Part 1 of 5: Dysautonomia Awareness Month Series
October is Dysautonomia Awareness Month. This week I am running a five part series looking at the biological evidence behind the symptoms that are most frequently dismissed across PoTS, ME/CFS, Long COVID and related conditions. We are starting with brain fog.
Brain fog is described by patients as thinking through wet concrete. Words disappear mid-sentence. Reading the same paragraph four times without retaining it. Forgetting why you walked into a room seconds after leaving the last one. It is one of the most disabling symptoms reported across this community and for a long time one of the most dismissed.
The research now tells a different story. Three distinct biological mechanisms have been identified and documented in peer-reviewed literature. Here is what the science shows.
1. Dopamine nerve terminal loss is measurable on a brain scan
Liu JH, Bhatt M, Meyer JH, et al. Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms. eBioMedicine. 2026;130:106339.
Published in September 2026 in eBioMedicine, this study from the Centre for Addiction and Mental Health (CAMH) and the University of Toronto used positron emission tomography (PET) brain imaging to measure dopamine neuron health directly in Long COVID patients.
The researchers compared 24 Long COVID patients against 24 healthy controls, measuring levels of vesicular monoamine transporter 2 (VMAT2), a protein found on dopamine-releasing nerve terminals. VMAT2 acts as a proxy for the health and density of the dopamine system.
The findings were unambiguous. Long COVID patients showed a 16 to 20% reduction in VMAT2 across multiple regions of the striatum, the brain structure involved in motivation, memory and movement. The ventral striatum, the region most associated with motivation and apathy, showed the greatest loss. The imaging results correlated directly with specific symptoms: reduced markers in the apathy-associated region tracked with memory problems while reduced markers in the planning region tracked with slowed movement and loss of motivation.
This is not a vague suggestion that something may be wrong. It is measurable, visible biological damage on a brain scan, with a dose-response relationship between the degree of loss and the severity of symptoms. A full decoded piece on this study is available here: https://dysautonomiadecoded.substack.com/p/long-covid-is-damaging-the-brains
A separate line of research from the same group identified elevated neuroinflammation in the identical brain regions. The working hypothesis is that inflammatory cells are damaging dopamine nerve endings, or that the nerve injury itself is triggering further inflammation. Both processes appear to be occurring simultaneously in the same locations.
2. Cerebral blood flow is reduced even at rest in PoTS
Seeley MC, Gallagher C, Denman RA, et al. Brain perfusion abnormalities in patients with postural tachycardia syndrome. Heart Rhythm. 2025.
In PoTS, one of the primary drivers of brain fog is haemodynamic rather than inflammatory. When a person with PoTS stands up, the blood vessels in the lower body fail to constrict appropriately. Blood pools in the periphery, venous return to the heart is reduced and less oxygenated blood reaches the brain.
This study used brain SPECT imaging in PoTS patients and found that 61% showed abnormal cerebral perfusion, particularly in the prefrontal cortex, the region governing executive function, decision making and working memory. Critically, the hypoperfusion was present even when patients were lying down, not just on standing.
This matters clinically. It explains why brain fog in PoTS does not simply resolve with rest. The brain is being consistently undersupplied with oxygen not only during exertion but as a baseline state. It also explains why many patients report that their cognitive symptoms are among the most persistent, even on days when their physical symptoms are better managed.
Earlier work by Kharraziha and colleagues using cerebral oximetry during tilt table testing found a significant, quantifiable reduction in cerebral tissue oxygen saturation on standing in PoTS patients compared to healthy controls, corroborating the perfusion findings with a different measurement modality.
3. Neuroinflammation is active and visible across conditions
Blitshteyn S, et al. Cerebral hypoperfusion as an overlapping pathophysiological mechanism across PoTS, ME/CFS and Long COVID. ImmunoTargets and Therapy. 2026.
The 2026 review from Stanford identified cerebral hypoperfusion as one of the primary overlapping mechanisms across PoTS, ME/CFS and Long COVID. It does not show up on a standard blood test. It shows up on a specialised brain scan that most patients are never offered.
Beyond perfusion, imaging studies have now documented active microglial activation in ME/CFS and Long COVID patients: the brain’s own immune cells in a state of chronic inflammatory response. Microglia are the central nervous system’s primary immune cell. When activated, they release inflammatory cytokines that disrupt neuronal signalling, impair synaptic transmission and alter neurotransmitter availability. The cognitive consequences include slowed processing speed, impaired working memory and difficulty with word retrieval, precisely the symptom profile patients describe.
For a deeper look at how the brain changes structurally across ME/CFS and Long COVID, a full decoded piece is available here: https://dysautonomiadecoded.substack.com/p/your-brain-looks-different-if-you
What is significant about the convergence of these findings is that they point to the same outcome through different mechanisms. Dopamine loss reduces the neurochemical substrate for motivation and memory. Hypoperfusion starves the brain of oxygen at rest. Neuroinflammation disrupts the signalling environment. In a patient with Long COVID who also has PoTS, more than one of these processes may be operating simultaneously.
What this means in practice
Standard blood panels do not capture any of this. A normal full blood count does not measure dopamine nerve terminal density. It does not detect cerebral perfusion deficits. It does not image microglial activation. When routine bloods come back unremarkable, it does not mean nothing is wrong. It means the tests ordered were not designed to detect what is actually happening.
The research exists. The imaging exists. The biological mechanisms are characterised in peer-reviewed journals. Brain fog in PoTS, ME/CFS and Long COVID is not a symptom without a substrate. It has multiple, measurable, documented substrates. The gap is not in the evidence. It is in whether that evidence reaches the clinicians and systems that patients rely on.
Tomorrow we are looking at post-exertional malaise and the cellular studies that prove the crash is not deconditioning. See you then!
The views and opinions expressed in Dysautonomia Decoded are my own and do not represent those of my employer or any affiliated organisation.
References
Liu JH, Bhatt M, Meyer JH, et al. Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms. eBioMedicine. 2026;130:106339. https://doi.org/10.1016/j.ebiom.2026.106339
Seeley MC, Gallagher C, Denman RA, et al. Brain perfusion abnormalities in patients with postural tachycardia syndrome. Heart Rhythm. 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC11775248/
Blitshteyn S, et al. Cerebral hypoperfusion as an overlapping pathophysiological mechanism across PoTS, ME/CFS and Long COVID. ImmunoTargets and Therapy. 2026. https://doi.org/10.2147/ITT.S467118
Kharraziha I, et al. Cerebral oximetry during tilt table testing in postural orthostatic tachycardia syndrome. 2019.
So that's why it felt like I had a measurable drop in brainpower, memory, and energy after I had COVID a few times. I hope they figure out treatment soon.
"It's not in your head" is the sentence my pain clients wait years to hear from a doctor.
Thank you for laying out the biology. People living with these conditions get dismissed first and diagnosed later, and the dismissal becomes its own injury.
Looking forward to the rest of the series.