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Aim: To determine whether intrasubject reproducibility could be observed in the frontal cortex and to assess the mental-health status of subjects in each session.
Methods: We measured changes in oxygenated hemoglobin concentration ([oxy-Hb]) during a letter version of the verbal fluency task using near-infrared spectroscopy imaging in twenty healthy adults over two sessions approximately two months apart. Additionally, the mental-health status of the subjects in each session was evaluated according to the State–Trait Anxiety Inventory, the Zung Self-rating Depression Scale, the Profile of Mood States, and the revised edition of the Neuroticism–Extroversion–Openness Personality Inventory. The association between those scores and [oxy-Hb] changes during the verbal fluency task in each session was investigated.
Results: Performance on the verbal fluency task was about equal across the two sessions, and frontal activation during the task was observed globally in approximately the same region. In the test–retest reliability, acceptable values were shown in both the Intraclass Correlation Coefficients of the mean [oxy-Hb] changes and the correlation coefficients of the whole waveforms for each subject in the two sessions. Mental-health status as measured by several questionnaires was within the healthy range, and no correlation with the frontal activation was seen, except in several channels.
Conclusion: The current results suggest that the measurement experience exerted very little influence, except for in a very small region. In addition, the intrasubject reproducibility of frontal activation measured by multi-channel near-infrared spectroscopy was well demonstrated in mentally healthy subjects at intervals of two months.
NEAR-INFRARED SPECTROSCOPY (NIRS) is a non-invasive technique that measures changes in the relative hemoglobin concentration using near-infrared light.1 Near-infrared light at 700–1000 nm has a high transparency in a living body. Using this property, NIRS imaging can measure cortical function as assessed by the changes in cerebral oxygenated hemoglobin ([oxy-Hb]) and deoxygenated hemoglobin ([deoxy-Hb]) concentration.2–4
NIRS imaging has various advantages: near-infrared light is non-invasive and safe, NIRS has a high-time resolution of 0.1 s, and subjects can be examined under natural conditions in a sitting posture. Given these advantages, NIRS imaging has the potential to be applied to bedside monitoring of brain function in clinical settings. In fact, several studies have shown activation differences between healthy controls and patients with schizophrenia,5–7 mood disorder,5,8,9 post-traumatic stress disorder,10 panic disorder,11–13 and eating disorder.14 These investigations have revealed frontal dysfunction in psychiatric patients, and some studies have even shown differences in activation patterns by disorder. These studies are almost all of cross-sectional design. However, it is important for clinical applications to confirm inter-session variability in cerebral activation within individuals.
Several studies have reported multiple measurements of the cerebral cortex of healthy volunteers using NIRS. Sato et al.15 demonstrated sufficient within-subject reproducibility of the NIRS signal amplitude, the location of activation centers, and the time-course of activation for each subject in the sensorimotor cortex during a finger-tapping task at mean intervals of 6 months. Plichta et al.16 have also shown similar results in sensorimotor activation assessed by event-related design at intervals of 3 weeks.
Watanabe et al.17 examined the reproducibility of frontal activation during the word fluency task in five subjects at mean intervals of 6–7 months. This research concluded that the reliability of NIRS for these tasks was acceptable for use in clinical studies. Kono et al.18 also demonstrated the considerable replicability of [oxy-Hb] changes in the prefrontal cortex during a category version of the verbal fluency task over four repeated sessions at weekly intervals. Moreover, Schecklmann et al.19 confirmed the short- (3 weeks) and long-term (1 year) reliability of frontal function with a large sample. These previous studies have indicated acceptable reliability. In usual treatment, however, changes in the patient's condition are generally evaluated on a monthly basis. The test–retest reliability at intervals of several months has not been examined.
In this study, we measured the [oxy-Hb] changes during a letter version of the verbal fluency task using NIRS imaging in healthy adults over two sessions approximately two months apart to determine whether temporal changes could be observed in the frontal cortex. Additionally, past studies have not shown the mental-health status of subjects, although Schecklmann et al.19 proposed that the reduction of [oxy-Hb] changes in the second session could partly result from lower stress, arousal, and physiological activation. Thus, in the present study, the mental-health status of subjects in each session was described, and the association between the [oxy-Hb] changes during the verbal fluency task and the mental-health status in each session was investigated.
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The present study examined [oxy-Hb] changes during VFT using NIRS imaging in healthy adults over two repeated sessions, and the association between the [oxy-Hb] changes during the VFT and mental-health status in each session. The task performance of the VFT was about equal in the two sessions, and the frontal activation during the task was observed globally in approximately the same channels. The results in the present study replicated those of previous studies examining the reliability of multi-time measurements.15–19 These findings suggest that there may be little change in frontal activation during the VFT in healthy participants.
As for the results of the time-course analysis, no significant differences between the two sessions were obtained in several channels using the mean [oxy-Hb] change values during the entire period. However, the [oxy-Hb] changes during the task in the first session were larger than in the second session in the right superior frontal region. This finding could be explained by the fact that novelties are processed in the right frontal cortex, while cognitive practices are processed in the left prefrontal cortex.31 The [oxy-Hb] changes in the post-task periods in the first session were partly larger than in the second session in the anterior prefrontal region. It is difficult to explain the mechanism of the difference in the post-task periods. Two previous studies have indicated an [oxy-Hb] re-increase in the post-task period in patients with schizophrenia.5,7 There might be a possibility that the frontal activation pattern in the post-task period as well as during the task represents some kinds of individual states such as lower stress, arousal, and physiological activation as pointed out by Schecklmann et al.19
In test–retest reliability, acceptable values were shown in both the ICC of the mean [oxy-Hb] changes and the correlation coefficients of the whole waveforms for each subject in the two sessions. The ICC analyses indicate high reliability at the group and region of interest (ROI) but not at a single channel or single subject, as was repeatedly confirmed in previous studies.16,18,19 The time-course similarity of the activation waveforms across the session within each subject, as shown in Figure 2, revealed that the waveform pattern was similar in the two sessions. The temporal characteristics of frontal activation might distinguish between subjects, rather than reflect sensitivity to mental-health status.
In fact, the mental-health statuses as measured by the questionnaires did not correlate with frontal activation in most channels. This is partly because the questionnaire scores in the present subjects showed only a small variation within a normal range. These results suggest that small fluctuations in the mental health status of a healthy person might not affect the frontal activation. In a small region of the frontal cortex, however, the [oxy-Hb] changes were significantly correlated with subscores of the personality and mood scale. The present association between ‘Openness’ and ‘Extraversion’ in the NEO–PI–R (or NEO Five Factor Inventory [NEO-FFI]) and the function of the frontal cortex roughly confirms several previous results,32,33 and the present findings speculate that the frontal function might be related to personality. However, the significant associations between the scores in the questionnaires and [oxy-Hb] changes should be observed in both sessions if personality is associated with frontal activation. A correlation between these scores and the [oxy-Hb] changes was found in only one session in the present study, and thus our findings are tentative. We did not perform a multivariate analysis to examine the relationship among these factors in the present study, because each score in the questionnaires showed small variation within the healthy range, and was not significantly correlated with frontal function, as described above.
There are several limitations to this study. First, we performed NIRS investigations just twice. Second, for the sake of simplicity, we examined only young adults: a previous study has shown age-dependent differences in cerebral activation using NIRS.34 Third, we did not examine the variation of the [deoxy-Hb] changes excluded from the analysis. Finally, the problem of multiple comparisons might have led to an increase in the alpha error in the analysis of the time-course changes and the association between frontal activation and mental-health status.
In conclusion, the current results suggest that the measurement experience had very little influence, except for in a very small region of the brain, and that the intrasubject reproducibility of frontal activation measured by multi-channel NIRS was acceptably demonstrated in mentally healthy subjects at intervals of two months. Further studies addressing multiple repeated measurements at longer intervals, and investigating healthy subjects who exhibit high scores in the questionnaire in terms of their mental-health status are needed to clarify the variation of frontal activation in healthy adults.