Background: Pathological mental fatigue after mild traumatic brain injury (TBI-MF) is characterized by pronounced mental fatigue after moderate cognitive activity. We aimed in the following study to investigate neuronal activity in frontal cortex and relate it to cognitive performance during a longer test session.
Methods: We recruited individuals with TBI-MF (n=20) more than 5 months after injury and age-matched healthy individuals (n=20). We used functional near-infrared spectroscopy (fNIRS) to assess hemodynamic changes (oxygenated hemoglobin) in the frontal cortex during prolonged cognitive activity. A block of six neuro-psychological tests was performed in sequence and was repeated once. A sustained-attention test was done between blocks. In total, the test procedure took 2 ½ hours. 
 
Results: The TBI-MF group demonstrated an altered functional brain activity in the frontal cortex during cognitive tests. No difference in brain activity between the two test sessions was found, and this was the case for both groups. Group differences in brain activity were detected already during the first test session relating to the test for conflict processing and processing speed. The fNIRS adapted Stroop-Simon test, measuring brain activity for each single task, showed a generally lower event-related activity in the frontal polar area, ventrolateral motor cortex, and dorsolateral prefrontal cortex. The fNIRS assessment for processing speed (Digit Symbol Coding) demonstrated more widespread activity in the frontal cortex in the TBI-MF group as compared to controls. The controls improved their processing speed in the second session while the TBI-MF group performed at a similar level (interaction, p<0.01). The TBI-MF group reported reduced mental energy after the test session.
Conclusion: An altered neuronal activity in the frontal cortex was found already from the start in the TBI-MF group compared to healthy controls when performing cognitive tasks over a longer period. The controls improved in processing speed during the second test session, while the TBI-MF group remained at a similar level - indicating a reduced efficiency. The reduced efficiency may result in the experience of mental fatigue after an extended mental activity.

Altered neuronal activity in the frontal cortex in individuals suffering from mental fatigue after a mild traumatic brain injury