Cerebral hemodynamics in newborn infants exposed to speech sounds: a whole-head optical topography study.

Considerable knowledge on neural development related to speech perception has been obtained by functional imaging studies using near-infrared spectroscopy (optical topography). In particular, a pioneering study showed stronger left-dominant activation in the temporal lobe for (normal) forward speech (FW) than for (reversed) backward speech (BW) in neonates. However, it is unclear whether this stronger left-dominant activation for FW is equally observed for any language or is clearer for the mother tongue. We hypothesized that the maternal language elicits clearer activation than a foreign language in newborns because of their prenatal and/or few-day postnatal exposure to the maternal language. To test this hypothesis, we developed a whole-head optode cap for 72-channel optical topography and visualized the spatiotemporal hemodynamics in the brains of 17 Japanese newborns when they were exposed to FW and BW in their maternal language (Japanese) and in a foreign language (English). Statistical analysis showed that all sound stimuli together induced significant activation in the bilateral temporal regions and the frontal region. They also showed that the left temporal-parietal region was significantly more active for Japanese FW than Japanese BW or English FW, while no significant difference between FW and BW was shown for English. This supports our hypothesis and suggests that the few-day-old brain begins to become attuned to the maternal language. Together with a finding of equivalent activation for all sound stimuli in the adjacent measurement positions in the temporal region, these findings further clarify the functional organization of the neonatal brain.

Quantification of systemic interference in optical topography data during frontal lobe and motor cortex activation: an independent component analysis.

Functional near-infrared optical topography (OT) is used to non-invasively measure the changes in oxygenated and deoxygenated haemoglobin (Δ[HbO2], Δ[HHb]) and hence investigate the brain haemodynamic changes, which occur in response to functional activation at specific regions of the cerebral cortex. However, when analysing functional OT data the task-related systemic changes should be taken into account.Here we used an independent component analysis (ICA) method on the OT [HbO2] signal, to determine the task-related independent components and then compared them with the systemic measurements (blood pressure, heart rate, scalp blood flow) to assess whether the components are due to systemic noise or neuronal activation. This analysis can therefore extract the true OT haemodynamic neuronal response and hence discriminate between regional activated cortical areas and global haemodynamic changes.

Visualizing Neuropharmacological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder Using Functional Near-Infrared Spectroscopy.

Objective: In the current study, we explored the neural substrate for acute effects of guanfacine extended release (GXR) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD), using functional near-infrared spectroscopy (fNIRS). Methods: Following a GXR washout period, 12 AD HD children (6-10 years old) performed a go/no-go task before and 3 h after GXR or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design study. In the primary analysis, fNIRS was used to monitor the right prefrontal cortical hemodynamics of the participants, where our former studies showed consistent dysfunction and osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine hydrochloride (ATX) elicited recovery. We examined the inter-medication contrast, comparing the effect of GXR against the placebo. In the exploratory analysis, we explored neural responses in regions other than the right prefrontal cortex (PFC). Results: In the primary analysis, we observed no significant main effects or interactions of medication type and age in month (two-way mixed ANCOVA, Fs < 0.20, all ps > .05). However, in the post-hoc analysis, we observed significant change in the oxy-Hb signal in the right angular gyrus (AG) for inter-medication (one sample t-test, p < 0.05, uncorrected, Cohen's d = 0.71). Conclusions: These results are different from the neuropharmacological effects of OROS-MPH and ATX, which, in an upregulated manner, reduced right PFC function in ADHD children during inhibitory tasks. This analysis, while limited by its secondary nature, suggested that the improved cognitive performance was associated with activation in the right AG, which might serve as a biological marker to monitor the effect of GXR in the ADHD children.

Atypical Dynamic-Connectivity Recruitment in Attention-Deficit/Hyperactivity Disorder Children: An Insight Into Task-Based Dynamic Connectivity Through an fNIRS Study.

Connectivity between brain regions has been redefined beyond a stationary state. Even when a person is in a resting state, brain connectivity dynamically shifts. However, shifted brain connectivity under externally evoked stimulus is still little understood. The current study, therefore, focuses on task-based dynamic functional-connectivity (FC) analysis of brain signals measured by functional near-infrared spectroscopy (fNIRS). We hypothesize that a stimulus may influence not only brain connectivity but also the occurrence probabilities of task-related and task-irrelevant connectivity states. fNIRS measurement (of the prefrontal-to-inferior parietal lobes) was conducted on 21 typically developing (TD) and 21 age-matched attention-deficit/hyperactivity disorder (ADHD) children performing an inhibitory control task, namely, the Go/No-Go (GNG) task. It has been reported that ADHD children lack inhibitory control; differences between TD and ADHD children in terms of task-based dynamic FC were also evaluated. Four connectivity states were found to occur during the temporal task course. Two dominant connectivity states (states 1 and 2) are characterized by strong connectivities within the frontoparietal network (occurrence probabilities of 40%-56% and 26%-29%), and presumptively interpreted as task-related states. A connectivity state (state 3) shows strong connectivities in the bilateral medial frontal-to-parietal cortices (occurrence probability of 7-15%). The strong connectivities were found at the overlapped regions related the default mode network (DMN). Another connectivity state (state 4) visualizes strong connectivities in all measured regions (occurrence probability of 10%-16%). A global effect coming from cerebral vascular may highly influence this connectivity state. During the GNG stimulus interval, the ADHD children tended to show decreased occurrence probability of the dominant connectivity state and increased occurrence probability of other connectivity states (states 3 and 4). Bringing a new perspective to explain neuropathophysiology, these findings suggest atypical dynamic network recruitment to accommodate task demands in ADHD children.

Distinct Methylphenidate-Evoked Response Measured Using Functional Near-Infrared Spectroscopy During Go/No-Go Task as a Supporting Differential Diagnostic Tool Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Comorbid Children.

Attention deficit/hyperactivity disorder (ADHD) has been frequently reported as co-occurring with autism spectrum disorder (ASD). However, ASD-comorbid ADHD is difficult to diagnose since clinically significant symptoms are similar in both disorders. Therefore, we propose a classification method of differentially recognizing the ASD-comorbid condition in ADHD children. The classification method was investigated based on functional brain imaging measured by near-infrared spectroscopy (NIRS) during a go/no-go task. Optimization and cross-validation of the classification method was carried out in medicated-naïve and methylphenidate (MPH) administered ADHD and ASD-comorbid ADHD children (randomized, double-blind, placebo-controlled, and crossover design) to select robust parameters and cut-off thresholds. The parameters could be defined as either single or averaged multi-channel task-evoked activations under an administration condition (i.e., pre-medication, post-MPH, and post-placebo). The ADHD children were distinguished by significantly high MPH-evoked activation in the right hemisphere near the midline vertex. The ASD-comorbid ADHD children tended to have low activation responses in all regions. High specificity (86 ± 4.1%; mean ± SD), sensitivity (93 ± 7.3%), and accuracy (82 ± 1.6%) were obtained using the activation of oxygenated-hemoglobin concentration change in right middle frontal, angular, and precentral gyri under MPH medication. Therefore, the significantly differing MPH-evoked responses are potentially effective features and as supporting differential diagnostic tools.

Exploring attentive task-based connectivity for screening attention deficit/hyperactivity disorder children: a functional near-infrared spectroscopy study.

Connectivity impairment has frequently been associated with the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Although the connectivity of the resting state has mainly been studied, we expect the transition between baseline and task may also be impaired in ADHD children. Twenty-three typically developing (i.e., control) and 36 disordered (ADHD and autism-comorbid ADHD) children were subjected to connectivity analysis. Specifically, they performed an attention task, visual oddball, while their brains were measured by functional near-infrared spectroscopy. The results of the measurements revealed three key findings. First, the control group maintained attentive connectivity, even in the baseline interval. Meanwhile, the disordered group showed enhanced bilateral intra- and interhemispheric connectivities while performing the task. However, right intrahemispheric connectivity was found to be weaker than those for the control group. Second, connectivity and activation characteristics might not be positively correlated with each other. In our previous results, disordered children lacked activation in the right middle frontal gyrus. However, within region connectivity of the right middle frontal gyrus was relatively strong in the baseline interval and significantly increased in the task interval. Third, the connectivity-based biomarker performed better than the activation-based biomarker in terms of screening. Activation and connectivity features were independently optimized and cross validated to obtain the best performing threshold-based classifier. The effectiveness of connectivity features, which brought significantly higher training accuracy than the optimum activation features, was confirmed (88% versus 76%). The optimum screening features were characterized by two trends: (1) strong connectivities of right frontal, left frontal, and left parietal lobes and (2) weak connectivities of left frontal, left parietal, and right parietal lobes in the control group. We conclude that the attentive task-based connectivity effectively shows the difference between control and disordered children and may represent pathological characteristics to be feasibly implemented as a supporting tool for clinical screening.

Denoising of neuronal signal from mixed systemic low-frequency oscillation using peripheral measurement as noise regressor in near-infrared imaging.

Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique measuring hemodynamic changes including oxygenated ( O 2 Hb ) and deoxygenated (HHb) hemoglobin. Low frequency (LF; 0.01 to 0.15 Hz) band is commonly analyzed in fNIRS to represent neuronal activation. However, systemic physiological artifacts (i.e., nonneuronal) likely occur also in overlapping frequency bands. We measured peripheral photoplethysmogram (PPG) signal concurrently with fNIRS (at prefrontal region) to extract the low-frequency oscillations (LFOs) as systemic noise regressors. We investigated three main points in this study: (1) the relationship between prefrontal fNIRS and peripheral PPG signals; (2) the denoising potential using these peripheral LFOs, and (3) the innovative ways to avoid the false-positive result in fNIRS studies. We employed spatial working memory (WM) and control tasks (e.g., resting state) to illustrate these points. Our results showed: (1) correlation between signals from prefrontal fNIRS and peripheral PPG is region-dependent. The high correlation with peripheral ear signal (i.e., O 2 Hb ) occurred mainly in frontopolar regions in both spatial WM and control tasks. This may indicate the finding of task-dependent effect even in peripheral signals. We also found that the PPG recording at the ear has a high correlation with prefrontal fNIRS signal than the finger signals. (2) The systemic noise was reduced by 25% to 34% on average across regions, with a maximum of 39% to 58% in the highly correlated frontopolar region, by using these peripheral LFOs as noise regressors. (3) By performing the control tasks, we confirmed that the statistically significant activation was observed in the spatial WM task, not in the controls. This suggested that systemic (and any other) noises unlikely violated the major statistical inference. (4) Lastly, by denoising using the task-related signals, the significant activation of region-of-interest was still observed suggesting the manifest task-evoked response in the spatial WM task.

Intrinsic correlations of electroencephalography rhythms with cerebral hemodynamics during sleep transitions.

To examine the correlation between electroencephalography fluctuations (EEGF) and cerebral hemodynamics during sleep after eliminating influences from cardiovascular activity, we simultaneously measured EEGF, the cerebral hemoglobin concentration change, and mean arterial blood pressure (MAP) during the sleep of healthy human adults. The cerebral hemoglobin concentration change was measured at 88 positions covering the whole head, by optical topography. We extracted the intrinsic correlation between EEGF and the cerebral hemoglobin concentration change without MAP contributions through cross-correlation and partial correlation analyses considering time lags. We found that increases in the power of the alpha rhythm in EEGF were correlated with increases in oxygenated hemoglobin (oxy-Hb) and decreases in deoxygenated hemoglobin (deoxy-Hb) and that increases in the power of the sigma rhythm in EEGF were correlated with decreases in oxy-Hb and increases in deoxy-Hb. The former correlations tended to appear in the transition from sleep stage 2 to sleep stage 1, and the latter correlations tended to appear in the transition from sleep stage 1 to sleep stage 2. The former correlations were found in the inferior frontal and middle temporal gyri and the latter correlations were found in the superior frontal, middle frontal, and angular gyri.

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.

Extracting task-related activation components from optical topography measurement using independent components analysis.

Optical topography (OT) signals measured during an experiment that used activation tasks for certain brain functions contain neuronal-activation induced blood oxygenation changes and also physiological changes. We used independent component analysis to separate the signals and extracted components related to brain activation without using any hemodynamic models. The analysis procedure had three stages: first, OT signals were separated into independent components (ICs) by using a time-delayed decorrelation algorithm; second, task-related ICs (TR-ICs) were selected from the separated ICs based on their mean intertrial cross-correlations; and third, the TR-ICs were categorized by k-means clustering into TR activation-related ICs (TR-AICs) and TR noise ICs (TR-NICs). We applied this analysis procedure to the OT signals obtained from experiments using one-handed finger-tapping tasks. In the averaged waveform of the TR-AICs, a small overshoot can be seen for a few seconds after the onset of each task and a few seconds after it ends, and the averaged waveforms of the TR-NICs have an N-shaped pattern.

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.

Technique for designing and evaluating probe caps used in optical topography of infants using a real head model based on three dimensional magnetic resonance images.

We have developed an effective technique for aiding the design and evaluating the performance of the probe caps used to perform optical topography (OT) on infants. To design and evaluate a probe cap, it is necessary to determine the measurement positions for conducting OT on the brain surface of subjects. One technique for determining these positions on the brain surface is to find their three-dimensional (3D) coordinates using a 3D magnetic space digitizer, which consists of a 3D magnetic source and a 3D magnetic sensor. The problem with this technique is that it takes a long time to determine all the measurement points on the subject's head and it is difficult to use with infants. It is a particular problem with infants who cannot support their own heads. Therefore, we have developed a real model of an infant subject's head based on 3D magnetic resonance (MR) images. The model is made from an optical-curable resin using 3D computer-aided-format coordinate data taken from 3D MR image-format coordinate data. We have determined the measurement positions on the surface of the model corresponding to a scalp using a 3D magnetic space digitizer and displayed the positions on a 3D MR image of the infant's brain. Using this technique, we then determined the actual 72 measurement positions located over the entire brain surface area for use with our new whole-head probe cap for neonates and infants. This method is useful for evaluating the performance of and designing probe caps.

Adaptive algorithm utilizing acceptance rate for eliminating noisy epochs in block-design functional near-infrared spectroscopy data: application to study in attention deficit/hyperactivity disorder children.

Functional near-infrared spectroscopy (fNIRS) signals are prone to problems caused by motion artifacts and physiological noises. These noises unfortunately reduce the fNIRS sensitivity in detecting the evoked brain activation while increasing the risk of statistical error. In fNIRS measurements, the repetitive resting-stimulus cycle (so-called block-design analysis) is commonly adapted to increase the sample number. However, these blocks are often affected by noises. Therefore, we developed an adaptive algorithm to identify, reject, and select the noise-free and/or least noisy blocks in accordance with the preset acceptance rate. The main features of this algorithm are personalized evaluation for individual data and controlled rejection to maintain the sample number. Three typical noise criteria (sudden amplitude change, shifted baseline, and minimum intertrial correlation) were adopted. Depending on the quality of the dataset used, the algorithm may require some or all noise criteria with distinct parameters. Aiming for real applications in a pediatric study, we applied this algorithm to fNIRS datasets obtained from attention deficit/hyperactivity disorder (ADHD) children as had been studied previously. These datasets were divided for training and validation purposes. A validation process was done to examine the feasibility of the algorithm regardless of the types of datasets, including those obtained under sample population (ADHD or typical developing children), intervention (nonmedication and drug/placebo administration), and measurement (task paradigm) conditions. The algorithm was optimized so as to enhance reproducibility of previous inferences. The optimum algorithm design involved all criteria ordered sequentially (0.047 mM mm of amplitude change, 0.029 mM mm / s of baseline slope, and 0.6 × interquartile range of outlier threshold for each criterion, respectively) and presented complete reproducibility in both training and validation datasets. Compared to the visual-based rejection as done in the previous studies, the algorithm achieved 71.8% rejection accuracy. This suggests that the algorithm has robustness and potential to substitute for visual artifact-detection.

Erratum: Adaptive algorithm utilizing acceptance rate for eliminating noisy epochs in block-design functional near-infrared spectroscopy data: application to study in attention deficit/hyperactivity disorder children.

[This corrects the article DOI: 10.1117/1.NPh.5.4.045001.].

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.

Functional optical signal analysis: a software tool for near-infrared spectroscopy data processing incorporating statistical parametric mapping.

Optical topography (OT) relies on the near infrared spectroscopy (NIRS) technique to provide noninvasively a spatial map of functional brain activity. OT has advantages over conventional fMRI in terms of its simple approach to measuring the hemodynamic response, its ability to distinguish between changes in oxy- and deoxy-hemoglobin and the range of human participants that can be readily investigated. We offer a new software tool, functional optical signal analysis (fOSA), for analyzing the spatially resolved optical signals that provides statistical inference capabilities about the distribution of brain activity in space and time and by experimental condition. It does this by mapping the signal into a standard functional neuroimaging analysis software, statistical parametric mapping (SPM), and forms, in effect, a new SPM toolbox specifically designed for NIRS in an OT configuration. The validity of the program has been tested using synthetic data, and its applicability is demonstrated with experimental data.

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.

Prefrontal Function Engaging in External-Focused Attention in 5- to 6-Month-Old Infants: A Suggestion for Default Mode Network.

The present study used functional near-infrared spectroscopy (fNIRS) to measure 5- to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-month-old infants watched video clips of Peek-a-Boo (social signal) performed by an anime character (AC) or a human, and hand movements without social signal performed by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while behaviors including looking time were recorded simultaneously. NIRS data showed that infants' hemodynamic responses in the PFC generally decreased due to these stimuli, and the decrease was most prominent in the frontopolar (FP), covering medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC. Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly, behavioral data revealed significantly longer looking times when Peek-a-Boo was performed by an AC than by a human. No significant difference between Peek-a-Boo and non-Peek-a-Boo conditions was observed in either measure. These findings indicate that infants at this age may prefer stimuli with more salient features, which may be more effective in attracting their attentions. In conjunction with our previous findings on responses to self-name calling in infants of similar age, we hypothesize that the dynamic function of the MPFC and its vicinity (as part of default mode network (DMN): enhanced by self-focused stimuli, attenuated by externally focused stimuli), which is consistently observed in adults, may have already emerged in 5- to 6-month-old infants.

Tutorial on platform for optical topography analysis tools.

Optical topography/functional near-infrared spectroscopy (OT/fNIRS) is a functional imaging technique that noninvasively measures cerebral hemoglobin concentration changes caused by neural activities. The fNIRS method has been extensively implemented to understand the brain activity in many applications, such as neurodisorder diagnosis and treatment, cognitive psychology, and psychiatric status evaluation. To assist users in analyzing fNIRS data with various application purposes, we developed a software called platform for optical topography analysis tools (POTATo). We explain how to handle and analyze fNIRS data in the POTATo package and systematically describe domain preparation, temporal preprocessing, functional signal extraction, statistical analysis, and data/result visualization for a practical example of working memory tasks. This example is expected to give clear insight in analyzing data using POTATo. The results specifically show the activated dorsolateral prefrontal cortex is consistent with previous studies. This emphasizes analysis robustness, which is required for validating decent preprocessing and functional signal interpretation. POTATo also provides a self-developed plug-in feature allowing users to create their own functions and incorporate them with established POTATo functions. With this feature, we continuously encourage users to improve fNIRS analysis methods. We also address the complications and resolving opportunities in signal analysis.