Effects of mild hypoxic hypoxia on poststimulus undershoot of blood-oxygenation-level-dependent fMRI signal in the human visual cortex (original) (raw)

Gray matter nulled and vascular space occupancy dependent fMRI response to visual stimulation during hypoxic hypoxia

NeuroImage, 2012

Two cerebral blood volume (CBV)-weighted fMRI techniques, gray matter nulled (GMN) and vascular space occupancy (VASO)-dependent techniques at spatial resolution of 2 × 2 × 5 mm 3 , were compared in the study investigating functional responses in the human visual cortex to stimulation in normoxia (inspired O 2 = 21%) and mild hypoxic hypoxia (inspired O 2 = 12%). GMN and VASO signals and T 2 * were quantified in activated voxels. While the CBV-weighted signal changes in voxels activated by visual stimulation were similar in amplitude in both fMRI techniques in both oxygenation conditions, the number of activated voxels during hypoxic hypoxia was significantly reduced by 72 ± 22% in GMN fMRI and 66 ± 23% in VASO fMRI. T 2 * prolonged in GMN and VASO activated voxels in normoxia by 1.6 ± 0.5 ms and 1.7 ± 0.5 ms, respectively. In hypoxia, however, T 2 * shortened in GMN-activated voxels by 0.7 ± 0.6 ms (p b 0.001 relative to normoxia), but prolonged in VASO-activated ones by 1.1 ± 0.6 ms (p b 0.05 relative to normoxia). The data show that the hemodynamic responses to visual stimulation were not affected by hypoxic hypoxia, but T 2 * increases by both CBV-weighted fMRI techniques were smaller in activated voxels in hypoxia. The mechanisms influencing GMN fMRI signal in both oxygenation conditions were explored by simulating effects of the oxygen extraction fraction (OEF) and partial voluming with cerebral spinal fluid (CSF) and white matter in imaging voxels. It is concluded that while GMN fMRI data point to increased, rather than decreased OEF during visual stimulation in hypoxia, partial voluming by CSF is likely to affect the CBV quantification by GMN fMRI under the experimental conditions used.

Hyperoxia modified activation-induced blood oxygenation level-dependent response of human visual cortex (V1): an event-related functional magnetic resonance imaging study

Neuroscience Letters, 2001

To investigate the effect that hyperoxia has on the blood oxygenation level-dependent (BOLD) response to visual stimulation of human V1, an event-related functional magnetic resonance imaging technique was applied. The eventrelated paradigm consisted of 2 s of stimulation by a checkerboard reversing at a frequency of 8 Hz, followed by 18 s of control scans. The peak height and peak time of the BOLD response curves were compared under normoxic and hyperoxic conditions. It was found that the peak height was larger and the peak time shorter for hyperoxia than for normoxia. These results suggest that hyperoxia modi®ed the activation-induced hemodynamic response of human V1. q

Time-dependent effects of hyperoxia on the BOLD fMRI signal in primate visual cortex and LGN

NeuroImage, 2007

Hyperoxia is present in many anaesthesia protocols used in animal blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. However, little data exist on the influence of hyperoxia on the magnitude of stimulus-induced relative changes in BOLD fMRI signal (ΔBOLD%). No study to date has investigated these effects in a timeresolved manner, although cerebral vasoregulation offers sites for a timedependent interaction of hyperoxia and ΔBOLD%. Here we investigated time-dependent effects of an inspiratory oxygen fraction of 90%. We tightly clamped end tidal CO 2 and body temperature and recorded physiological parameters relevant to rCBF in (fentanyl/isoflurane) anaesthetized monkeys while using visual stimulation to elicit ΔBOLD%. To clarify whether changes in ΔBOLD% arose from changes in baseline blood oxygenation or rather altered neuronal or vascular reactivity, we directly measured changes in rCBV using monocrystalline ion oxide nanoparticles (MION) as contrast agent. In visual cortex we found a biphasic modulation of stimulus-induced ΔBOLD% under hyperoxia: We observed first a significant decrease in ΔBOLD% by −24% for data averaged over the time interval of 0-180 min post onset of hyperoxia followed by a subsequent recovery to baseline. rCBV response amplitudes were decreased by 21% in the same time interval (0-180 min). In the LGN, we neither found a significant modulation of ΔBOLD% nor of MION response amplitude. The cerebrovascular effects of hyperoxia may, therefore, be regionally specific and cannot be explained by a deoxyhemoglobin dilution model accounting for plasma oxygenation without assuming altered neuronal activity or altered neurovascular coupling.

Negative Dip in BOLD fMRI Is Caused by Blood Flow— Oxygen Consumption Uncoupling In Humans

NeuroImage, 2002

The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect. © 2002 Elsevier Science Key Words: functional magnetic resonance imaging; blood oxygen level-dependent (BOLD) effect; cerebral blood oxygen saturation; cerebral autoregulation; cerebrovascular reserve capacity.

Effects of hyperoxia and hypocapnia on regional venous oxygen saturation in the primary visual cortex in conscious humans

British Journal of Anaesthesia, 1999

Hyperoxia can improve oxygen delivery in patients exposed to hypocapnia for neurosurgical procedures but this effect may be modified by regional differences in the degree of hypocapnic vasoconstriction. Using functional magnet resonance imaging (fMRI), we have investigated the influence of hyperoxia on blood flow and blood oxygenation in the primary visual cortex in hypocapnic volunteers. Consecutive fMRI measurements were performed in 10 awake, male volunteers during hypocapnia (mean PE'CO 2 3.3 (SD 0.1) kPa) and normocapnia (PE'CO 2 5-3 (0.1) kPa) at F\Q 2 values of 0.21 and 1.0, respectively. Hypocapnia significantly reduced the pixel count in the primary visual cortex (median 169 (quartiles 34-246) vs 21 (0-40) pixels at an F\Q 2 of 0.21). Additional hyperoxia had no influence on this reduction in pixel count (16 (0-28) pixels at F|Q 2 1.0 vs 21 (0-40) pixels at F|Q 2 0.21). Hyperoxia did not influence hypocapnic vasoconstriction in the primary visual cortex. These data suggest that in the primary visual cortex, administration of oxygen alone may not be sufficient to improve oxygen delivery under hypocapnic conditions. BrJAnaesth 1999; 83: 835-8

Increases in oxygen consumption without cerebral blood volume change during visual stimulation under hypotension condition

Journal of Cerebral Blood Flow & Metabolism, 2006

The magnitude of the blood oxygenation level-dependent (BOLD) signal depends on cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO 2 ). Thus, it is difficult to separate CMRO 2 changes from CBF and CBV changes. To detect the BOLD signal changes induced only by CMRO 2 responses without significant evoked CBF and CBV changes, BOLD and CBV functional magnetic resonance imaging (fMRI) responses to visual stimulation were measured under normal and hypotension conditions in isoflurane-anesthetized cats at 4.7 T. When the mean arterial blood pressure (MABP) decreased from 89610 to 5061 mm Hg (mean6standard deviation, n = 5) by infusion of vasodilator sodium nitroprusside, baseline CBV in the visual cortex increased by 28.4%68.3%. The neural activity-evoked CBV increase in the visual cortex was 10.8%6 3.9% at normal MABP, but was negligible at hypotension. Positive BOLD changes of + 1.8%60.5% (gradient echo time = 25 ms) at normal MABP condition became prolonged negative changes of À1.2%60.3% at hypotension. The negative BOLD response at hypotension starts approximately 1 sec earlier than positive BOLD response, but similar to CBV change at normal MABP condition. Our finding shows that the negative BOLD signals in an absence of CBV changes are indicative of an increase in CMRO 2 . The vasodilator-induced hypotension model simplifies the physiological source of the BOLD fMRI signals, providing an insight into spatial and temporal CMRO 2 changes.

Cerebral blood volume changes during the BOLD post-stimulus undershoot measured with a combined normoxia/hyperoxia method

NeuroImage, 2019

Cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) signal measurements make it possible to estimate steady-state changes in the cerebral metabolic rate of oxygen (CMRO 2) with a calibrated BOLD method. However, extending this approach to measure the dynamics of CMRO 2 requires an additional assumption: that deoxygenated cerebral blood volume (CBV dHb) follows CBF in a predictable way. A test-case for this assumption is the BOLD poststimulus undershoot, for which one proposed explanation is a strong uncoupling of flow and blood volume with an elevated level of CBV dHb during the post-stimulus period compared to baseline due to slow blood volume recovery (Balloon Model). A challenge in testing this model is that CBV dHb differs from total blood volume, which can be measured with other techniques. In this study, the basic hypothesis of elevated CBV dHb during the undershoot was tested, based on the idea that the BOLD signal change when a subject switches from breathing a normoxic gas to breathing a hyperoxic gas is proportional to the absolute CBV dHb. In 19 subjects (8F), dual-echo BOLD responses were measured in primary visual cortex during a flickering radial checkerboard stimulus in normoxia, and the identical experiment was repeated in hyperoxia (50% O 2 /balance N 2). The BOLD signal differences between normoxia and hyperoxia for the pre-stimulus/baseline, stimulus, and post-stimulus periods were compared using an equivalent BOLD signal calculated from measured R 2 * changes to eliminate signal drifts. Relative to the pre-stimulus baseline, the average BOLD signal change from normoxia to hyperoxia was negative during the undershoot period (p=0.0251), consistent with a reduction of CBV dHb , and contrary to the prediction of the Balloon Model. Based on these results, the BOLD post-stimulus undershoot does not represent a

MRI of Functional Deactivation: Temporal and Spatial Characteristics of Oxygenation-Sensitive Responses in Human Visual Cortex

NeuroImage, 1999

Magnetic resonance imaging (MRI) of neuronal ''activation'' relies on the elevation of blood flow and oxygenation and a related increase of the blood oxygenation level-dependent (BOLD) MRI signal. Because most cognitive paradigms involve both switches from a low degree of activity to a high degree of activity and vice versa, we have undertaken a baseline study of the temporal and spatial characteristics of positive and negative BOLD MRI responses in human visual cortex. Experiments were performed at 2.0 T using a multislice gradient-echo EPI sequence (TR ‫؍‬ 1 s, mean TE ‫؍‬ 54 ms, flip angle 50°) at 2 ؋ 2-mm 2 spatial resolution. Activation and ''deactivation'' processes were accomplished by reversing the order of stimulus presentations in paradigms using homogeneous gray light and an alternating checkerboard as distinct functional states. For sustained stimulation (H60 s) the two conditions resulted in markedly different steady-state BOLD MRI signal strengths. The transient responses to brief stimulation (I18 s) differed insofar as activation processes temporally separate positive BOLD and negative undershoot effects by about 10 s, whereas negative BOLD effects and undershoot contributions overlap for deactivation processes. Apart from differences in stimulus features (e.g., motion) the used activation and deactivation protocols revealed similar maps of neuronal activity changes.

The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal

NeuroImage, 2003

To study the behavior of cerebral physiological parameters and to further the understanding of the functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) effect, multisource frequency-domain near-infrared and BOLD fMRI signals were recorded simultaneously during motor functional activation in humans. From the near-infrared data information was obtained on the changes in cerebral blood volume and oxygenation. To relate our observations to changes in cerebral blood flow the well-known "balloon" model was employed. Our data showed that the deoxyhemoglobin concentration is the major factor determining the time course of the BOLD signal. The increase in cerebral blood oxygenation during functional activation is due to an increase in the velocity of blood flow, and occurs without significant swelling of the blood vessels.

Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals

Journal of Cerebral Blood Flow & Metabolism, 2002

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level—dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and nega...