Effort and Fatigue-related Functional Connectivity in Mild Traumatic Brain Injury
Amy E. Ramage1*, David F. Tate2, Anneliese B. New3, Jeffrey D. Lewis4 and Donald A. Robin1
1 University of New Hampshire, United States 2 University of Missouri–St. Louis, United States 3 TIRR memorial Hermann Hospital, United States 4 Uniformed Services University of the Health Sciences, United States
Mental fatigue in healthy individuals is observed under conditions of high cognitive demand, particularly when effort is required to perform a task for a long time – thus fatigue and effort are closely related. In brain injured individuals, mental fatigue can be a persistent and debilitating symptom. Presence of fatigue after brain injury is prognostic for return to work/school and engagement in activities of daily life. As such, it should be a high priority for treatment in this population, but because there is little understanding of its behavioral and neural underpinnings, the target for such treatment is unknown. Here, the neural underpinnings of fatigue and effort are investigated in active duty service members with mild traumatic brain injury (mTBI) and demographically-matched orthopedic controls.
Participants performed a Constant Effort task for which they were to hold a predefined effort level constant for long durations during fMRI scanning. The task allowed investigation of the neural systems underlying fatigue and their relationship with sense of effort. While brain activation associated with effort and fatigue did not differentiate the mTBI and controls, functional connectivity amongst active brain regions did. The mTBI group demonstrated immediate hyper-connectivity that increased with effort level but diminished quickly when there was a need to maintain effort.
Controls, in contrast, demonstrated a similar pattern of hyper-connectivity, but only when maintaining effort. Connectivity, particularly between the left anterior insula, rostral anterior cingulate cortex, and right-sided inferior frontal regions, correlated with effort-level and state fatigue in mTBI participants.
These connections also correlated with effort level in the Control group, but only the connection between the left insula and superior medial frontal gyrus correlated with fatigue, suggesting a differing pattern of connectivity. These findings align, in part, with the dopamine imbalance and neural efficiency hypotheses that pose key roles for medial frontal connections with insular or striatal regions in motivating or optimizing performance. The data propose a complex link between sense of effort, fatigue, and mTBI that is centered in what may be an inefficient neural system due to brain trauma that warrants further investigation.
Keywords: Mild Traumatic Brain Injury (mTBI), Fatigue, effort, Functional Connectivity, fMRI
Received: 28 Sep 2018; Accepted: 17 Dec 2018.
Edited by: Marco Sarà, San Raffaele Cassino, Italy
Reviewed by: Joseph Bleiberg, National Intrepid Center of Excellence (NICoE), United States Ralph G. Depalma, United States Department of Veterans Affairs, United States
Copyright: © 2018 Ramage, Tate, New, Lewis and Robin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.