(Dr. Baraniuk finds damage to a critical nerve pathway that connects regions of the brain involved in fatigue and pain production and autonomic nervous system regulation. The damage, which affects the integrity of the nerve axons, is unusual and suggests GWS and perhaps ME/CFS are not related to demyelinating disorders such as multiple sclerosis. His model suggests that the attention of people with GWS/ME/CFS gets pulled again and again away from the outside world and onto pain and other signals in the body, making it difficult for them to concentrate and carry out tasks).
The ME/CFS/FM Connection
As you read this blog on Baraniuk’s Gulf War Syndrome study bear in mind three things:
- Baraniuk felt his brain proteome findings of seven years ago (yes, seven) fit ME/CFS/FM/GWS patients
- all the participants in this study fit the criteria for chronic fatigue syndrome (ME/CFS) and 50% fit the criteria for fibromyalgia (FM)
- when I asked Dr. Baraniuk if ‘all roads lead to Rome’; ie if he thought GWI and ME/CFS and other disorders had similar brain issues his answer suggested he did. At one point in the paper he pointed out that similar brain structures are involved in chronic fatigue syndrome and GWI.
We won’t know until we know but it’s very possible these findings or something close to them will apply to people with chronic fatigue syndrome and fibromyalgia as well.
“Functional Neurobiology”: Looking for Fatigue and Pain in the Brain
Given that the fatigue and pain in Gulf War Syndrome tend to occur in parallel; ie., the worse the fatigue, the worse the pain that was present, Baraniuk looked for the roots of both. Noting that the orbitofrontal cortex and the prefrontal cortex both play a role in producing fatigue and pain states, Baraniuk zeroed on connecting fibers called the fronto-occipatal fasiculus (IFOF) that connect these two organs and the insula.
Think of the IFOF as a bundle of wires connecting the prefrontal cortex – the seat of decision-making center of the brain – to the insula – an autonomic nervous system regulator and the seat of the interoceptive process. Studies have shown that increased ‘connectivity’; i.e. increased activity between the prefrontal cortex and the insula plays a role in producing and maintaining chronic pain states.
The IFOF is composed of white matter, and in this study Baraniuk used diffusion tensor imaging (DTI) to see if this pathway was different in GWS patients vs healthy controls. The options were no change, a loss of white matter ‘integrity’, decreased axonal functioning (axons are the main nerve bundles), and/or demyelination and inflammation
Unusual Form of Nerve Damage Found – Demyelination Not Present
The study found option three – decreased functioning of the axons was present in the people with GWS and ME/CFS.
This suggested that neither demyelination or neuroinflammation was occurring. Instead, something called increased axial diffusity, which refers to weakened nerve axons, was present and importantly, was associated with increased fatigue and pain; the weaker the IFOF axons were – the more pain and fatigue these patients were experiencing.
The images indicate that in GWS, these nerve bundles break down and may have trouble forming connections. This suggests that the brain circuitry, rather than any specific brain area, is disrupted in people with the condition. News Scientist
Again, these less robust axons have not been demyelinated; i.e. the myelin sheaths covering the nerves have not been attacked. Instead, they appear to be dysmyelinated, a process characterized by defective development and functioning.
“the changes appear distinct from multiple sclerosis, major depression, Alzheimer’s disease and other neurodegenerative diseases,” Rayhan, lead author of the study
The really intriguing thing is how rare this kind of nerve damage is. Baraniuk stated that hundred’s of studies have found increased demyelination but the increased axonal diffusity found in this study is rare.
Instead of being related to multiple sclerosis and other demyelinating disorders (acute disseminated encephalomyelitis, Neuromyelitis Optica, transverse myelitis, etc., GWI and perhaps ME/CFS/FM may be more related to such rare illnesses as the leukodystrophies (Pelizaeus–Merzbacher disease, Canavan disease, phenylketonuria).
According to one article low blood flows could play a role. Chronic states of low blood flow (ischemia), for instance, are associated with increased diffusity, an intriguing finding given that Baraniuk’s brain proteome study suggested brain circulatory problems play a role in ME/CFS/FM. Several studies have found reduced brain blood flows in ME/CFS, and Dr. Natelson’s study suggests that besides reduced brain blood flows, a significant number of people with ME/CFS may have increased lactate, cognitive issues, and small frontal lobe lesions.
- See: The Splitter: Researcher Asserts ‘Brain-damaged’ Subset Present in Chronic Fatigue Syndrome (ME/CFS)
While measures suggestive of demyelination were not significant we should note that a trend towards significance was present suggesting that a larger study could have shown demyelination as well. (Those measures were not correlated, however, with increased fatigue and pain.)
Baraniuk isn’t interested in just displaying his results; he has a model of GWS/ME/CFS he wants to get out, and in that model the trouble starts at the top of the spinal cord, takes a turn at the prefrontal cortex, winds along the IFOF, and ends up in the insula and other related areas of the brain.
Baraniuk noted that the signals from the body entering the brain take a direct path from the dorsal horn of the spinal cord to the prefrontal cortex. That straight shot has implications; if the ‘gates’ of the dorsal horn are broken, it can slam the PFC so hard with stimuli that it will, in effect, short the PFC out leaving its pain matrix in a twitchy and over-sensitized state. This kind of out of control spinal cord-prefrontal cortex roadway has been shown to play a role in producing pain problems such as allodynia (sensitivity to touch).
Why Executives Don’t Have ME/CFS (and keep their jobs) – the Prefrontal Cortex Issue
The prefrontal cortex plays a key role in ‘executive functioning’. Having trouble planning or decision-making? How’s your attention span? Problem solving ability? Mental flexibility? Feel like you’ve lost a little mental flexibility? I sure have….
The prefrontal cortex provides a kind of ‘mental sketch pad’ we use to plan and organize our lives. Lose that mental sketch pad and you’re more or less at the whims of your environment.
Distracted Neurons: the Focus Problem in ME/CFS
“This tract of axons links cortical gray matter regions involved in fatigue, pain, emotional and reward processing. This bundle also supports activity in the ventral attention network, which searches for unexpected signals in the surrounding environment that may be inappropriately interpreted as causing pain or being dangerous. Altered function in this tract may explain the increased vigilance and distractibility observed in veterans.” lead author Rakib Rayhan
We’ve outlined problems with planning, short-term memory, etc. and there’s more. That ‘live wire’ the study indicated has taken a beating in GWS, the IFOF, also connects to a network (ventral attention network (VAN)) which is in charge of scouring our environment for unexpected threats. The study suggested that that network is on overdrive, and that spells more trouble for executive functioning and task completion.
Trouble keeping focus and tending to flit from one task to another has been a hallmark of my ME/CFS from the beginning. Consider that every time VAN switches on your attention to the task at hand is broken. In fact, increased VAN activity has been shown to be directly correlated to decreased goal focused activity (called DAN activity).
We saw this earlier with an Australian cognitive study which indicated people with ME/CFS are continuously dropping out of a task (losing focus) and then jumping back in. Think how much energy it takes to lose your way during a task and then have to scramble back in and refocus again and again and again.
The Pain of it All
“Pain and fatigue are perceptions, just like other sensory input, and Gulf War Illness could be due to extensive damage to the structures that facilitate them. Some of the veterans we studied feel pain when doing something as simple as putting on a shirt. Now we have something to tell them about why their lives have been so greatly affected.” Rayhan, lead author of study
Increased axial diffusity in the corticospinal tract suggested that the pathways descending into the spinal cord that reduce pain may be bollixed as well resulting in increased pain.
A Punishing Situation
No wonder the authors characterized the situation as ‘punishing’ .
During the onset of noxious stimuli these regions coordinate responses that provide a punishing teaching signal that leads to altered decision making based upon these painful cues…
The brain regions involved tell us in no uncertain fashion what to avoid and how to act. Could this damaged ‘wire’ be why every little move can sometimes seem fraught with danger or pain?
The scenario evoked doesn’t sound like fun at all; first, the dorsal horn of the spinal cord slams the prefrontal cortex with pain and sensory data weakening our ability to plan and carry out tasks. At the same time that’s happening the IFOF connection to the fatigue and pain centers is humming – further weakening our ability to focus.
With the brains alert system (VAN) on full-bore, attempts to focus on a task tend to be diverted back into monitoring the environment for something unexpected ( hyperarousal), or into the heightened pain sensations present.
This model – increased levels of pain, increased interoception and increased VAN activity – suggests the attention of people with GWS/ME/CFS gets pulled again and again away from the outside world and onto pain and other signals in the body.
Baraniuk sums the problem up in a typically understated manner….
Nociceptive stimuli can involuntarily capture attention and interfere with on – going behavior
The problem is that that ‘on-going behavior’ is what makes up most of our productive lives. The ability to plan and carry out tasks is an important part of being human. Having little or no ‘on-goingness’ could leave us at the whim of our distracted, beaten up neural networks.
If some sort of neurologically based distracting process is at the heart of ME/CFS/FM/GWI, etc., it would probably behoove us to become adept at harnessing and hopefully increasing what amount of focused attention we have. (One study suggests rates of ADHD are increased in ME/CFS and fibromyalgia.) I’ve always wondered how somebody like myself who was naturally drawn towards meditative type activities found them so difficult post ME/CFS.
It also begs the question how useful organizational or ‘anti-diversion’ tools may be in these disorders, and whether it’s possible to create new neural pathways that build up focus, create feelings of well-being (instead of pain), etc. We’re going to be looking this more in future. Johanne Starke’s blog on ways to create calm while using the internet is a first step in that direction…
- Check out Seven Ways to Stop the Internet from Aggravating Your Chronic Fatigue Syndrome (ME/CFS) and FM Symptoms
When Time Heals Nothing – A Different Type of Subset Entirely
The problems in GWS may get worse, not better over time. In an interview Baraniuk said he’s found ‘three symptom areas’ (ie subsets) that correspond to what stage of the illness GWI vets are in, and that “The guys who were robust and leading the charge on this 10 years ago are now using canes.” That’s an amazing finding for an illness triggered by events that happened over 20 years ago. Time – the great healer – appears to have made things worse.
Baraniuk’s comments about chronologically based subsets is interesting given similar statements from Dr. Broderick who is finding distinct differences in young women with ME/CFS with recent onset and older women who’ve had the disorder longer.
Neglect Dogs Gulf War Illness Research
It’s not clear how many of this studies findings will apply to ME/CFS but one thing’s for sure – GWI patients have received the same, if not worse kind of neglect from the federal establishment that the ME/CFS community has endured. Six months ago Dr. Stephen Coughlin, an immunologist at the Veteran Affairs Office, resigned while accusing the VA of manipulating and hiding data and basically doing everything it could to ensure Gulf War Illness was not taken seriously. Coughlin asserted the VA did not want anything published that might prove GWI is a neurological condition.
“If the studies produce results that do not support the [VA's] unwritten policy, they do not release them… On the rare occasions when embarrassing study results are released, data are manipulated to make them unintelligible… Anything that supports the position that Gulf War illness is a neurological condition is unlikely to ever be published.” Dr. Stephen Coughlin
Baraniuk, as he has with ME/CFS, stepped right into the middle of the controversy, stating “If 30% of Congress got sick, or 30% of Manhattan got sick, there would have been an outcry”.
Most recently, Secretary of Veteran Affairs Shinseki’s gutting of the independent review board to research Gulf War Illness suggested the VA was trying to reverse the understanding that GWI was a physical illness. One advocate called the removal of the Chair and half the boards members ‘retaliation’ for Coughlin’s testimony.
The ME/CFS Connection
Major differences between GWI and ME/CFS do exist; in an interview the authors of the paper attributed the GWS findings to environmental factors such as exposure to Sarin gas, nerve agents, anti-nerve agent pills and the ‘industrial-strength’ bug spray the vets used copiously. It’s clear ME/CFS can be initiated or exacerbated by exposures to a variety of toxins including pesticides, formaldehyde, mold, etc., but most cases of ME/CFS appear to be triggered by infection and Dr. Klimas has found distinct differences in immune function between the two disorders.
It may be we’re seeing different variations of the same disorder showing up in ME/CFS, GWS, etc.; i.e. we see evidence of a chemotherapy/radiation induced ME/CFS-like state in cancer survivors; we have the nerve agent/pesticide/toxin induced ME/CFS-like state in GWS; the infection induced subset in ME/CFS, the trauma induced subset in fibromyalgia. Only time will tell whether these disorders show up with similar neurobiological findings.
Next Baraniuk wants to analyse similar scans of people with chronic fatigue syndrome or fibromyalgia….
- Coming Up Shortly – Baraniuk’s exercise studies indicate GWS and ME/CFS brains have similar metabolic dysfunction…