Table demonstrates that the baseline values for each dependent measure were not significantly different between the tilt and centrifuge test sessions. Both centrifugation and tilt resulted in a modulation of CFV as measured by transcranial Doppler that were linked to stimulation frequency (Figure ). CFV responses were dependent on frequency of stimulation (P < 0.01) and demonstrated significant changes within each frequency cycle (P < 0.01) that differed by frequency (Frequency × Cycle interaction, P < 0.01). While CFV during centrifugation at 0.5 Hz tended to be lower than during tilt (P = 0.07), the change within the cycle was very similar. The CFV responses shown in Figure may have been due to factors unrelated to the otoliths, such as driving pressure or changes in arterial CO2 levels. For example, there was a significant effect on blood pressure at brain level of both frequency of stimulation (P < 0.01) and position within cycle (P < 0.01) that differed by frequency (Frequency × Cycle interaction, P < 0.01). In addition, blood pressure was significantly higher during centrifugation than tilt at all frequencies (P < 0.01). However, the patterns of the blood pressure and CFV changes were different. For example, as shown in the left panel (0.03125 Hz) of Figure , CFV increased during both the +25° and -25° tilt positions whereas blood pressure increased only during the +25° tilt position. Similarly at 0.25 and 0.5 Hz, blood pressure increased during the first half of the cycle (i.e. moving from upright to pitch forward and back to upright) at the same time CFV decreased. Thus CFV was decreasing even though driving pressure was increasing. Thus, while blood pressure consistently increased somewhere between a quarter (slowest frequency) and half way into the cycle (fastest frequency), CFV demonstrated bimodal peaks at the slowest frequency and decreases at the fastest frequency (Figure ). This would again suggest a disparity in the response of the two variables. These data therefore suggest that otolith activation at various frequencies likely directly affects cerebral blood flow.
Figure 3 Cerebral Blood Flow Response to Vestibular Stimulation. Response of subjects to five frequencies of stimulation averaged over 40 cycles for 0.5 Hz, 20 cycles for 0.25 Hz, 10 cycles of 0.125 Hz, and 5 cycles of 0.0625 Hz and 0.03125 Hz. Cerebral flow velocity (more ...)
Changes in end tidal CO2, an indicator of arterial CO2, were similarly disparate from those in CFV. First, end tidal CO2 was also affected by both frequency of stimulation (P < 0.01) and position within cycle (P < 0.01) that differed by frequency (Frequency × Cycle interaction, P < 0.01). In addition end tidal CO2 was significantly lower during centrifugation with translation at 0.5 Hz. However, examination of individual frequencies showed differing patterns. For example, at 0.03125 Hz, end tidal CO2 increased at +25° and decreased at -25°, while CFV increased at both +25° and -25°. Similarly at 0.25 and 0.5 Hz, end tidal CO2 did not change within the cycle, while CFV decreased significantly. These data demonstrate that changes in end tidal CO2 cannot completely explain position-related changes in CFV.
While there was no significant difference in responses to either sinusoidal tilt or translation during centrifugation at the four slowest frequencies, CFV was 6.8 ± 0.3% lower during centrifugation. Since end tidal CO2 was also 1.6 ± 0.3 mmHg lower, based on the cerebrovascular reactivity of 2.6%/mmHg, approximately two thirds of the 6.8% decrease could be explained by the centrifugation-related hypocapnia.
Changes in CFV are likely mediated through changes in CVR. Since CFV is normally regulated to maintain flow relatively constant in the face of changing perfusion pressure--a phenomenon known as cerebral autoregulation [22
] -- changes in CVR could result from changes in blood pressure (autoregulation) or changes in otolith afferent activity (vestibular). Figure demonstrates that changes in CVR within the motion cycle were similar to the changes in blood pressure, suggesting an autoregulatory response. However, if CVR changes were solely autoregulatory in nature, CFV would have remained constant throughout motion. The fact that CFV was changing throughout the cycles indicates CVR changes were not sufficient to maintain flow indicating that a non-autoregulatory component was influencing CVR and causing changes in flow.
To further explore the role of frequency in the response of CFV to vestibular activation, we examined the correlation between CFV and either chair position or velocity of motion throughout the cycle (Figure ). As can be seen in Figure , during tilt, changes in CFV in the low frequency range (0.0625-0.125 Hz) were especially correlated to position (left panel), whereas those in the high frequency range (0.25-0.5 Hz) were especially correlated to the velocity of motion (right panel). Correlations between CFV and the velocity of motion were significantly lower in the 0.03125-0.125 Hz ranges compared to the 0.25-0.5 Hz ranges for both tilt and centrifugation. A generally opposite pattern was demonstrated for position (left panel), where correlations between CFV and position were ~0.6 for tilt at 0.0625 & 0.125 Hz, decreasing to ~0.4 at the higher frequencies. Interestingly, at the lowest frequency for position, the correlation was only 0.2.
Figure 4 Relationship between Vestibular Inputs and Cerebral Blood Flow Response. Correlation between position (left panel) or velocity (right panel) and cerebral flow velocity (CFV) at the various frequencies. Changes in CFV were correlated to velocity only at (more ...)