Altered Rich-Club and Frequency-Dependent Subnetwork Organization in Mild Traumatic Brain Injury: A MEG Resting-State Study

Abstract

Functional brain connectivity networks exhibit “small-world” characteristics and some of these networks follow a “rich-club” organization, whereby a few nodes of high connectivity (hubs) tend to connect more densely among themselves than to nodes of lower connectivity. The Current study followed an “attack strategy” to compare the rich-club and small-world network organization models using Magnetoencephalographic (MEG) recordings from mild traumatic brain injury (mTBI) patients and neurologically healthy controls to identify the topology that describes the underlying intrinsic brain network organization. We hypothesized that the reduction in global efficiency caused by an attack targeting a model's hubs would reveal the “true” underlying topological organization. Connectivity networks were estimated using mutual information as the basis for cross-frequency coupling. Our results revealed a prominent rich-club network organization for both groups. In particular, mTBI patients demonstrated hyper-synchronization among rich-club hubs compared to controls in the δ band and the δ-γ1, θ-γ1, and β-γ2 frequency pairs. Moreover, rich-club hubs in mTBI patients were overrepresented in right frontal brain areas, from θ to γ1 frequencies, and underrepresented in left occipital regions in the δ-β, δ-γ1, θ-β, and β-γ2 frequency pairs. These findings indicate that the rich-club organization of resting-state MEG, considering its role in information integration and its vulnerability to various disorders like mTBI, may have a significant predictive value in the development of reliable biomarkers to help the validation of the recovery from mTBI. Furthermore, the proposed approach might be used as a validation tool to assess patient recovery.

Impaired rich club and increased local connectivity in children with traumatic brain injury: Local support for the rich?

“…Reduced rich club connectivity in patients with TBI might indicate that it is difficult for these patients to maintain or repair the core network given the biological cost. These results are in conflict with the increased rich club connectivity that was observed in studies examining rich club organization in patients with TBI based on functional MRI data (Antonakakis et al, 2017;Hillary et al, 2014). In contrast to reported converging results in healthy adults when directly comparing functional and structural networks (Honey et al, 2009;Meier et al, 2016;Skudlarski et al, 2008; van Reijmer et al (2015) in older adults with white matter hyperintensities for example demonstrated a clear decoupling.…”

“…To date, only two studies have explored the rich club organization using graph theoretical analysis in adults with TBI (Antonakakis, Dimitriadis, Zervakis, Papanicolaou, & Zouridakis, ; Hillary et al, ), albeit studying functional connectomes (using functional MRI). The results of these studies show increased functional connectivity in the rich club of patients with TBI.…”

Alterations in Dynamic Spontaneous Network Microstates in Mild Traumatic Brain Injury: A MEG Beamformed Dynamic Connectivity Analysis

“…Dimitriadis et al (2015b) using phase-synchronization quantified intra-frequency couplings at the sensor level and showed that significantly different patterns were seen mostly in the delta band, whereas Alhourani et al (2016) used the same metric at the source level and showed reduced local efficiency in different brain regions in mTBI patients. In a follow-up study, Antonakakis and colleagues (2015, 2016, 2017a) showed less dense for mTBIs in which was in line with (Rapp et al, 2015), and later (Antonakakis et al, 2017b) that mTBIs obtained a higher synchronization among rich-club hubs. More recently, Li et al (2018) showed a denser causality network for mTBI patients, whereas Kaltiainen et al (2018) underlined that aberrant theta-band activity can provide an early objective sign of brain abnormality after mTBI.…”

“…The current study included fifty right-handed healthy controls (HC) (29.25 ± 9.1 years of age) and thirty right-handed mTBI patients (29.33 ± 9.2 years of age) (Gouridakis et al, 2012). All clinical information including selection criterions and patients’ demographics were reviewed and provided by certified clinicians and they are available in our previous studies (Gouridakis et al, 2012; Antonakakis et al, 2016; 2017a,b). The HC group was determined at UTHSC-Houston and the recruitment of the mTBI patients was done by three trauma centers in the greater Houston metropolitan area.…”

Modeling the Switching behavior of Functional Connectivity Microstates (FCμstates) as a Novel Biomarker for Mild Cognitive Impairment

“…Based on the aforementioned methodological evidences in microscale, it is significant to explore the repertoire of intra and cross frequency interactions across brain rhythms and brain areas under the same integrated graph model (Antonakakis et al, 2017;Dimitriadis et al, , 2017bDimitriadis et al, , 2018a.…”