Meet the Scientist: Dr Mark Zinn: The Central Autonomic Network and ME/CFS

August 16, 2021


Guest blog by Dylan Murphy 

Mark Zinn is the co-founder of the Neuro Cognitive Research Institute along with his late wife Marcie (who died from herpes encephalitis and ME/CFS). 

He has expertise in quantitative and tomographic methods of EEG analysis to test theoretical premises in research involving neuro-cognitive disorders. He has also served as a research consultant (2011-2014) at the Stanford School of Medicine to study cognitive impairment in infection associated chronic diseases such as ME/CFS. 

Dr Zinn’s ongoing research into the brain regions involved in the autonomic nervous system at DePaul University is an attempt to understand how brain dysregulation can result in the symptoms experienced by people with neurocognitive diseases. He is the author of numerous research papers in this field, and his latest research paper – co-authored with his late wife and Prof. Leonard Jason is the subject of the conversation below. 

“In the patient group, we observed a significant reduction in brain activity immediately following the exercise and the reduction worsened after 24 hours. But in control group, we observed a significant increase immediately after exercise, that increased further after 24 hours…”  

“…reduced activation within the central autonomic network may serve as a neurobiological indicator for PEM, which is the most debilitating feature of this illness,”

Dr Mark Zinn. 

The research: 

Definitions: 

  1. An electroencephalogram (EEG) is a recording of brain activity.  
  1. swLORETA is a state-of-the-art electrical neuroimaging technique that allows for more accurate mapping of neuronal activities of the brain in three-dimensions. 
  1. The central autonomic network (CAN) is a set of brain regions that work together in a tightly coordinated fashion to regulate the body’s internal balance. Signs and symptoms of autonomic dysregulation include orthostatic intolerance, dizziness, fatigue, and other symptoms that can relate to ME/CFS. 

1. How did you get involved in ME/CFS research? 

I got involved in the research about 11 years ago, soon after my wife Marcie was diagnosed with herpes encephalitis. Fortunately, she came into contact with Dr Jose Montoya at Stanford Medical Center and he diagnosed her with ME.  

He invited Marcie to be on the team for the newly formed Stanford ME/CFS initiative to conduct a major research project involving quantitative EEG. I became involved in the project to help with analyzing the data using eLORETA (3-dimensional analysis of EEG signals).  

The results were very promising and our presentation was well-received at the 2014 Stanford ME/CFS Symposium as well as the IACFS/ME Conference in San Francisco where we first met Prof. Leonard Jason.  

Having finished our project at Stanford, Marcie and I decided to move to Chicago in 2015 to continue our work with Prof. Jason at DePaul University. I went on to get my PhD. in psychology with Prof. Jason as my mentor. 

2. Your latest research examined the autonomic nervous network and its relationship to post exertional malaise (PEM) in people with ME. Can you briefly explain what the autonomic nervous network is? 

The central autonomic network is a set of brain regions that work together in a tightly coordinated fashion for regulating our internal ‘steady state’.  

It is involved everything you do throughout the day and night, controlling your body states by making adjustments like a thermostat. Depending on momentary demands, it optimizes your blood circulation, heart-rate, blood pressure, body temperature, digestion, sleep/wake cycle, cognition, and many other functions.  

Signs and symptoms of autonomic dysregulation include difficulty standing upright (orthostatic intolerance), debilitating fatigue, light-headedness/dizziness, nausea and GI symptoms, brain fog, irregular heartbeat, and shortness of breath. 

3. In your study you note that brain regions associated with central fatigue are also involved in central autonomic processing. How does this relate to the main objective of your study? 

From the Stanford eLORETA study, we learned that certain brain regions with abnormal function were closely tied to autonomic function. The objective of the pilot study was to measure effects of physical exertion in the brain – but just targeting key regions known to be involved in maintaining and regulating the autonomic nervous system. 

4. How did you seek to measure post exertional malaise (PEM) in the study? 

To study post-exertional malaise, we decided to record the participants’ EEG before and after performing moderately strenuous exercise involving a basic handgrip challenge.  

A defining aspect of PEM is that it often lasts 24 hours or more. So, we had everyone come back the next day and measured their EEG again to assess for changes that might occur after a 24-hour period. 

5. Your study aimed to quantify the effects of physical exertion on central autonomic function in people with ME/CFS. What statistically significant findings did your study observe? 

In the patient group, we observed a significant reduction in brain activity immediately following the exercise and the reduction worsened after 24 hours. But in control group, we observed a significant increase immediately after exercise, that increased further after 24 hours.  

With the EEG, we were also able to look at brain rhythms and we found that certain frequencies predicted this change more than other frequencies. So, for example, frequencies involved in driving sensorimotor signalling during task performance predicted greater likelihood for autonomic dysregulation following exercise. 

Similarly, frequencies having to do with cognitive inhibition and attention also predicted greater likelihood for more autonomic dysregulation following exercise. 

6. If the findings of your study are confirmed by further research how might this be of use in the diagnosis, treatment and understanding of ME/CFS? 

Overall reduced activation within the central autonomic network may serve as a neurobiological indicator for PEM, which is the most debilitating feature of this illness.  

Our research protocol could be used in the clinic for measuring subtle changes in brain function triggered by moderate exercise in order to capture features of PEM.  

In the ME research field, there has been a lot of mixed and contradictory findings, but there may be more agreement within the context of the central autonomic network.  

In addition, patients with severe ME may have a difficult time performing maximal cardiopulmonary exercise tests, but the handgrip exercises we used are a more practical method that could be performed on most patients, even at the bedside.  

Quantitative EEG adds sensitivity for confirming neurological aspects of PEM and monitoring treatment effectiveness over time. More research is needed to sort all the diagnostic and treatment implications, but these results are promising. 

7. What further actions are needed by public health authorities to help improve the life outcomes for people with ME/CFS? 

The healthcare system and general public need to be made aware of reasons for the wide-ranging autonomic symptoms reported by patients with ME.  

When there are no major indications on routine tests, patients are typically told there is nothing wrong, but there may be follow-up tests for autonomic dysfunction from post-viral/immune responses in the brain, resulting in extreme fatigue.  

People with ME may look fine on the outside while their body is failing to maintain steady-state on the inside. Objective findings of PEM validate the illness while demonstrating that worsening symptoms are due to an underlying neurological condition that needs to be taken seriously.  

There needs to be funding set aside for the intensive study of the central autonomic network in relation to nearly all aspects of this debilitating disease. 

8. Do you have plans for any future ME research that would follow up your CAN study?  

I plan to make the CAN the main focus of my research, adding heart-rate variability as a peripheral autonomic measure to study mind-heart interactions. Our NIH grant application for conducting a much larger study on CAN functioning in ME was dismissed by the ME/CFS special interest panel, sadly.  

Getting funding has been difficult and this pilot study was done without any funding whatsoever. We've submitted another grant application to NIA to study neurological factors in neuro-covid symptoms in older and younger people as well as adolescents. This will involve collaborations with researchers at North-western University and Lurie Children's Hospital in Chicago.  

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