Native non-prototypicality in vowel perception induces prominent neuromagnetic mismatch intensities in non-native speakers: a pilot study.

Neural mismatch response resulting from the difference between prediction and observation is related to change detection and discrimination. Robust neuromagnetic brain activity of auditory mismatch-related perception occurs in response to non-prototypical vowels in across-category contrasts for first-language speakers. However, whether this non-prototypicality effect applies to within-category vowel perception remains to be elucidated. Here, healthy Japanese adults (n = 7) were subjected to magnetoencephalography (MEG) while watching a silent movie, and passively listened to synthesized English vowels /i/. We observed the source-level mismatch effect to the mid-high near-front vowel deviant [ɪ] with the most non-prototypical, unspecified feature in the participants' native language system. The mismatch effect recruited the left posterior superior temporal sulcus with a peak latency of 225 ms post-stimulus onset. We further studied whether a longer F1 distance between vowel pairs would increase mismatch-activated intensities, however, we did not observe neuromagnetic changes when the prototypical anchor standard [i] was compared with three non-prototypical deviants differing in first resonance frequency (F1) values. Our results indicate that an F1 increase in within-category upper front vowel perception is a strong activator of mismatch responses measured by source-level activated intensities for non-native listeners.

Head errors of syntactic dependency increase neuromagnetic mismatch intensities.

Mismatch-related brain activation in healthy individuals is an important area of neural investigation. Previously, we evaluated sentence-level syntactic dependencies, composed of a head and a dependent between two syntactically related words in head-initial English structures. We demonstrated that prominent mismatch effects were induced by within-category dependent errors when semantic interpretation was preserved. However, the following issues were not addressed: (1) whether head errors of syntactic dependency in head-final structures would elicit large mismatch field (MMF) intensities, and (2) whether an MMF effect of syntactic errors would be seen in the left superior temporal cortex alone. In this study, auditory MMFs were obtained by magnetocephalography (MEG) from healthy Japanese adults (n = 8) who were subjected to a passive auditory oddball paradigm with syntactically legal or illegal utterances and single words in Japanese. The results demonstrate that the source waveforms had significantly higher MMF cortical activation in response to the head error, which involved altered polarity of the predicate. This resulted in a syntactically incorrect and semantically incomprehensible expression, when compared to the syntactically correct expression and the non-structural lexical item. This mismatch effect, with a peak latency of 164 ms, was confined to the anterior region of the left superior temporal cortex. The current results clearly indicate that the representation of syntactic dependency is stored in long-term memory and tends to be activated in automatic auditory processing.

Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS.

While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD), an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS), which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs) and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level.

Exploring effective multiplicity in multichannel functional near-infrared spectroscopy using eigenvalues of correlation matrices.

Recent advances in multichannel functional near-infrared spectroscopy (fNIRS) allow wide coverage of cortical areas while entailing the necessity to control family-wise errors (FWEs) due to increased multiplicity. Conventionally, the Bonferroni method has been used to control FWE. While Type I errors (false positives) can be strictly controlled, the application of a large number of channel settings may inflate the chance of Type II errors (false negatives). The Bonferroni-based methods are especially stringent in controlling Type I errors of the most activated channel with the smallest [Formula: see text] value. To maintain a balance between Types I and II errors, effective multiplicity ([Formula: see text]) derived from the eigenvalues of correlation matrices is a method that has been introduced in genetic studies. Thus, we explored its feasibility in multichannel fNIRS studies. Applying the [Formula: see text] method to three kinds of experimental data with different activation profiles, we performed resampling simulations and found that [Formula: see text] was controlled at 10 to 15 in a 44-channel setting. Consequently, the number of significantly activated channels remained almost constant regardless of the number of measured channels. We demonstrated that the [Formula: see text] approach can be an effective alternative to Bonferroni-based methods for multichannel fNIRS studies.

Determination of epileptic focus side in mesial temporal lobe epilepsy using long-term noninvasive fNIRS/EEG monitoring for presurgical evaluation.

Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8-16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures. Four spontaneous seizures were successfully recorded out of the six patients. To determine oxy-Hb amplitude, the period-average values of oxy-Hb across 20 s from the EEG- or clinically defined epileptic onset were calculated for both hemispheres from the simultaneously recorded fNIRS data. The average oxy-Hb values for the temporal lobe at the earlier EEG- or clinically defined epileptic onsets were greater for the epileptic side than for the contralateral side after EEG activity suppression, spike train, and clinical seizure in all four cases. The true laterality was determined based on the relief of seizures by selective amygdalo-hippocampectomy. Thus, oxy-Hb amplitude could be a reliable measure for determining the epileptic focus side. Long-term simultaneous fNIRS/EEG measurement serves as an effective tool for recording spontaneous seizures. Cerebral hemodynamic measurement by fNIRS would serve as a valuable supplementary noninvasive measurement method for presurgical evaluation of MTLE.

Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD children: a fNIRS study.

The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.

Neuropharmacological effect of methylphenidate on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy.

The current study aimed to explore the neural substrate for methylphenidate effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 22 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after methylphenidate or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Twenty-two age- and gender-matched normal controls without methylphenidate administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices, and this activation was absent in premedicated ADHD children. The reduced right prefrontal activation was normalized after methylphenidate but not placebo administration in ADHD children. These results are consistent with the neuropharmacological effects of methylphenidate to upregulate the dopamine system in the prefrontal cortex innervating from the ventral tegmentum (mesocortical pathway), but not the noradrenergic system from the parietal cortex to the locus coeruleus. Thus, right prefrontal activation would serve as an objective neurofunctional biomarker to indicate the effectiveness of methylphenidate on ADHD children in attentional control. fNIRS monitoring enhances early clinical diagnosis and the treatment of ADHD children, especially those with an inattention phenotype.

Optimizing the general linear model for functional near-infrared spectroscopy: an adaptive hemodynamic response function approach.

An increasing number of functional near-infrared spectroscopy (fNIRS) studies utilize a general linear model (GLM) approach, which serves as a standard statistical method for functional magnetic resonance imaging (fMRI) data analysis. While fMRI solely measures the blood oxygen level dependent (BOLD) signal, fNIRS measures the changes of oxy-hemoglobin (oxy-Hb) and deoxy-hemoglobin (deoxy-Hb) signals at a temporal resolution severalfold higher. This suggests the necessity of adjusting the temporal parameters of a GLM for fNIRS signals. Thus, we devised a GLM-based method utilizing an adaptive hemodynamic response function (HRF). We sought the optimum temporal parameters to best explain the observed time series data during verbal fluency and naming tasks. The peak delay of the HRF was systematically changed to achieve the best-fit model for the observed oxy- and deoxy-Hb time series data. The optimized peak delay showed different values for each Hb signal and task. When the optimized peak delays were adopted, the deoxy-Hb data yielded comparable activations with similar statistical power and spatial patterns to oxy-Hb data. The adaptive HRF method could suitably explain the behaviors of both Hb parameters during tasks with the different cognitive loads during a time course, and thus would serve as an objective method to fully utilize the temporal structures of all fNIRS data.

Neuropharmacological effect of atomoxetine on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy.

The current study aimed to explore the neural substrate for atomoxetine effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 15 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after atomoxetine or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Fifteen age-, gender-, and intelligence quotient-matched normal controls without atomoxetine administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices. The right prefrontal and parietal activation was normalized after atomoxetine administration in ADHD children. This was in contrast to our previous study using a similar protocol showing methylphenidate-induced normalization of only the right prefrontal function. fNIRS allows the detection of differential neuropharmacological profiles of both substances in the attentional network: the neuropharmacological effects of atomoxetine to upregulate the noradrenergic system reflected in the right prefrontal and inferior parietal activations and those of methylphenidate to upregulate the dopamine system reflected in the prefrontal cortex activation.

Language-specific cortical activation patterns for verbal fluency tasks in Japanese as assessed by multichannel functional near-infrared spectroscopy.

In Japan, verbal fluency tasks are commonly utilized as a standard paradigm for neuropsychological testing of cognitive and linguistic abilities. The Japanese "letter fluency task" is a mora/letter fluency task based on the phonological and orthographical characteristics of the Japanese language. Whether there are similar activation patterns across languages or a Japanese-specific mora/letter fluency pattern is not certain. We investigated the neural correlates of overt mora/letter and category fluency tasks in healthy Japanese. The category fluency task activated the bilateral fronto-temporal language-related regions with left-superior lateralization, while the mora/letter fluency task led to wider activation including the inferior parietal regions (left and right supramarginal gyrus). Specific bilateral supramarginal activation during the mora/letter fluency task in Japanese was distinct from that of similar letter fluency tasks in syllable-alphabet-based languages: this might be due to the requirement of additional phonological processing and working memory, or due to increased cognitive load in general.

[Strategy on dealing with noisy NIRS data: implications on functional neuroimaging on swallowing].

Functional near-infrared spectroscopy (fNIRS) may be suited for functional monitoring during swallowing as it is comparatively immune to body movement. However, still fNIRS measurement on swallowing poses a technical problem that it may often involve motion artifacts. Although there is no single way to solve this problem, technical insights have been available form related studies in the past. Here we introduce two examples for analyzing data rich in motion artifacts putting emphasis on temporal structures of the data. The first is about fNIRS assessment of language function during overt naming tasks. Since data were temporally continuous, we adopted a general linear model with regression to a canonical hemodynamic response function to extract cortical activations related to overt naming tasks. The second example is about fNIRS assessment on go/no-go task performance with or without methylphenidate administration in Attention Deficit Hyperactivity Disorder (ADHD) children. Since data were disrupted by unexpected motion artifacts, we simplified temporal data structures by averaging to extract only robust signals. Thus, we indicated that the optimum analytical strategy varies depending on the temporal structures of the data.

Multichannel fNIRS assessment of overt and covert confrontation naming.

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks. Thirty right-handed, healthy adult volunteers underwent both naming tasks and cortical hemodynamics measurement using fNIRS. The overt naming task recruited the classical left-hemisphere language areas (left inferior frontal, superior and middle temporal, precentral, and postcentral gyri) exemplified by an increase in the oxy-Hb signal. Activations were bilateral in the middle and superior temporal gyri. However, the covert naming task recruited activation only in the left-middle temporal gyrus. The activation patterns reflected a major part of the functional network for overt word production, suggesting the clinical importance of fNIRS in the diagnosis of aphasic patients.

Right prefrontal activation as a neuro-functional biomarker for monitoring acute effects of methylphenidate in ADHD children: An fNIRS study.

An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age- and gender-matched normal controls without MPH administration were also monitored. Relative to control subjects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely normalized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would contribute to early clinical diagnosis and treatment of ADHD children.

Stable and convenient spatial registration of stand-alone NIRS data through anchor-based probabilistic registration.

For functional neuroimaging with near-infrared spectroscopy (NIRS), we recently introduced a probabilistic registration method that uses a reference magnetic resonance image (MRI) database instead of the subject's own MRI, and probabilistically registers the NIRS optode or channel positions onto a canonical brain template in the standard stereotactic brain coordinate systems. As an alternative method, we devised an anchor-based registration method utilizing roughly obtained anchor positions on the scalp instead of strictly defined landmarks such as 10/20 landmarks. This method uses a spherical coordinate system to seek a position in the reference MRI database that corresponds to the anchor position, and eventually presents NIRS optode and channel positions in the standard stereotactic brain coordinate system. For comparison against conventional probabilistic registration, we simulated NIRS optode holder placement on 100 synthesized virtual heads, and found holistic tendencies for probe position estimations were similar between the two methods. Comparison among anchor-based probabilistic registration, conventional probabilistic registration, and SPM-based registration via co-registration to a subject's own MRI revealed that intra-method variability was comparable to a small inter-method variability. Thus, anchor-based registration is a practical alternative, especially to avoid burdening a subject and to reduce experimental time.

Clinically-oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children. METHODS: Following an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5 h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task. RESULTS: There was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC. CONCLUSIONS: The improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children. SIGNIFICANCE: MPH-effect assessment in ADHD children using fNIRS can be performed within a 3 h stay at a hospital during a single visit, and thus may be integrated into clinical practice.

Structural atlas-based spatial registration for functional near-infrared spectroscopy enabling inter-study data integration.

OBJECTIVE: The use of functional near-infrared spectroscopy (fNIRS) is growing, leading to a need for methods to summarise data from multiple studies. However, this is difficult using the current channel-based methods when experiments do not share a common channel (CH) arrangement. Thus, we proposed and implemented a CH-independent analysis method for summarising fNIRS data. METHODS: We defined sub-regions as spatial bins to organise fNIRS data. Sub-regions were defined on the standard brain surface based on macro- and micro-structural information. After probabilistically estimating CH location in standard stereotaxic brain space, the CH-based data were reorganised into these spatial bins to evaluate sub-region-based activation. RESULTS: Sub-regions with sizes corresponding to fNIRS spatial resolution were defined. We demonstrated this method by integrating data from two of our fNIRS studies that shared the same region of interest but used different channel arrangements. CONCLUSIONS: Using this method, data from multiple fNIRS studies with different CH arrangements can be integrated in standard brain space, while keeping in mind the brain structure-function relationship. SIGNIFICANCE: The current method will facilitate an effective use of accumulating fNIRS data by allowing integration of data from multiple studies.

Activation in ventro-lateral prefrontal cortex during the act of tasting: an fNIRS study.

The act of tasting is the product of inseparable integrative behavior consisting of multi-sensory processing and orolingual motor coordination. Often tasting-induced brain activity is looked at in a reductionist manner as a set of isolated components. However, brain activity as a whole during tasting may not simply be the sum of isolated brain responses; therefore, attempting to look at the cortical activation in a more holistic manner is important. Using functional near-infrared spectroscopy (fNIRS), we assessed cortical responses during tasting, contrasting observed neuronal activation of the lateral prefrontal cortex (LPFC), of 19 healthy participants before and during tasting of 8ml of sweet-based solutions. To examine the activated brain structure, we estimated the anatomical regions of the measured location in standard brain space. We also included simple tongue tapping movement (TT) and word fluency (WF) tasks as comparative functional markers. Significant activity was found in channels (CHs) estimated to be in the bilateral oral motor areas during the TT task, and those in the LPFC, primarily in the left hemisphere, during the WF task. During the tasting task, significant activation was observed in CHs estimated to lie in the ventral part of pre- and post-central gyri as well as in the ventro-LPFC (VLPFC). The activated regions partly overlapped with those detected during TT or WF tasks, but extended more anteriorly and ventrally. Our study suggests that, in addition to tongue motor areas, the VLPFC is involved in the act of tasting.

Influences of food-name labels on perceived tastes.

We examined whether food identity information presented as name labels would influence perception of basic tastes. To test this hypothesis, we used 10 aqueous taste solutions consisting of 2-3 of the 5 basic tastes in different ratios and presented them with one of these food names: "lemon," "coffee jelly," "caramel candy," and "consomme soup." Forty-six participants tasted samples presented with either food-name labels or random number labels. We found that participants who tasted samples with food-name labels rated tastes with significantly higher liking and familiarity scores than those presented with random numbers, especially when the names and tastes were perceived as being congruent. Though an effect on perceived intensity was not as prominent, we observed cases in which intensity ratings significantly changed. Effects of identity information have been shown in olfaction and flavors. This study demonstrates the first experimental evidence that identity information given as names also influence the perception of unimodal basic tastes.

Modulation of biting procedures induced by the sensory evaluation of cheese hardness with different definitions.

This study seeks to clarify the bite process in individuals who assess cheese hardness to confirm the relationships among hardness definitions, their causative bite procedures, targeted intra-oral mechanical events, and judgment. Subjects were required to bite and evaluate samples using two different definitions of hardness. We measured an intra-oral bite time-force profile using a tactile pressure-measurement system with a sheet sensor unobtrusively inserted into the subject's mouth along with a sample. The first bite profile was an exploratory procedure adjusted to optimize perception of the designated textural attribute. From the temporal modification of the bite profile, we could estimate the bite parameter that was targeted as the sensory information for a particular texture attribute. We examined inter-definition and inter-subject variations in the relationship between hardness judgment and its sensory source estimated from the bite procedure. We demonstrated that the bite measurement could elucidate both the bite procedures and sensory information for hardness evaluation. Different definitions induced different bite procedures that resulted in a change in the sensory signal. The definition also affected inter-subject variability in bite procedures and sensory-judgment correspondence.

First bite for hardness judgment as haptic exploratory procedure.

This study examines whether the modulation of biting behavior while subjects are engaged in food texture judgment can be explained as an intra-oral exploratory procedure optimized for recognizing a specified sensory attribute. Subjects were asked to compare two cheese samples for "the force required to penetrate the sample with the molar teeth" (the definition for "hardness" used in this study). Based on this definition, we hypothesize that the subjects targeted the first peak of the bite time-force profile (i.e. the intra-oral phenomenon of the initial fracture) as an essential property for judgment. We observed significant elongation of the first peak in the judgmental biting, compared to the biting without judgment, for all subjects. Shortening of the second peak (teeth-to-teeth contact) duration and decrease of the second peak force were also observed for all subjects. These active biting modulations suggested that the first peak was targeted for judgment, whereas the second peak was not targeted. The sample with greater maximum force or time-integral of the bite force at the first peak was also judged as requiring greater force; these agreements were statistically significant. This result confirmed that the parameters related to the first peak were targeted as judgmental cues. We concluded that the biting behavior in hardness judgment functions as the exploratory procedure and was optimized for encoding the target sensory properties.