Elsevier

NeuroImage

Volume 57, Issue 3, 1 August 2011, Pages 991-1002
NeuroImage

Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task

https://doi.org/10.1016/j.neuroimage.2011.05.012Get rights and content

Abstract

Brain activity during a verbal fluency task (VFT) has been the target of many functional imaging studies. Most studies using near-infrared spectroscopy (NIRS) have reported major activation in the frontal pole, but those using PET or fMRI have not. This led us to hypothesize that changes in the NIRS signals measured in the forehead during VFT were due to changes in skin blood flow. To test this hypothesis, we measured NIRS signals and the Doppler tissue blood flow signals in the foreheads of 50 participants. The measurements were performed while each participant produced words during two 60-s periods with an interval of 100 s. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance – 5 mm (NEAR channels) – to measure NIRS signals that originated exclusively from surface tissues. The oxygenated hemoglobin (oxyHb) concentration in the FAR and NEAR channels, as well as the Doppler blood flow signal, increased in a similar manner during the two periods of word production; the signal increase in the first period was twice as high as that in the second period. Accordingly, the mean changes in oxyHb concentration in the FAR channels were correlated closely with the changes in the NEAR channels (R2 = 0.91) and with the integrated Doppler skin blood flow signal (R2 = 0.94). Furthermore, task-related NIRS responses disappeared when we blocked skin blood flows by pressing a small area that covered a pair of optodes. Additionally, changes in the FAR channel signals were correlated closely with the magnitude of pulsatile waves in the Doppler signal (R2 = 0.92), but these signals were not highly correlated with the pulse rate (R2 = 0.43). These results suggest that a major part of the task-related changes in the oxyHb concentration in the forehead is due to task-related changes in the skin blood flow, which is under different autonomic control than heart rate.

Research highlights

► NIRS signals on the forehead are due to the VFT-related changes in skin blood flow. ► Pulsatile magnitude in Doppler signal can explain NIRS response. ► Pulsatile rate in Doppler signal did not correlate well with the NIRS response. ► The VFT-related NIRS signals would be under different autonomic control than HR.

Introduction

A verbal fluency task (VFT) is a neuropsychological test that is widely used to assess cognitive function in the frontal cortex (Klumpp and Deldin, 2010). In the task, participants are asked to generate as many words as possible within a specified time limit in response to a letter or a semantic cue. Brain activity during a VFT, especially a letter-cued VFT, has been the target of many functional imaging studies. However, the results of these studies disagree with each other depending on the method of functional imaging used. On the one hand, studies that have used near-infrared spectroscopy (NIRS) have reported considerable activity in the frontal pole, including in Brodmann's area 10 (Azechi et al., 2010, Herrmann et al., 2003, Herrmann et al., 2004, Kakimoto et al., 2009, Kameyama et al., 2004, Kameyama et al., 2006, Matsuo et al., 2000, Suto et al., 2004, Takizawa et al., 2008, Takizawa et al., 2009), in addition to activation in the dorsolateral prefrontal cortex (Azechi et al., 2010, Kakimoto et al., 2009, Kameyama et al., 2004, Kameyama et al., 2006, Schecklmann et al., 2008, Suto et al., 2004, Takizawa et al., 2008, Takizawa et al., 2009). On the other hand, studies using functional magnetic resonance imaging (fMRI) have reported activity in the dorsolateral prefrontal cortex (Abrahams et al., 2003, Brammer et al., 1997, Curtis et al., 1998, Phelps et al., 1997) but not in the frontal pole. This might be due to defects in the frontal pole signals resulting from susceptibility effects in fMRI. However, other studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT), which are both unaffected by susceptibility effects, have also reported major activation in the left dorsolateral prefrontal cortex (Audenaert et al., 2000, Elfgren and Risberg, 1998, Hock et al., 1997, Ravnkilde et al., 2002) but no major activation in the frontal pole.

This marked discrepancy of results across imaging methods led us to hypothesize that the reported VFT-related NIRS signals measured on the forehead mostly reflected changes in skin blood flow rather than in the brain activation in the frontal pole. Because the NIRS optodes are placed on the forehead skin, the detected light is influenced not only by hemodynamic changes in the gray matter but also by changes in optical properties in all other tissue layers (i.e., scalp, skull, CSF, and white matter), especially through hemodynamic changes in the scalp layer (Kohno et al., 2007, Saager and Berger, 2008, Yamada et al., 2009, Zhang et al., 2007, Tachtsidis et al., 2008).

To test this hypothesis in the VFT, we measured NIRS signals and the Doppler tissue blood flow signal on the foreheads of 50 participants. The measurements were performed while each participant produced words in response to a letter cue during two 60-s periods. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance of 5 mm (NEAR channels) to measure NIRS signals that originated exclusively from surface tissues (Fukui et al., 2003, Hiraoka et al., 1993, Hoshi et al., 2005, Okada et al., 1997, Saager and Berger, 2008, Umeyama and Yamada, 2009, Yamada et al., 2009). We further investigated whether the FAR channel signals would disappear if hemodynamic changes in the scalp layer were suppressed by adding pressure to the skin. In this article, we show that task-related NIRS signals in the forehead can in large part be explained by changes in the skin blood flow.

Section snippets

Participants

Fifty healthy volunteers participated in this study (36 males and 14 females; age 18 to 50 years, median = 22 years). Four additional participants were tested but excluded from the analysis due to large artifacts. All participants were neurologically normal and naive to the task. The study received approval from the Institutional Review Board, and all participants provided written informed consent according to institutional guidelines.

Tasks

Each participant sat on a comfortable chair in an

Task-related NIRS and Doppler responses

A typical example of FAR-channel signals recorded from a single participant (Fig. 3, ch1–11) showed clear increases in ΔoxyHb (red) and small decreases in ΔdeoxyHb (blue) over all channels on the forehead during the two word-generation periods (shaded). In the present study, we examined ΔoxyHb, which reflects the blood flow more directly than ΔdeoxyHb (Hoshi et al., 2001). It is worth noting that the increase in the ΔoxyHb signal in the first block was approximately twice as large as the

Discussion

The purpose of this study was to demonstrate that VFT-related NIRS signals measured on the forehead mostly reflected changes in skin blood flow rather than brain activation in the frontal pole. We demonstrated that conventional NIRS signals measured in the FAR channels on the forehead with an optode separation distance of 30 mm showed remarkable a resemblance with three types of signals: NIRS signals in the NEAR channel with a short optode separation of 5 mm, the Doppler signal averaged with a

Conclusions

The results from 50 healthy participants showed a possibility that the majority of the changes in NIRS signals measured on the forehead during the letter-cued VFT would reflect task-related changes in skin blood flow that might be controlled by a local autonomic innervation in the forehead. Our results indicate that skin blood flow must be taken into account when NIRS is used for functional brain imaging in the task that would induce sympathetic hyperactivation.

The following are the

Acknowledgments

We are grateful to Yoko Hoshi, Shinji Umeyama, Qianqian Fang, Satoru Kohno and Toru Yamada for their discussion of the effects of optode distance on NIRS signals and to Akihiro Ishikawa for technical information services. The study was partly supported by Grants-in-Aid for Scientific Research (A) #21240029 to S. K., Grants-in-Aid for Exploratory Research #20650038 and #23650220 to T. T., and by a grant from the High-tech Research Center program (MEXT) at Juntendo University.

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