Detection of resting state functional connectivity using partial correlation analysis: A study using multi-distance and whole-head probe near-infrared spectroscopy.

Multichannel near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that enables easy-to-use and noninvasive measurement of changes in blood oxygenation levels. We developed a clinically-applicable method for estimating resting state functional connectivity (RSFC) with NIRS using a partial correlation analysis to reduce the influence of extraneural components. Using a multi-distance probe arrangement NIRS, we measured resting state brain activity for 8min in 17 healthy participants. Independent component analysis was used to extract shallow and deep signals from the original NIRS data. Pearson's correlation calculated from original signals was significantly higher than that calculated from deep signals, while partial correlation calculated from original signals was comparable to that calculated from deep (cerebral-tissue) signals alone. To further test the validity of our method, we also measured 8min of resting state brain activity using a whole-head NIRS arrangement consisting of 17 cortical regions in 80 healthy participants. Significant RSFC between neighboring, interhemispheric homologous, and some distant ipsilateral brain region pairs was revealed. Additionally, females exhibited higher RSFC between interhemispheric occipital region-pairs, in addition to higher connectivity between some ipsilateral pairs in the left hemisphere, when compared to males. The combined results of the two component experiments indicate that partial correlation analysis is effective in reducing the influence of extracerebral signals, and that NIRS is able to detect well-described resting state networks and sex-related differences in RSFC.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains.

The diaphragmatic activities during trunk movements.

In order to investigate how the diaphragm and trunk muscles are recruited during various voluntary movements, we recorded EMG signals and video images simultaneously and analyzed EMGs of the diaphragm and trunk muscles during the voluntary movements that required trunk muscles. During trunk movements, the duration of the diaphragmatic activity became irregular and the intensity of the activity increased. Further analysis revealed that the diaphragmatic activities were consisted of two components, such as respiratory and non-respiratory activities during voluntary movements. Our results led to the idea that the diaphragmatic activities may be controlled from different control mechanisms of central nervous system.

Explicit Performance in Girls and Implicit Processing in Boys: A Simultaneous fNIRS-ERP Study on Second Language Syntactic Learning in Young Adolescents.

Learning a second language (L2) proceeds with individual approaches to proficiency in the language. Individual differences including sex, as well as working memory (WM) function appear to have strong effects on behavioral performance and cortical responses in L2 processing. Thus, by considering sex and WM capacity, we examined neural responses during L2 sentence processing as a function of L2 proficiency in young adolescents. In behavioral tests, girls significantly outperformed boys in L2 tests assessing proficiency and grammatical knowledge, and in a reading span test (RST) assessing WM capacity. Girls, but not boys, showed significant correlations between L2 tests and RST scores. Using functional near-infrared spectroscopy (fNIRS) and event-related potential (ERP) simultaneously, we measured cortical responses while participants listened to syntactically correct and incorrect sentences. ERP data revealed a grammaticality effect only in boys in the early time window (100-300 ms), implicated in phrase structure processing. In fNIRS data, while boys had significantly increased activation in the left prefrontal region implicated in syntactic processing, girls had increased activation in the posterior language-related region involved in phonology, semantics, and sentence processing with proficiency. Presumably, boys implicitly focused on rule-based syntactic processing, whereas girls made full use of linguistic knowledge and WM function. The present results provide important fundamental data for learning and teaching in L2 education.

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.

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.

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.

Evoked potential mapping of the rostral region by frameless navigation system in Mexican hairless pig.

There is an increasing need for a pig model for use in functional brain studies, but a system for determining precise stereotactic coordinates has yet to be developed. Thus, we devised a frameless navigation system for stereotactic positioning, and measured coordinates for the rostral region and the primary somatosensory cortex in the pig brain. Raw coordinates for somatic evoked potential recordings were obtained by passive optical tracking. The location was registered to a computed tomographic image in reference to four stable skull landmarks: the upper margin of each auditory meatus, the external occipital protuberance, and the point where the interfrontal suture crosses a line drawn between the two supraorbital foramina ("IF" point). The cortical position with the greatest response in evoked potential was mapped -51.0 ± 4.67 mm rostro-caudally, 9.1 ± 1.19 mm medio-laterally, and -8.8 ± 0.48 mm dorso-ventrally (means ± SD; n=3) to the IF point. These results show that frameless registration is useful for coordinate-based evoked-potential mapping of the rostral region of the Mexican hairless pig.

Activity patterns of the diaphragm during voluntary movements in awake cats.

The diaphragm is an important inspiratory muscle, and is also known to participate in the postural function. However, the activity of the diaphragm during voluntary movements has not been fully investigated in awake animals. In order to investigate the diaphragmatic activity during voluntary movements such as extending or rotating their body, we analyzed the electromyogram (EMG) of the diaphragm and trunk muscles in the cat using a technique for simultaneous recordings of EMG signals and video images. Periodic respiratory discharges occurred in the left and right costal diaphragm when the cat kept still. However, once the cat moved, their periodicity and/or synchrony were sometimes buried by non-respiratory activity. Such non-periodic diaphragmatic activities during voluntary movements are considered as the combination of respiratory activity and non-respiratory activity. Most of the diaphragmatic activities started shortly after the initiation of standing-up movements and occurred after the onset of trunk muscle activities. Those activities were more active compared to the normal respiratory activity. During rotation movements, left and right diaphragmatic activities showed asymmetrical discharge patterns and higher discharges than those during the resting situation. This asymmetrical activity may be caused by taking different lengths of each side of the diaphragm and trunk muscles. During reaching movements, the diaphragmatic activity occurred prior to or with the onset of trunk muscle activities. It is likely that diaphragmatic activities during reaching movements and standing-up movements may have been controlled by some different control mechanisms of the central nervous system. This study will suggest that the diaphragmatic activity is regulated not only by the respiratory center but also by inputs from the center for voluntary movements and/or sensory reflex pathways under the awake condition.