A NIRS-fMRI investigation of prefrontal cortex activity during a working memory task.

Near-infrared spectroscopy (NIRS) is commonly used for studying human brain function. However, several studies have shown that superficial hemodynamic changes such as skin blood flow can affect the prefrontal NIRS hemoglobin (Hb) signals. To examine the criterion-related validity of prefrontal NIRS-Hb signals, we focused on the functional signals during a working memory (WM) task and investigated their similarity with blood-oxygen-level-dependent (BOLD) signals simultaneously measured by functional magnetic resonance imaging (fMRI). We also measured the skin blood flow with a laser Doppler flowmeter (LDF) at the same time to examine the effect of superficial hemodynamic changes on the NIRS-Hb signals. Correlation analysis demonstrated that temporal changes in the prefrontal NIRS-Hb signals in the activation area were significantly correlated with the BOLD signals in the gray matter rather than those in the soft tissue or the LDF signals. While care must be taken when comparing the NIRS-Hb signal with the extracranial BOLD or LDF signals, these results suggest that the NIRS-Hb signal mainly reflects hemodynamic changes in the gray matter. Moreover, the amplitudes of the task-related responses of the NIRS-Hb signals were significantly correlated with the BOLD signals in the gray matter across participants, which means participants with a stronger NIRS-Hb response showed a stronger BOLD response. These results thus provide supportive evidence that NIRS can be used to measure hemodynamic signals originating from prefrontal cortex activation.

Emotional responses to music: towards scientific perspectives on music therapy.

Neurocognitive research has the potential to identify the relevant effects of music therapy. In this study, we examined the effect of music mode (major vs. minor) on stress reduction using optical topography and an endocrinological stress marker. In salivary cortisol levels, we observed that stressful conditions such as mental fatigue (thinking and creating a response) was reduced more by major mode music than by minor mode music. We suggest that music specifically induces an emotional response similar to a pleasant experience or happiness. Moreover, we demonstrated the typical asymmetrical pattern of stress responses in upper temporal cortex areas, and suggested that happiness/sadness emotional processing might be related to stress reduction by music.

High cognitive function of an ALS patient in the totally locked-in state.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of upper and lower motor neurons. Patients with ALS progressively lose their ability to control voluntary movements and occasionally enter the totally locked-in state (TLS), in which they cannot move any part of their bodies including the eyes. In this study, we clarified the preserved abilities and reorganization of the motor system of a 73-year-old patient with ALS in the TLS using optical topography, a recently developed extension of near-infrared spectroscopy. The patient performed four cognitive tasks: dichotic listening, covert singing, word fluency, and motor imagery. The bilateral prefrontal and bilateral sensorimotor areas were activated during the two language-related tasks (dichotic listening task and the word fluency), the right prefrontal and sensorimotor areas during the covert singing task, and the right prefrontal and dorsal sensorimotor areas during the motor imagery task. Contralateral sensorimotor activation was not observed in the motor imagery task. These results suggest that cognitive functions can be preserved in ALS in the TLS, with sensorimotor areas playing an important role.

Cortical responses to Mozart's sonata enhance spatial-reasoning ability.

OBJECTIVE: In this study, we examined the effects of Mozart's music on spatial-reasoning ability by near-infrared spectroscopy (NIRS). METHODS: The subjects comprised five males and five females (aged 25-35 years). They were administered the seven original core subtests of the Japanese version of the Tanaka B-type intelligence test, which includes a spatial-reasoning subtest. We used three different music conditions: Mozart's sonata (K. 448), Beethoven and a silent control condition. Moreover, we used optical topography to assess the effects of music on brain function with a spatial-reasoning subtest. RESULTS: We found that exposure to Mozart's sonata enhanced cognitive performance in intelligence tests when compared with results obtained upon exposure to Beethoven or silence. In addition to the expected temporal cortex activation, we report dramatic results revealing differences in activation in the dorsolateral prefrontal cortex and the occipital cortex, both of which are expected to be important for spatial-temporal reasoning. DISCUSSION: We suggest the possibility of a direct priming effect being responsible for preferential activation, and open the door to understanding the potential effects of Mozart's music.

Ethical considerations of neuroscience research: the perspectives on neuroethics in Japan.

Recent technologies and developments in neuroscience have contributed to remarkable scientific discoveries, and have also raised many new philosophical, ethical, legal, and social issues. Research in "neuroethics" has identified various ethical issues, which will be difficult for current biomedical ethics to resolve from both an experimental and a social perspective, such as criminal applications of brain scans, incidental findings during non-clinical brain imaging, and cognitive enhancement. Although American and European neuroscience societies have demonstrated immediate, concrete reactions to these ethical issues, including academic conferences, study programs, and publications, Japanese neuroscientists have so far produced little response. Ethics is tightly linked with one's religion, nationality, culture, and social background, whereas science is tightly linked with the demand, economics, and politics of the society to which individuals belong. Taken together, it is important and necessary for Japanese neuroscientists to consider the ethical problems in Japanese neuroscience. In this paper, we first review the history of neuroethics in the world, and then report the less-developed ethical issues in the Japanese neuroscience community, focusing on neuroimaging and manipulative neuroscience as a first step in discussing how to apply principles in neuroethics to this rapidly progressing field of research.

Comparison of light intensity on the brain surface due to laser exposure during optical topography and solar irradiation.

Optical topography (OT), which is based on the near-infrared spectroscopy, is a powerful tool for observing brain activity noninvasively. To estimate the effect of laser exposure on the brain, photon-distribution profiles in bald heads of adults and neonates during the OT were calculated using the photon-diffusion equation. These calculations showed that although the absolute values of the intensity depend on details of the head model, the relative values of OT exposure to sunlight exposure were less sensitive to the model details. As an example, the light intensities on the brain surface during OT obtained by using a commercially available system were about 2% for adults and 3% for neonates of those values obtained under midday sunlight on a sunny day in midsummer. These values were obtained under the reasonable assumptions with a large safety factor.

Within-subject reproducibility of near-infrared spectroscopy signals in sensorimotor activation after 6 months.

Near-infrared spectroscopy (NIRS) can measure the product of the optical path length and the concentration change in oxygenated hemoglobin (DeltaC'oxy), deoxygenated hemoglobin (DeltaC'deoxy), and their sum (DeltaC'total) in the human cerebral cortex, and it has been used for noninvasive investigation of human brain functions. We evaluate the within-subject reproducibility of the NIRS signals by repeated measurement of the sensorimotor cortex in healthy adults taken over a period of about 6 months using near-infrared (NIR) topography. The maximum signal amplitudes and the location of activation centers are compared between two sessions for each subject. The signal amplitudes vary between sessions and no consistent tendency in the changes is found among subjects. However, the distance between the activation centers identified in two sessions is relatively small, within 20 mm on average across subjects, which is comparable to the smallest distance between measurement positions in the NIR topography (21 mm). Moreover, within-subject comparisons of signal time courses show high correlation coefficients (>0.8) between the two sessions. This result, demonstrating a high within-subject reproducibility of the temporal information in NIRS signals, particularly contributes to the development of a new application of NIRS.

Intersubject variability of near-infrared spectroscopy signals during sensorimotor cortex activation.

We investigate the intersubject signal variability of near-infrared spectroscopy (NIRS), which is commonly used for noninvasive measurement of the product of the optical path length and the concentration change in oxygenated hemoglobin (DeltaC'oxy) and deoxygenated hemoglobin (DeltaC'deoxy) and their sum (DeltaC'total) related to human cortical activation. We do this by measuring sensorimotor cortex activation in 31 healthy adults using 24-measurement-position near-infrared (NIR) topography. A finger-tapping task is used to activate the sensorimotor cortex, and significant changes in the hemisphere contralateral to the tapping hand are assessed as being due to the activation. Of the possible patterns of signal changes, 90% include a positive DeltaC'oxy, 76% included a negative DeltaC'deoxy, and 73% included a positive DeltaC'total. The DeltaC'deoxy and DeltaC'total are less consistent because of a large intersubject variability in DeltaC'deoxy; in some cases there is a positive DeltaC'deoxy. In the cases with no positive DeltaC'oxy in the contralateral hemisphere, there are cases of other possible changes for either or both hemispheres and no cases of no change in any hemoglobin species in either hemisphere. These results suggest that NIR topography is useful for observing brain activity in most cases, although intersubject signal variability still needs to be resolved.

Effects of alcohol on hemodynamic and cardiovascular reaction in different genotypes.

This study assessed hemodynamic changes associated with alcohol intake in people who have different sensitivities to alcohol due to an inactive form of mitochondrial aldehyde dehydrogenase (ALDH). People with ALDH2*1/*2 are more sensitive to alcohol than people with ALDH2*1/*1. Six ALDH2*1/*1 subjects and four ALDH2*1/*2 subjects participated in this study. The subjects drank whisky with water (0.4 ml/kg of ethanol). Optical topography (Hitachi Medical Corporation: ETG-100) was used to measure hemodynamic changes in an occipital region during visual stimulation. Hemodynamic changes, heart rate, mean blood pressure, and reaction time were measured 20 min before, immediately after, and 20, 40, and 60 min after alcohol intake. Breath-alcohol concentration was measured at each of the assessment points. After alcohol intake, the hemodynamic peak value, peak time, reaction time, and heart rate of the ALDH2*1/*2 subjects differed from those of the ALDH2*1/*1 subjects. The hemodynamic peak value and reaction time gradually increased 60 min after alcohol exposure, and the peak time was shortest 20 min after alcohol intake. These results might reflect different acetaldehyde levels causing changes in the reactivity of the vascular smooth muscle and cerebral activity in the visual cortex.

Concurrent fNIRS-fMRI measurement to validate a method for separating deep and shallow fNIRS signals by using multidistance optodes.

It has been reported that a functional near-infrared spectroscopy (fNIRS) signal can be contaminated by extracerebral contributions. Many algorithms using multidistance separations to address this issue have been proposed, but their spatial separation performance has rarely been validated with simultaneous measurements of fNIRS and functional magnetic resonance imaging (fMRI). We previously proposed a method for discriminating between deep and shallow contributions in fNIRS signals, referred to as the multidistance independent component analysis (MD-ICA) method. In this study, to validate the MD-ICA method from the spatial aspect, multidistance fNIRS, fMRI, and laser-Doppler-flowmetry signals were simultaneously obtained for 12 healthy adult males during three tasks. The fNIRS signal was separated into deep and shallow signals by using the MD-ICA method, and the correlation between the waveforms of the separated fNIRS signals and the gray matter blood oxygenation level-dependent signals was analyzed. A three-way analysis of variance ([Formula: see text]) indicated that the main effect of fNIRS signal depth on the correlation is significant [[Formula: see text], [Formula: see text]]. This result indicates that the MD-ICA method successfully separates fNIRS signals into spatially deep and shallow signals, and the accuracy and reliability of the fNIRS signal will be improved with the method.

Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke: a comparison with functional MRI.

BACKGROUND AND PURPOSE: Motor functional recovery from stroke can occur, but the mechanisms underlying this restorative process remain to be elucidated. We used near-infrared spectroscopic (NIRS) topography in comparison with functional MRI (fMRI) to evaluate the compensatory motor activation of cortical regions in patients who recovered from hemiparesis after cortical cerebral infarction. METHODS: We examined 6 right-handed patients who suffered cerebral infarction of the middle cerebral artery territory with minimal or mild residual contralateral hemiparesis (4 men and 2 women, 59 to 79 years old, all had left hemiparesis). Both fMRI and NIRS were studied during a hand movement task at chronic stages. Five right-handed, normal subjects (3 men and 2 women, 44 to 81 years old) served as controls. RESULTS: fMRI and NIRS detected very similar cerebral cortical activation, although NIRS detected only superficial activation. The spatial resolution of NIRS was less than that of fMRI, but NIRS provided a dynamic profile of activation. Normal subjects activated predominantly the contralateral primary sensorimotor cortex and supplementary motor areas during each hand movement. All the stroke patients exhibited the normal activation pattern during normal hand movement. On affected hand movement, the stroke patients showed extended activation not only in the contralateral motor cortex but also in the ipsilateral motor cortex (primary motor cortex and supplementary motor areas). CONCLUSIONS: Both fMRI and NIRS studies provided evidence for the contribution of ipsilateral motor cortical compensation or reorganization to the recovery from poststroke hemiparesis. The result demonstrated that NIRS was a unique tool to monitor poststroke alterations in cortical motor functions.

Arranging optical fibres for the spatial resolution improvement of topographical images.

Optical topography is a method for visualization of conical activity. Ways of improving the spatial resolution of the topographical image with three arrangements of optical fibres are discussed. A distribution of sensitivity is obtained from the phantom experiment, and used to reconstruct topographical images of an activation area of the brain with the fibres in each arrangement. The correlations between the activated area and the corresponding topographical images are obtained, and the effective arrangement of the optical fibres for improved resolution is discussed.

Acute effects of alcohol on hemodynamic changes during visual stimulation assessed using 24-channel near-infrared spectroscopy.

The purpose of this study was to evaluate the effects of alcohol on hemodynamic changes induced by visual stimulation. Ten healthy human subjects were examined using Optical Topography((R)) (Hitachi Medical Corporation: ETG-100). Each subject gradually drank 0.4 ml/kg alcohol over 10 min. Changes in oxy-hemoglobin (Hb), deoxy-Hb and total-Hb concentration were measured five times: 20 min before alcohol intake, immediately after alcohol intake, and at 20, 40 and 60 min after alcohol intake. A questionnaire was used to assess subjective feelings of alcohol. Blood-alcohol concentration (BAC) was estimated from ethanol concentration in expired air four times: immediately after alcohol intake and at 20, 40 and 60 min after alcohol intake. The visual stimulation tool was a checkerboard. It showed alternations of black and red patterns at a frequency of 8 Hz. The stimulus was displayed for 10 s after a rest of 30 s. The stimulus was repeated 10 times. Oxy-Hb concentration increased and deoxy-Hb concentration decreased during visual stimulation before and after alcohol intake, despite changes in the score of subjective feelings of alcohol and BAC. Alcohol intake does not significantly affect hemodynamic changes caused by visual stimulation in the visual cortex.

The concept of 'developing the brain': a new natural science for learning and education.

From the viewpoint of biology, learning and education can be defined as the processes of forming neuronal connections in response to external environmental stimuli, and of controlling or adding appropriate stimuli, respectively. Learning and education can thus be studied as a new field of natural sciences with the entire human life span as its subject, thus including various problems such as fetal environment, childcare, language acquisition, general/special education, and rehabilitation. Non-invasive imaging of higher-order brain functions in humans will clarify the brain's developmental processes, and will provide various evidence for learning sciences. This new approach is called 'developing the brain' or 'brain science and education'. The origin of the concept and its present state are described and its future prospects are briefly analyzed.

Correlation between prefrontal cortex activity during working memory tasks and natural mood independent of personality effects: an optical topography study.

Interactions between mood and cognition have drawn much attention in the fields of psychology and neuroscience. Recent neuroimaging studies have examined a neural basis of the mood-cognition interaction that which emphasize the role of the prefrontal cortex (PFC). Although these studies have shown that natural mood variations among participants are correlated with PFC activity during cognitive tasks, they did not control for personality differences. Our aim in this study was to clarify the relationship between natural mood and PFC activity by partialling out the effects of personality. Forty healthy adults completed self-report questionnaires assessing natural mood (the Profile of Mood States) and personality (the NEO Five-Factor Inventory and the Behavioral Inhibition/Activation Systems scales). They performed verbal and spatial working memory (WM) tasks while their PFC activity was measured using optical topography, a non-invasive, low-constraint neuroimaging tool. Correlation analysis showed that the level of negative mood was inversely associated with PFC activity during the verbal WM task, which replicated our previous findings. Furthermore, the negative correlation between negative mood and PFC activity remained significant after controlling for participants' personality traits, suggesting that natural mood is an independent contributing factor of PFC activity during verbal WM tasks.

Simultaneous measurement of neuronal activity and cortical hemodynamics by unshielded magnetoencephalography and near-infrared spectroscopy.

The correlation between neuronal activity and cortical hemodynamics, namely, neurovascular coupling (NVC), is important to shed light on the mechanism of a variety of brain functions or neuronal diseases. NVC can be studied by simultaneously measuring neuronal activity and cortical hemodynamics. Consequently, noninvasive measurements of the NVC have been widely studied using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, electromagnetic interference between EEG and fMRI is still a major problem. On the other hand, near-infrared spectroscopy (NIRS) is another promising tool for detecting cortical hemodynamics because it can be combined with EEG or magnetoencephalography (MEG) without any electromagnetic interference. Accordingly, in the present study, a simultaneous measurement system-combining an unshielded MEG using a two-dimensional gradiometer based on a low-Tc superconducting quantum interference device (SQUID) and an NIRS using nonmagnetic thin probes-was developed. This combined system was used to simultaneously measure both an auditory-evoked magnetic field and blood flow change in the auditory cortex. It was experimentally demonstrated that the combined unshielded MEG/NIRS system can simultaneously measure neuronal activity and cortical hemodynamics.

Correlation of within-individual fluctuation of depressed mood with prefrontal cortex activity during verbal working memory task: optical topography study.

Previous studies showed that interindividual variations in mood state are associated with prefrontal cortex (PFC) activity. In this study, we focused on the depressed-mood state under natural circumstances and examined the relationship between within-individual changes over time in this mood state and PFC activity. We used optical topography (OT), a functional imaging technique based on near-infrared spectroscopy, to measure PFC activity for each participant in three experimental sessions repeated at 2-week intervals. In each session, the participants completed a self-report questionnaire of mood state and underwent OT measurement while performing verbal and spatial working memory (WM) tasks. The results showed that changes in the depressed-mood score between successive sessions were negatively correlated with those in the left PFC activation for the verbal WM task (ρ = -0.56, p < 0.05). In contrast, the PFC activation for the spatial WM task did not co-vary with participants' mood changes. We thus demonstrated that PFC activity during a verbal WM task varies depending on the participant's depressed mood state, independent of trait factors. This suggests that using optical topography to measure PFC activity during a verbal WM task can be used as a potential state marker for an individual's depressed mood state.

Synchronous activity of two people's prefrontal cortices during a cooperative task measured by simultaneous near-infrared spectroscopy.

The brain activity during cooperation as a form of social process is studied. We investigate the relationship between coinstantaneous brain-activation signals of multiple participants and their cooperative-task performance. A wearable near-infrared spectroscopy (NIRS) system is used for simultaneously measuring the brain activities of two participants. Each pair of participants perform a cooperative task, and their relative changes in cerebral blood are measured with the NIRS system. As for the task, the participants are told to count 10 s in their mind after an auditory cue and press a button. They are also told to adjust the timing of their button presses to make them as synchronized as possible. Certain information, namely, the "intertime interval" between the two button presses of each participant pair and which of the participants was the faster, is fed back to the participants by a beep sound after each trial. When the spatiotemporal covariance between the activation patterns of the prefrontal cortices of each participant is higher, the intertime interval between their button-press times was shorter. This result suggests that the synchronized activation patterns of the two participants' brains are associated with their performance when they interact in a cooperative task.

Application of near-infrared spectroscopy to measurement of hemodynamic signals accompanying stimulated saliva secretion.

We aim to test the feasibility of using near-infrared spectroscopy (NIRS) for indirect measurement of human saliva secretion in response to taste stimuli for potential application to organoleptic testing. We use an NIRS system to measure extracranial hemodynamics (Hb-signals around the temples) of healthy participants when taste stimuli are taken in their mouths. First, the Hb-signals and volume of expelled saliva (stimulated by distilled-water or sucrose-solution intake) are simultaneously measured and large Hb-signal changes in response to the taste stimuli (Hb-responses) are found. Statistical analysis show that both the Hb response and saliva volume are larger for the sucrose solution than for the distilled water with a significant correlation between them (r = 0.81). The effects of swallowing on the Hb-signals are investigated. Similar Hb responses, differing from the sucrose solution and distilled water, are obtained even though the participants swallow the mouth contents. Finally, functional magnetic resonance imaging is used to identify possible sources of the Hb signals corresponding to salivation. Statistical analysis indicates similar responses in the extracranial regions, mainly around the middle meningeal artery. In conclusion, the identified correlation between extracranial hemodynamics and the saliva volume suggests that NIRS is applicable to the measurement of hemodynamic signals accompanying stimulated saliva secretion.