Reprinted with the kind permission of Cort Johnson and Health Rising.
The bad news for fibromyalgia and ME/CFS is that the most complex, impenetrable and difficult to understand organ of all – the brain – appears to be heavily involved in both diseases. The good news is that the NIH aims to leapfrog its ability to understand and treat brain diseases with its mighty Brain Initiative.
In the third of three blogs looking at the research efforts of tomorrow and their potential impact on fibromyalgia and chronic fatigue syndrome (ME/CFS), Health Rising looks at the biggest effort of all: the Brain Initiative.
The Brain Initiative
We’ve always suspected that technology is going to provide the answers for diseases like fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS), and nowhere are technological advances more important or necessary than in the brain. With its 100 billion neurons and 100 trillion connections encased in its difficult to penetrate bone helmet, it’s easily the hardest organ to get at and understand – and possibly the most important.
Almost all of the symptoms associated with FM and ME/CFS such as the fatigue, pain, cognitive issues, sleep and stimuli problems could conceivably have their origin in the brain. While brain scans regularly find abnormalities in FM, for instance, they’re not precise enough to tell us which neurons, astrocytes or glial cells are causing the problems in these diseases. Similarly, while magnetic stimulation and other brain stimulation techniques can be helpful, they’re still crude techniques that lack the ability to target specific brain cells.
On April 2, 2013, the White House proposed a 10-year project — the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) – to unlock the mysteries of the brain. This Manhattan style project brought together a roster of experts to “catalyze an interdisciplinary effort of unprecedented scope.” After a year of work, the group reported a series of goals:
- To classify all the cells in the brain in order to learn how to tweak what
- To produce a full “connectome” of all the millions of connective circuits in the brain
- Understanding the electrical and chemical activity each type of neuron in the brain engages in
- Finding new ways to affect brain activity
New tools need to be developed to succeed at each of these goals. The data gathered will be so immense as to require that new statistical methods be produced to adequately analyze it.
The Brain Initiative started funding projects in 2014. Here are some of its recently funded projects:
FIXING THE BRAIN
Changing Brain Activity
Electromagnetic tools (e.g., transcranial magnetic stimulation and others) offer powerful possibilities for resetting brain functioning in FM and other diseases, but are still relatively crude. Because they’re not nearly as precise as we might want, they tend to activate all the cells in a given area – including cells which are acting normally. These MIT researchers have developed a “magnetothermal toolbox” that they believe will allow them to locate and activate specific neurons in the brain – thereby paving the way for more precise ways of stimulating or de-stimulating the brain.
The goal in FM might be to activate pain-inhibiting circuits; in ME/CFS, to activate motor cortex circuits that are impeding movement or to deactivate circuits that pay attention to background stimuli.
Transcranial Magnetic Stimulation to the Rescue?
More resources are being devoted to transcranial magnetic stimulation (TMS) than any other non-invasive brain technology. Why? Because the technology uses coils to deliver electrical stimulation that have the power to alter negative patterns of brain activity. However, TMS is not precise enough yet to deliver the goods.
This MIT group is developing miniaturized rTMS elements that will allow them to alter brain activity more precisely and at deeper levels of the brain (where many of the problems with FM and ME/CFS may lie). As an added bonus, these elements will allow them to map the brain with unprecedented precision.
Another Massachusetts group will combine TMS with MRIs in order to simultaneously stimulate multiple brain regions – a real need given the different brain regions involved in diseases like fibromyalgia and chronic fatigue syndrome. Imagine resolving your pain, fatigue, cognitive and stimuli issues all at once. It’s an integrated approach like this that will be needed to return the brain to homeostasis.
Focused…Really Focused Ultrasounds
Blood flows through the brain appear to be a big deal with both ME/CFS and fibromyalgia. Dr. Byron Hyde, for instance, believes brain imaging scans that measure blood flows can be used to not only diagnose people with ME/CFS, but to tell what kind of ME/CFS they have.
Newer functional ultrasounds being developed now that use acoustic signals to measure blood vessel volume, however, put older techniques to shame. They’re about 10 times more precise.
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The Salk Institute found that low intensity ultrasound can actually regulate the activity of neurons in the brain. They’ll use their grant to find ways to optimize the use of a novel technique called “sonogenetics” to use sound waves to do just that.
Another effort involves creating gaseous nanovesicles (really, really, really small vesicles) derived from microbes that can be introduced into the brain which, their creators believe, will create an even more “revolutionary leap” in our ability to view the brain – particularly in its deeper levels. As an added bonus, it may be possible to use this technology to actually modulate brain activity at a very deep level.
Overactive sensorimotor regions of the brain may be contributing to the problems with stimuli, concentration and fatigue, and the thalamus may be at the root of many problems in ME/CFS and FM. Another research effort will produce a wearable FUS cap that’s designed to modulate the activity of just these regions.
Shhh…..A Quiet TMS
Transcranial magnetic stimulation (TMS) may be non-invasive, but they are noisy, uncomfortable, potentially unsafe over time and not as effective as they might be. This Duke University study will attempt to create not just a quiet but an inaudible TMS (a qTMS or quiet TMS) machine that is more tolerable, safer, more precise and even more effective.
A Walk Down Memory Lane Again?
Short-term memory may seem to be like a thing of the past in ME/CFS and FM, and memory issues are a problem in many neurological diseases. Unfortunately, no treatment can fix memory problems, but hopefully they’ve met their match in a Northwestern University effort that will use a new brain stimulation procedure called “HF-Stim” to enhance the hippocampal-cortical networks which enable us to have memories.
UNDERSTANDING THE BRAIN
The Inflammation Behind Neuroinflammation
Neuroinflammation is a hot, hot topic in ME/CFS and FM, but again current brain imaging techniques cannot tell us which types of astrocytes, glial cells and neurons contribute to it. This study will employ DREADDS ( Designer Receptors Exclusively Activated by Designer Drugs) to determine which kinds of cells are producing neuroinflammation.
The Zinns have shown that EEGs provide a powerful tool for understanding ME/CFS, but as with some other imaging technologies the spatial resolution of EEGs is poor. Researchers can demonstrate that brain abnormalities are present, but precisely identifying their origin is difficult. Enter the Virtual Brain Electrode project which will load red blood cells with magnetic particles in order for researchers to indicate exactly which part of the brain those pathogenic EEG signals are coming from.
Many functional MRI studies in fibromyalgia and chronic fatigue syndrome (ME/CFS) have demonstrated problems in brain functioning during a task or event. For instance, last year a study indicated that the activity in areas of FM patients’ brains that are tasked with assessing pain levels didn’t just increase but remained increased following a small pain event. That helped researchers to understand why the pain in FM hangs around long after a painful event has occurred.
Researchers can broadly determine which areas of the brain are activated or under activated in FM and ME/CFS but they can’t tell why. Determining that will require learning which neurons or immune cells are being activated. The new technology under development should enable them to tell which kinds of neurons (inhibitory/excitatory) or glial cells are to blame. That will help them determine which kinds of treatment might be best.
Metabolism has emerged as a huge issue in chronic fatigue syndrome and reductions in brain metabolism have been associated with fibromyalgia, as well, but again, it’s not clear what is causing these changes. This effort will seek to provide much the same result as the last one but in a different way. It aims to be able to identify the different kinds of neurons, glial and other cells that are contributing to the metabolic alterations seen on fMRIs, thus providing what the authors believe will be a paradigm shift for the field.
Blood, of course, flows through the blood vessels, but we know little about how those blood vessels affect the all important blood flows in the brain. Given the high rate of migraine in FM and ME/CFS and the distinct possibility that blood vessel problems are involved in ME/CFS, this effort trying to learn how microvascular changes in blood vessels affect blood flows across the brain could reap dividends.
Another problem with fMRIs is their low spatial resolution. They’re good at giving us broad pictures of activity across the brain but lack precision at a more local level. This effort will combine fMRIs with other brain imaging technologies to provide three-dimensional maps at the microscopic level of the brain when it is active. Researchers would be able to learn precisely where the pain, for instance, is being generated in the brains of FM patients.
The NIH’s Brain Initiative (BI) project aims to revolutionize our understanding of how the brain works and how to treat its diseases. If the BI gets even close to its goals, we should expect new technologies that provide vastly better views of the brain and vastly improved methods of treating it to show up over the next ten years. Given the degree to which the brain likely contributes to both FM and ME/CFS, that would be good news indeed.
About the Author: ProHealth is pleased to share information from Cort Johnson. Cort has had myalgic encephalomyelitis /chronic fatigue syndrome for over 30 years. The founder of Phoenix Rising and Health Rising, he has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.