Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation - PubMed (original) (raw)

Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

D Malonek et al. Proc Natl Acad Sci U S A. 1997.

Abstract

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

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Figures

Figure 1

Simultaneous measurement of cortical reflection and CBF. (A) An image of the cortical surface, the location of slit used for imaging spectroscopy, the tip of LDF probe, and the reflection of its beam from the cortex. The yellow spot marks the cortical region that was illuminated by the LDFs laser during the measurements. (B, C, and E) Cortical response to visual stimulation. Black curves represent response to short stimulus (2 sec), and red curves represent its response to long stimulus (10 sec, composed of 2 on, 2 off, 2 on, 2 off, 2 on). Each curve is the average response to 24 stimulation periods during a single experiment. (B) LDF response. Its onset (arrow) lags after stimulus onset by ≈1.5 sec. (C) Cortical reflection change: 605-nm illumination. The response is biphasic, and its onset leads the LDF response by ≈1 sec. Long stimulus duration attenuates the second phase, which almost vanishes. Notice that increased reflection is downward. (D) The vascular response (“initial dip”) at different flow levels and at different times after the stimulus onset. We compare the early response to the short stimulus (black curve in C), when CBF was at equilibrium, with that obtained when CBF was elevated and a second delayed stimulus followed, by subtracting the short stimulus curve from the long stimulus curve (red curve in C). In D, when this difference, i.e., the net response to the second stimulus, shown in red, is shifted in time and superimposed on the response to the first stimulus (black line), the two curves are nearly identical. The second stimulus was given when CBF increased by ≈15%. (E) Cortical reflection change: 570-nm illumination. Similar to reflection changes at 605-nm illumination, the response onset leads the LDF response by 1 sec. The response is maintained throughout stimulus duration, for both short and long durations.

Figure 2

Dynamics of various vascular responses. Total hemoglobin concentration (Hbt, green line) leads CBF response (black line) throughout the response cycle for both the short stimulus (A) and the repeated stimuli (B). Each curve is the average response to 24 stimulation periods during a single experiment. Horizontal arrows mark the temporal difference between the curves when they had reached 50% of their maximal amplitude (marked by thin, vertical lines) during the uprising phase and during the decay to baseline. HbR curve appears to lead all other components, and it reaches its peak before all other curves. Notice the delays of both the CBF (marked by arrow) and the HbO2 onsets after the stimulus onsets. At onset, Hbt change is entirely composed of HbR elevation, whereas at the later phase it is predominantly HbO2. Because of fluctuations of HbO2 (and thus Hbt) before stimulation, its onset is determined as time when its rate of change increased. Asterisks mark the maximum of HbO2 and the minimum of HbR.

Figure 3

Correlated dynamics of CBF to HbR and to Hbt for short stimulus. Phase plots show the dependence of CBF changes on HbR and Hbt after 2 sec of stimulation. Along the curves, intervals between the circles represent 0.5 sec, and the first four segments (five circles) are during stimulation. An asterisk marks the stimulus onset, and an arrow marks the onset of CBF, when an observable change in its rate of change is detected. (A) After stimulation onset (pink asterisk), HbR increases, whereas no observable change in CBF is seen for more than a second. As CBF starts to increase (arrow), the rate of change of HbR starts to decrease and becomes negative 1 sec later. At the last phase of the response (red asterisk), an inverse relation between the parameters is seen; an increase in CBF is accompanied by a decrease in HbR and vice versa. (B) An exponential dependence of CBF on Hbt is seen during the first 4.5 sec after stimulus onset. Throughout the response cycle, changes in Hbt lead changes in CBF by about 1–2 sec.

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Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation - PubMed (original) (raw)