A neural network model for development of reaching and pointing based on the interaction of forward and inverse transformations.

Pointing is one of the communicative actions that infants acquire during their first year of life. Based on a hypothesis that early pointing is triggered by emergent reaching behavior toward objects placed at out-of-reach distances, we proposed a neural network model that acquires reaching without explicit representation of 'targets'. The proposed model controls a two-joint arm in a horizontal plane, and it learns a loop of internal forward and inverse transformations; the former predicts the visual feedback of hand position and the latter generates motor commands from the visual input through random generation of the motor commands. In the proposed model, the motor output and visual input were represented by broadly tuned neural units. Even though explicit 'targets' were not presented during learning, the simulation successfully generated reaching toward visually presented objects at within-reach and out-of-reach distances.

Influence of Pleasant and Unpleasant Auditory Stimuli on Cerebral Blood Flow and Physiological Changes in Normal Subjects.

The prefrontal cortex (PFC) plays an important role in emotion and emotional regulation. The valence asymmetry hypothesis, proposes that the left/right asymmetry of the PFC activity is correlated with specific emotional responses to stressors. However, this hypothesis still seems to leave room for clarifying neurophysiological mechanisms. The purpose of the present study was to investigate the effects of stimuli with positive and negative valence sounds (hereafter PS, NS) selected from the International Affective Digitized Sounds-2 on physiological and physiological responses, including PFC activity in normal participants. We studied the effect of both stimuli using 12 normal subjects (mean age 26.8 years) on cerebral blood oxygenation in the bilateral PFC by a multi-channel NIRS, alpha wave appearance rate in theta, alpha, beta by EEG, autonomic nervous function by heart rate, and emotional conditions by the State-Trait Anxiety Inventory (STAI) and the visual analogue scale (VAS). PS was selected over 7.00 and NS were fewer than 3.00 in the Pleasure values. Sounds were recorded during 3 s and reproduced at random using software. Every task session was designed in a block manner: seven rests with Brown Noise (30 s) and six tasks (30 s) blocks. All participants performed each session in random order with eyes closed. A paired Student's t-test was used for comparisons (P<0.05). PFC activity showed increases bilaterally during both stimuli with a greater activation of the left side in PS and a tendency of more activation by NS in the right PFC. Significantly greater alpha wave intensity was obtained in PS. Heart rate tended to show smaller values in PS. The STAI level tended to show smaller values in PS, and a significantly greater VAS score was obtained in PS which indicated 'pleasant'. Despite the limitations of this study such as the low numbers of the subjects, the present study indicated that PS provided pleasant psychological and physiological responses and NS unpleasant responses. The PFC was activated bilaterally, implying a valence effect with the possibility of a dominant side.

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.

Relationships Between Gum-Chewing and Stress.

Studies have shown that chewing is thought to affect stress modification in humans. Also, studies in animals have demonstrated that active chewing of a wooden stick during immobilization stress ameliorates the stress-impaired synaptic plasticity and prevents stress-induced noradrenaline release in the amygdala. On the other hand, studies have suggested that the right prefrontal cortex (PFC) dominates the regulation of the stress response system, including the hypothalamic-pituitary-adrenal (HPA) axis. The International Affective Digitized Sounds-2 (IADS) is widely used in the study of emotions and neuropsychological research. Therefore, in this study, the effects of gum-chewing on physiological and psychological (including PFC activity measured by NIRS) responses to a negative stimulus selected from the IADS were measured and analyzed. The study design was approved by the Ethics Committee of Tokyo Dental College (No. 436). We studied 11 normal adults using: cerebral blood oxygenation in the right medial PFC by multi-channel NIRS; alpha wave intensity by EEG; autonomic nervous function by heart rate; and emotional conditions by the State-Trait Anxiety Inventory (STAI) test and the 100-mm visual analogue scale (VAS). Auditory stimuli selected were fewer than 3.00 in Pleasure value. Sounds were recorded in 3 s and reproduced at random using software. Every task session was designed in a block manner; seven rests: Brown Noise (30 s) and six task blocks: auditory stimuli or auditory stimuli with gum-chewing (30 s). During the test, the participants' eyes were closed. Paired Student's t-test was used for the comparison (P<0.05). Gum-chewing showed a significantly greater activation in the PFC, alpha wave appearance rate and HR. Gum-chewing also showed a significantly higher VAS score and a smaller STAI level indicating 'pleasant'. Gum-chewing affected physiological and psychological responses including PFC activity. This PFC activation change might influence the HPA axis and ANS activities. In summary, within the limitations of this study, the findings suggest that gum-chewing reduced stress-related responses. Gum-chewing might have a possible effect on stress coping.

A Computational Model for Aperture Control in Reach-to-Grasp Movement Based on Predictive Variability.

In human reach-to-grasp movement, visual occlusion of a target object leads to a larger peak grip aperture compared to conditions where online vision is available. However, no previous computational and neural network models for reach-to-grasp movement explain the mechanism of this effect. We simulated the effect of online vision on the reach-to-grasp movement by proposing a computational control model based on the hypothesis that the grip aperture is controlled to compensate for both motor variability and sensory uncertainty. In this model, the aperture is formed to achieve a target aperture size that is sufficiently large to accommodate the actual target; it also includes a margin to ensure proper grasping despite sensory and motor variability. To this end, the model considers: (i) the variability of the grip aperture, which is predicted by the Kalman filter, and (ii) the uncertainty of the object size, which is affected by visual noise. Using this model, we simulated experiments in which the effect of the duration of visual occlusion was investigated. The simulation replicated the experimental result wherein the peak grip aperture increased when the target object was occluded, especially in the early phase of the movement. Both predicted motor variability and sensory uncertainty play important roles in the online visuomotor process responsible for grip aperture control.

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.

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.

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.

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

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.

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.

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.