Multi-modal normalization of resting-state using local physiology reduces changes in functional connectivity patterns...

Area of Science:

• Neuroimaging
• Brain Injury Research
• Systems Neuroscience

Background:

• Resting-state functional magnetic resonance imaging (rs-fMRI) using Blood Oxygenation Level Dependent (BOLD) signals is a sensitive marker for brain network changes after mild traumatic brain injury (mTBI).
• However, BOLD signal alterations may be confounded by physiological changes in cerebrovascular physiology and neurovascular coupling, not solely by neuronal connectivity changes.
• Understanding these confounders is crucial for accurate interpretation of rs-fMRI findings in mTBI.

Purpose of the Study:

• To investigate the impact of altered cerebral blood flow (CBF) on functional connectivity (FC) measurements in individuals with mTBI.
• To introduce and evaluate a normalization method for rs-fMRI data that accounts for baseline CBF (CBF₀) variations.
• To determine if accounting for CBF₀ can better differentiate mTBI-related network connectivity changes from physiological confounds.

Main Methods:

• Multi-modal neuroimaging data, including BOLD rs-fMRI, baseline CBF (CBF₀), and cerebrovascular reactivity (CVR) via hypercapnic challenge, were collected from 23 mTBI subjects and 27 healthy controls.
• Group comparisons of CVR and CBF₀ were performed.
• A novel normalization method incorporating regional perfusion (CBF₀) was applied to FC calculations to assess its effect on group differences.

Main Results:

• No significant group differences in CVR were found within the studied networks.
• mTBI subjects exhibited significantly higher baseline CBF₀ compared to healthy controls.
• Applying the CBF₀ normalization method reduced the observed differences in FC between mTBI subjects and controls, suggesting it can isolate neuronal connectivity changes.

Conclusions:

• Baseline cerebral blood flow is elevated in mTBI patients and can influence rs-fMRI derived functional connectivity.
• A normalization approach accounting for CBF₀ is essential for accurately assessing network connectivity alterations post-mTBI.
• This multi-modal approach enhances the understanding of brain network dysfunction following mTBI by controlling for physiological confounders.