Sex differences in cerebral perfusion changes after mild traumatic brain injury: Longitudinal investigation and correlation with outcome.

Cerebral blood flow (CBF) is known to have marked developmental sex differences. We investigated whether gender differences exert modulatory effect on mild traumatic brain injury (mTBI) from both neuropsychological testing and brain CBF changes using a longitudinal design from acute stage to subacute 1 month post-injury. Our results supported that cognitive information processing speed (IPS), as one of core cognitive impairments following mTBI, were at least partially independent from other self-reported syndromes, such as post concussive symptom and posttraumatic stress disorder, and that it can be selectively impaired in specific male mTBI individuals. The gender difference of this cognitive domain in healthy control attenuated following mTBI and only male patients showed impaired language fluency accompanying with increased CBF changes compared with male controls. The increased CBF in the posterior parietal cortex (PPC) can predict much worse cognitive IPS performance in male patients. In contrast, female patients with mTBI displayed no impairments on any neuropsychological performance, and female sex may be a protective factor against neuropsychological impairments. Moreover, the significant interaction effect of time and gender exhibited in the left inferior frontal cortex (Broca's area). Simple effect test suggested gender differences in this area was mainly derived from the patients group at later subacute but not acute phase, for the reduced CBF at subacute mainly in the male patients. Thus, the current findings suggest that regional CBF may provide an objective biomarker for tracking gender modulatory effect on mTBI and its potentially pathological recovery process.