Does gravity affect functional cerebral blood flow response?

Abstract

Cerebral blood flow (CBF) is critical for proper neuronal function. Since flow is dependent on perfusion pressure, the cerebrovasculature dilates/constricts in response to driving pressure to maintain flow relatively constant. This process is termed autoregulation and essential to maintaining flow in the upright posture when the effect of gravity results in an 20 mmHg reduction in perfusion pressure to the brain due to the hydrostatic gradient. Up regulation of CBF has been used extensively to localize cognitive activation, i.e. functional imaging. However, due to technical constraints the majority of this work has been done with subjects in the supine position. The recent development of transcranial Doppler (TCD) allows the continuous measurement of cerebral flow velocity (CFV) in the main cerebral arteries. By measuring flow velocity during cognitive tasks, we are able to perform functional TCD. To assess whether gravity had an effect on the functional response to a cognitive task (Trails A & B), we performed functional TCD on subjects in both the upright and supine positions. In addition to cerebral flow velocity in the anterior (ACA) and middle cerebral arteries (MCA) (TCD), we measured beat-by-beat blood pressure (Finapres) and breath-by-breath end tidal CO2 (PETCO2) via nasal cannula (Datex-Ohmeda). Subjects were randomly assigned to either the supine or upright position, performed the task, and then moved to the other position, and performed the same task with different number and letter patterns. Upon going from the supine to upright position, subjects demonstrated a non-significant reduction in both ACA (-44%) and MCA (-32%) flow. In contrast mean arterial pressure increased (817 to 914 mmHg) although non-significant, while PETCO2 did not change (40.81.3 vs 40.01.7 mmHg). During cognitive activation with either the Trails A or B there was a significant increase in flow associated with reductions in cerebrovascular resistance (CVR). Interestingly, this functional activation was attenuated in the upright posture (only significant in the MCA). Surprisingly, the functional activation was also reduced in Trails B compared to Trails A. This was likely the consequence of the hypocapnia that was only present during the Trails B assessment. These data highlight the possibility that functional response to cognitive activation may be affected by body position. Since our healthy control subjects demonstrate an attenuated response, one might postulate that patients with an impaired cerebrovasculature and already attenuated response in the supine position may be at even more risk when upright. Further work is necessary to determine what role perfusion pressure may play in functional cerebral blood flow response and how this attenuated response may impact on functional cognitive performance (See Figure 1).