Naohiro Takemura

Correlation between asymmetry of spontaneous oscillation of hemodynamic changes in the prefrontal cortex and anxiety levels: a near-infrared spectroscopy study

Abstract. According to the valence asymmetry hypothesis, the left/right asymmetry of prefrontal cortex (PFC) activity is correlated with specific emotional responses to mental stress and personality traits. Here, we evaluated the relation between emotional state and asymmetry in PFC activity at rest by using near-infrared spectroscopy (NIRS). We measured spontaneous oscillation of oxyhemoglobin (oxy-Hb) concentrations in the bilateral PFC at rest in normal adults employing two-channel NIRS. In order to analyze left/right asymmetry of PFC activity at rest, we calculated the laterality index at rest (LIR) (see text). We investigated the correlation between the LIR and anxiety levels evaluated by the State-Trait Anxiety Inventory (STAI) test. We found that the right PFC was more active at rest than the left PFC, corresponding to a higher anxiety level measured by the STAI; that is, subjects with right-dominant activity at rest showed higher STAI scores, while those with left-dominant oxy-Hb changes at rest showed lower STAI scores. Aging had no significant effect on the relation. The present results obtained by NIRS are consistent with the valence asymmetry hypothesis. We emphasize NIRS may be a useful tool for objective assessment of anxiety levels.

Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions

Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

Ginkobiloba Extract Improves Working Memory Performance in Middle-Aged Women: Role of Asymmetry of Prefrontal Cortex Activity During a Working Memory Task

In order to clarify the mechanism through which extract of Ginkgo biloba leaves (EGb) improves cognitive function, we examined the effects of EGb on cerebral blood oxygenation in the prefrontal cortex (PFC) and on performance during a working memory task, using near-infrared spectrometry (NIRS). First, we evaluated differences in behavioral performance of the Sternberg working memory test (ST) and in the activation pattern of the PFC during ST between 15 young and 19 middle-aged healthy women. Then, we examined the effect of EGb (120 mg/day for 6 weeks) on ST performance and PFC activation pattern in the middle-aged group. The middle-aged group exhibited a longer reaction time (RT) in ST than the young group and showed a different PFC activation pattern during ST, i.e., the middle-aged group showed bilateral activation while the young group showed right-dominant activation. In the middle-aged group, administration of EGb for 6 weeks shortened the RT of ST and changed the PFC activation pattern to right-dominant, like that in the young group. The results indicate the PFC plays a role in the physiological cognitive function-enhancing effect of EGb. EGb might improve working memory function in middle-aged individuals by counteracting the occurrence of aging-related hemispheric asymmetry reduction.

Effects of Acupuncture on Anxiety Levels and Prefrontal Cortex Activity Measured by Near-Infrared Spectroscopy: A Pilot Study.

There is increasing evidence that acupuncture is useful in treating somatic and psychological disorders caused by stress; however, the physiological basis of the effect remains unclear. In the present study, we evaluated the effect of acupuncture on psychological conditions (i.e., anxiety) and prefrontal cortex (PFC) activity. We studied 10 patients with anxiety disorders and measured anxiety levels by means of the State-Trait Anxiety Inventory (STAI), including state anxiety (STAI-1) and trait anxiety (STAI-2). Employing a two-channel NIRS device, we measured oxy-Hb concentration in the bilateral PFC at rest, and evaluated asymmetry of the PFC activity by calculating the Laterality Index at Rest (LIR). The patients were treated by acupuncture at Yui Clinic in Osaka. The treatment significantly decreased the STAI-1 score (p<0.001), but not the STAI-2 score (p>0.05). The NIRS measurements indicated the presence of spontaneous oscillations of oxy-Hb in the bilateral PFC at rest before and after the treatment. Notably LIR decreased significantly in 7 out of the 10 subjects (p<0.01), while 3 subjects showed an increasing tendency. The present pilot study indicates that acupuncture is effective in decreasing anxiety levels in patients with anxiety disorders. Our NIRS data suggest that acupuncture may alter the balance of PFC activity at rest, resulting in relaxation effects. Our NIRS data suggest that acupuncture changes the balance of PFC activity toward left-dominant, resulting in relaxation effects on the patients.

Bayesian prediction of anxiety level in aged people at rest using 2-channel NIRS data from prefrontal cortex.

The aim of this study was to predict mental stress levels of aged people at rest from two-channel near-infrared spectroscopy (NIRS) data from the prefrontal cortex (PFC). We used the State-Trait Anxiety Inventory (STAI) for the mental stress index.We previously constructed a machine learning algorithm to predict mental stress level using two-channel NIRS data from the PFC in 19 subjects aged 20-24 years at rest (Sato et al., Adv Exp Med Biol 765:251-256, 2013). In the present study, we attempted the same prediction for aged subjects aged 61-79 years (10 women; 7 men). The mental stress index was again STAI. After subjects answered the STAI questionnaire, the NIRS device measured oxy- and deoxy-hemoglobin concentration changes during a 3-min resting state. The algorithm was formulated within a Bayesian machine learning framework and implemented by Markov Chain Monte Carlo. Leave-one-subject-out cross-validation was performed.Average prediction error between the actual and predicted STAI values was 5.27. Prediction errors of 12 subjects were lower than 5.0. Since the STAI score ranged from 20 to 80, the algorithm appeared functional for aged subjects also.

New method of analyzing NIRS data from prefrontal cortex at rest.

The aim of this study was to develop a simple technique for objective assessment of mental stress levels by measuring hemoglobin concentration changes in the bilateral prefrontal cortex (PFC) at rest, employing two-channel near-infrared spectroscopy (NIRS). Each subject was instructed to think about nothing in particular for 3 min and then to complete the State-Trait Anxiety Inventory (STAI) test. Next, NIRS measurements were taken and the left/right asymmetry of PFC activity at rest was evaluated by calculating the proposed Laterality Index at Rest (LIR). There was a significant positive correlation between the LIR and STAI score in 39 subjects. The present method allowed evaluation of mental stress level from NIRS data in the PFC at rest.

A Bayesian Algorithm for Anxiety Index Prediction Based on Cerebral Blood Oxygenation in the Prefrontal Cortex Measured by Near Infrared Spectroscopy

Stress-induced psychological and somatic diseases are virtually endemic nowadays. Written self-report anxiety measures are available; however, these indices tend to be time consuming to acquire. For medical patients, completing written reports can be burdensome if they are weak, in pain, or in acute anxiety states. Consequently, simple and fast non-invasive methods for assessing stress response from neurophysiological data are essential. In this paper, we report on a study that makes predictions of the state-trait anxiety inventory (STAI) index from oxyhemoglobin and deoxyhemoglobin concentration changes of the prefrontal cortex using a two-channel portable near-infrared spectroscopy device. Predictions are achieved by constructing machine learning algorithms within a Bayesian framework with nonlinear basis function together with Markov Chain Monte Carlo implementation. In this paper, prediction experiments were performed against four different data sets, i.e., two comprising young subjects, and the remaining two comprising elderly subjects. The number of subjects in each data set varied between 17 and 20 and each subject participated only once. They were not asked to perform any task; instead, they were at rest. The root mean square errors for the four groups were 6.20, 6.62, 4.50, and 6.38, respectively. There appeared to be no significant distinctions of prediction accuracies between age groups and since the STAI are defined between 20 and 80, the predictions appeared reasonably accurate. The results indicate potential applications to practical situations such as stress management and medical practice.

Gender and Age Analyses of NIRS/STAI Pearson Correlation Coefficients at Resting State

According to the valence asymmetry hypothesis, the left/right asymmetry of PFC activity is correlated with specific emotional responses to mental stress and personality traits. In a previous study we measured spontaneous oscillation of oxy-Hb concentrations in the bilateral PFC at rest in normal adults employing two-channel portable NIRS and computed the laterality index at rest (LIR). We investigated the Pearson correlation coefficient between the LIR and anxiety levels evaluated by the State-Trait Anxiety Inventory (STAI) test. We found that subjects with right-dominant activity at rest showed higher STAI scores, while those with left dominant oxy-Hb changes at rest showed lower STAI scores such that the Pearson correlation coefficient between LIR and STAI was positive. This study performed Bootstrap analysis on the data and showed the following statistics of the target correlation coefficient: mean=0.4925 and lower confidence limit=0.177 with confidence level 0.05. Using the KS-test, we demonstrated that the correlation did not depend on age, whereas it did depend on gender.

Physiological Mechanism of Increase in Deoxy-hemoglobin Concentration During Neuronal Activation in Patients with Cerebral Ischemia: A Simulation Study with the Balloon Model

Patients with cerebral ischemia or brain tumor have been reported to exhibit an increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying this hemodynamic response pattern are unclear. In this study, we performed a simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864, 1998). We hypothesized that the oxygen extraction rate during the rest period (E 0) in the patients is larger than in normal subjects, because the cerebral blood flow and the speed at which the blood passes through the brain tissues are lower in the patients. The simulation result showed an increase of deoxy-Hb as well as oxy-Hb, especially when E 0 is extremely high. Thus, the results of our simulation suggest that the increase of deoxy-Hb during activation in patients with ischemia or brain tumor is caused by an increased oxygen extraction rate at rest, compared with that of healthy adults.