Uncovering latent deficits due to mild traumatic brain injury by using normobaric hypoxia stress

Memory deficits and other cognitive symptoms frequently associated with mTBI are commonly thought to resolve within 7-10 days. This generalization is based principally on observations made in individuals who are in the unstressed environmental conditions typical of a clinic and so does not consider the impact of physiologic, environmental, or psychological stress. Normobaric hypoxic stress can be generated with normal mean sea level (MSL) air, which is about 21% oxygen (O2) and 78% nitrogen (N), by reducing the percentage of O2 and increasing the percentage of N so that the resultant mixed-gas has a partial pressure of O2 approximating that of specified altitudes. This technique was used to generate normobaric hypoxic equivalents of 8,000, 12,000, and 14,000 feet above MSL in a group of 36 volunteers with a mTBI history and an equal number of controls matched on the basis of age, gender, tobacco smoking consumption, weight, height, and body mass index. Short-term visual memory was tested using the Matching to Sample (M2S) subtest of the BrainCheckers analog of the Automated Neuropsychological Assessment Metrics. Although there were no significant differences in M2S performance between the two groups of subjects at MSL, with increased altitude, the mTBI group performance was significantly worse than that of the control group. When the subjects were returned to MSL, the difference disappeared. This finding suggests that the "hypoxic challenge" paradigm developed here has potential clinical utility for assessing the effects of mTBI in individuals who appear asymptomatic under normal conditions.