Fibromyalgia pain reduced by rTMS

A report from a group in France, published in the journal Brain, describes the effects of repetitive transcranial magnetic stimulation (rTMS) on self-reported average pain intensity recorded at baseline (before treatments), during 10 days of daily stimulation and then at 15, 30 and 60 days after the finish of treatments.
Thirty patients were divided up in a double blind fashion with one group getting sham treatment while the other got rTMS. Outcomes that were measured, meaning what effects were monitored during the study based on the researchers hypotheses, included depression monitoring scales, quality of life scales, scales that monitor how much pain interferes with the patient's functioning as well as the amount of pain a predetermined amount of pressure caused.
Twenty six of the original thirty, 13 in each group, were monitored through day 60 and the group that received the real rTMS had a significant reduction in pain , fatigue, morning tiredness, general activity and sleep at least two weeks after the last session was completed. The affective pain reduction was more long lasting than the sensory effects.
There were no significant side effects that occurred, as is the case with almost all of the studies that have been published in the last few years that adhere to published guidelines.
This group concluded that rTMS "...induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia."
Once again it seems that inducing neuroplasticity can help rebalance the maladaptive patterns that chronic pain syndromes have created. Is it the magic bullet we all hope for? Or is it snake oil? Or maybe something somewhere in between the two? Could this be another step in the right direction, opening the huge black box that is our brain just a little bit more?

Brain Mechanics at MIT

Just read a very insightful article by Ed Boyden "an assistant professor in the MIT Media Lab and MIT Department of Biological Engineering, where he leads the Neuroengineering and Neuromedia Group." Link
He goes into some very insightful thoughts on how to approach the problems associated with fixing problems in the brain, particularly how to view the brain as a complex system that demand you approach a dysfunctional subsystem the same way a computer engineer would: by abstracting the problem and ignoring the surrounding complexity. He goes on to note that the tools could use to fix various problems will depend on what the nature of the problem is. Should we use something focal and invasive, or noninvasive yet cruder with regards to spatial resolution?
Boyden goes on with some nice thoughts about, you guessed it: TMS!
I have to admit I would love to have attended the Neuroengineering panel at the MIT Emerging Technologies Conference.
As I have said before, we are just starting to open the black box that is the brain and technology like TMS and fMRI, used by scientists like Boyden, are going to, at the very least, kick a wedge to keep that door cracked open.

Migraines Zapped with tDCS

The same group ( I trained with them learning the technical aspects of tDCS and TMS) at Harvard that I have written about in the past just had an article published about one of their trials in IEEE Spectrum Online .

The gist of the article is that by using tDCS (low voltage electricity that runs through the brain via a couple of electrodes at very specific locations on the skull) migraineurs were getting some serious relief. The study is currently ongoing so the results have yet to be seen.

"The investigators, Dr. Felipe Fregni and Soroush Zaghi, both of Harvard Medical School, have recruited 24 patients who suffer migraine headaches at least 15 times per month. At scheduled intervals, which may or may not coincide with migraines, Fregni attaches electrodes to a subject’s scalp and passes 2 milliamps of current through the brain, targeting the locus of pain. Two months into the study, he is encouraged by what he is seeing. “In the initial sample, the results went in the direction we predicted,” he says. One of the main themes that I walked away from my week at Harvard with was that the brain is a HUGE BLACK BOX!!!! The breadth and depth of our understanding of how and why the brain works the way it does is superficial at best. As a result of the basic science that is going on with all of the new tools available to researchers, including TMS and fMRI, we are starting to crack open the box. But every little tidbit we figure out just makes me realize that the volume of the box is staggering."

A colleague asked me recently what the proposed mechanism of action was for tDCS and TMS. My short answer was "I don't really know". The long answer has to do with re-balancing the excitatory and inhibitory inputs of certain areas of the brain that affect areas "down stream" from the area of action.

"Following that theory, what triggers migraines is just an extreme example of what causes ordinary headaches in the normal brain. “If you stay up all night, three days in a row, and there are loud sounds and bright lights, you’re going to get a headache, too,” Fregni says. For people with migraines it just takes much less stress because the baseline of activity in certain areas of the brain is much higher, he says.
 Neurons, the cells that carry messages throughout the brain, are constantly receiving electrical inputs from surrounding cells. They integrate the voltage signals, and if the total is strong enough the neuron fires—sending a pulse of voltage out to other neurons to which it’s connected.
 During tDCS, the current hyperpolarizes the afflicted area of the brain, making the neurons less likely to fire. In the short term, the treatment usually staves off an encroaching attack, but tDCS could have long-term benefits as well. Many studies have determined that when repeatedly exposed to a hyperpolarizing current, neurons eventually become less excitable, a process called long-term depression. The stimulation would take advantage of that phenomenon to prime the migraine-prone regions of the brain so that one great flash of light would not be enough to overload the whole system."

Migraines Zapped with tDCS

The same group ( I trained with them learning the technical aspects of tDCS and TMS) at Harvard that I have written about in the past just had an article published about one of their trials in IEEE Spectrum Online .

The gist of the article is that by using tDCS (low voltage electricity that runs through the brain via a couple of electrodes at very specific locations on the skull) migraineurs were getting some serious relief. The study is currently ongoing so the results have yet to be seen.

"The investigators, Dr. Felipe Fregni and Soroush Zaghi, both of Harvard Medical School, have recruited 24 patients who suffer migraine headaches at least 15 times per month. At scheduled intervals, which may or may not coincide with migraines, Fregni attaches electrodes to a subject’s scalp and passes 2 milliamps of current through the brain, targeting the locus of pain. Two months into the study, he is encouraged by what he is seeing. “In the initial sample, the results went in the direction we predicted,” he says. One of the main themes that I walked away from my week at Harvard with was that the brain is a HUGE BLACK BOX!!!! The breadth and depth of our understanding of how and why the brain works the way it does is superficial at best. As a result of the basic science that is going on with all of the new tools available to researchers, including TMS and fMRI, we are starting to crack open the box. But every little tidbit we figure out just makes me realize that the volume of the box is staggering."

A colleague asked me recently what the proposed mechanism of action was for tDCS and TMS. My short answer was "I don't really know". The long answer has to do with re-balancing the excitatory and inhibitory inputs of certain areas of the brain that affect areas "down stream" from the area of action.

"Following that theory, what triggers migraines is just an extreme example of what causes ordinary headaches in the normal brain. “If you stay up all night, three days in a row, and there are loud sounds and bright lights, you’re going to get a headache, too,” Fregni says. For people with migraines it just takes much less stress because the baseline of activity in certain areas of the brain is much higher, he says.
 Neurons, the cells that carry messages throughout the brain, are constantly receiving electrical inputs from surrounding cells. They integrate the voltage signals, and if the total is strong enough the neuron fires—sending a pulse of voltage out to other neurons to which it’s connected.
 During tDCS, the current hyperpolarizes the afflicted area of the brain, making the neurons less likely to fire. In the short term, the treatment usually staves off an encroaching attack, but tDCS could have long-term benefits as well. Many studies have determined that when repeatedly exposed to a hyperpolarizing current, neurons eventually become less excitable, a process called long-term depression. The stimulation would take advantage of that phenomenon to prime the migraine-prone regions of the brain so that one great flash of light would not be enough to overload the whole system."

TMS Demonstrates Increased Cerebral Blood Flow

Nice write up on an article in Science showing that TMS causes an increase in cerebral blood flow as a result of increased neuronal activity. I will get my hands on the actual article and see what it has to say. But regardless, this is some interesting data which helps open the black box that is the brain just a little bit wider. Nice work by the group at Cal.

Neuroscientists connect neural activity and blood flow in new brain stimulation technique

By Sarah Yang, Media Relations | 27 September 2007

BERKELEY – Neuroscientists at the University of California, Berkeley, have for the first time measured the electrical activity of nerve cells and correlated it to changes in blood flow in response to transcranial magnetic stimulation (TMS), a noninvasive method to stimulate neurons in the brain.

Their findings, reported in the Sept. 28 issue of the journal Science, could substantially improve the effectiveness of brain stimulation as a therapeutic and research tool.

With technological advances over the past decade, TMS has emerged as a promising new tool in neuroscience to treat various clinical disorders, including depression, and to help researchers better understand how the brain functions and is organized.

TMS works by generating magnetic pulses via a wire coil placed on top of the scalp. The pulses pass harmlessly through the skull and induce short, weak electrical currents that alter neural activity. Yet the relative scarcity of data describing the basic effects of TMS, and the uncertainty in how the method achieves its effects, prompted the researchers to conduct their own study.

"There are potentially limitless applications in both the treatment of clinical disorders as well as in fundamental research in neuroscience," said Elena Allen, a graduate student at UC Berkeley's Helen Wills Neuroscience Institute (HWNI) and co-lead author of the study. "For example, TMS could be used to help determine what parts of the brain are used in object recognition or speech comprehension. However, to develop effective applications of TMS, it is first necessary to determine basic information about how the technique works."

Other techniques for studying neural activity in humans, such as functional magnetic resonance imaging (fMRI) or electroencephalogram (EEG), only measure ongoing activity. TMS, on the other hand, offers the opportunity to non-invasively and reversibly manipulate neural activity in a specific brain area.

In a set of experiments, the researchers used TMS to generate weak, electrical currents in the brain with quick 2- to 4-second bursts of magnetic pulses to the visual cortex of cats. Direct measurements of the electrical discharge of nerve cells in the region in response to the pulses revealed that TMS predictably caused an initial flurry of neural activity, significantly increasing cell firing rates. This increased activity lasted 30 to 60 seconds, followed by a relatively lengthy 5 to 10 minutes of decreased activity.

What the researchers were able to determine for the first time was that the neural response to TMS correlated directly to changes in blood flow to the region. Using oxygen sensors and optical imaging, the researchers found that an initial increase in blood flow was followed by a longer period of decreased activity after the magnetic pulses were applied.

"This long-lasting suppression of activity was surprising," said Brian Pasley, a graduate student at HWNI and co-lead author of the study. "We're still trying to understand the physiological mechanisms underlying this effect, but it has implications for how TMS could be used in clinical applications."

The critical confirmation of the connection between blood flow and neural activity means that researchers can use TMS to alter neural activity, and then use fMRI, which tracks blood flow changes, to assess how the nerve cells respond over time.

"One of the most exciting applications of TMS is the ability to non-invasively modify neural activity in specific ways," said Pasley. "The brain is malleable, so brain stimulation may be used to alter and promote specific functions, like learning and memory, or suppress abnormal activity that underlies neurological disorders. If we can figure out the right ways to stimulate the brain, TMS will likely be useful in attempts to improve neural function."

The researchers noted that one of the difficulties in using TMS for specific applications is the fact that its effects vary in different brain regions and individuals.

"Using TMS is inherently challenging because its neural effects can be so variable," said Ralph Freeman, UC Berkeley professor of vision science and optometry and principal investigator of the study. "Fortunately, we can determine empirically what the end result is by making measurements with fMRI. This should be valuable to clinicians who must evaluate the effectiveness of a stimulation treatment. In turn, fMRI may serve as a guide to determine adjustments in treatment parameters."

The study was also co-authored by Thang Duong, a UC Berkeley graduate student in vision science. The National Eye Institute of the National Institutes of Health and the National Science Foundation helped support this research.