESTEROL
It is mid-life levels once more which appear to pose the greatest problem. Like high blood pressure, high levels of cholesterol raise the risk of stroke and microvascular disease. But cholesterol is also thought to be involved in the mechanism which causes amyloid protein plaques - the protein deposits that characterise Alzheimer's disease - to build up. Again if you are over 40 or have a family history, get your cholesterol checked. The Department of Health recommends a total cholesterol level of less than 5.0mmol/l.


NOT SMOKING
This had been an area of confusion, as some studies had suggested nicotine could have a protective effect - with the chemical reducing plaques when administered to animals in water. But the way in which we smoke tobacco, and the other chemicals inhaled in the process, negates this benefit. As well as raising the risk of vascular disease - a risk factor for dementia - smoking can result in low oxygen levels in the brain which in turn can promote the production of the protein found in brain plaques.
It is possible the following may have an impact:


ALCOHOL

There is no need to start drinking if you do not already
In fact the studies are quite clear that drinking a modest amount appears to protect against cognitive decline. Moderate drinking is defined as keeping within the recommended daily limits - up to two small glasses of wine for a woman, and three for a man. The problem is that these studies compare drinkers with non-drinkers - and people who abstain may do so for health reasons, which in turn may affect their chances of developing dementia. The message is if you are drinking within your weekly guidelines there is no need to stop, but there is no need to take up drinking or increase the amount you consume, as heavy drinking may in fact increase your risk.


FOLLOWING A MEDITERRANEAN DIET
Several recent studies have highlighted the potential for this diet to reduce the risk of Alzheimer's Disease. It involves eating lots of fruit and vegetables, whole grain foods, fish and plenty of olive oil, but it is relatively low in dairy products and processed foods. Further long term research is needed to confirm the effects of eating this way.
BEING SOCIALLY ACTIVE
Some evidence suggests that an active social life throughout life can be protective, with both the social ties one enjoys with others and non-physical leisure time deemed important. However, examining these factors and designing studies which can separate their effects is very difficult - consequently the conclusions which can be drawn from results are limited. One particular study has found that being single and living alone is a risk factor for dementia: social isolation is thought to have negative effects on health generally, increasing depression and cardiovascular disease.
Studies have also suggested that engaging in non-physical leisure activities such as gardening, and knitting may have a protective effect, a benefit that is likely to accumulate gradually over decades.
But the jury is out on:


BRAIN TRAINING
It sounds both attractive and plausible that giving your brain a "workout" could guard against dementia, and there is some evidence that very intensive brain training under strict conditions can improve specific functions like reasoning and problem solving. But there is no evidence as yet that doing a crossword a day or a number puzzle - or even learning a new language at 50 - will protect against dementia. That does mean they do not - simply that the proof that they do is presently lacking.
VITAMIN SUPPLEMENTS
There is no consistent evidence either way as to whether B vitamin supplements - folic acid, vitamin B12 or B6 - are effective in reducing the incidence of dementia. Research continues. However vitamin E supplements, which it was once hoped could prevent and even reverse early neurodegenerative changes, have not appeared to be effective in trials.

Wednesday, February 3, 2010

Escitalopram and Enhancement of Cognitive Recovery Following Stroke

The new issue of *Archives of General Psychiatry* (Vol. 67 No. 2)includes a study: "Escitalopram and Enhancement of Cognitive RecoveryFollowing Stroke."The authors are Ricardo E. Jorge, MD; Laura Acion, MS; David Moser, PhD;Harold P. Adams Jr, MD; & Robert G. Robinson, MD.

ContextAdjunctive restorative therapies administered during the first fewmonths after stroke, the period with the greatest degree of spontaneousrecovery, reduce the number of stroke patients with significant disability.

Objective: To examine the effect of escitalopram on cognitive outcome. Wehypothesized that patients who received escitalopram would show improvedperformance in neuropsychological tests assessing memory and executivefunctions than patients who received placebo or underwent ProblemSolving Therapy.DesignRandomized trial.SettingStroke center.

Participants: One hundred twenty-nine patients were treated within 3 months followingstroke. The 12-month trial included 3 arms: a double-blind placebo-controlled comparison of escitalopram (n = 43) with placebo (n = 45),and a nonblinded arm of Problem Solving Therapy (n = 41).Outcome MeasuresChange in scores from baseline to the end of treatment for theRepeatable Battery for the Assessment of Neuropsychological Status(RBANS) and Trail-Making, Controlled Oral Word Association, WechslerAdult Intelligence Scale-III Similarities, and Stroop tests.

Result: sWe found a difference among the 3 treatment groups in change in RBANStotal score (P < .01) and RBANS delayed memory score (P < .01). Afteradjusting for possible confounders, there was a significant effect ofescitalopram treatment on the change in RBANS total score (P < .01,adjusted mean change in score: escitalopram group, 10.0; nonescitalopramgroup, 3.1) and the change in RBANS delayed memory score (P < .01,adjusted mean change in score: escitalopram group, 11.3; nonescitalopramgroup, 2.5). We did not observe treatment effects in otherneuropsychological measures.

Conclusions: When compared with patients who received placebo or underwent ProblemSolving Therapy, stroke patients who received escitalopram showedimprovement in global cognitive functioning, specifically in verbal andvisual memory functions. This beneficial effect of escitalopram wasindependent of its effect on depression. The utility of antidepressantsin the process of poststroke recovery should be further investigated.

Friday, January 15, 2010

Neuroimaging May Shed Light On How Alzheimer's Disease Develops

ScienceDaily (Jan. 14, 2010) — Current Alzheimer's disease (AD) research indicates that accumulation of amyloid-beta (Aβ) protein plaques in the brain is central to the development of AD. Unfortunately, presence of these plaques is typically confirmed only at autopsy. In a special issue of the journal Behavioural Neurology, researchers review the evidence that Positron emission tomography (PET) can image these plaques during life. This exciting new technique provides researchers with an opportunity to test the amyloid hypothesis as it occurs in living patients.


In a review article with over 100 references, Dr. Gil Rabinovici and Dr. William Jagust from the University of California, San Francisco and Berkeley, summarize the results of experiments from their laboratories and others using the Aβ tracer Pittsburgh Compound-B (PIB). This compound binds to Aβ protein and allows the mapping of plaques in the brains of AD and non-AD volunteer subjects.
They report that PIB-PET can detect Aβ deposits in a significant proportion of cognitively normal older subjects and that these deposits are associated with brain atrophy even in the absence of cognitive symptoms. By the time patients develop mild cognitive impairment (MCI) amyloid load in the brain appears to have reached a plateau. As patients progress to dementia, neurodegeneration and cognitive decline proceed independently of further amyloid accumulation.


The authors interpret these results as consistent with a model in which amyloid deposition plays a critical early role on the path to AD, beginning years before onset of symptoms and triggering a series of events which ultimately leads to cognitive decline and dementia. While the use of PIB-PET is currently limited to research centers because of the compound's very short radioactive half-life (20 minutes), new amyloid imaging agents with longer half-lives are under development for more widespread use. Amyloid imaging is already playing an important role in the development of amyloid-based therapies for AD, and Dr. Rabinovici and Dr. Jagust speculate that in the future amyloid imaging will assist clinicians in identifying patients with mild or atypical symptoms who may be candidates for anti-amyloid treatments.


Writing in the article, the authors state, "PIB-PET has provided us with our first in vivo glance at the dynamic relationship between amyloid deposition, clinical symptoms, and structural and functional changes in the brain in the continuum between normal aging and AD…In the future, Aβ imaging will likely supplement clinical evaluation in selecting patients for anti-amyloid therapies both during drug development and in the clinic."

Exercise Associated With Preventing, Improving Mild Cognitive Impairment

ScienceDaily (Jan. 14, 2010) — Moderate physical activity performed in midlife or later appears to be associated with a reduced risk of mild cognitive impairment, whereas a six-month high-intensity aerobic exercise program may improve cognitive function in individuals who already have the condition, according to two reports in the January issue of Archives of Neurology, one of the JAMA/Archives journals.


Mild cognitive impairment is an intermediate state between the normal thinking, learning and memory changes that occur with age and dementia, according to background information in one of the articles. Each year, 10 percent to 15 percent of individuals with mild cognitive impairment will develop dementia, as compared with 1 percent to 2 percent of the general population. Previous studies in animals and humans have suggested that exercise may improve cognitive function.


In one article, Laura D. Baker, Ph.D., of the University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues report the results of a randomized, controlled clinical trial involving 33 adults with mild cognitive impairment (17 women, average age 70). A group of 23 were randomly assigned to an aerobic exercise group and exercised at high intensity levels under the supervision of a trainer for 45 to 60 minutes per day, four days per week. The control group of 10 individuals performed supervised stretching exercises according to the same schedule but kept their heart rate low. Fitness testing, body fat analysis, blood tests of metabolic markers and cognitive functions were assessed before, during and after the six-month trial.
A total of 29 participants completed the study. Overall, the patients in the high-intensity aerobic exercise group experienced improved cognitive function compared with those in the control group.


These effects were more pronounced in women than in men, despite similar increases in fitness. The sex differences may be related to the metabolic effects of exercise, as changes to the body's use and production of insulin, glucose and the stress hormone cortisol differed in men and women.
"Aerobic exercise is a cost-effective practice that is associated with numerous physical benefits. The results of this study suggest that exercise also provides a cognitive benefit for some adults with mild cognitive impairment," the authors conclude. "Six months of a behavioral intervention involving regular intervals of increased heart rate was sufficient to improve cognitive performance for an at-risk group without the cost and adverse effects associated with most pharmaceutical therapies."


In another report, Yonas E. Geda, M.D., M.Sc., and colleagues at Mayo Clinic, Rochester, Minn., studied 1,324 individuals without dementia who were part of the Mayo Clinic Study of Aging. Participants completed a physical exercise questionnaire between 2006 and 2008. They were then assessed by an expert consensus panel, who classified each as having normal cognition or mild cognitive impairment.


A total of 198 participants (median or midpoint age, 83 years) were determined to have mild cognitive impairment and 1,126 (median age 80) had normal cognition. Those who reported performing moderate exercise -- such as brisk walking, aerobics, yoga, strength training or swimming -- during midlife or late life were less likely to have mild cognitive impairment. Midlife moderate exercise was associated with 39 percent reduction in the odds of developing the condition, and moderate exercise in late life was associated with a 32 percent reduction. The findings were consistent among men and women.


Light exercise (such as bowling, slow dancing or golfing with a cart) or vigorous exercise (including jogging, skiing and racquetball) were not independently associated with reduced risk for mild cognitive impairment.
Physical exercise may protect against mild cognitive impairment via the production of nerve-protecting compounds, greater blood flow to the brain, improved development and survival of neurons and the decreased risk of heart and blood vessel diseases, the authors note. "A second possibility is that physical exercise may be a marker for a healthy lifestyle," they write. "A subject who engages in regular physical exercise may also show the same type of discipline in dietary habits, accident prevention, adherence to preventive intervention, compliance with medical care and similar health-promoting behaviors."
Future study is needed to confirm whether exercise is associated with the decreased risk of mild cognitive impairment and provide additional information on cause and effect relationships, they conclude.

Neural Thermostat Keeps Brain Running Efficiently

ScienceDaily (Jan. 15, 2010) — Our energy-hungry brains operate reliably and efficiently while processing a flood of sensory information, thanks to a sort of neuronal thermostat that regulates activity in the visual cortex, Yale researchers have found.
actions of inhibitory neurons allow the brain to save energy by suppressing non-essential visual stimuli and processing only key information, according to research published in the January 13 issue of the journal Neuron.
"It's called the iceberg phenomenon, where only the tip is sharply defined yet we are aware that there is a much larger portion underwater that we can not see," said David McCormick, the Dorys McConnell Duberg Professor of Neurobiology at Yale School of Medicine, researcher of the Kavli Institute of Neuroscience and co-senior author of the study. "These inhibitory neurons set the water level and control how much of the iceberg we see. We don't need to see the entire iceberg to know that it is there."


The brain uses the highest percentage of the body's energy, so scientists have long wondered how it can operate both efficiently and reliably when processing a deluge of sensory information. Most studies of vision have concentrated on activity of excitatory neurons that fire when presented with simple stimuli, such as bright or dark bars. The Yale team wanted to measure what happens outside of the classical field of vision when the brain has to deal with more complex scenes in real life.
By studying brains of animals watching movies of natural scenes, the Yale team found that inhibitory cells in the visual cortex control how the excitatory cells interact with each other.
"We found that these inhibitory cells take a lead role in making the visual cortex operate in a sparse and reliable manner," McCormick said.
James Mazer was co-senior author of the paper with McCormick. Bilal Haider, a Yale graduate student, was lead author. Other Yale authors of the paper were Matthew R. Krause, Alvaro Duque, Yuguo Yu and Jonathan Touryan.


The work was funded by the National Eye Institute and the Kavli Foundation.