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.

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 leftdominant 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.

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.

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.

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.