An Investigation of the Default Mode Interference Hypothesis in Mild Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and lifelong disability throughout developed nations, resulting in an emotional burden on the patients and a vast financial burden on the nation. While the majority of these cases are mild in nature, current clinical imaging often fails to perceive the extent of this subtle injury, making it difficult to predict which of these individuals will go on to suffer from persistent post concussive symptoms. Through the use of resting state functional MRI (fMRI), resting state cerebral perfusion, and task based fMRI, we test the hypothesis that the diffuse neuronal damage associated with mild TBI (mTBI) interrupts large-scale network function resulting in cognitive and neuropsychological symptoms. The Default Mode Interference Hypothesis suggests that the interactions within and between the Default Mode Network (DMN), Task Positive Network (TPN), and Salience Network (SN) are associated with cognitive performance. Therefore, we focused our investigation upon these three networks. Using resting state fMRI on prospectively collected data, our results demonstrate reduced resting state functional connectivity (rs-FC) within the DMN and TPN, but increased rs-FC between the three networks across the acute, sub-acute, and chronic stages of injury. Furthermore, the alterations noted in rs-FC are exacerbated in mTBI patients with persistent symptoms and are associated with reduced cognitive performance. Through the use of resting state cerebral perfusion, our findings demonstrate an altered balance in network perfusion of the DMN and TPN that is more prominent in mTBI patients with greater symptom severity. Finally, through the use of task based fMRI during the N-back working memory paradigm, we note that mTBI patients reveal reduced deactivation of regions of the DMN, over recruitment of regions of the TPN, as well as regions of novel recruitment. Further, mTBI patients demonstrate reduced segregation between the DMN and TPN during the most cognitively demanding task. These findings provide strong evidence for the Default Mode Interference Hypothesis in mTBI. Through lending support that altered communication within these large-scale neural networks contributes to the persistence of post concussive symptoms, we provide a potential avenue for therapeutic intervention to mitigate post concussive symptoms.