Dual Role for Immune Cells in the Brain.

Endothelial cells and macrophages work together to transmit and modulate the strength of inflammatory immune signals to the brain. (Credit: Image: Courtesy of Jamie Simon, Salk Institute for Biological Studies.)

Source: ScienceDaily

-----------------------------

ScienceDaily (Jan. 16, 2010) — We all have at one time or another experienced the typical signs of an infection: the fever, the listlessness, the lack of appetite. They are orchestrated by the brain in response to circulating cytokines, the signaling molecules of the immune system. But just how cytokines' reach extends beyond the almost impenetrable blood-brain barrier has been the topic of much dispute.

In their latest study, researchers at the Salk Institute for Biological Studies describe how, depending on the nature of the stimulus, resident macrophages lined up along the blood-brain barrier play opposing roles in the transmission of immune signals into the brain.
"These macrophages act as accelerators to enlist the brain's participation in dealing with immune insults, but when necessary slam on the brakes to prevent the central inflammatory response from going overboard," explains postdoctoral researcher Jordi Serrats, Ph.D., who co-led the study with Jennifer C. Schiltz, Ph.D., formerly a postdoctoral researcher in the Salk's Neuronal Structure and Function Laboratory and now an assistant professor at the Uniformed Services University in Bethesda, Maryland.
The Salk researchers' findings, which are published in the Jan. 14, 2010 edition of the journal Neuron, may pave the way for novel therapies for sufferers of chronic neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's, Alzheimer's and prion diseases, in which central inflammatory mechanisms play an important role.
"The fact that we have identified a potent anti-inflammatory mechanism in the brain presents a new target to intervene in the wide range of central nervous system diseases that possess an inflammatory component," says the study's senior author, Paul E. Sawchenko, Ph.D., a professor in the Neuronal Structure and Function Laboratory.
In response to an infection, inflammatory cytokines such as interleukin-1 are generated at the site of infection. These cytokines circulate in the blood and communicate with neurons in the brain to engage the hypothalamo-pituitary-adrenal (HPA) axis, an integral part of the brain's stress response machinery. The HPA axis involves the interaction of the hypothalamus, the pituitary gland, which sits just below the hypothalamus and the adrenal glands at the top of the kidneys.
Like a central command center, the hypothalamus sends out corticotropin-releasing factor, which stimulates the pituitary gland to secrete adrenocorticotropic hormone. The latter signals the adrenal glands to ramp up the production of glucocorticoids, which mobilize energy reserves to cope with inflammatory insults. But they also act as very powerful immunosuppressants preventing excessive cytokine production and immune cell proliferation.
"Cytokines are big molecules that don't cross the blood-brain barrier freely," says Sawchenko. "The question of how these molecules access the brain to trigger this whole array of adaptive responses such as fever, inactivity, sleepiness, and activation of the brain's stress response machinery has been a nagging problem in the side of neuroimmunology for many years."
Earlier research by Sawchenko and others suggested a vascular route whereby cytokines interact with vessel walls to generate secondary messengers, which then engage the relevant circuitry in the brain. Tightly packed endothelial cells, which line almost 400 miles of narrow capillaries throughout the brain, are perfectly positioned to record circulating immune signals but they require a very strong signal to become activated. Perivascular macrophages, on the other hand, are more sensitive but don't have direct access to the bloodstream.
To disentangle the exact role of these two cell types, Serrats took advantage of the macrophages' ability to engulf and ingest solid particles. He injected liposomes containing clodronate, a drug that can cause cell death, into the lateral cerebral ventricle. The liposomes were taken up by the macrophages, which were selectively killed off.
Without perivascular macrophages, the animals were unable to respond to blood-borne interleukin-1 and initiate the brain's so-called acute phase responses, which help the body deal with the challenge at hand but also cause the familiar feeling of "being sick." But to their surprise, the Salk researchers found that the same cells put a damper on the pro-inflammatory activities of endothelial cells, which form the lining of blood vessels and are only stirred to action-but very powerfully once they are-when they encounter lipopolysaccharide, a key component of the cell wall of certain bacteria.
"Many neurodegenerative diseases are worsened by systemic inflammation or infections," says Sawchenko. "Once we identify the molecules that mediate the two-way communication between perivascular macrophages and endothelial cells we can develop strategies for managing the adverse health consequences of central inflammatory responses."
Researchers who also contributed to the study include postdoctoral researchers Borja García-Bueno, Ph.D., and Teresa M. Reyes, Ph.D., at the Salk Institute as well as Nico van Rooijen, Ph.D., a professor at the Vrije Universiteit Medical Center in Amsterdam, The Netherlands.
The work was funded in part by the Clayton Medical Research Foundation, the National Institutes of Health, the Spanish Ministry of Education and Science and CIBERsam.

Story Source:
Adapted from materials provided by Salk Institute, via EurekAlert!, a service of AAAS.

How Music 'Moves' Us: Listeners' Brains Second-Guess the Composer.

New research predicts that expectations about what is going to happen next in a piece of music should be different for people with different musical experience and sheds light on the brain mechanisms involved. (Credit: iStockphoto/Anna Bryukhanova)

Source: ScienceDaily

------------------------------

ScienceDaily (Jan. 16, 2010) — Have you ever accidentally pulled your headphone socket out while listening to music? What happens when the music stops? Psychologists believe that our brains continuously predict what is going to happen next in a piece of music. So, when the music stops, your brain may still have expectations about what should happen next.

A new paper published in NeuroImage predicts that these expectations should be different for people with different musical experience and sheds light on the brain mechanisms involved.
Research by Marcus Pearce Geraint Wiggins, Joydeep Bhattacharya and their colleagues at Goldsmiths, University of London has shown that expectations are likely to be based on learning through experience with music. Music has a grammar, which, like language, consists of rules that specify which notes can follow which other notes in a piece of music. According to Pearce: "the question is whether the rules are hard-wired into the auditory system or learned through experience of listening to music and recording, unconsciously, which notes tend to follow others."
The researchers asked 40 people to listen to hymn melodies (without lyrics) and state how expected or unexpected they found particular notes. They simulated a human mind listening to music with two computational models. The first model uses hard-wired rules to predict the next note in a melody. The second model learns through experience of real music which notes tend to follow others, statistically speaking, and uses this knowledge to predict the next note.
The results showed that the statistical model predicts the listeners' expectations better than the rule-based model. It also turned out that expectations were higher for musicians than for non-musicians and for familiar melodies -- which also suggests that experience has a strong effect on musical predictions.
In a second experiment, the researchers examined the brain waves of a further 20 people while they listened to the same hymn melodies. Although in this experiment the participants were not explicitly informed about the locations of the expected and unexpected notes, their brain waves in responses to these notes differed markedly. Typically, the timing and location of the brain wave patterns in response to unexpected notes suggested that they stimulate responses that synchronise different brain areas associated with processing emotion and movement. On these results, Bhattacharya commented, "… as if music indeed 'moves' us!"
These findings may help scientists to understand why we listen to music. "It is thought that composers deliberately confirm and violate listeners' expectations in order to communicate emotion and aesthetic meaning," said Pearce. Understanding how the brain generates expectations could illuminate our experience of emotion and meaning when we listen to music.

Story Source:
Adapted from materials provided by University of Goldsmiths London.
Journal Reference:
Pearce MT, Ruiz MH, Kapasi S, Wiggins G, Bhattacharya J. Unsupervised statistical learning underpins computational, behavioural, and neural manifestations of musical expectation. NeuroImage, 2009; DOI: 10.1016/j.neuroimage.2009.12.019

Neural Thermostat Keeps Brain Running Efficiently.

A 'neuronal thermostat' keeps our energy-hungry brains operating reliably and efficiently while processing a flood of sensory information, new research has found. (Credit: iStockphoto)

Source: ScienceDaily

------------------------

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.

The 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.

Story Source:
Adapted from materials provided by Yale University.
Journal Reference:
Bilal Haider, Matthew R. Krause, Alvaro Duque, Yuguo Yu, Jonathan Touryan, James A. Mazer, David A. McCormick. Synaptic and Network Mechanisms of Sparse and Reliable Visual Cortical Activity during Nonclassical Receptive Field Stimulation. Neuron, 2010; 65 (Issue 1): 107-121 DOI: 10.1016/j.neuron.2009.12.005

Blocking the function of an enzyme in the brain with a specific kind of vitamin E can prevent nerve cells from dying after a stroke.

Source: ScienceDaily

---------------------------

In a study using mouse brain cells, scientists found that the tocotrienol form of vitamin E, an alternative to the popular drugstore supplement, stopped the enzyme from releasing fatty acids that eventually kill neurons.
The Ohio State University researchers have been studying how this form of vitamin E protects the brain in animal and cell models for a decade, and intend to pursue tests of its potential to both prevent and treat strokes in humans.
"Our research suggests that the different forms of natural vitamin E have distinct functions. The relatively poorly studied tocotrienol form of natural vitamin E targets specific pathways to protect against neural cell death and rescues the brain after stroke injury," said Chandan Sen, professor and vice chair for research in Ohio State's Department of Surgery and senior author of the study.
"Here, we identify a novel target for tocotrienol that explains how neural cells are protected."
The research appears online and is scheduled for later print publication in the Journal of Neurochemistry.
Vitamin E occurs naturally in eight different forms. The best-known form of vitamin E belongs to a variety called tocopherols. The form of vitamin E in this study, tocotrienol or TCT, is not abundant in the American diet but is available as a nutritional supplement. It is a common component of a typical Southeast Asian diet.
Sen's lab discovered tocotrienol vitamin E's ability to protect the brain 10 years ago. But this current study offers the most specific details about how that protection works, said Sen, who is also a deputy director of Ohio State's Heart and Lung Research Institute.
"We have studied an enzyme that is present all the time, but one that is activated after a stroke in a way that causes neurodegeneration. We found that it can be put in check by very low levels of tocotrienol," he said. "So what we have here is a naturally derived nutrient, rather than a drug, that provides this beneficial impact."
Sen and colleagues had linked TCT's effects to various substances that are activated in the brain after a stroke before they concluded that this enzyme could serve as an important therapeutic target. The enzyme is called cystolic calcium-dependent phospholipase A2, or cPLA2.
Following the trauma of blocked blood flow associated with a stroke, an excessive amount of glutamate is released in the brain. Glutamate is a neurotransmitter that, in tiny amounts, has important roles in learning and memory. Too much of it triggers a sequence of reactions that lead to the death of brain cells, or neurons -- the most damaging effects of a stroke.
Sen and colleagues used cells from the hippocampus region of developing mouse brains for the study. They introduced excess glutamate to the cells to mimic the brain's environment after a stroke.
With that extra glutamate present, the cPLA2 enzyme releases a fatty acid called arachidonic acid into the brain. Under normal conditions, this fatty acid is housed within lipids that help maintain cell membrane stability.
But when it is free-roaming, arachidonic acid undergoes an enzymatic chemical reaction that makes it toxic -- the final step before brain cells are poisoned in this environment and start to die. Activation of the cPLA2 enzyme is required to release the damaging fatty acid in response to insult caused by high levels of glutamate.
Sen and colleagues introduced the tocotrienol vitamin E to the cells that had already been exposed to excess glutamate. The presence of the vitamin decreased the release of fatty acids by 60 percent when compared to cells exposed to glutamate alone.
Brain cells exposed to excess glutamate followed by tocotrienol fared much better, too, compared to those exposed to only the damaging levels of glutamate. Cells treated with TCT were almost four times more likely to survive than were cells exposed to glutamate alone.
Though cPLA2 exists naturally in the body, blocking excessive function of this enzyme is not harmful, Sen explained. Scientists have already determined that mice genetically altered so they cannot activate the enzyme achieve their normal life expectancy and carry a lower risk for stroke.
Sen also noted that the amount of tocotrienol needed to achieve these effects is quite small -- just 250 nanomolar, a concentration about 10 times lower than the average amount of tocotrienol circulating in humans who consume the vitamin regularly.
"So you don't have to gobble up a lot of the nutrient to see these effects," he said.
The National Institutes of Health supported this work.
The study was co-authored by Savita Khanna, Sashwati Roy and Cameron Rink of the Department of Surgery and Narasimham Parinandi and Sainath Kotha of the Department of Internal Medicine, all at Ohio State; and Douglas Bibus of the University of Minnesota.

Story Source:
Adapted from materials provided by Ohio State University. Original article written by Emily Caldwell.

Identifying Thoughts Through Brain Codes Leads to Deciphering the Brain's Dictionary.

Additionally, the team was able to predict where the activation would be for a previously unseen noun. A computer program assigned a score to each word for each of the three dimensions, and that score predicted how much brain activation there would be in each of 12 specified brain locations. The theory generated a prediction of the activation for apartment based only on the patterns derived from the other 59 words. As one slice of the observed brain image from a human participant (left) and the theory (right) shows, the theory makes precise predictions, particularly about the two shelter-related coding areas in this slice (circled), where brighter red indicates more activation. (Credit: Carnegie Mellon University)

Source: ScienceDaily

-------------------------

ScienceDaily (Jan. 13, 2010) — Two hundred years ago, archaeologists used the Rosetta Stone to understand the ancient Egyptian scrolls. Now, a team of Carnegie Mellon University scientists has discovered the beginnings of a neural Rosetta Stone. By combining brain imaging and machine learning techniques, neuroscientists Marcel Just and Vladimir Cherkassky and computer scientists Tom Mitchell and Sandesh Aryal determined how the brain arranges noun representations. Understanding how the brain codes nouns is important for treating psychiatric and neurological illnesses.

"In effect, we discovered how the brain's dictionary is organized," said Just, the D.O. Hebb Professor of Psychology and director of the Center for Cognitive Brain Imaging. "It isn't alphabetical or ordered by the sizes of objects or their colors. It's through the three basic features that the brain uses to define common nouns like apartment, hammer and carrot."
As the researchers report January 12 in the journal PLoS One, the three codes or factors concern basic human fundamentals:
how you physically interact with the object (how you hold it, kick it, twist it, etc.);
how it is related to eating (biting, sipping, tasting, swallowing); and
how it is related to shelter or enclosure.
The three factors, each coded in three to five different locations in the brain, were found by a computer algorithm that searched for commonalities among brain areas in how participants responded to 60 different nouns describing physical objects. For example, the word apartment evoked high activation in the five areas that code shelter-related words.
In the case of hammer, the motor cortex was the brain area activated to code the physical interaction. "To the brain, a key part of the meaning of hammer is how you hold it, and it is the sensory-motor cortex that represents 'hammer holding,'" said Cherkassky, who has a background in both computer science and neuroscience.
The research also showed that the noun meanings were coded similarly in all of the participants' brains. "This result demonstrates that when two people think about the word 'hammer' or 'house,' their brain activation patterns are very similar. But beyond that, our results show that these three discovered brain codes capture key building blocks also shared across people," said Mitchell, head of the Machine Learning Department in the School of Computer Science.
This study marked the first time that the thoughts stimulated by words alone were accurately identified using brain imaging, in contrast to earlier studies that used picture stimuli or pictures together with words. The programs were able to identify the thought without benefit of a picture representation in the visual area of the brain, focusing instead on the semantic or conceptual representation of the objects.
Additionally, the team was able to predict where the activation would be for a previously unseen noun. A computer program assigned a score to each word for each of the three dimensions, and that score predicted how much brain activation there would be in each of 12 specified brain locations. The theory generated a prediction of the activation for apartment based only on the patterns derived from the other 59 words. As one slice of the observed brain image from a human participant (left) and the theory (right) shows, the theory makes precise predictions, particularly about the two shelter-related coding areas in this slice (circled), where brighter red indicates more activation.
To test the theory, the team used the word scores to identify which word a participant was thinking about, just by analyzing the person's brain activation patterns for that word. The program was able to tell which of the 60 words a participant was thinking about, with a rank accuracy as high as 84 percent for two of the participants, and an average rank accuracy of 72 percent across all 10 participants (where pure guessing would be accurate 50 percent of the time).
One absent code in the study that is essential for the human species concerns sex or love or reproduction. "Our vocabulary of 60 test nouns lacked any words related to the missing dimension, such as 'spouse' or 'boyfriend' or even 'person,'" Just said. "We certainly expect some human dimension to be part of the brain's coding of nouns, in addition to the three dimensions we found."
"With psychiatric and neurological illnesses, the meanings of certain concepts are sometimes distorted," Just said. "These new techniques make it possible to measure those distortions and point toward a way to 'undistort' them. For example, a person with agoraphobia, the fear of open spaces, might have an exaggerated coding of the shelter dimension. A person with autism might have a weaker coding of social contact."
Another implication is in developing and testing domain expertise at the neural level. "We teach to the mind but we are shaping the brain, and now we can give the brain a test of how well it has learned a concept," says Just. "If an instructor knows how an advanced concept is represented in the brains of experts in that area, she will be able to teach to the brain test. We can do it for hammers and carrots right now. In the near future isotope and telomere may soon be on some brain researcher's agenda."
The research was funded by grants from the W.M. Keck Foundation and the National Science Foundation.

Story Source:
Adapted from materials provided by Carnegie Mellon University, via EurekAlert!, a service of AAAS.

Journal Reference:
1. Just et al. A Neurosemantic Theory of Concrete Noun Representation Based on the Underlying Brain Codes. PLoS ONE, 2010; 5 (1): e8622 DOI: 10.1371/journal.pone.0008622

Using Light and Genes to Probe the Brain.

Source: Scientific American

-----------------------------

Optogenetics emerges as a potent tool to study the brain's inner workings
By Gary Stix

-----------------------------

In 1979 Francis Crick, famed co-discoverer of DNA’s structure, published an article in Scientific American that set out a wish list of techniques needed to fundamentally improve understanding of the way the brain processes information. High on his wish list was a method of gaining control over specific classes of neurons while, he wrote, “leaving the others more or less unaltered.”
Over the past few years Crick’s vision for targeting neurons has begun to materialize thanks to a sophisticated combination of fiber optics and genetic engineering. The advent of what is known as optogenetics has even captured popular attention because of its ability to alter animal behavior—one research group demonstrated how light piped into a mouse’s brain can drive it to turn endlessly in circles. Such feats have inspired much public comment, including a joke made by comedian Jay Leno in 2006 about the prospect for an optogenetically controlled fly pestering George W. Bush.
Controlling a subordinate or a spouse with a souped-up laser pointer may be essential for science-fiction dystopia and late-night humor, but in reality optogenetics has emerged as the most important new technology for providing insight into the numbingly complex circuitry of the mammalian brain. It has already furnished clues as to how neural miswiring underlies neurological and mental disorders, including Parkinson’s disease and schizophrenia.
A seminal event that sparked widespread neuroscience interest came in 2005, when Karl Deisseroth and his colleagues at Stanford University and at the Max Planck Institute for Biophysics in Frankfurt demonstrated how a virus could be used to deliver a light-sensitive gene called channelrhodopsin-2 into specific sets of mammalian neurons. Once equipped with the gene (taken from pond algae), the neurons fired when exposed to light pulses. A box on Crick’s list could be checked off: this experiment and ones that were soon to follow showed how it would be possible to trigger or extinguish selected neurons, and not their neighbors, in just a few milliseconds, the speed at which they normally fire. Hundreds of laboratories worldwide have since adopted Deisseroth’s technique.
A 38-year-old psychiatrist by training who still sees patients once a week, Deisseroth entered the field of bioengineering because of his frustration over the inadequate tools available to research and treat mental illness and neurodegenerative disorders. “I have conducted many brain-stimulation treatments in psychiatry that suffered greatly from a lack of precision. You can stimulate certain cells that you want to target, but you also stimulate all of the wrong cells as well,” he says. Instead of just observing the effects from a drug or an implanted electrode, optogenetics brings researchers closer to the fundamental causes of a behavior.
Since 2005 Deisseroth’s laboratory—at times in collaboration with leading neuroscience groups—has assembled a powerful tool kit based on channelrhodopsin-2 and other so-called opsins. By adjusting the opening or closing of channels in cell membranes, opsins can switch neurons on or turn them off. Molecular legerdemain can also manipulate just a subset of one type of neuron or control a circuit between groups of selected neurons in, say, the limbic system and others in the cortex. Deisseroth has also refined methods for delivering the opsin genes, typically by inserting into a virus both opsin genes and DNA to turn on those genes.
To activate the opsins, Deisseroth’s lab has attached laser diodes to tiny fiber-optic cables that reach the brain’s innermost structures. Along with the optical fibers, electrodes are implanted that record when neurons fire. “In the past year what’s happened is that these techniques have gone from being something interesting and useful in limited applications to something generalizable to any cell or question in biology,” Deisseroth says.

Most compelling, however, are experiments that have demonstrated te relevance of optogenetics to both basic science and medicine. At the Society for Neuroscience meeting in Chicago last October, Michael Häusser of University College London reported on an optogenetics experiment that showed how 100 neurons could trigger a memory stored in a much larger ensemble of about 100,000 neurons, suggesting how the technique may be used to understand memory formation.
Last spring Deisseroth’s group published an optogenetics study that helped to elucidate the workings of deep-brain stimulation, which uses electrodes implanted deep in the brain to alleviate the abnormal movements of Parkinson’s disease. The experiment called into question the leading theory of how the technology works—activation of an area called the subthalamic nucleus. Instead the electrodes appear to exert their effects on nerve fibers that reach the subthalamic nucleus from the motor cortex and perhaps other areas. The finding has already led to a better understanding of how to deploy deep-brain electrodes. Given its fine-tuned specificity, optoelectronics might eventually replace deep-brain stimulation.
Although optogenetic control of human behavior may be years away, Deisseroth comments that the longer-range implications of the technology must be considered: “I’m not writing ethics papers, but I think about these issues every day, what it might mean to gain understanding and control over what is a desire, what is a need, what is hope.”

Note: this story was originally printed with the title "A Light in the Brain"

Deep Brain Stimulation Successful for Treatment of Severely Depressive Patient.

Source: ScienceDaily

----------------------------

ScienceDaily (Jan. 11, 2010) — A team of neurosurgeons at Heidelberg University Hospital and psychiatrists at the Central Institute of Mental Health, Mannheim have for the first time successfully treated a patient suffering from severe depression by stimulating the habenula, a tiny nerve structure in the brain. The 64-year-old woman, who had suffered from depression since age 18, could not be helped by medication or electroconvulsive therapy. Since the procedure, she is for the first time in years free of symptoms.

Scientific studies have shown that the habenula is hyperactive in depression, the idea was to downregulate this structure by deep brain stimulation. The surgical procedure is based on a hypothesis of how the habenula is involved in depression that was first formulated by Dr. Alexander Sartorius, psychiatrist at the Central Institute for Mental Health (CIMH; Director: Professor Andreas Meyer-Lindenberg; former Director CIMH Professor Fritz Henn, Brookhaven National Laboratory, New York). The stereotactic procedure at the Neurosurgery Department of Heidelberg University Hospital (Medical Director: Professor Andreas Unterberg) was performed by Dr. Karl Kiening, head of stereotactic neurosurgery. The concept of habenula stimulation and the case study were published in the leading scientific journal Biological Psychiatry.

A new treatment option for therapy-resistent depression:
Depression is a common psychiatric illness; some one third of patients do not respond to medication or psychotherapy. Electroconvulsive therapy, used for such severe or treatment resistant cases, is also not always effective. This was also the case for the Heidelberg/Mannheim patient, who never reached sustained remission after electroconvulsive therapy.
In deep brain stimulation, electrodes are inserted into the brain and are connected with wires under the skin to an electronic impulse generator implanted in the chest. The electrodes emit current that continuously stimulates specific areas of the brain. This therapy, also described as "brain pacemaker," is already used successfully for patients suffering from Parkinson's disease or other movement disorders.
Depressive patients have already been treated with electrostimulation with some success. However, two other areas of the brain were stimulated, located in the forebrain or midbrain regions. The habenula (Latin for the diminutive of reins) is located further downstream next to the brain stem. "We decided to stimulate the habenula because it is involved is the control of three major neurotransmitter systems, which are known to be disturbed in depression,'" explained psychiatrist Dr. Alexander Sartorius from the Central Institute of Mental Health.
The neurosurgical implantation of two electrodes demands utmost precision in planning and performance. The target area is about half as large as the others that are typically targeted for movement disorders, and in addition, is located in the middle of the brain, i.e. in the wall of what is known as the 'third ventricle'. Implanting the electrodes in the two habenulae therefore requires the utmost precision that can currently be achieved with stereotactic instruments. "The neurosurgery department at Heidelberg University Hospital is optimally equipped for demanding procedures such as this with among other things, the new intraoperative highfield MRI," says Dr. Kiening.

Multicenter study on habenula stimulation in preparation:
The success of the procedure was confirmed when the electrode was accidentally switched off: the patient had a bicycle accident which required surgery for which an ECG had to be made as preparation. The brain pacemaker was switched off and was not reactivated for a few days, and the depression promptly returned. A few weeks after reactivation, the patient completely recovered again.
The neurosurgeons in Heidelberg and the psychiatrists in Mannheim now want to build on this positive experience and are planning a clinical study in which the habenula stimulation is to be implemented for severely depressive patients at five psychiatric-neurosurgery centers in Germany. "We aim to show that habenula stimulation has a better success rate than other target areas attempted for depression and that it is also safe to use," says Dr. Sartorius, Coordinating Investigator of the proposed study.

Story Source:
Adapted from materials provided by University Hospital Heidelberg.

Journal Reference:
1.Sartorius et al. Remission of Major Depression Under Deep Brain Stimulation of the Lateral Habenula in a Therapy-Refractory Patient. Biological Psychiatry, 2010; 67 (2): e9 DOI: 10.1016/j.biopsych.2009.08.027

Statistics Page

map counter



blog counter


flag counter