Functional-structural large-scale brain networks are correlated with neurocognitive impairment in acute mild traumatic brain injury

Abstract

Background: This study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment.

Methods: Seventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses.

Results: Compared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05).

Conclusions: Our findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Keywords: Graph theory analysis; cognitive decline; diffusion tensor imaging (DTI); mild traumatic brain injury (mTBI); resting-state functional MRI.

Figure 1

Flow chart of data analysis. SC matrix and FC matrix is computed from fMRI and DTI respectively based on the AAL116 atlas. FC-SC coupling strength is calculated as the correlation between FC and SC matrices. DTI, diffusion tensor imaging; fMRI, functional magnetic resonance imaging; SC, structural connectivity; FC, functional connectivity; AAL, automated anatomical labeling.

Figure 2

Flow chart of the participants enrollment. mTBI, mild traumatic brain injury; MoCA, Montreal Cognitive Assessment; rs-fMRI, Resting-state functional magnetic resonance imaging.

Figure 3

Global topology organization of the healthy controls (red) and mTBI (green). (A) Functional network measures of the global topology organization of the HCs and mTBI. (B) Structural network measures of the global topology organization of the HCs and mTBI. * denotes significant group differences. HC, healthy control; mTBI, mild traumatic brain injury; AUC, area under the curve.

Figure 4

Regional organization of all participants. (A) Functionally, regions showing decreased and increased nodal centralities in acute mTBI patients compared with healthy controls, including nodal degree, nodal local efficiency and nodal efficiency. (B) Structurally, regions showing decreased and increased nodal centralities in acute mTBI patients compared with healthy controls, including nodal degree, nodal betweenness, nodal clustering coefficient and nodal efficiency. Correction for multiple comparisons was performed using Bonferroni method (P<0.05). L, left; R, right; mTBI, mild traumatic brain injury.

Figure 5

Functional-structural connectivity coupling at both the group-level and the individual level. (A) Functional-structural connectivity coupling of the mTBI at the group-level. (B) Functional-structural connectivity coupling of healthy controls at the group-level (C) Functional-structural connectivity coupling of the mTBI and healthy control participants at the individual-level. FC, functional connectivity; SC, structural connectivity; mTBI, mild traumatic brain injury.