Hemodynamic Coupling Research Articles

Long Duration Stimuli and Nonlinearities in the Neural–Haemodynamic Coupling

Recent studies have shown that the haemodynamic responses to brief (<2 secs) stimuli can be well characterised as a linear convolution of neural activity with a suitable haemodynamic impulse response. In this paper, we show that the linear convolution model cannot predict measurements of blood flow responses to stimuli of longer duration (>2 secs), regardless of the impulse response function chosen. Modifying the linear convolution scheme to a nonlinear convolution scheme was found to provide a good prediction of the observed data. Whereas several studies have found a nonlinear coupling between stimulus input and blood flow responses, the current modelling scheme uses neural activity as an input, and thus implies nonlinearity in the coupling between neural activity and blood flow responses. Neural activity was assessed by current source density analysis of depth-resolved evoked field potentials, while blood flow responses were measured using laser Doppler flowmetry. All measurements were made in rat whisker barrel cortex after electrical stimulation of the whisker pad for 1 to 16 secs at 5 Hz and 1.2 mA (individual pulse width 0.3 ms).

The effect of sensorimotor activation on functional connectivity mapping with MRI

The correlations in the fluctuations in the blood oxygenation level-dependent (BOLD) MRI signal between anatomically distinct regions of the cortex that are known components of functional systems have been previously studied as possible indicators of functional connectivity. The objective of this study was to examine the effect of sensorimotor brain activity, as assessed by task-based functional magnetic resonance imaging (fMRI), on functional connectivity indices in the same region. Regions of activation for sequential finger motion were determined using a task-based, block-design fMRI study. Functional connectivity measurements based on interregional correlations were acquired at rest and during continuous, sequential finger motion. Connectivity indices were determined using normalized mean correlations within and between three regions of interest activated for the finger motion task. Connectivity indices were also determined for a control region that was not activated for the task. Continuous motor tasks performed during BOLD measurements did not significantly affect the functional connectivity as compared to the connectivity at rest within or between regions known to be activated by the task. However, there appeared to be a trend suggesting a slight reduction in connectivity indices during the motor task. The connectivity within and between those areas not activated for the task remained unchanged between conditions. These results suggest that in the motor system investigated, the recruitment of neurons to perform a specific task may moderately reduce the degree of hemodynamic coupling within and between regions.

Spatiotemporal quantification of cerebral blood flow during functional activation in rat somatosensory cortex using laser-speckle flowmetry.

Laser-speckle flowmetry was used to characterize activation flow coupling after electrical somatosensory stimulation of forepaw and hindpaw in the rat. Quantification of functional activation was made with high transverse spatial (microm) and temporal (msec) resolution. Different activation levels and duration of stimulation were quantitatively investigated, and were in good agreement with previous laser-Doppler measurements. Interestingly, the magnitude but not the overall shape of the response was found to scale with stimulus amplitude and the distance from the activation centroid. The results provide new insights about the spatial characteristics of cerebral blood flow response to functional activation, and the method should lead to improved understanding of the coupling of neuronal activity and hemodynamics under normal and pathologic conditions.

Comparability of functional MRI response in young and old during inhibition

When using fMRI to study age-related cognitive changes, it is important to establish the integrity of the hemodynamic response because, potentially, it can be affected by age and disease. However, there have been few attempts to document such integrity and no attempts using higher cognitive rather than perceptual or motor tasks. We used fMRI with 28 healthy young and older adults on an inhibitory control task. Although older and young adults differed in task performance and activation patterns, they had comparable hemodynamic responses. We conclude that activation during cognitive inhibition, which was predominantly increased in elders, was not due to vascular confounds or specific changes in hemodynamic coupling.

Nonesterified fatty acids and endothelial dysfunction

Nonesterified fatty acids (NEFA) induce vascular effects, such as the inhibition of insulin-induced nitric oxide (NO) production. In small arteries, relaxation is largely NO-independent. We aimed to assess the effect of elevated NEFA on NO-independent vasodilation. Protocols were performed before and after 120 min of a lipid emulsion infusion. We performed: (1) the flow-induced dilatation of the brachial artery (NO-dependent), (2) intrabrachial bradykinin (BK) infusion before and after inhibition of prostaglandins (PG) and NO and (3) intraarterial infusion of ouabain, a Na +/K + ATPase blocker, alone or in combination with BaCl 2, a potassium channel blocker. No changes in flow-mediated vasodilation were induced by elevated NEFA. After the inhibition of PG and NO, BK increased forearm blood flow (FBF) similarly, indicating that the increase in FBF is not dependent on NO and PG production. However, elevated NEFA blunt FBF on both occasions. Coinfusion of ouabain with BaCl 2 caused a significant decline in FBF in baseline condition (−48±5%, p<0.01). This effect on FBF was blunted at high NEFA (−28±2%, p<0.01 vs. baseline condition). In conclusion, elevated NEFA do not impair NO-dependent vasodilation; this effect appears to be mediated by a reduced potassium-mediated vasodilation. This makes more likely their negative action on metabolism and haemodynamic coupling.

Information transfer in microvascular networks.

The adequate and efficient functioning of the circulatory system requires coordination of vessel diameters and of vascular responses to local and remote stimuli. Such coordination implies transfer of information about functional status and demands to all parts of the vascular system. In the peripheral circulation, blood flow must be controlled locally to accommodate spatial variations in demand. This requires information transfer from peripheral vessels to the more proximal vessels that feed and drain them. Principal mechanisms available for this information transfer are hemodynamic coupling, diffusive and convective transport of metabolites, and responses conducted along vessel walls. Current knowledge of these mechanisms is reviewed here. Theoretical models provide a framework for examining how information transfer mechanisms and vascular responses are integrated, so as to provide short-term regulation of blood flow and long-term structural adaptation of microvascular networks.

Bayesian Estimation of Dynamical Systems: An Application to fMRI

This paper presents a method for estimating the conditional or posterior distribution of the parameters of deterministic dynamical systems. The procedure conforms to an EM implementation of a Gauss–Newton search for the maximum of the conditional or posterior density. The inclusion of priors in the estimation procedure ensures robust and rapid convergence and the resulting conditional densities enable Bayesian inference about the model parameters. The method is demonstrated using an input–state–output model of the hemodynamic coupling between experimentally designed causes or factors in fMRI studies and the ensuing BOLD response. This example represents a generalization of current fMRI analysis models that accommodates nonlinearities and in which the parameters have an explicit physical interpretation. Second, the approach extends classical inference, based on the likelihood of the data given a null hypothesis about the parameters, to more plausible inferences about the parameters of the model given the data. This inference provides for confidence intervals based on the conditional density.

The Effect of Normal Aging on the Coupling of Neural Activity to the Bold Hemodynamic Response

The use of functional neuroimaging to test hypotheses regarding age-related changes in the neural substrates of cognitive processes relies on assumptions regarding the coupling of neural activity to neuroimaging signal. Differences in neuroimaging signal response between young and elderly subjects can be mapped directly to differences in neural response only if such coupling does not change with age. Here we examined spatial and temporal characteristics of the BOLD fMRI hemodynamic response in primary sensorimotor cortex in young and elderly subjects during the performance of a simple reaction time task. We found that 75% of elderly subjects (n=20) exhibited a detectable voxel-wise relationship with the behavioral paradigm in this region as compared to 100% young subjects (n=32). The median number of suprathreshold voxels in the young subjects was greater than four times that of the elderly subjects. Young subjects had a slightly greater signal:noise per voxel than the elderly subjects that was attributed to a greater level of noise per voxel in the elderly subjects. The evidence did not support the idea that the greater head motion observed in the elderly was the cause of this greater voxel-wise noise. There were no significant differences between groups in either the shape of the hemodynamic response or in its the within-group variability, although the former evidenced a near significant trend. The overall finding that some aspects of the hemodynamic coupling between neural activity and BOLD fMRI signal change with age cautions against simple interpretations of the results of imaging studies that compare young and elderly subjects.

Catheter obstruction effect on pulsatile flow rate--pressure drop during coronary angioplasty.

The coupling of computational hemodynamics to measured translesional mean pressure gradients with an angioplasty catheter in human coronary stenoses was evaluated. A narrowed flow cross section with the catheter present effectively introduced a tighter stenosis than the enlarged residual stenoses after balloon angioplasty; thus elevating the pressure gradient and reducing blood flow during the measurements. For resting conditions with the catheter present, flow was believed to be about 40 percent of normal basal flow in the absence of the catheter, and for hyperemia, about 20 percent of elevated flow in the patient group. The computations indicated that the velocity field was viscous dominated and quasi-steady with negligible phase lag in the delta p(t)-u(t) relation during the cardiac cycle at the lower hydraulic Reynolds numbers and frequency parameter. Hemodynamic interactions with smaller catheter-based pressure sensors evolving in clinical use require subsequent study since artifactually elevated translesional pressure gradients can occur during measurements with current angioplasty catheters.

Branching patterns and autoregulatory responses of juxtamedullary afferent arterioles.

The spatial organization of autoregulatory responses (AR) was assessed in couples of afferent arterioles (AA), either grouped as anatomic pairs or branched sequentially along the same arcuate arterial branch (ArcB). With blood-perfused juxtamedullary nephron (JMN) preparations, AR were elicited by raising blood perfusion pressure from 60 to 120 mmHg and quantified by videomicroscopy as pressure-induced constrictions. Paired AA had unequal lengths (long-to-short ratio, 1.9 +/- 0.1; n = 36); however, no statistical difference in AR was found between long and short AA at juxtaglomerular or early AA (EAA) sites. Sequentially branched AA had the same length heterogeneity as paired AA (proximal-to-distal AA length ratio, 2.0 +/- 0.2; n = 30). However, AR exhibited a significant axial gradient, being higher in distal than in proximal AA or ArcB sites. In both AA branching patterns, EAA and nearby sites of the feed arteries had similar AR. Hence, our results are consistent with hemodynamic coupling in paired JMN. Around branching sites, AR are spatially organized in a way consistent with electrotonic vascular coupling.

Cerebral oxygenation changes during motor and somatosensory stimulation in humans, as measured by near-infrared spectroscopy.

Functional cortical activation is coupled to changes of cerebral hemodynamics and metabolism. These changes have been used in positron emission tomography and recently developed functional magnetic resonance techniques to localize task-related cortical activation. Near-infrared spectroscopy has the potential to monitor changes of intracerebral blood oxygenation during functional activation (Villringer 1993, Hoshi 1993). We proceeded from a rather global, cognitive stimulus to experimental paradigms which entail a more localized cerebral activation and which have been examined by other functional techniques. In establishing a simple motor and a vibratory stimulus we sought a means to further examine the issue of coupling of neuronal function and cerbral hemodynamics. In recent experiments we were able to demonstrate that these stimulation models are useful to retrieve additional information about oxygenation dependent signal changes in functional MRI (Kleinschmidt 1994, Obrig 1994). As near-infrared spectroscopy has a good temporal resolution, we were also interested in the time course of local oxygenation changes.

Developmental changes in the acetylcholine influence on heart muscle of Rana catesbeiana: in situ and in vitro effects.

The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages II-XVIII) and postmetamorphic (3-609 g) Rana catesbeiana was analyzed in situ (circulatory system intact) and in vitro (isolated heart or ventricular strip preparations). Topical application of ACh to the heart in situ resulted in a dose-dependent decrease in heart rate and in a slight decrease in systolic ventricular pressure in all developmental stages. Injection of acetylcholine into the ventricle lumen in situ caused a dose-dependent transient decrease in systolic ventricular pressure, with little heart rate effect. Intraventricular ACh injection also changed the hemodynamic coupling between ventricle and conus arteriosus, generating a biphasic pressure profile in the conus due to sequential contractions of the ventricle and of the conus. In situ the sensitivity of the ventricle to ACh decreased during larval development, with the lowest sensitivity in small postmetamorphic adults. ACh applied in vitro to cardiac muscle strips or small hearts produced a negative inotropic effect. The ACh dose necessary to induce a 50% reduction in muscle strip contraction force in vitro decreased substantially during larval development, indicating an increase in ACh sensitivity with development. The effects of ACh both in vitro and in situ were diminished or eliminated by topical application or injection of atropine, suggesting the presence of muscarinic cholinergic receptors. After preincubation with the acetylcholinesterase blocker eserine, injection of ACh into the conus arteriosus decreased systolic ventricular pressure with a delay of 4-10 seconds, probably representing the minimum blood circulation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial mechanics and coronary flow dynamics.

The interaction between cardiac mechanics and coronary flow is highlighted here. Left ventricular (LV) structure and geometry are related to coronary flow dynamics and used in the analysis of experimental coronary flow data. The important role of the collagen mesh in the generation of the intramyocardial pressure (IMP), the pressure in the interstitial fluid, at a wide range of loading conditions is emphasized. The calculated IMP, based on a structural model of the LV myocardium, can explain most of the observed coronary compression characteristics under a variety of loading and contractility conditions. A more general compression function, the extravascular compressive pressure (ECP), is suggested to define coronary compression and is presented here based on the dynamics of the coronary inflow under constant perfusion conditions. Coronary compression is shown to be affected by fluid transport and the bi-directional coupling of coronary hemodynamics and IMP dynamics.