Effects of Total Sleep Deprivation on Vigilant Attention and Proinflammatory Cytokine Biomarkers in Adults with Mild Traumatic Brain Injury

Lillian Skeiky, Ph.D., Vera Y. Matrosova, Ph.D., Michael Smith, Ph.D., Elizabeth C. Metzger, M.S.P.H., J. Kent Werner, M.D., Ph.D.

INTRODUCTION: Total sleep deprivation (TSD) degrades vigilant attention, impairs immune function, and reduces operational readiness in the Warfighter. Mild traumatic brain injury (mTBI) has also been associated with deficits in vigilant attention, increased proinflammatory cytokine activation, and sleep problems, all of which may impact operational readiness. Warfighters may continue to experience mTBI-related symptoms, even following the acute phase of the injury. Moreso, even those Warfighters recovered from mTBI may be more vulnerable to performance deficits and health consequences when exposed to stressors.

Little is known about the effects of TSD on cognitive performance and inflammatory response in those with a history of mTBI. Here, we examined the effects of TSD on vigilant attention performance and inflammatory response in adults with a history of mTBI and in healthy controls.

METHODS: Twenty-five adults (9 females, 16 males; 9 with a history of mTBI, ages 40.3 ± 8.3) underwent 38-hours of at-home TSD. Vigilant attention was assessed roughly every 2-3 hours during wakefulness by a 5-minute psychomotor vigilance test (PVT). Blood was drawn at roughly 38-hour of TSD, and again following recovery sleep. The MSD proinflammatory panel kit was assayed from plasma.

RESULTS: TNF-α concentration following TSD was significantly higher in plasma of mTBI participants, as compared to healthy controls (P < 0.05), with the levels decreased following recovery sleep (P > 0.05). Our results also show that those with mTBI had significantly more lapses on the PVT during TSD (P < 0.05), as compared to healthy controls. 

DISCUSSION: While our mTBI participants were out of the acute injury phase, our data suggest that TSD may expose cognitive and proinflammatory cytokine-related vulnerabilities in those with mTBI. These results are highly relevant to the Warfighter as individuals with a history of mTBI may be subjected to periods of sustained sleep loss, particularly in operational environments, and may be particularly vulnerable to performance deficits and TSD-induced cytokine activation. While we measured inflammatory response in the periphery, some studies suggest that TSD may cause neuroinflammation, which may contribute to cognitive deficits. It is possible that this effect may be exacerbated in those with mTBI.  Our future work will seek to compare the effects of TSD on neuronally derived markers of inflammatory response in healthy adults and in those with mTBI.