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Intra Brainstem Connectivity Is Impaired In Chronic Fatigue Syndrome

Friday 25 October 2019


From NeuroImage: Clinical:



Intra brainstem connectivity is impaired in chronic fatigue syndrome

Leighton R Barndena, Zack Y Shanab, Donald R Stainesa, Sonya Marshall-Gradisnika, Kevin Fineganc, Timothy Irelandc, Sandeep Bhutac

Available online 19 October 2019, 102045

Under a Creative Commons license.

Copyright © 2019 Elsevier B.V. or its licensors or contributors. ScienceDirect ® is a registered trademark of Elsevier B.V.


  • RAS connectivity was detected in HC and CFS groups both during rest and task.
  • Strong connections were active for CFS from hippocampus to midbrain and medulla.
  • RAS connectivity was diminished in CFS in the brainstem and to the hippocampus.
  • RAS nuclei generate oscillatory signals which facilitate thalamocortical signal coherence.
  • Impaired RAS affects cortical coherence necessary for attention, memory and problem solving.


In myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), abnormal MRI correlations with symptom severity and autonomic measures have suggested impaired nerve signal conduction within the brainstem.

Here we analyse fMRI correlations to directly test connectivity within and from the brainstem.

Resting and task functional MRI (fMRI) were acquired for 45 ME/CFS (Fukuda criteria) and 27 healthy controls (HC).

We selected limited brainstem reticular activation system (RAS) regions-of-interest (ROIs) based on previous structural MRI findings in a different ME/CFS cohort (bilateral rostral medulla and midbrain cuneiform nucleus), the dorsal Raphe nucleus, and two subcortical ROIs (hippocampus subiculum and thalamus intralaminar nucleus) reported to have rich brainstem connections.

When HC and ME/CFS were analysed separately, significant correlations were detected for both groups during both rest and task, with stronger correlations during task than rest.

Strong hippocampal connections with midbrain and medulla nuclei were detected for ME/CFS.

When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task.

In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity. RAS neuron oscillatory signals facilitate coherence in thalamo-cortical oscillations.

Brainstem RAS connectivity deficits can explain autonomic changes and diminish cortical oscillatory coherence which can impair attention, memory, cognitive function, sleep quality and muscle tone, all symptoms of ME/CFS.


Full article…



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