Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

Abstract

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO₂) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO₂ occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO₂ and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

Introduction

Near infrared spectroscopy (NIRS) is a noninvasive optical recording technique that can measure brain activity in vivo by detecting features of the hemodynamic response of the brain to neural activity. It has several advantages over PET and fMRI, which also measure hemodynamic response parameters, in that it combines reasonable spatial resolution with a temporal resolution of ∼1–10 ms. This excellent temporal resolution makes it possible to filter out noisy signals associated with physiological processes (e.g., Gratton and Corballis, 1995). Additionally, the ability to gather spectroscopic information with NIRS allows one to separately characterize changes in oxyhemoglobin and deoxyhemoglobin—an ability that affords a less ambiguous analysis of activity-induced volume and metabolic changes than (e.g.) blood oxygen level-dependent (BOLD) fMRI alone. Optical techniques such as NIRS are therefore well suited to study the nature of neurovascular coupling. NIRS has the added virtues of being portable and relatively low cost, allowing for its routine use with subjects of all ages (including infants) and in situations where PET and fMRI scans are unaffordable or impossible (e.g., in settings requiring substantial motion, even at bedside).

NIRS has been used to study a variety of neuronal processes, including vision (e.g., Villringer et al., 1993, Meek et al., 1995, Wobst et al., 2001, the motor and/or somatosensory system (e.g., Beese et al., 1998, Obrig et al., 1996b, Steinbrink et al., 2000, as well as higher cognitive functions such as language (e.g., Hock et al., 1997, Sakatani et al., 1998, Watanabe et al., 1998, and frontal brain activation with the Wisconsin Card Sorting Task (Fallgatter and Strik, 1998). These studies have generally relied on blocked designs where stimuli are presented for a period lasting from a few seconds to several minutes, followed by a period of rest or fixation. In contrast to blocked designs are event-related designs, which have been used by EEG researchers for decades and more recently with fMRI (Buckner et al., 1996). It has been shown that single event designs can be successfully used with NIRS (Obrig et al., 2000), but since the peak response in a region is considerably smaller with an event-related design than with a blocked design, it is an open question whether rapid presentation event-related designs, which assume that hemodynamic responses are linearly additive (Boynton et al., 1996), can be successfully used with current NIRS instruments. A recently published study (Schroeter et al., 2002) indicates that such designs can be used to study cognitive processes with NIRS when the interstimulus interval is as long as 12 sec. We extend this further by collecting event-related data with an interstimulus interval as small as 5 s.

An important benefit of event-related experimental designs for NIRS is that they more efficiently average and reduce the contribution of confounding physiological signals. Previous research by our lab (Boas et al., 2002) and elsewhere (Wobst et al., 2001) indicates that data generated from stimuli presented in a blocked manner can include signals generated from physiological processes such as breathing and heart rate, and Mayer waves (low-frequency arterial pressure fluctuations), all of which are possibly physiological responses synchronized with the stimulus (Franceschini et al., 2000). The influence of these physiological processes on the detected signals is a matter of particular concern for experimental tasks eliciting changes in the measured hemodynamic parameters with amplitudes similar in magnitude to those elicited by the background physiological processes themselves (Gratton and Corballis, 1995).

An important attribute of the NIRS technique is its ability to separate out the oxyhemoglobin and deoxyhemoglobin contributions to the hemodynamic response function, making it suitable for exploring issues related to the hemodynamic response function. Issues that we examine here include the onset times of HbO, HbT, and HbR, early deoxygenation, the time to peak response of these species, and the poststimulus response.

The early deoxygenation occurs during the first several seconds of the hemodynamic response at the locus of neural activity after the presentation of a brief stimulus, which is then followed by a more pronounced decrease in deoxygenation as oxyhemoglobin flows into the area (Frostig et al., 1990). This so-called “initial dip” may be important for improving spatial localization of the neuronal signal. Evidence for early deoxygenation comes from fMRI and invasive optical imaging. It has been reported in research involving several species including the cat (Frostig et al., 1990), the rat (Jones et al., 2001), and the human Menon et al., 1995, Hu et al., 1997; yet the very existence of the dip is a matter of controversy, for it is inconsistently found. Because those who find the dip have generally studied the visual cortex and those who do not find the dip have not, we tested the hypothesis that different parts of the cortex behave differently with respect to their hemodynamic response functions. In this study, we compared the hemodynamic response functions generated from human motor and visual cortices using rapid presentation event-related paradigms, finding significant differences between the areas. We also examine the poststimulus recovery of the response function and find that the poststimulus overshoot of the deoxyhemoglobin cannot be described by the common explanation of a delayed recovery of the total hemoglobin concentration Mandeville et al., 1998, Leite, et al., 2002. We discuss these results in the context of vascular models.