Reproducibility and variance of a stimulation-induced hemodynamic response in barrel cortex of awake behaving mice (original) (raw)
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Laminar Analysis of Cerebral Blood Flow in Cortex of Rats by Laser-Doppler Flowmetry
Journal of Cerebral Blood Flow & Metabolism, 1997
Laser-Doppler flowmetry (LDF) is a reliable method for estimation of relative changes of CBF. The measurement depth depends on wavelength of the laser light and the separation distance of transmitting and recording optical fibers. We designed an LDF probe using two wavelengths of laser light (543 nm and 780 nm), and three separation distances of optical fibers to measure CBF in four layers of the cerebral cortex at the same time. In vitro comparison with electromagnetic flow measurements showed linear relationship between LDF and blood flow velocity at four depths within the range relevant to physiologic measurements. Using artificial brain tissue slices we showed that the signal for each channel decreased in a theoretically predictable fashion as a function of slice thickness. Application of adenosine at various depths in neocortex of halothane-anesthetized rats showed a predominant CBF increase at the level of application. Electrical stimulation at the surface of the cerebellar cortex demonstrated superficial predominance of increased CBF as predicted from the distribution of neuronal activity. In the cerebellum, hypercapnia increased CBF in a heterogeneous fashion, the major increase being at apparent depths of approximately 300 and 600 microns, whereas in the cerebral cortex, hypercapnia induced a uniform increase. In contrast, the CBF response to cortical spreading depression in the cerebral cortex was markedly heterogeneous. Thus, real-time laminar analysis of CBF with spatial resolution of 200 to 300 microns may be achieved by LDF. The real-time in depth resolution may give insight into the functional organization of the cortical microcirculation and adaptive features of CBF regulation in response to physiologic and pathophysiologic stimuli.
Neuroimage, 2001
Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and changes in the concentration of the endogenous paramagnetic contrast agent deoxygenated hemoglobin. Changes in the blood oxygen level-dependent (BOLD) signal result from a complex interplay of blood volume, flow, and oxygen consumption. Optical imaging spectroscopy (OIS) has been used to measure changes in blood volume and saturation in response to increased neural activity, while laser Doppler Flowmetry (LDF) can be used to measure flow changes and is now commonplace in neurovascular research. Here, we use concurrent OIS and LDF to examine the hemodynamic response in rodent barrel cortex using electrical stimulation of the whisker pad at varying intensities. Spectroscopic analysis showed that stimulation produced a biphasic early increase in deoxygenated hemoglobin (Hbr), followed by a decrease below baseline, reaching minima at ϳ3.7 s. There was no evidence for a corresponding early decrease in oxygenated hemoglobin (HbO 2 ), which simply increased after stimulation, reaching maximum at ϳ3.2 s. The time courses of changes in blood volume (CBV) and blood flow (CBF) were similar. Both increased within a second of stimulation onset and peaked at ϳ2.7 s, after which CBV returned to baseline at a slower rate than CBF. The changes in Hbr, Hbt, and CBF were used to estimate changes in oxygen consumption (CMRO 2 ), which increased within a second of stimulation and peaked ϳ2.2 s after stimulus onset. Analysis of the relative magnitudes of CBV and CBF indicates that the fractional changes of CBV could be simply scaled to match those of CBF. We found the relationship to be well approximated by CBV ؍ CBF 0.29 . A similar relationship was found using the response to elevated fraction of inspired carbon dioxide (FICO 2 ).
Blood flow increases linearly in rat somatosensory cortex with increased whisker movement frequency
Brain Research, 1998
It has long been known that the level of neuronal activity is correlated to the level of localized blood flow. Despite the importance of functional hyperemia in the brain, the relationship between blood flow and electrical activity has not been clearly demonstrated parametrically in a single region of cerebral cortex. We investigated both the magnitude and temporal characteristics of the blood flow response in somatosensory cortex while varying the frequencies of whisker movement. The full whisker pad on one side of the rat's face was repeatedly moved for 13 s at frequencies of 1.5, 2, 3, 4, 6, 8, and 10.5 Hz, and the resulting changes in blood flow were quantified Ž. using Laser-Doppler flowmetry LDF. The magnitude of the blood flow response increased linearly with increasing frequency while the temporal parameters of time to half maximal value and time to return halfway to baseline after stimulus termination did not vary. Baseline blood flow levels were elevated by breathing rats on a 5% CO mixture. No significant alteration in the LDF plateau response to whisker 2 movement was observed compared to normal air, suggesting sustained vasodilation reserve capacity remained after CO-induced 2 vasodilation. These data demonstrate linear blood flow responses to presumptive linear increases in neuronal activity with sufficient vascular reserve capacity to overcome moderate CO-induced dilation, and support the use of blood flow changes in neuroimaging 2 studies. They provide a framework to study the neurobiological signal transduction mechanisms coupling neuronal electrical activity with regional alterations in blood flow. q 1998 Elsevier Science B.V.
Brain Research, 1998
. Regional alterations in cerebral blood flow CBF are widely used as a surrogate for neuronal function based on an intact coupling Ž . between changes in regional CBF and metabolism, activation-flow coupling AFC . To further investigate parameters affecting AFC, we Ž . have implemented a rat model with electrical forepaw stimulation under a-chloralose anesthesia using laser Doppler LD measurements of flow parameters through thinned skull over contralateral somatosensory cortex. Signal averaging of the LD response was used to improve reproducibility. A characteristic flow response to electrical forepaw stimulation was reliably recorded from the somatosensory cortex using signal averaging. Stimulation at 5 Hz maximized the LD response, and constant current stimulation up to 1 mA did not induce changes in systemic blood pressure. The shape of the flow response consisted of an initial peak followed by a steady state plateau phase which was observed for stimulation durations longer than 4 s. When individual LD parameters of velocity, red blood cell Ž . Ž . concentration CRBC , and cerebral blood flow CBF were compared, changes in LD were primarily attributable to changes in CBF LD rather than LD . This finding was also observed during hypercapnia. Characterization of AFC in the model provides a velocity CRBC background for future studies of the effects of pharmacological manipulation or pathophysiological states. q 1998 Elsevier Science B.V. All rights reserved.
Brain Research, 2011
A method for long-term, repeated, semi-quantitative measurements of cerebral microflow at the same region of interest (ROI) with high spatial resolution was developed and applied to mice subjected to focal arterial occlusion. A closed cranial window was chronically implanted over the left parieto-occipital cortex. The anesthetized mouse was placed several times, e.g., weekly, under a dynamic confocal microscope, and Rhodamine B-isothiocyanate-dextran was each time intravenously injected as a bolus, while microflow images were video recorded.
Neuroimage, 2007
This study compares laser Doppler flowmetry (LDF) and arterial spin labeling (ASL) for the measurement of functional changes in cerebral blood flow (CBF). The two methods were applied concurrently in a paradigm of electrical whisker stimulation in the anaesthetised rat. Multi-channel LDF was used, with each channel corresponding to different fiber separation (and thus measurement depth). Continuous ASL was applied using separate imaging and labeling coils at 3 T. Careful experimental set up ensured that both techniques recorded from spatially concordant regions of the barrel cortex, where functional responses were maximal. Strong correlations were demonstrated between CBF changes measured by each LDF channel and ASL in terms of maximum response magnitude and response timecourse within a 6-s-long temporal resolution imposed by ASL. Quantitatively, the measurements of the most superficial LDF channels agreed strongly with those of ASL, whereas the deeper LDF channels underestimated consistently the ASL measurement. It was thus confirmed that LDF quantifies CBF changes consistently at a superficial level, and for this case the two methods provided concordant measures of functional CBF changes, despite their essentially different physical principles and spatiotemporal characteristics.
Local and global contributions to hemodynamic activity in mouse cortex
Imaging techniques such as functional magnetic resonance imaging seek to estimate neural signals in local brain regions through measurements of hemodynamic activity. However, hemodynamic activity is accompanied by large vascular fluctuations of unclear significance. To characterize these fluctuations and their impact on estimates of neural signals, we used optical imaging in visual cortex of awake mice. We found that hemodynamic activity can be expressed as the sum of two components, one local and one global. The local component reflected presumed neural signals driven by visual stimuli in the appropriate retinotopic region. The global component constituted large fluctuations shared by larger cortical regions, which extend beyond visual cortex. These fluctuations varied from trial to trial, but they did not constitute noise; they correlated with pupil diameter, suggesting that they reflect variations in arousal or alertness. Distinguishing local and global contributions to hemodynamic activity may help understand neurovascular coupling and interpret measurements of hemodynamic responses.
Journal of Cerebral Blood Flow & Metabolism, 1996
Laser-Doppler flowmetry (LDF) is very pop ular for measurements of dynamic changes of cerebral blood flow (CBF). We studied whether changes of CBF measured by LDF correlate with CBF measured by the [14C]iodoantipyrine (lAP) technique in the range relevant for most physiological experiments (-30-+ 130%). LDF was recorded biparietally by two laser-Doppler probes in halothane-anesthetized rats. Absolute CBF was mea sured in tissue samples of both parietal cortices after [14C]iodoantipyrine was given i. v. CBF of one hemi sphere was reduced by an episode of cortical spreading depression (CSD), which markedly reduces the respon siveness of the ipsilateral cortical CBF to vasoactive stimuli for up to 30 min, while CBF regulation of the contralateral cortex remains intact. CBF was measured