Comment; Impaired connectivity in the brainstem should be expected as it’s metabolically active. ME/CFS impairs mitochondrial oxidative phosphorylation. The brainstem is involved in transmission & modulation of signals from higher in the brain. Impairment of the reticular activating system involved in wakefulness & its activity to “alert” various areas of the brain would also be expected to be affected, to a lesser degree.
Leighton RBarndenaZack YShanabDonald RStainesaSonyaMarshall-GradisnikaKevinFinegancTimothyIrelandcSandeepBhutacShow morehttps://doi.org/10.1016/j.nicl.2019.102045Get rights and contentUnder a Creative Commons licenseopen access
Highlights
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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.
Abstract
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. In ME/CFS, connections were absent between medulla and midbrain nuclei, although hippocampal connections with these nuclei were enhanced. 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.
Graphical abstract
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