Daily rhythm of cerebral blood flow velocity

Abstract

BACKGROUND: CBFV (cerebral blood flow velocity) is lower in the morning than in the afternoon and evening. Two hypotheses have been proposed to explain the time of day changes in CBFV: 1) CBFV changes are due to sleep-associated processes or 2) time of day changes in CBFV are due to an endogenous circadian rhythm independent of sleep. The aim of this study was to examine CBFV over 30 hours of sustained wakefulness to determine whether CBFV exhibits fluctuations associated with time of day. METHODS: Eleven subjects underwent a modified constant routine protocol. CBFV from the middle cerebral artery was monitored by chronic recording of Transcranial Doppler (TCD) ultrasonography. Other variables included core body temperature (CBT), end-tidal carbon dioxide (EtCO2), blood pressure, and heart rate. Salivary dim light melatonin onset (DLMO) served as a measure of endogenous circadian phase position. RESULTS: A non-linear multiple regression, cosine fit analysis revealed that both the CBT and CBFV rhythm fit a 24 hour rhythm (R2 = 0.62 and R2 = 0.68, respectively). Circadian phase position of CBT occurred at 6:05 am while CBFV occurred at 12:02 pm, revealing a six hour, or 90 degree difference between these two rhythms (t = 4.9, df = 10, p < 0.01). Once aligned, the rhythm of CBFV closely tracked the rhythm of CBT as demonstrated by the substantial correlation between these two measures (r = 0.77, p < 0.01). CONCLUSION: In conclusion, time of day variations in CBFV have an approximately 24 hour rhythm under constant conditions, suggesting regulation by a circadian oscillator. The 90 degree-phase angle difference between the CBT and CBFV rhythms may help explain previous findings of lower CBFV values in the morning. The phase difference occurs at a time period during which cognitive performance decrements have been observed and when both cardiovascular and cerebrovascular events occur more frequently. The mechanisms underlying this phase angle difference require further exploration.

Figure 1

24-hour Cosine Curve fit to Mean Core Body Temperature (°F). Time course of CBT according to time of day. Shown is a double plot of the group (n = 11) mean levels (+/- SEM) of CBT (blue diamonds) fit with a 24-hour cosine curve (purple squares). Time of day is shown on the abscissa. The ordinate shows CBT values (degrees F). The vertical line indicates where the data was double plotted. Also displayed in the upper right corner is the non-linear cosine curve fit for mean CBT, R² = 0.62. The overall mean circadian phase position of the minimum was 6:05 am.

Figure 2

24-hour Cosine Curve fit to Mean Cerebral Blood Flow Velocity (cm/sec). Time course of CBFV according to time of day. Shown is a double plot of the group (n = 11) mean levels (+/- SEM) of CBFV (blue diamonds) fit with a 24-hour cosine curve (purple squares). Time of day is shown on the abscissa. The ordinate shows CBFV values (cm/sec). The vertical line indicates where the data was double plotted. Also displayed in the upper right corner is the non-linear cosine curve fit for mean CBFV, R² = 0.67. The overall mean circadian phase position of the minimum was 12:02 pm.

Figure 3

Mean CBT and CBFV Aligned to CBT Nadir. Time course of mean CBFV and mean CBT aligned to the nadir of CBT and then averaged. Shown is a double plot of the group (n = 11) mean levels (+/-SEM) of CBT (purple squares) and CBFV (blue circles) aligned to the phase of the circadian temperature cycle. Circadian time in degrees is shown on the abscissa. The ordinate on the left shows CBT values (degrees F) and CBFV (cm/sec) on the right. The vertical line indicates the CBT nadir.

Figure 4

Mean CBT and CBFV Aligned to Their Respective Nadir. Time course of mean CBFV and mean CBT aligned to each of their respective nadirs and then averaged. Shown is a double plot of the group (n = 11) mean levels (+/-SEM) of CBT (purple squares) and CBFV (blue circles) aligned to the phase of the circadian temperature cycle. Circadian time in degrees is shown on the abscissa. The ordinate on the left shows CBT values (degrees F) and CBFV (cm/sec) on the right. The vertical line indicates both the CBT nadir and the CBFV nadir. The correlation coefficient between the aligned rhythms is 0.77 (p < 0.01).