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. 2025 Jun;52(6):5081-5090.
doi: 10.1002/mp.17772. Epub 2025 Mar 21.

Investigation of neuro-vascular reactivity on fMRI study during visual activation in people with multiple sclerosis using EEG and hypercapnia challenge

Wanyong Shin  1 , Balu Krishnan  2 , Ajay Nemani  1 , Daniel Ontaneda  1 , Mark J Lowe  1
Affiliations

Investigation of neuro-vascular reactivity on fMRI study during visual activation in people with multiple sclerosis using EEG and hypercapnia challenge

Wanyong Shin et al. Med Phys. 2025 Jun.

Abstract

Background: People with multiple sclerosis (MS) exhibit a different pattern of blood oxygenation level-dependent (BOLD) activation on functional magnetic resonance imaging (fMRI) studies when compared to healthy control (HC).

Purpose: The objective of this study is to determine whether observed differences in BOLD activation between people with MS (pwMS) and HC participants are due to the differences of neurovascular coupling, cerebral blood flow (CBF) or actual neuronal activity.

Methods: We investigated the neuronal activation in pwMS (n = 11) and age- and sex-matched HC participants (n = 15) using simultaneous electroencephalogram (EEG) and fMRI measures during a visual task (VT) and hypercapnia condition.

Results: Significant neurovascular coupling is observed in both HC and pwMS. Neuro-vascular coupling ratios are not significantly different between groups. However, we observe significantly lower CBF increase during VT and higher quantitative CBF at a rest state in pwMS than in HC (p < 0.05). From the multiple regression model, in HC group, we found that the BOLD contrast change during VT is best predicted by the EEG power change during VT (Student t-score = 2.64, p = 0.022), and the CBF change during hypercapnia (Student t-score = 2.59, p = 0.024). In pwMS, the BOLD contrast change during VT is negatively predicted by the CBF change during VT (Student t-score = -4.02, p = 0.003).

Conclusion: These findings could explain that BOLD activation in pwMS is mainly determined by the blood flow change during activation rather than the direct neuronal activation measures or hemodynamic vascular reactivity during hypercapnia challenge, suggesting that altered vasodilatory effects in response to task activation in pwMS might be linked to impaired cerebral hemodynamics, possibly leading to the widely observed abnormal BOLD activation in fMRI studies of pwMS.

Keywords: EEG; cerebral blood flow; fMRI; hypercapnia; multiple sclerosis; neurovascular coupling.

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Conflict of interest statement

Daniel Ontaneda declares a conflict of interest: Research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis. Consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Genzyme, Janssen, Novartis, and Merck. Other authors have no conflicts to disclose.

Figures

FIGURE 1
FIGURE 1
The processing pipeline for simultaneous EEG‐fMRI involving EEG recordings acquired inside and outside the MRI scanner. The pipeline includes multiple steps for artifact correction and spectral decomposition of EEG data to quantify electrophysiological correlates to blood oxygenation level–dependent (BOLD) signal changes. The final step involves estimating the percentage change in 4‐Hz signal power during the task and relating it to the BOLD signal change. ICA, independent component analysis.
FIGURE 2
FIGURE 2
Percentage change of EEG power and MRI measures during visual activation in healthy control (HC, white) and people with multiple sclerosis (pwMS, gray) groups. * Indicates the significant difference between groups (p < 0.05) between patients with multiple schelosis (pwMS) and healthy controls (HC). ΔBOLD/ΔCBFVT/CO2: BOLD contrast/CBF change during visual activation/hypercapnia challenge (%); qCBF0: quantitative CBF at the rest (mL/100/min); RSFA, resting state fluctuation of amplitude (%); ΔCMRO2VT, cerebral metabolic rate of oxygen consumption change during visual activation (%); ΔEEGVT, EEG power change during the visual activation (%).
FIGURE 3
FIGURE 3
Plots of multicollinearity of MR and EEG measures. White and black circles indicate healthy controls (HC) and people with multiple sclerosis (pwMS) groups, respectively. The dashed and solid lines indicate the statistically significant linear trend (p < 0.05) in HC and pwMS.
See this image and copyright information in PMC

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