“Spectroscopic Analysis of Neural Activity in Brain: Increased Oxygen Consumption Following Activation of Barrel Cortex” (original) (raw)
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Spectroscopic analysis of neural activity in brain: increased oxygen consumption following …
Neuroimage, 2000
This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy . A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxyand deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of ϳ10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO 2 ). Evidence for increased oxygen consumption (CMRO 2 ) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO 2 peaking ϳ2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.
NeuroImage, 2001
Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554 -564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (⍀), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, ⍀ ؍ 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < ⍀ < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter ⍀ is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.
Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses
NeuroImage, 2008
Trial-by-trial variability in local field potential (LFP), tissue partial pressure of oxygen (PO2), cerebral blood flow (CBF), and deoxyhemoglobin-weighted optical imaging of intrinsic signals (OIS) were tested in the rat somatosensory cortex while fixed electrical forepaw stimulation (1.0-ms pulses with amplitude of 1.2 mA at a frequency of 6 Hz) was repeatedly applied. The changes in the cerebral metabolic rate of oxygen (CMRO2) were also evaluated using a hypotension condition established by our group based on the administration of a vasodilator. Under normal conditions, CBF, PO2, and OIS showed positive signal changes (48%, 32%, and 0.42%, respectively) following stimulation. Over multiple trials, the CBF responses were well correlated with the integral of the LFP amplitudes (sigmaLFP) (Rmean=0.78), whereas a lower correlation was found between PO2 and sigmaLFP (Rmean=0.60) and between OIS and sigmaLFP (Rmean=0.54). Under the hypotension condition the LFP responses were preserved, but the CBF responses were suppressed and the PO2 and OIS changes were negative (-12% and -0.28%, respectively). In this condition, the trial-by-trial variations in PO2 and OIS were well correlated with the variability in sigmaLFPs (Rmean= -0.77 and -0.76, respectively), indicating a single trial coupling between CMRO2 changes and sigmaLFP. These findings show that CBF and CMRO2 signals are more directly correlated with neural activity compared to blood oxygen-sensitive methods such as OIS and BOLD fMRI.
Neuron, 2004
hemodynamic changes is required for interpreting perfusion-based functional imaging results as indicative of at the University of California, Los Angeles Los Angeles, California 90024 actual brain activity. Recent studies have arrived at differing conclusions regarding the linearity (Logothetis et al., 2001) or nonlinearity (Devor et al., 2003) of coupling between neuronal activity and hemodynamic re-Summary sponses.
Journal of Cerebral Blood Flow & Metabolism, 2001
Changes in cerebral blood flow (CBF) using laser-Doppler and microvascular O 2 oxygen tension using oxygendependent phosphorescence quenching in the rat somatosensory cortex were obtained during electrical forepaw stimulation. The signal-averaged CBF response resulting from electrical forepaw stimulation consisted of an initial peak (t ס 3.1 ± 0.8 seconds after onset of stimulation), followed by a plateau phase that was maintained throughout the length of the stimulus. In contrast, microvascular O 2 tension changes were delayed, reached a plateau level (t ס 23.5 ± 1.7 seconds after the onset of stimulation) that remained for the length of the stimulus and for several seconds after stimulus termination, and then returned to baseline. Using Fick's equation and these dynamic measurements, changes in the calculated cerebral metabolic rate of oxygen (CMRO 2 ) during functional stimulation were determined. The calculated CMRO 2 response initially was comparable with the CBF, but with protracted stimulation, CMRO 2 changes were approximately one-third that of CBF changes. These results suggest that a complex relation exists, with comparable changes in CBF and CMRO 2 initially occurring after stimulation but excessive changes in CBF compared with CMRO 2 arising with protracted stimulation. Key Words: Cerebral blood flow-Cerebral metabolic rate of O 2 -Oxygendependent phosphorescence quenching.
Blood volume and hemoglobin oxygenation response following electrical stimulation of human cortex
NeuroImage, 2006
Our understanding of perfusion-based human brain mapping techniques relies on a detailed knowledge of the relationship between neuronal activity and cerebrovascular hemodynamics. We performed optical imaging of intrinsic signals at wavelengths sensitive to total hemoglobin (Hbt; which correlate with cerebral blood volume (CBV)) and deoxygenated hemoglobin (Hbr) directly in humans during neurosurgical operations and investigated the optical signals associated with bipolar cortical stimulation at a range of amplitudes. Cortical stimulation elicited a rapid focal increase in Hbr (initial dip) in all subjects. An equally rapid increase in Hbt (<200 ms), with a slightly higher signal-to-noise ratio, was also highly localized for <2 s in spite of the non-columnar nature of the stimulus, after which the signal spread to adjacent gyri. A later decrease in Hbr (>3 s), which is relevant to the blood oxygen level dependent (BOLD) signal, was poorly localized. Increasing the stimulus amplitude elicited a linear increase in the area of the optical signal for Hbt and the initial dip but not the late decrease in Hbr, and a nonlinear increase in optical signal amplitude with a plateau effect for initial dip, Hbt and late decrease in Hbr. D
NeuroImage, 2008
The dynamics of blood oxygen delivery and tissue consumption produced by evoked stimulation of the rat somato-sensory cortex were investigated. Tissue oxygen tension (P O2 ) and laser Doppler flowmetry (LDF) measurements were recorded under two experimental conditions: normal, which represented both oxygen delivery and consumption, and suppressed CBF (achieved using a vasodilator), which only represented tissue oxygen consumption. Forepaw stimulation for 10 s produced increases of 27.7% and 48.8% in tissue P O2 and LDF signal under normal conditions, respectively. The tissue P O2 response peaked 9.8 s after stimulation onset and did not show any early transient decreases indicating that measurable oxygen deficits are not required to increase the delivery of oxygen by blood flow. Under suppressed CBF conditions, the LDF signal was mostly suppressed while the tissue P O2 decreased by 11.7% and reached a minimum 10.8 s after stimulation onset. These data were analyzed using a dynamic model that described the transport of oxygen from blood to tissue. In order to explain the differences between the model prediction of the tissue P O2 changes and the experimental data, several hypothetical scenarios were considered, such as changes in the vascular volume, permeability-surface area or arterial oxygenation. The increase in tissue P O2 was found to probably require the recruitment of upstream oxygen from larger arteries as well as increases in the vascular volume at the oxygen exchange sites. The amplitude of the estimated tissue tension of oxygen delivered was about 2.7× larger than the estimated consumption under normal conditions (45.7% vs. 17.1%, respectively).
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 ).