A Very Exciting Presentation
Two years ago, Marcie and Mark Zinn produced what I thought were the two most exciting presentations of a very exciting Stanford Symposium. They had used a technology called qLoretta to analyze EEG findings in a way that hadn’t been done before and the effort appeared to have paid off.
It’s been two years since the Zinn’s asserted a widespread pattern of reduced activation was present in ME/CFS patients brains
Mark Zinn proclaimed that chronic fatigue syndrome was going to teach the medical profession a lot about the brain. The problems they found were so widespread that the Zinn’s asserted ‘a global expression of CNS hypoactivation” was present, and that ME/CFS patients might be in the grips of an “limbic encephalopathy”.
Mark Zinn felt their findings would bring ME/CFS patients relief; their studies indicated that their cognitive and other problems were real, but that was the last we heard from them for over two years. Their two Stanford papers were never published (the last two Stanford newsletters have listed them as under review) and they moved to Chicago to begin work with Lenny Jason.
This year they’ve published one study with new participants, one case report and one review. Co-authored by Dr. Jason and the two Zinn’s the study contained 18 ME/CFS patients from Dr. Jason’s DePaul University ME/CFS in Chicago.
Is It Real?
The Zinn’s grabbed a big bull by the horns regarding cognition and ME/CFS immediately when they noted the discrepancy between the degree to which people with ME/CFS report cognitive problems and the extent with which they’ve shown up in studies. They noted a recent meta-analysis whose results (deficits in attention, memory and reduced responsiveness) contrasted strongly with the many issues patients report (deficits in selective and sustained, attention, speech, planning, decision making, error correction, reading and speech comprehension, information processing speed, and visuospatial ability.) This disconnect between study results and patient reports has led some to believe that ME/CFS is a somatization disorder with no underlying pathophysiological problems.
The QEEG studies done in ME/CFS, however, would disagree with that assessment. No less than ten studies in ME/CFS, they report, suggest an underlying pathophysiology is present. Why have QEEG studies been so adept at plucking out problems? Possibly because they measure pathophysiology at the cellular level – which many people believe is where the action is in ME/CFS. Because QEEG testing assesses nervous system activity by the millisecond they may be more likely to pick up rapid changes in the dynamics of the brain than other approaches such as fMRI’s.
The brain is no longer thought of as an organ whose different parts can be a assessed separately. Pathology in the brain is not just a function of damage to a region of the brain – say the prefrontal cortex or brain stem. Pathological problems occur more commonly when different parts of the brain fail to interact with each other correctly.
How well the different regions of the brain regions connect or pass information to each other is particularly important with regard to cognition The brain, the Zinn’s point out is an “information processing device” that relies on continuous flows of information across it to maintain the body’s homeostasis and to figure out what to do next.
Network Model of Brain Pathology to Explain ME/CFS
In this study the Zinn’s used the Menon Triple Networks model of brain pathology to inform their findings. The model hypothesizes that three core networks in the brain regulate arousal, attention, and general access to cognitive abilities. All three must work together for cognitive processes to work well. The brain must rouse itself, then focus on something (salience network), and then use it’s cognitive capabilities (central executive network) to analyze what it’s attention was grabbed by. Any issues with any one of these spells trouble.
Much brain research now focuses on the effectiveness of the networks present in the brain
Some of these regions are impaired in ME/CFS. The anterior insula, for instance, is a key player in the salience network and an object of interest in ME/CFS and FM. If the anterior insula is unable to filter out irrelevant from non-irrelevant stimuli, the brains ability to focus on a single problem will be impaired. Or if the anterior insula focuses too much attention on less relevant issues or stimuli problems with anxiety or pain can result.
Getting easily upset or anxious over small things that failed to bother one before and/or problems with pain sensitivity (e.g. too much attention being focused on internal stimuli), could derive from problems with the anterior insula telling a person to focus on irrelevant stimuli.
In their review the Zinn’s asserted that attempts to focus on one region of the brain while ignoring how that region interacts with other regions of the brain has resulted in research findings that under estimate the size of the cognitive problems present in ME/CFS.
This study looked at “cortical source density” across the brain and then used that information to determine how three networks were functioning in people with chronic fatigues syndrome (ME/CFS) and healthy controls.
Results
Alpha Rhythms Down
The study found reduced alpha and alpha-2 sources across the entire occipital lobe and extending into portions of the parietal, temporal and limbic lobes. Alpha rhythms show up most strongly in a waking and rested state – two states that wired and tired ME/CFS patients probably have little familiarity with. These alpha waves play a critical role in a bunch of brain processes that are not doing too well in ME/CFS including information processing (slowed), attention (down), inhibition (definitely harder to do post-ME/CFS). All in all, alpha rhythms are strongly associated with the ability to engage in “executive functioning” which includes the ability to plan and engage in tasks.
The reduced alpha wave activity found across a large part of the brain (occipital, parietal, temporal, and limbic regions) can help explain why it’s so difficult sometimes for people with ME/CFS to get into action, and why they have both sensory and movement problems.
Delta Rhythms Increased
In contrast to the decreased alpha rhythms, the Zinn’s found increased delta rhythms across another large swath of the brain (frontal-limbic regions in the superior frontal gyrus, the entire cingulate gyrus, medial frontal gyrus, orbito-frontal cortex, middle frontal gyrus, insula, superior temporal gyrus and in the rectal gyrus (ouch!)).
Brain Gears Not Meshing
The Zinn’s also found evidence that the three modes were not synchronized well in ME/CFS. In order for the brain to work properly it should arouse itself, focus on a task and then carry it out. The Zinn’s found evidence of lags in all three phases. The brain took longer than normal to arouse itself, stumbled as it tried to focus on a task, and then stumbled again as it tried to carry it out. It was as if the gears were not meshing properly.
The gears were not meshing in the ME/CFS patients brains.
That made sense given prior studies finding delayed reaction times as well as the slowed movements sometimes seen in ME/CFS. In order for someone to move their arm the motor cortex needs to be activated and then it needs to activate the movement centers of the brain. Problems with both parts of the brain were demonstrated years ago in ME/CFS. The lags in the ability of the different parts of the brain to communicate with each other could help explain why that is.
The Zinn’s also referred feelings of derealization (brain fog), problems with spatial orientation and the difficulties some patients have in a) driving a car and b) getting lost when they do so.
As in their presentation two years ago, the Zinn’s referred to hypoactive mental states that might be able to interrupt consciousness to such a degree as to bring on vegetative states. They also noted that the weakened coupling they found within the salience network – which determines how much attention to pay to internal or external stimuli – could be producing the different hypersensitivities found in ME/CFS.
Plus the problems with the salience network and its weakened connectivity with the DMN network could lead to problems with self-reflection and mental activity. At least in my case, I feel that my capacity for self-reflection – which I assume requires being in a rested yet wakeful state – was diminished greatly after getting ME/CFS.
A Case Report
In January of this year the Zinn’s published a case report of one patient which may further help explain ME/CFS.
qEEG / LORETA in Assessment of Neurocognitive Impairment in a Patient with Chronic Fatigue Syndrome: A Case Report Marcie L Zinn*, Mark A Zinn, and Leonard A Jason. DePaul University, Center for Community Research, Chicago, IL. Received date: 14 Jan 2016; Accepted date: 27 Jan 2016; Published date: 30 Jan 2016. Clin Res 2(1): doi, http://dx.doi.org/10.16966/2469-6714.110
As we’ve seen the Zinn’s data suggests that arousal and attention are inhibited in ME/CFS. It turns out that our attention is grabbed when a novel event causes the reticular formation of the brain to wake up the cortex. The cortex then filters out the irrelevant information and processes the relevant formation. Problems with this process show up in difficulty paying attention and anxiety.
This process of arousal and attention is related to something known as phase locking which occurs when millions of neurons become synchronized on the order of milliseconds in order to assess a new event. During phase shifts the neurons become unsynchronized so that a new set of neurons can become recruited to assess the next event.
The Zinn’s found very fast phase shifts and locks in their patient. Phase shifts need to last long enough for the brain to recruit enough neurons to assess new event but that didn’t appear to be happening in the ME/CFS patient. Plus the phase lock process was being broken so quickly that the few neurons that were engaged didn’t have the time needed to analyze the event. The Zinn’s proposed this pattern was consistent with the slowed information processing times and other problems in ME/CFS. They stated
These deregulated states represent the brain during non-optimal functioning, rendering it inefficient for most types of information processing functioning, whether it is executive functioning, memory, perceptual reasoning or information processing speed.
Conclusion
If your attention span has become shorter, if you can’t remember things, if you often lose your train of thought, if you make silly mistakes, even if you’re anxious a lot or can’t move well – the good news from this study is that that’s not you – it’s probably your brain.
To sum up
- Reduced alpha rhythms across large parts of the brain could help explain the problems with information processing, executive functioning and even movement found in ME/CFS.
- Problems with brain connectivity could help explain the slowed movements, brain fog, spatial disorientation and other cognitive problems found.
- Very fast phase shifts and locks suggests the brains of ME/CFS patients may not being able to recruit enough neurons or use them for a long enough time to be effective.
With three publications under their belts thus far the Zinn’s are doing well with Lenny Jason at DePaul University. Next up a talk with Marcie Zinn and a look at their review paper on the brain including the possible causes of the brain problems they’ve found.
In your opinion, what kinda drugs or therapy could help this? I know different meditations can help with alpha, beta, etc.
I’m afraid I have no idea but when I talk with Marcie I will ask her if she has any suggestions. I think one problem may be that a lot of things may be able to cause this. I don’t know if meditation can shift these brain rhythms into a more optimal mode of functioning. I know that it can help with brain issues but I don’t know if can effect this kind of issue. That will take some more research.
Hi Sipora, Cort – I’ve had severe problems with brain fog. In the last year I’ve been taking an Rx called Nuvigil, which has helped. (Not back to 100%, but better.) It’s expensive (*with* insurance coverage, ~$300/mo for me), but I haven’t found anything else that even begins to help. Would be keenly interested in whether they have an idea about what might be causing the problems and what other treatments might help.
Hello Cort, This is my first post on your site though I have been reading for some time. Thank you for the information that you share, and thanks to all who share in the conversations! So much of what I read here relates to my health challenges though I have not been diagnosed with CFS/ME. HOWEVER, I have lived with Traumatic Brain Injury, and subsequent concussions now labeled Post Concussion Syndrome for several decades and almost all the symptoms and challenges that I live with are described in the articles and posts here, esp. cognitive and executive functions. I wonder if my TBI diagnosis is covering up CFS/ME and/or if at the core the dysfunctions are really the same, as being desrcibed in latest research. I have not pushed for a CSF/ME diagnosis as I try to fly “under the radar” with traditional medicine, using it appropriately when needed but mostly have found that more integrative and holistic approaches produce results, even if not producing “cure” (i.e. meditation and visualization, craniosacral therapy, acupuncture, herbs, etc.). My past experiences with drugs have been exceedingly negative; I don’t have much resilience to deal with negative side effects so I avoid most drugs. I have intuitively “known” for a long time that my challenges are far beyond and more complex than traditional approaches to brain injuries (i.e. merging with immune and digestive systems, and far more complex brain functions than have been known in the past… as this study). Have others who live with TBI posted on your site, sharing the similar health challenges between TBI and CFS/ME? I am also interested to know more about meditation affecting these particular brain rhythms, as a long time meditator who continues to live with severe brain challenges. With gratitude…you are all in my thoughts and prayers daily. Should I post my query in a separate post rather than a response post?
I have just learned about a supplement called Sulbutiamine. It is a B1 ( thiamine) derivative that crosses the blood brain barrier more easily than regular thiamine. It is reported to boost dopamine in key brain areas to help with fatigue and with motivation. Has anyone tried this ?
I have tried Mucuna Puriens which increases dopamine. I didn’t stay on it as it didn’t seem to be doing anything for me. There is evidence it increases dopamine, not just anecdotal.
Hi this article was so informative.I have had CFS/ME complicated by major depression,Complex PTSD & anxiety disorder for 26 years. This all makes so much sense to me and explains so much.Crazy as it may seem, when I thought my brain was going to disintegrate 7 years ago I started studying a degree in business. It took 6 years to complete, I crashed many times, had numerouse extensio ns assignments & missed exams which I sat later, one I got the time wrong. But I got there because I loved what I was learning, it stimulated my mind,once I learnt how to read text books,take notes,use a laptop, use a library etc. Sheer determination was the force that kept me going and black coffee during lectures.It wouldn’t be for everyone but it saved my sanity.i now read to stimulate my brain loads of non fiction and meditate using deep breathing to rest my brain. I still the symptoms stated in the article but so much better. Working is still a challenge because of the long periods of concentration & fatigue.
I use microcurrent from a tens unit with ear buds set to an alpha wave hertz setting. It works, but I quit using that setting as all I ended up being was wired and tired, as in no stamina. I still use the unit to stimulate the vagus nerve. I found a relatively inexpensive unit for the microcurrent and have had good results with reducing atrial fibrillation and increasing ATP,, but not to a level that was too much as the alpha wave setting was.
Since many systems are reduced to a hypo state in ME/CFS, just speeding up the brain won’t entirely help. It is like picking up one corner of a cloth sheet with 12 corners. There is also a low endocrine system, for instance. Without the endocrine system cooperating to pick up the speed of overall functioning, just stimulating the brain won’t have any lasting benefit and often causes more fatigue and slowness. This nut can’t be cracked by means of just stimulating the brain or speeding up/increasing some aspect of the endocrine functioning or supporting mitochondrial health in any particular way, etc. To me, an overall balance is better for health and functioning than having one aspect speeded up, even when the overall balance is slow and low. A lot of us try to use medications, supplements, etc. to bring up as many of the affected systems as possible. If this can be done to the level of normal, hurrah! That is rare. If it can be done to the level of low normal, still hurrah–this is a lot better than it was before. Bringing up everything in balance to gain a 10% or more improvement is worth it.
I would certainly look at mold being a big player
Yes! Mold is what finally sent me over the edge. I had varying mild symptoms for years, but then I had daily exsposure to mold that sent my herpes simple 1 into overdrive and my life has been hell since.
The Real disease we have to cure is TMCNGAS. Which stands for. The Medical Community Not Giving A Shit. Am I right people?
YES!
Thanks Felicia! It’s good to know somebody else gets it!
Absolutely! 🙂
sound and light machines can help shift brain wave patterns but they may be too stimulating for a lot of people. i find using one at the dentist helps a lot with my fear. if someone has seizure problems they should not use the light component, only the sound. this method is called brain entrainment.
I was reading some info about brain wave entrainment and noted that it has also used to improve heart rate variability, another factor which has been suggested to be a problem in people with CFS;
http://mentalhealthdaily.com/2015/04/01/benefits-of-brainwave-entrainment-technology/
This article is definitely in line with my experience getting EEGs 20 years ago at different sites–a number of sites each time but a different pattern of them each time. The therapist, who was giving me neurofeedback treatments, said that my Alpha rhythms were low and Delta rhythms were high, compared to normal people. I have ME/CFS. The neurofeedback system itself did not help. Occasionally it seemed to help very briefly, for a few hours. Mostly not even that. But the evaluation of my brain rhythms and the finding that they are slower than normal seemed very significant to me. Finally research is starting to catch up. I hope that this type of research will continue and the studies will be larger and replicated. Nothing is a more major issue, in my view, than the memory and cognitive problems, the brain symptoms, in ME/CFS. A person can have low energy, poor sleep, pain, low endocrine functioning, PEM, but when a person’s mind is no longer reliable and functional, that is on the track of “game over”. For most of us it is not yet game over, but we can start to see it coming. This area of dysfunction has been rated by patients as the most serious and difficult problem we experience–not the one that the doctors, researchers and definition creators see as the most major one–but the one that patients know takes down quality of life above all. Here is to more research attention for these issues.
I agree that it is probably the most difficult problem that I face. I was struck by the possible completeness of it; not only may it cause typical cognitive problems including executive functioning (planning, etc.) but anxiety and movement issues as well. Could my “anxiety” or difficulty settling down and attention issues simply be due to my brain not being able to screen out irrelevant issues or if looked at internally – internal stimuli?
This is so interesting – when I was at my most I’ll, I felt like my brain was somehow split and, to be able to think about things properly, it felt like I had to pull my brain together like a pair of curtains to get it to work. That makes a lot of sense after reading this.
A lot of this matches my experience pretty closely. I have consistently low alpha in the occipital and parietal regions that’s been very difficult to increase. When QEEG and other EEG specialists have looked at the scans, they’ve said they find it hard to imagine the discomfort, etc. that is likely there as a result. I suspect that’s the same for many or most with ME/CFS.
EEG neurofeedback has helped increase rear alpha slightly, but it’s been difficult to maintain the improvements. I think something else is driving the brainwave imbalances in ME/CFS, something more primary like endocrine/immune dysfunction, PTSD, etc. But practically speaking, once the dysfunctional neural pattern/s are initiated, I think it’s possible that correcting the brainwave imbalances could have a corrective effect on the other disturbances (endocrine, autonomic, etc.) that likely exist.
why allways so few people that are investigated? this is in statistics even not relevant. we need urgently larger numbers that are investigated. Only than, we can find causes…
Of course we want more people in these studies, but of course they’re relevant as well. All these studies are analyzed statistically; if they weren’t significant they wouldn’t make it to publication. The problem is that we don’t know if they will be validated.
Big studies don’t just pop overnight, though. First sometimes you need to smaller studies – like this one – to get researchers interested, particularly in this underfunded field. Hopefully this study will trigger larger studies. .
Who cares about the cause. The fix is what is important. Regulating the nervous system then everything else falls in line. It clearly comes from different forms of stress.
I agree that this is interesting!
I wonder if it could explain that feeling of being partially paralyzed – when it takes an effort of will to even pick up a toothbrush.
I wonder if Brain Sync CDs would help with this problem.
Since practicing mold avoidance, I have felt a lot less brain fog.
I get that feeling too. I can plan, I can figure out what to do next, but initiating an action takes a real push of energy. Would be nice to have researchers figure out why.
I wonder if this explains why familiar music helps me get moving when I feel stuck (as long as there is no other noise). For ages I thought it was just a boost to my enthusiasm to help me push past reluctance, but at I read about Parkinson’s sufferers using Walkmans as music could stop them getting stuck when walking, something about it connecting various parts of the brain, and it felt like that’s what it is for me! Now if only I could find a similar aid to being concise…
Cort, they give any explanations why memory retrieval is so dysfunctional?
there is cognitive nausea (like inducing something akin to motion sickness but via thinking) and like with moving the body around, it takes so much more effort – thinking is not a pleasant experience.
I wonder how much we are accounting for people evolving their responses to questions to mask deficits to avoid humiliation. 50% of my conversations with anyone other than my close friends or spouse are just me distracting or diverting while I struggle to word find or to get back on track after any minor interruption or diversion from main topic made me forget the initial point and initial conversation.
In these studies and analyses were the comparisons made to standardized profiles of brain activity in the relevant regions or were the studies using control subjects? The reason I ask this is that standardized profiles are often based on clinical case studies and can be much less reliable than RCTs where subjects are directly matched with “healthy” controls and in brain MRI mapping comparisons they should be double blind.
Both the Stanford study – which was never published and was huge by the way – over 100 ME/CFS patients and the Chicago study used healthy controls. I don’t know about the blinding
Under-active and over-active brain. That’s me for sure. Tight now because I spent a week with my kids and grandkids (4) my brain is very slow, feels very foggy. I’m surprised I can write.
But my brain also feels over-active, every noise, light etc is amping up the orchestra in my brain and it’s definitely not in tune!
The extra slow, fogged-over brain is very familiar to me, in the morning as well as the rest of the day if I am extra tired. The speedy, over-sensitive dynamic in my case is also disorganized. It is an ADD type brain, which I have only developed since getting ME. My attention keeps branching off somewhere else. The ability to stay on track, stay focussed, to speak concisely and to summarize all leave. My brain is more jumpy and disorganized than high speed. But it does speed up in a compulsive way when I am actively trying to overcome its slowness and dysfunctionality. I can’t force it to be normal, unfortunately, but pushing it hard, I make it be dysfunctional in a different way–compulsive, unbounded, ceaseless. I might just keep doing something like reading or talking, well past my real limit and then have more than before to recover from the next few days.
So where are we at with this now? For heavens sakes there is so much about what may be wrong but how about ideas to regulate the brain again???