Haemodynamic and neural responses to hypercapnia in the awake rat

Martin, Chris; Jones, Myles; Martindale, John; Mayhew, John E. W.

doi:10.1111/j.1460-9568.2006.05135.x

Cited by 43 publications

(42 citation statements)

References 72 publications

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“…Although there is some controversy as to whether hypercapnia induces no change in neuronal firing rates (22,23) or a mild depression in firing rates due to reduced excitability (24,30,31), our signal increases would only be consistent with an increase in firing rate, which has not been reported. In addition to neuronal activity, it is important to consider other possible sources of hypercapnia-induced cell swelling.…”

Section: Discussioncontrasting

confidence: 55%

“…In this study, we induce mild hypercapnia, which modulates the BOLD signal (10,21) with negligible change to the underlying neuronal firing (22)(23)(24) or oxygen metabolism (25)(26)(27). This enables direct measurement of the vascular component of the DFMRI signal, providing a mechanism for distinguishing the contributions of neuronal activity and hemodynamics.…”

mentioning

confidence: 99%

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Evidence for a vascular contribution to diffusion FMRI at high b value

Miller

Bulte

Devlin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Recent work has suggested that diffusion-weighted functional magnetic resonance imaging (FMRI) with strong diffusion weighting (high b value) detects neuronal swelling that is directly related to neuronal firing. This would constitute a much more direct measure of brain activity than current methods and represent a major advance in neuroimaging. However, it has not been firmly established that the observed signal changes do not reflect residual vascular effects, which are known to exist at low b value. This study measures the vascular component of diffusion FMRI directly by using hypercapnia, which induces blood flow changes in the absence of a change in neuronal firing. Hypercapnia elicits a similar diffusion FMRI response to a visual stimulus including a rise in percent signal change with increasing b value, which was reported for visual activation. Analysis of the response timing found no evidence for an early response at high b value, which has been reported as evidence for a nonhemodynamic response. These results suggest that a large component of the diffusion FMRI signal at high b value is vascular rather than neuronal.brain activation ͉ diffusion MRI ͉ functional MRI ͉ neuronal swelling F unctional neuroimaging has enabled major advances in the study of normal and pathological brain function. However, the methods that provide the greatest coverage and spatial resolution, including positron emission tomography (1, 2) and magnetic resonance imaging (MRI) (3, 4), are indirect measures of neuronal activity based on metabolically driven changes in blood flow. These hemodynamic measures suffer from spatial and temporal confounds (5, 6), are nonlinearly related to neuronal firing (7,8), and depend on baseline hemodynamics that are uncoupled from the activity of interest (9, 10). An imaging method that detects neuronal activity more directly while achieving whole-brain coverage would therefore represent a significant advance for neuroscience.One alternative method is diffusion-weighted functional MRI (DFMRI), which attenuates the MRI signal in a manner that depends on the amount of motion (diffusion and flow) in the underlying tissue. In general, this attenuation is described by a factor exp(ϪbD), where D is the apparent diffusion coefficient of the local tissue, and b is an acquisition parameter that describes the strength of diffusion contrast. At low b value, true diffusive motion is more difficult to detect, and the ''apparent diffusion'' is dominated by local blood flow (11)(12)(13)(14). In general, diffusion weighting is directional, so that attenuation depends on the diffusion and flow parameters along the applied direction. Different signal sources have been proposed in DFMRI depending on the b value. Early work used low b value, which is thought to reflect tissue perfusion (11-16). Recent work suggested that DFMRI at high b value detects cellular swelling that is a direct consequence of neural firing (17, 18), which would constitute a more direct measure of neuronal activity.A recent study at high b valu...

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Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

Evidence for a vascular contribution to diffusion FMRI at high b value

Miller

Bulte

Devlin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…This might partly explain the fact that the measured average BPR BH value of 2.16 (relative to BPR VT ) was lower than the theoretical estimate of 3.1 derived from equation (3) for small perfusion changes. Other factors that might affect relative BPR levels are the differences in actual and assumed values for a, b, and k. Lastly, the relatively low value of BPR BH might indicate that this task evokes a nonzero level of metabolic activity (Martin et al, 2006). Nevertheless, these limitations do not negate the main finding of this work, the observed similarity in BOLD-perfusion relationship (as characterized from BPR values) between VT and REST conditions, and the dissimilarity between these conditions and the BH condition.…”

Section: Limitationsmentioning

confidence: 99%

Metabolic Origin of Bold Signal Fluctuations in the Absence of Stimuli

Fukunaga

Horovitz

Zwart

et al. 2008

J Cereb Blood Flow Metab

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Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging studies have shown the existence of ongoing blood flow fluctuations in the absence of stimuli. Although this so-called 'resting-state activity' appears to be correlated across brain regions with apparent functional relationship, its origin might be predominantly vascular and not directly representing neuronal signaling. To investigate this, we simultaneously measured BOLD and perfusion signals on healthy human subjects (n = 11) and used their ratio (BOLD/perfusion ratio or BPR) as an indicator of metabolic demand. BPR during rest and sleep was compared with that during a visual task (VT) and a breath-holding task (BH), which are challenges with substantial and little metabolic involvement, respectively. Within the visual cortex, BPR was 3.76±1.23 during BH, which was significantly higher than during the VT (1.76 ± 0.27) and rest (1.56 ± 0.41). Meanwhile, BPR values during VT and rest were not significantly different, suggesting a similar metabolic involvement. Eight subjects showed stage 1 and 2 sleep, during which temporally correlated BOLD and perfusion activity continued. In these subjects, there was no significant difference in BPR between the sleep and waking conditions (1.79 ± 0.54 and 1.66 ± 0.67, respectively), but both were lower than the BPR during BH. These data suggest that resting-state activity, at least in part, represents a metabolic process.

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“…The electrical stimulation parameters used throughout were 1.2 mA, frequency 5 Hz for 16 s. A 5 Hz stimulation frequency is known to result in the greatest magnitude of hemodynamic responses in the somatosensory cortex of the anesthetized rodent preparation (Martin et al, 2006), without producing a change in MABP, pCO 2 or heart rate.…”

Section: Animal Preparation and Surgerymentioning

confidence: 99%

Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling

Boorman¹,

Kennerley²,

Johnston³

et al. 2010

J. Neurosci.

150

144

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Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.

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Haemodynamic and neural responses to hypercapnia in the awake rat

Cited by 43 publications

References 72 publications

Evidence for a vascular contribution to diffusion FMRI at high b value

Evidence for a vascular contribution to diffusion FMRI at high b value

Metabolic Origin of Bold Signal Fluctuations in the Absence of Stimuli

Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling

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