Deficient neural activity subserving decision-making during reward waiting time in intertemporal choice in adult attention-deficit hyperactivity disorder.

AIM: Impulsivity, which significantly affects social adaptation, is an important target behavioral characteristic in interventions for attention-deficit hyperactivity disorder (ADHD). Typically, people are willing to wait longer to acquire greater rewards. Impulsivity in ADHD may be associated with brain dysfunction in decision-making involving waiting behavior under such situations. We tested the hypothesis that brain circuitry during a period of waiting (i.e., prior to the acquisition of reward) is altered in adults with ADHD. METHODS: The participants included 14 medication-free adults with ADHD and 16 healthy controls matched for age, sex, IQ, and handedness. The behavioral task had participants choose between a delayed, larger monetary reward and an immediate, smaller monetary reward, where the reward waiting time actually occurred during functional magnetic resonance imaging measurement. We tested for group differences in the contrast values of blood-oxygen-level dependent signals associated with the length of waiting time, calculated using the parametric modulation method. RESULTS: While the two groups did not differ in the time discounting rate, the delay-sensitive contrast values were significantly lower in the caudate and visual cortex in individuals with ADHD. The higher impulsivity scores were significantly associated with lower delay-sensitive contrast values in the caudate and visual cortex. CONCLUSION: These results suggest that deficient neural activity affects decision-making involving reward waiting time during intertemporal choice tasks, and provide an explanation for the basis of impulsivity in adult ADHD.

Application of functional near infrared spectroscopy as supplementary examination for diagnosis of clinical stages of psychosis spectrum.

AIM: Research efforts aiming at neuroimaging-aided differential diagnosis for psychiatric disorders have been progressing rapidly. A previous multisite study has developed a supplementary diagnostic system using functional near-infrared spectroscopy (fNIRS) that can be easily applied to clinical settings. However, few neuroimaging biomarkers have been developed for the psychosis spectrum with various clinical stages. METHODS: We employed the fNIRS as a clinical examination device for 143 participants, comprising 47 ultra-high risk for psychosis (UHR) individuals, 30 patients with first-episode psychosis (FEP), 34 patients with chronic schizophrenia (ChSZ), and 33 healthy controls, who were independent of the previous study. A 12-month follow-up measurement was also carried out on 34 UHR individuals (72%), 21 patients with FEP (70%), and 33 controls. The fNIRS algorithm variables used for classification were the intensity and timing of prefrontal activation following the start of the cognitive task as used in the previous multisite study. RESULTS: The discrimination rate by timing of activation was modest but it became acceptable after adjusting confounding factors. Discrimination by intensity of activation was not improved by similar adjustment. A total of 63.8%, 86.7%, and 81.3% patients were classified as UHR, FEP, and ChSZ, respectively; and 85.1%, 86.7%, and 71.9% of patients in these groups, respectively, were classified as being on the psychosis spectrum. In the follow-up measurement, 88.2% of individuals with UHR and 95.0% of patients with FEP were successfully classified into the psychosis spectrum group. CONCLUSION: The fNIRS for supplementary clinical examination could be validly applied to differentiating people with the psychosis spectrum in various clinical stages. The fNIRS is a candidate biological marker for aiding diagnosis of psychosis spectrum in routine clinical settings.

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.

Characterizing prefrontal cortical activity during inhibition task in methamphetamine-associated psychosis versus schizophrenia: a multi-channel near-infrared spectroscopy study.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

Magnetoencephalographic recording of auditory mismatch negativity in response to duration and frequency deviants in a single session in patients with schizophrenia.

AIM: Auditory mismatch negativity (MMN) and its magnetoencephalographic (MEG) counterpart (MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference. METHODS: Forty-two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole-head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence. RESULTS: Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness. CONCLUSION: These results, obtained by using a sequence-enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real-world clinical psychiatry settings.

Development of a neurofeedback protocol targeting the frontal pole using near-infrared spectroscopy.

AIM: Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. METHODS: We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. RESULTS: Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006). CONCLUSION: The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation.

Dorsolateral prefrontal hemodynamic responses during a verbal fluency task in hypomanic bipolar disorder.

OBJECTIVES: Neuroimaging studies have suggested prefrontal dysfunction in response to cognitive activation in bipolar disorder (BD). However, its characteristics in manic states have not been well understood. Thus, we compared prefrontal hemodynamic responses during a cognitive task between hypomanic and depressive states in BD. We then longitudinally compared hypomanic and subsequent euthymic states. METHODS: The prefrontal function of 27 patients with BD (11 hypomanic and 16 depressed) and 12 age- and gender-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Hypomanic symptoms were assessed using the Young Mania Rating Scale. Among the 11 hypomanic patients, eight participated in the second NIRS measurement after their hypomanic symptoms resolved. RESULTS: VFT performance did not differ among hypomanic, depressed, and HC groups. Both BD groups exhibited significantly lower activation during the VFT than HCs in the broader bilateral prefrontal cortex. Hemodynamic changes in the left dorsolateral prefrontal cortex (DLPFC) in the hypomanic patients with BD were significantly larger than those in the depressed patients. In addition, hypomanic symptom severity was positively correlated with activation in the left DLPFC and frontopolar cortex in patients with BD. Follow-up measurement of the hypomanic patients revealed that prefrontal activation was decreased after hypomanic symptoms resolved. CONCLUSIONS: Combining cross-sectional and longitudinal assessments, the present results suggest that prefrontal hemodynamic responses associated with cognitive activation differ between hypomanic and depressive states in BD. NIRS measurement could be a useful tool for objectively evaluating state-dependent characteristics of prefrontal hemodynamics in BD.

Social Function and Frontopolar Activation during a Cognitive Task in Patients with Bipolar Disorder.

BACKGROUND: It is important to understand the neural basis of functional impairments in patients with bipolar disorder (BD) in order to be able to address the recovery. Recently, neurocognitive impairment emerged as a predictor of psychosocial function. A number of functional brain imaging studies have shown that social function is associated with activation of the prefrontal cortex during a cognitive task in healthy adults, and in patients with major depressive disorder and schizophrenia. However, few studies have been conducted in patients with BD. METHODS: We performed multichannel near-infrared spectroscopy (NIRS) imaging to investigate the activation of the prefrontal cortex during a verbal fluency task (VFT). We also used the Social Adaptation Self-Evaluation Scale (SASS) to assess social functioning in patients with BD. Thirty-three depressed patients with BD and 65 age-, gender- and task performance-matched healthy controls (HCs) participated in this study. RESULTS: Depressed patients with BD showed reduced activation in the broader bilateral prefrontal cortex during the VFT compared to HCs. Moreover, a significant positive correlation was observed between the total SASS scores and right prefrontal activation in patients with BD. In the SASS subscores, the interest and motivation factor was also positively correlated with frontopolar activation. CONCLUSIONS: These results suggest an association between social function and prefrontal activation in depressed patients with BD. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social function.

Anxiety and performance: the disparate roles of prefrontal subregions under maintained psychological stress.

Despite increasing interest in anxiety and psychological stress in daily life, little is known about neural correlates that underlie maintained psychological stress and their relationship with anxiety. In particular, the activation characteristics of lateral prefrontal subregions and their relationship with anxiety and cognitive performance under maintained psychological stress remain unknown. This study used near-infrared spectroscopy (NIRS), a noninvasive and "real-world" functional neuroimaging method, to investigate the hemodynamic responses in wide areas of the prefrontal cortex (PFC) and the influence of anxiety under conditions of maintained stress induced by a continuous arithmetic task (2 sets, 15 min each) performed in a natural sitting posture. Although anxiety and performance are not directly correlated, the hemodynamic response in the medial portion of the lateral PFC (dorsolateral and frontopolar PFC) was significantly associated with anxiety, while hemodynamic responses in the ventrolateral PFC were associated with performance. Additionally, in the same medial region of the lateral PFC, trait and state anxieties were related to changes in deoxy- and oxy-hemoglobin concentrations, respectively. This NIRS finding suggests disparate roles for prefrontal subregions in anxiety and performance under psychological stress and may lead to a better understanding of neural correlates for anxiety in everyday life.

Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals.

The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders.

Genetic influences on prefrontal activation during a verbal fluency task in adults: a twin study based on multichannel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) studies have reported that prefrontal hemodynamic dysfunction during executive function tasks may be a promising biomarker of psychiatric disorders, because its portability and noninvasiveness allow easy measurements in clinical settings. Here, we investigated the degree to which prefrontal NIRS signals are genetically determined. Using a 52-channel NIRS system, we monitored the oxy-hemoglobin (oxy-Hb) signal changes in 38 adult pairs of right-handed monozygotic (MZ) twins and 13 pairs of same-sex right-handed dizygotic (DZ) twins during a letter version of the verbal fluency task. Heritability was estimated based on a classical twin paradigm using structured equation modeling. Significant genetic influences were estimated in the right dorsolateral prefrontal cortex and left frontal pole. The degrees of heritability were 66% and 75% in the variances, respectively. This implies that the prefrontal hemodynamic dysfunction observed during an executive function task measured by NIRS may be an efficient endophenotype for large-scale imaging genetic studies in psychiatric disorders.

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.

Electroencephalographic dipole source modeling of frontal intermittent rhythmic delta activity.

BACKGROUND: Frontal intermittent rhythmic delta activity (FIRDA) on electroencephalography (EEG) consists of a run of rhythmic delta waves with frontal predominance. Although FIRDA is a relatively common abnormal EEG finding, the underlying mechanisms that produce FIRDA remain unclear. The aim of this study was to investigate the cortical source of FIRDA using dipole source modeling. METHODS: We selected EEG epochs, including typical FIRDAs, from EEG recordings obtained using 25 scalp electrodes on 5 subjects. We averaged these epochs by arranging the negative peaks of the delta waves at the Fp electrodes and estimated dipoles for nine averaged waveforms. RESULTS: Averaged waveforms were explained by a single-dipole model in seven FIRDAs and by a two-dipole model in the remaining two FIRDAs with high reliability. Estimated dipoles had a radial orientation with respect to the frontal pole and were located in the medial frontal region. The anterior cingulate cortex was the most common dipole location. CONCLUSIONS: This is the first study to approach the fundamental FIRDA mechanism by dipole source modeling and to clarify that FIRDA may be generated from the medial frontal region, particularly from the anterior cingulate cortex.

Source localization of posterior slow waves of youth using dipole modeling.

AIM: Posterior slow waves of youth have a well-known electroencephalographic pattern that peaks in adolescence and usually disappears in adulthood. In general, posterior slow waves of youth are regarded as normal, but some reports have suggested that their presence is related to immature personalities or inappropriate social behavior. The physiological significance of this electroencephalographic pattern, however, remains unclear. The purpose of this study was to investigate the neural origins of posterior slow waves of youth using dipole source modeling. METHODS: Electroencephalographic epochs, including clear posterior slow waves of youth, were visually selected from electroencephalograms obtained from six normal adolescents using 25 scalp electrodes. The selected epochs were then averaged by arranging the negative peak of the slow waves at the occipital area of each epoch on the time axis. The averaged waveforms consisting of six right and one left posterior slow waves of youth were used for dipole source analysis. A single equivalent current dipole was estimated for the averaged waveforms. RESULTS: The best equivalent current dipoles were estimated to be located in or around the fusiform and middle occipital gyrus ipsilateral to the posterior slow waves of youth. CONCLUSIONS: The location of the estimated dipoles of posterior slow waves of youth was on the so-called ventral visual pathway. Further research is required to clarify the physiological significance of posterior slow waves of youth with respect to their origin.

An event-related fNIRS investigation of Japanese word order.

Japanese is a free word-order language, and allows both subject-object-verb (SOV) and object-subject-verb (OSV) orders. Our previous study using near-infrared spectroscopy (NIRS) imaging revealed that OSV sentences induce more activation in the left frontal lobe than SOV sentences. The present study develops our previous experiment: (1) by adopting an event-related design, and (2) by using sentences involving the adverb naze 'why', which plays a prominent role in recent linguistic studies. The results of our new experiment indicated that the cerebral activation in O why SV sentences was significantly larger than that in S why OV sentences, in the right anterior prefrontal region, which is consistent with the assumption that O why SV order is derived from S why OV order. We speculate that the activation observed in the anterior prefrontal cortex during the processing of the sentences involving 'why' might be due to the processing of higher-order function in the cerebral cortex.

Prefrontal dysfunction associated with a history of suicide attempts among patients with recent onset schizophrenia.

Suicide is a major cause of death in patients with schizophrenia, particularly among those with recent disease onset. Although brain imaging studies have identified the neuroanatomical correlates of suicidal behavior, functional brain activity correlates particularly in patients with recent-onset schizophrenia (ROSZ) remain unknown. Using near-infrared spectroscopy (NIRS) recording with a high-density coverage of the prefrontal area, we investigated whether prefrontal activity is altered in patients with ROSZ having a history of suicide attempts. A 52-channel NIRS system was used to examine hemodynamic changes in patients with ROSZ that had a history of suicide attempts (n = 24) or that lacked such a history (n = 62), and age- and sex-matched healthy controls (n = 119), during a block-design letter fluency task (LFT). Patients with a history of suicide attempts exhibited decreased activation in the right dorsolateral prefrontal cortex compared with those without such a history. Our findings indicate that specific regions of the prefrontal cortex may be associated with suicidal attempts, which may have implications for early intervention for psychosis.

Genome-wide association study of panic disorder in the Japanese population.

Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety. Although a number of association studies have been conducted, no gene has been identified as a susceptibility locus. In this study, we conducted a genome-wide association study of PD in 200 Japanese patients and the same number of controls, using the GeneChip Human Mapping 500 K Array Set. Genotypes were determined using the Bayesian Robust Linear Model with Mahalanobis (BRLMM) genotype calling algorithm. The genotype data were data-cleaned using criteria for SNP call rate (>or=95%), Hardy-Weinberg equilibrium (P>or=0.1%) and minor allele frequency (>or=5%). The significance level of the allele P-value was set at 1.0 x 10(-6), to make false discovery rate (FDR) <0.05. As a result, seven SNPs were significantly associated with PD, which were located in or adjacent to genes including PKP1, PLEKHG1, TMEM16B, CALCOCO1, SDK2 and CLU (or APO-J). Studies with other samples are required to confirm the results.

Asymmetry of prefrontal cortex activities and catechol-O-methyltransferase Val158Met genotype in patients with panic disorder during a verbal fluency task: near-infrared spectroscopy study.

We examined the relationship between the catechol-O-methyltransferase (COMT) Val158Met genotype and frontal lobe function by using multi-channel near-infrared spectroscopy (NIRS). The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a verbal fluency task in the frontal region of 71 patients with panic disorder (PD). The activation of [oxy-Hb] on the right lateral prefrontal cortex was observed in the Met/Met genotype of the COMT gene polymorphism of PD patient groups in the analysis of NIRS, which seems to be related to the autonomic dysfunction in the pathogenesis of PD.

Relationship between the prefrontal function during a cognitive task and the severity of the symptoms in patients with panic disorder: a multi-channel NIRS study.

To investigate whether prefrontal function during a cognitive task reflects the severity of panic disorder, the prefrontal function during a word fluency task in 109 panic disorder patients with or without agoraphobia was measured by multi-channel near-infrared spectroscopy (NIRS). [Oxy-Hb] changes in the left inferior prefrontal cortex were significantly associated with the frequency of panic attacks, and, in addition, [deoxy-Hb] changes in the anterior area of the right prefrontal cortex were significantly associated with the severity of agoraphobia. These results suggest that the prefrontal function in patients with panic disorder is associated with the disease state of disease in patients with panic disorder.

Intrasubject reproducibility of prefrontal cortex activities during a verbal fluency task over two repeated sessions using multi-channel near-infrared spectroscopy.

AIM: To determine whether intrasubject reproducibility could be observed in the frontal cortex and to assess the mental-health status of subjects in each session. METHODS: We measured changes in oxygenated hemoglobin concentration ([oxy-Hb]) during a letter version of the verbal fluency task using near-infrared spectroscopy imaging in twenty healthy adults over two sessions approximately two months apart. Additionally, the mental-health status of the subjects in each session was evaluated according to the State-Trait Anxiety Inventory, the Zung Self-rating Depression Scale, the Profile of Mood States, and the revised edition of the Neuroticism-Extroversion-Openness Personality Inventory. The association between those scores and [oxy-Hb] changes during the verbal fluency task in each session was investigated. RESULTS: Performance on the verbal fluency task was about equal across the two sessions, and frontal activation during the task was observed globally in approximately the same region. In the test-retest reliability, acceptable values were shown in both the Intraclass Correlation Coefficients of the mean [oxy-Hb] changes and the correlation coefficients of the whole waveforms for each subject in the two sessions. Mental-health status as measured by several questionnaires was within the healthy range, and no correlation with the frontal activation was seen, except in several channels. CONCLUSION: The current results suggest that the measurement experience exerted very little influence, except for in a very small region. In addition, the intrasubject reproducibility of frontal activation measured by multi-channel near-infrared spectroscopy was well demonstrated in mentally healthy subjects at intervals of two months.