Research Article: Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury

Date Published: January 27, 2017

Publisher: Public Library of Science

Author(s): Harm J. van der Horn, Edith J. Liemburg, Myrthe E. Scheenen, Myrthe E. de Koning, Jacoba M. Spikman, Joukje van der Naalt, Emmanuel Andreas Stamatakis.


Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Posttraumatic complaints, anxiety and depression were measured at two weeks post-injury. Patients were selected based on presence (n = 34) or absence (n = 20) of complaints. Resting-state fMRI scans were made approximately four weeks post-injury. High order independent component analysis resulted in 89 neural components that were included in subsequent graph analyses. No differences in graph measures were found between patients with mTBI and healthy controls. Regarding the two patient subgroups, degree, strength, local efficiency and eigenvector centrality of the bilateral posterior cingulate/precuneus and bilateral parahippocampal gyrus were higher, and eigenvector centrality of the frontal pole/ bilateral middle & superior frontal gyrus was lower in patients with complaints compared to patients without complaints. In patients with mTBI, higher degree, strength and eigenvector centrality of default mode network components were related to higher depression scores, and higher degree and eigenvector centrality of executive network components were related to lower depression scores. In patients without complaints, one extra module was found compared to patients with complaints and healthy controls, consisting of the cingulate areas. In conclusion, this research extends the knowledge of functional network connectivity after mTBI. Specifically, our results suggest that an imbalance in the function of the default mode- and executive network plays a central role in the interaction between emotion regulation and the persistence of posttraumatic complaints.

Partial Text

Cognitive and affective complaints reported by patients with mild traumatic brain injury (mTBI) still puzzle clinicians and scientists worldwide [1–4]. In the majority of patients with mTBI, these complaints are present without any impairments objectified with neuropsychological assessment [5–7] and/or abnormalities visible on computed tomography (CT) or conventional structural magnetic resonance imaging (MRI) scans [8–11]. A growing number of functional MRI (fMRI) studies suggest that (persistent) posttraumatic complaints after mTBI are associated with alterations in functional brain networks, especially with regard to the interaction between frontal/parietal networks, such as the default mode network, executive network and salience network [12–16]. This is not surprising, since these networks converge on prefrontal midline areas, which are vulnerable to traumatic brain injury [17–19], and because these networks and regions are important for emotion regulation [20,21]. However, much uncertainty still exists about the exact role of functional network dynamics in the pathophysiological mechanisms underlying sequelae of mTBI.

In this study, graph analysis of functional brain networks was performed in patients with uncomplicated mTBI in the sub-acute phase after injury, aimed to improve our understanding of the presence of posttraumatic complaints related to anxiety and depression after mTBI. A large patient sample was included, which provided us with sufficient power to detect possible group differences. None of the network measures differed between patients with mTBI and healthy controls, but in patient subgroups various differences were found in local network measures of prefrontal and parietal midline and parahippocampal areas. In patients with mTBI, associations were found between local network measures and depression scores, but not between any of the network measures and anxiety. Module decomposition was similar for all study groups, although patients without complaints showed one extra module compared to patients with complaints and healthy controls, which was composed of the cingulate areas.

In this study, a novel approach, consisting of high order ICA followed by graph analysis, was used to investigate functional brain networks in relation to complaints, anxiety and depression after mTBI. Interestingly, all network measures were similar for patients with mTBI and healthy controls, which might suggest that the influence of the injury itself in network function after mTBI is not that strong. Regarding patient subgroups, higher local graph measures were found in patients with complaints compared to patients without complaints, especially in default mode network related areas in the proximity of the posterior midline. In addition, higher values of these components were related to mood disturbances in patients with mTBI, while the opposite was true for components of the executive networks. It could be hypothesized that targeting mood problems after mTBI, with therapies focused on executive functioning, may lead to a reduction of complaints. More studies are required to further elucidate the complex alterations in functional networks after mTBI, with an emphasis on personality characteristics and emotion regulation.




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