Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue, 2023, Zuppichini et al

Highlights

• Multiple sclerosis (MS) patients experience fatigue and declines in cognitive speed.
• Whole-brain measures of metabolism have been associated with MS symptom severity.
• Prefrontal metabolism was uniquely associated with MS declines in cognitive speed.
• Prefrontal metabolism measures may be sensitive to cognitive speed declines in MS.

Abstract

Background
Most multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients.

Objective
Investigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS.

Methods
MS and healthy control (HC) participants were scanned using a dual-echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue.

Results
MS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group.

Conclusion
Prefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.

Paywall, https://www.msard-journal.com/article/S2211-0348(23)00575-8/fulltext#

 

Often there is the assumption that fatigue in ME is central: neurological or neuropsychiatric. Here a similar assumption is challenged in MS, which I think is important for us - particularly the maladaptive recruitment of networks from the FND world.

And in relation to normal-appearing white matter (NAWM) —