Thursday, January 31, 2008

Deep brain stimulation may improve memory


This is an extremely interesting, although preliminary finding. Please read the source article:




Memory enhancement induced by hypothalamic/fornix deep brain stimulation
Annals of Neurology
Volume 63, Issue 1, Date: January 2008, Pages: 119-123
Clement Hamani, Mary Pat McAndrews, Melanie Cohn, Michael Oh, Dominik Zumsteg, Colin M. Shapiro, Richard A. Wennberg, Andres M. Lozano

here @ Ann Neurol

Cheers,

Thomas

Source: CTV.CA




Updated Wed. Jan. 30 2008 8:44 AM ET


CTV.ca News Staff

TORONTO -- Canadian researchers have announced what they say is a world first: they have used deep brain stimulation to improve memory.

The discovery, published Wednesday in the Annals of Neurology, shows how an accidental finding during experimental treatment in a patient with normal memory may open the door to treating the symptoms of Alzheimer's disease.

Neurosurgeon Dr. Andres Lozano and a team at Toronto Western Hospital had been testing experimental deep brain stimulation to treat a 50-year-old man with a lifelong history of obesity. They had implanted electrode contacts into his hypothalamus, deep in his brain, and were looking for appetite suppressant sites by stimulating the electrodes.

That's when the patient suddenly experienced a feeling of "déjà vu." He reported the perception of being in a park with friends from when he was around 20 years old. As the intensity of the electrical stimulation was increased, the details became more vivid. 

"He understood that it was a sunny day. As we increased the stimulation, more details filled in. The colours of the scene became more vivid," Lozano told CTV News.

"This was for us a eureka moment in that we were not expecting it at all."

The contacts that most readily induced the memories were located in the man's hypothalamus and estimated to be close to the fornix, an arched bundle of fibres that carries signals within the limbic system, which is involved in memory and emotions. Stimulation was shown to drive the activity the temporal lobe and the hippocampus, important components of the brain's memory circuit.

In the year that followed, the man, who initially had normal memory, began scoring far higher on memory and learning tests -- as long as the electrodes, which remained in his brain, were stimulated through electrical currents from a pacemaker implanted near his collarbone.

Deep brain stimulation is currently being used by a handful of doctors to control the tremors of Parkinson's disease. It's also being experimented as a tool to lift chronic depression. Now, doctors think they've stumbled on to a new way of treating the symptoms of those with memory problems.

"We think that for those patients with Alzheimer's who are early on in their illness, where their memory is affected, it may be possible to go into circuits and increase their activity and in doing so, enhance their memory function," speculates Lozano.

"This is symptomatic therapy; that is to say, it is a therapy that improves the symptom of the illness. We don't think it will stop the natural history of the illness. We don't think it will stop the death of cells that occur in the brain," he adds. "It is something to improve the symptoms of the disease but not something that we expect will stop the disease in its tracks."

Toronto researchers have now implanted the device into six patients with Alzheimer's to see whether stimulating their memory is safe and if it releases memories locked away by the disease.

"So far, those patients are doing well and there have been no significant side effects of the surgery," says Lozano. "And we have some indications of some aspects of memory may be improving."

For neurologist Sandra Black of Sunnybrook Health Sciences Centre in Toronto, the findings are intriguing, although preliminary.

"I thought that scientifically, it is a very exciting study," she says. But she notes that it may not be a treatment that could be made widely available.

"It involves a very skilled neurosurgery team that would not be widely accessible. It involves putting foreign objects into the brain, and there may be safer alternatives," she says.

There are several dozen experimental drugs being tested for the treatment of Alzheimer's. But so far, scientists say no medication has come close to restoring memory as profoundly as this deep brain stimulation has done.

The accidental discovery has now led to a pilot study that is underway in Toronto in which Lozano and a team are studying the possibility of improving memory in patients with Alzheimer's by stimulating the memory circuits in the brain.

Mary-Pat McAndrews, a neuropsychologist who was part of the Lozano research team says the aim is not to cure Alzheimer's, but to provide Alzheimer's patients with a longer time in which they could function independently.

"Ideally, what we would be looking for is something that would allow us to provide them with some additional memory assistance and therefore have a real and genuine impact on life," she says.

With a report from CTV medical specialist Avis Favaro and producer Elizabeth St. Philip




The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation

1: J Neurosurg. 2008 Jan;108(1):132-8.

Division of Neurosurgery, Toronto Western Hospital, Ontario, Canada.

OBJECTIVES: To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model. METHODS: Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5'-bromo-2'-deoxyuridine (BrdU) 1-7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery. RESULTS: Animals receiving AN high-frequency stimulation (2.5 V, 90 musec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation. CONCLUSIONS: High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.

PMID: 18173322 [PubMed - in process]

Monday, January 28, 2008

Alternative Treatments For Depression: Transcranial Magnetic Stimulation (TMS) May Improve Mood, But Awaits FDA Approval

An article from Medicalnewstoday

While common treatments for depression such as prescription drugs, psychotherapy and electroconvulsive therapy usually provide relief from even the most severe cases for depression, there are people who do not feel they benefit from these treatments, and because of such look for alternative means to combat this serious medical condition.

One other option is Transcranial Magnetic Stimulation (TMS), which hasn't yet been approved by the Food and Drug Administration to treat depression, but may be available through a clinical trial.

This non-invasive method excites neurons in the brain by using weak electric currents, which are delivered to the brain by rapidly changing magnetic fields, also known as electromagnetic induction.

It is believed that this nerve stimulation improves mood and there's some evidence it may make nerve-cell connections more efficient. Because of this, TMS has shown promise as a non-invasive treatment of depression.

Alternative to Electroconvulsive Therapy?
For people who cannot find relief from traditional treatments for depression, TMS may seem to be a more desirable treatment than electroconvulsive therapy (ECT), which it has been compared to, simply because it is non-invasive, does not require anesthesia, and is not associated with convulsions, all of which are associated with ECT.

TMS also appears to have fewer and less serious side effects, such as memory loss and confusion, both of which are associated with ECT.

How TMS Works
Completely non-invasive and painless, TMS involves placing an electromagnetic coil against the patient's scalp. An electric current passes through this coil that creates a magnetic pulse, which causes small electrical currents in the brain.

These currents stimulate nerve cells in the region of the brain involved in mood regulation and depression.

Why It Works
Physicians and medical researchers are not yet exactly clear on why this nerve cell stimulation works; however, it is believed that stimulating the brain can change how it works and that by stimulating the regions associated with mood regulation, mood can be improved.

In some types of TMS, brain activity is suppressed. In other types, brain activity is increased. In either case, the changes may be associated with improved mood. These improvements in symptoms may last for days or weeks, according to the Mayo Clinic, a not-for-profit medical practice with locations in Minnesota, Arizona and Florida.

Keep in mind that researchers are still trying to determine the best dosage of stimulation and the best area of the brain to stimulate.

Who May Benefit
Remember, TMS remains experimental, which means it is not to be used as a first-line treatment against depression. Currently, it is only available in the United States through clinical trials.

In countries where TMS has been approved to treat depression, it's generally used to treat people who haven't experienced improvements with standard treatments.

To determine if you or someone you know is a candidate for this experimental procedure, you will need talk to your doctor to see if it may be a good option for you or for a loved one who is suffering from depression.

Who Should Not Undergo TMS
Certain people should not undergo TMS because of increased or unknown risks to their health. These include anyone with: metal implants in the head, who may be pregnant or who has a pacemaker.

Additionally, TMS is not suited for patients who suffer from recurring migraines, who has had a stroke or who has a family history of seizures. And, if you have had neurosurgery, TMS is not for you.

TMS Side Effects
Despite being non-invasive, TMS does pose a risk of adverse side effects, with the most concerning being the increased risk of seizure. Because of that risk, the International Society for Transcranial Stimulation (ISTS) advises "that the procedure be performed only when medical help is quickly available and that those who administer it be trained as first responders who can provide emergency medical help," according to the Mayo Clinic.

According to the ISTS, other common side effects and adverse health problems associated with TSI include lightheadedness, headache, pain at the site where the electromagnetic coil is placed against the scalp, tingling, spasms or contractions of facial muscles.

The Long-Term Outlook
Because TMS prompts changes in brain function, it is important to understand that there may be unknown long-term adverse side effects associated with the treatment.

While research has not yet determined any negative long-term side effects, it is important to talk to your medical doctor or mental health specialist to understand the possibilities here and to weigh these carefully with your medical professional.

Remember, TMS is currently available through clinical trials only, so your treating physician or mental health professional will have to help you find a clinical trial that will work for you and your unique situation.

About the Author
Kellie Fowler is an award-winning writer and has written for Associated Press, PR Newswire, Fortune 500 companies, newspapers, national business and healthcare magazines. She is regular contributor to http://www.depression-help-resource.com, a website providing information about types of depression, treatment options and depression related articles and resources.

http://www.depression-help-resource.com

Sleep and rTMS. Investigating the link between transcranial magnetic stimulation, sleep, and depression

PMID: 10590965
 

TITLE: Sleep and rTMS. Investigating the link between transcranial magnetic stimulation, sleep, and depression.

AUTHORS: G Hajak, S Cohrs, F Tergau, U Ziemann, W Paulus, E Rüther
AFFILIATION: Department of Psychiatry, Georg-August University, Göttingen, Germany.
REFERENCE: Electroencephalogr Clin Neurophysiol Suppl 1999 51():315-21

Sunday, January 27, 2008

NAcc Localization for DBS




An interesting take on

Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression. Neuropsychopharmacology 2007 Apr 11; [Epub ahead of print]

by the Neurocritic.

Minds and Magnets

An experimental treatment offers promise for some patients whose depression resists standard medications and shock therapy.

By Michael Craig Miller, M.D.
Newsweek

Relief: Pascual-Leone administers repetitive TMS to a patient with depression

ast a year of disabling depression. Numerous psychiatric treatments failed to provide longed-for relief. Life was miserable until they began receiving an experimental treatment with a clumsy name: repetitive transcranial magnetic stimulation, or repetitive TMS.

This magnetism has nothing to do with magnets applied to the skin or with animal magnetism, the charlatanry invented by Franz Mesmer in the 19th century, although skeptics have worried that people cured by repetitive TMS have merely been mesmerized. Repetitive TMS uses real magnetic fields to induce changes in brain function, and there's some evidence it may make nerve-cell connections more efficient. It may modify how regions of the brain work together to regulate mood. It's a cousin of "shock therapy," or electroconvulsive therapy (ECT). Unlike ECT, however, it does not require anesthesia. It's localized, so side effects have been mild; some patients experience headache or scalp discomfort.

TMS was developed more than 20 years ago by neurologists studying brain function, rather than treatment. The technique exploits the relationship between electric currents and magnetic fields. When an electric current in a wire changes, it creates a magnetic field. That magnetic field can create an electrical current in another wire. In repetitive TMS, a coil that is shaped, for example, like a doughnut or figure-8 is held over the scalp. By rapidly changing the charge in the coil, the magnetic field induces an electric current in the brain that is strong enough to activate nerve cells below the scalp. The coil may look large, but the area affected can be as small as a pea. In contrast, ECT causes a generalized or whole-brain seizure, with electrical changes throughout the brain.

This modicum of intrusiveness appealed to Mark. One day when he was 15, he told his parents he was going to the library, but he went to a nearby bridge instead, planning to jump. Police rescued him. Two years of repeated hospitalization, medication and psychotherapy did not help; so he began ECT. It worked, but he required monthly maintenance treatments that were embarrassing and disruptive because he could not function well in the days around the periodic treatments.

Mark's mother found out about repetitive TMS from a news report almost 10 years ago when he was 17. She tracked down Dr. Alvaro Pascual-Leone of the Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center in Boston. Within two weeks of treatment he received as part of a study, Mark developed a more positive outlook. He has needed maintenance treatment every four months or so, but it has not interfered with intellectual functioning the way ECT did. He finished high school, and earned two college degrees in education. Now he's a teaching assistant, optimistic that he will realize his goal of being a teacher.

Is Mark's success story unusual? No more unusual than any other success story among people with hard-to-treat depression. Such sufferers commonly cycle through many treatments before they find the one that helps. Trial-and-error is the state of the art, since no one can predict which treatment will work for a given patient. The question for researchers—and the U.S. Food and Drug Administration, which is reviewing its status—is whether repetitive TMS should join antidepressants and ECT as an approved treatment for depression.

In early experiments, data were inconsistent, partly because there were no guidelines. Repetitive TMS treatment varies depending on the part of the brain targeted, the precision of the targeting, the intensity of the signal and the number of cycles per second, among other factors.

Individuality should be celebrated, but it makes research more difficult: subjects in depression studies are never a uniform group. As we learn more about the brain, we hope to know which people have which kind of depression. One day, measurements of brain activity may also help guide how and precisely where to administer repetitive TMS. Until then, we will have limited ability to predict how many and which people might respond to repetitive TMS or any other therapy.

Despite the problems, recent results are encouraging. Most studies involve patients who haven't been helped by anything else and are therefore less likely than average to feel improvement. Yet as practitioners refine their methods, they seem to be getting better results. In one randomized controlled study of almost 70 patients based in the state of Washington, subjects were given either repetitive TMS or a sham (placebo) treatment. In the repetitive TMS group, about 30 percent had a significant response and 20 percent had a complete remission (compared with 6 percent and 3 percent in the sham group). In Australia, 50 patients were assigned either to repetitive TMS or sham treatment. A significant response was seen in 44 percent of patients receiving repetitive TMS (8 percent in the sham group). More than a third in the repetitive TMS group had a complete remission, compared with none in the sham group.

Success in these studies may be due to modifications in how the treatment was given. Patients are now receiving stimuli of higher intensity, a larger number of stimuli in each repetitive TMS session and more stimulation sessions. And in the Australian study, patients had both the left and the right sides of the brain treated. Researchers note, however, that it is harder to create a placebo condition for repetitive TMS. The researchers know which treatment they are giving, and often the patients can tell the difference, too.

In fact, Anne entered one of Dr. Pascual-Leone's trials almost 10 years ago and anticipated that she might receive the sham treatment. But she knew right away that she had been placed in the repetitive TMS group. She felt a characteristic head tapping and twitching in her face that she now knows so well that she can tell the technicians when they have focused on the wrong spot. Her mood improved after the first treatment. At the end of the two-week course, she was dramatically better.

Anne had been expecting twins in a pregnancy that became complicated. One child, a son, died. Her daughter remained in a precarious state in the hospital for four months. Grief and worry led to postpartum depression and hallucinatory psychosis. Anne could barely function. She tried antidepressants, but felt no better until receiving repetitive TMS. In the last few years, she has had short courses of repetitive TMS about four times a year. She now works in a business with her husband, takes care of her children and describes herself as becoming what she was before she became depressed: a happy person.

The stories of Anne and Mark are stirring, but experts are still quite cautious. A relatively small number of patients have been treated so far, and the number of patients evaluated in controlled trials is also very limited. The maximum period of benefit averages around four months, at which point maintenance treatment can be offered and seems to work well. Though less intrusive than ECT, the treatment does require a complicated machine that has to be operated by a skilled technician in a controlled environment. It may have fewer side effects than medications, but it is more expensive and less convenient. There is also much to learn about how repetitive TMS interacts with standard drug treatments.

Repetitive TMS is already available for depression treatment in Canada, Australia, New Zealand, Israel and the European Union. The FDA may rule on repetitive TMS as a depression treatment in early 2007. Approval here would be good for Anne and Mark, because they now pay out of pocket for a treatment that costs about $300 per session. They don't feel they've been mesmerized. "If there was going to be a placebo effect," asked Anne, "couldn't it have happened sooner with one of the medications I tried?" Their interest in talking about their experience is propelled by vivid memories of the pain of depression and the subsequent relief. They know the hard work of living with the illness and the frustration of trial-and-error treatment. They encourage people to stay with it. Like many health-care professionals and patients, they hope depressed patients will have more options available. Because right now, there are still too few.

—Miller is editor in chief of the Harvard Mental Health Letter and a member of the faculty of Harvard Medical School. For more information go to health.harvard.edu/NEWSWEEK.

Psychiatry's Shocking New Tools




Psychiatry's Shocking New Tools

By Samuel K. Moore

First Published March 2006
Electronic implants and electromagnetic pulses are picking
up where psychoactive drugs have failed

Electrode implant stimulates consciousness

Researchers report in today's issue of Nature that they have improved brain function in a minimally conscious patient by implanting electrodes into his brain.

Schiff et al used deep brain stimulation (DBS), an experimental surgical technique that has previously been used to treat Parkinson's Disease and depression, to increase the level of arousal and motor control in the patient, who had been in a minimally conscious state for more than 6 years.

Neurologists define disorders of consciousness according to specific criteria based on behavioural responses. According to these criteria, levels of consciousness or arousal are thought of as existing in a continuum, from unconscious with eyes closed (coma), through unconscious with eyes open (the vegetative state) to conscious and intermittently responsive (the minimally conscious state).

The patient, a 38-year-old male, had been in a minimally conscious state for six and a half years following severe traumatic brain injury incurred during a violent attack. Since his injury, he occasionally tried to utter words and move his head, but was otherwise unable to communicate, and the doctors who performed the emergency surgery on him believed that he would not recover.

Neuroimaging studies had shown that although the patient sustained damage to much of his cerebral cortex, certain essential parts of the cortex remained intact. The researchers theorized that he had remained in the minimally conscious state because of an impairment in the brain's arousal system.

They therefore implanted the electrodes into the thalamus ("deep chamber"), which lies in the centre of the brain, and is involved in arousal, control of movements, and  relaying sensory information to the cerebral cortex. The thalamus is divided into a large number of nuclei, all of which contain a specific type of neuron. Little is known about the properties of these cells, but it is known that they project to diffuse areas of the cortex.

The researchers therefore reasoned that electrically stimulating these cells may activate the undamaged parts of the patient's cortex and lead to an improvement in his condition. Because the brain does not contain sensory receptors, implantation of the electrodes was completely painless

Within 2 days of having the electrodes implanted into his brain, the patient's condition had improved dramatically. He began opening his eyes for long periods of time, and responding to voices by turning his head in both directions.

In the months following the implantation, the researchers experimented to determine the most effective patterns of stimulation. During this time, the patient was able not only to name but also to use objects. He was, for example, capable of raising a cup to his mouth. He was also able to swallow food, so that he could be fed by mouth; beforehand, he was being fed via a tube inserted into his stomach.

To determine that it was the electrodes and not some other factor that led to an improvement in their patient's condition, the researchers then switched the electrical stimulation on and off periodically. They observed that the highest levels of arousal, as defined by the patient's ability to respond to his environment and perform limb movements, correlated with the stimulation. And, compared with before the surgery, some functions were improved during the periods at which there was no stimulation. This suggests that the stimulation had a beneficial carry-on even after the electrodes were switched off.

This is the first time that DBS has been used to treat such a condition, and the results provide a great deal of hope for a better prognosis for patients in the minimally conscious state. However, this study involved only one patient, so larger clinical trials are needed. And it is unlikely that such a treatment would be beneficial for patients who are in a persistent vegetative state or coma.

Friday, January 25, 2008

ISTS Board



President
Sarah H. Lisanby, USA








Vice-President
Chip Epstein, USA









Secretary - Treasurer 
Thomas E. Schlaepfer, Germany/USA









Boardmember
Mark George, USA








Boardmember
Paul Fitzgerald, Australia










Boardmember
Leon Grunhaus, Israel










Boardmember
Ulf Ziemann, Germany


Test of Brain Device Is Setback for Maker





January 23, 2008

Test of Brain Device Is Setback for Maker


Any impact that Tuesday’s plunging stock markets might have had on Northstar Neuroscience was lost in the bad news released before trading began — results from a crucial clinical trial showed that its brain-stimulating device failed to help stroke victims recover the use of their arms and hands.

Northstar, which is based in Seattle, said it would drop efforts to have the therapy approved by regulators. Northstar’s stock, which ended Nasdaq trading on Friday at $8.36, plunged as low as $1.09 before recovering slightly to end the day at $1.37, down 83.6 percent.

The trial results highlighted the hit-or-miss nature of efforts to develop devices that use electrical stimulation or magnetic fields to treat brain and nerve disorders.

Mindful of successes treating conditions as diverse as epilepsy, deafness and chronic pain, device makers have been investing heavily in what James Cavuoto, publisher of Neurotech Reports, forecasts will be a $3.6 billion neurotechnology market this year.

Northstar has focused on the brain’s outer layer, or cortex, as opposed to deep-brain stimulation or stimulation of the spinal cord or major nerves before they enter the brain. The company has studied treatment of major depression and the chronic ringing in the ears called tinnitus by stimulating various regions of the cortex, but it had bet heavily on reaching the market first with stroke therapy after initial research produced promising data.

“To put it mildly, we are extremely surprised and disappointed by these results,” said John S. Bowers Jr., Northstar’s president and chief executive, in a conference call with analysts.

In the trial, stroke victims who had lost control of a hand or arm received either vigorous physical therapy or the physical therapy as well as gentle stimulation from the Northstar Renova, a device the size of a pocket watch that was implanted in the upper chest and connected to the brain by a wire.

Northstar said that analysis of results after four weeks showed that the group getting only physical therapy had done much better than previous research had indicated — so much so that there was no advantage to the stimulator. Preliminary data from patients followed for 24 weeks showed no change in the pattern, Northstar said.

Looking for a silver lining for patients if not investors, Mr. Bowers told analysts that the trial might have demonstrated the value of providing aggressive physical therapy for all stroke victims.

Vagus Nerve Stimulation (VNS) website




This is an excellent site with information on VNS Research.

Monday, January 21, 2008

MagVenture

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MagVenture A/S
Ph: +45 4439 0426
Fax:+45 44991544
Lucernemarken 15
DK - 3520 Farum
Denmark

Magstim


The Magstim Company Ltd
Spring Gardens
Whitland
Carmarthenshire
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SA34 0HR
Switchboard: +44 (0)1994 240798
Fax: +44 (0)1994 240061

Neuronetics

One Great Valley Parkway, Suite 2
Malvern, PA 19355
Tel: 610-640-4202
Fax: 610-640-4206
Email: info@neuronetics.com