A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury, 2024, Arabshahi et al.

[SNT Gatchaman]

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury
Soroush Arabshahi; Sohae Chung; Alaleh Alivar; Prin X. Amorapanth; Steven R. Flanagan; Farng-Yang A. Foo; Andrew F. Laine; Yvonne W. Lui

BACKGROUND AND PURPOSE
Several recent works using resting-state fMRI suggest possible alterations of resting-state functional connectivity after mild traumatic brain injury. However, the literature is plagued by various analysis approaches and small study cohorts, resulting in an inconsistent array of reported findings. In this study, we aimed to investigate differences in whole-brain resting-state functional connectivity between adult patients with mild traumatic brain injury within 1 month of injury and healthy control subjects using several comprehensive resting-state functional connectivity measurement methods and analyses.

MATERIALS AND METHODS
A total of 123 subjects (72 patients with mild traumatic brain injury and 51 healthy controls) were included. A standard fMRI preprocessing pipeline was used. ROI/seed-based analyses were conducted using 4 standard brain parcellation methods, and the independent component analysis method was applied to measure resting-state functional connectivity. The fractional amplitude of low-frequency fluctuations was also measured. Group comparisons were performed on all measurements with appropriate whole-brain multilevel statistical analysis and correction.

RESULTS
There were no significant differences in age, sex, education, and hand preference between groups as well as no significant correlation between all measurements and these potential confounders. We found that each resting-state functional connectivity measurement revealed various regions or connections that were different between groups. However, after we corrected for multiple comparisons, the results showed no statistically significant differences between groups in terms of resting-state functional connectivity across methods and analyses.

CONCLUSIONS
Although previous studies point to multiple regions and networks as possible mild traumatic brain injury biomarkers, this study shows that the effect of mild injury on brain resting-state functional connectivity has not survived after rigorous statistical correction. A further study using subject-level connectivity analyses may be necessary due to both subtle and variable effects of mild traumatic brain injury on brain functional connectivity across individuals.


Link | PDF (American Journal of Neuroradiology) [Open Access]

 

[SNT Gatchaman]

up to 15% of patients have prolonged postconcussive symptoms, which include a broad range of somatic, behavioral, and emotional issues and can significantly impact the quality of life. Attempting to unpack the underlying pathophysiology of mTBI remains central to a better understanding of this injury. Specifically, relating structural injuries to functional deficits remains a challenge. It is known that WM injury can occur after mTBI; thus, fMRI has naturally been used to investigate potential related disruption of coordinated neural activity.

Several recent works using resting-state fMRI (rs-fMRI) suggest that there may be some alterations of resting-state functional connectivity (rs-FC) after mTBI.

For example, using a seed-based method, Mayer et al reported a decreased rs-FC within the default mode network and increased connectivity between the default mode network and lateral prefrontal cortex in mTBI participants [...] However, their later study showed no significant differences using an independent component analysis (ICA) approach in a larger cohort [...] Similarly, Amir et al 15 found decreased connectivity between the right lateral parietal and precuneus region of the default mode network

In this study, an unbiased, broad, and comprehensive approach was used to investigate rs-FC changes for individuals with mTBI compared to healthy normals using a sizable prospective study cohort, refraining from any a priori assumptions, and using rigorous, multilevel statistical analyses.

Functional connectivity, characterized by synchronized low-frequency fluctuations of the BOLD signal across distinct brain regions, was measured to investigate group differences in rs-FC using 2 methods

By means of a broad approach using several popular and generally used methods, the results of this study show no statistically significant differences between subjects with mTBI and matched healthy controls measured by whole-brain rs-FC after multiple comparison corrections. The findings are consistent across multiple functional connectivity measures and methods applied to our well-characterized cohort of subjects with mTBI using rigorous statistical analysis. A few differences could be seen before correction for multiple comparisons, though these are only variably aligned with what has been previously reported in the literature.