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Simultaneous monitoring of brain activity with near-infrared spectroscopy and electroencephalography allows spatiotemporal reconstruction of the hemodynamic response regarding the concentration changes in oxyhemoglobin and deoxyhemoglobin that are associated with recorded brain activity such as cognitive functions. However, the accuracy of state estimation during mental arithmetic tasks is often different depending on the length of the segment for sampling of NIRS and EEG signals. This study compared the results of a self-organizing map and ANOVA, which were both used to assess the accuracy of state estimation. We conducted an experiment with a mental arithmetic task performed by 10 participants. The lengths of the segment in each time frame for observation of NIRS and EEG signals were compared with the 30-s, 1-min, and 2-min segment lengths. The optimal segment lengths were different for NIRS and EEG signals in the case of classification of feature vectors into the states of performing a mental arithmetic task and being at rest.

The prefrontal cortex (PFC) plays an important role in emotion and emotional regulation. The valence asymmetry hypothesis, proposes that the left/right asymmetry of the PFC activity is correlated with specific emotional responses to stressors. However, this hypothesis still seems to leave room for clarifying neurophysiological mechanisms. The purpose of the present study was to investigate the effects of stimuli with positive and negative valence sounds (hereafter PS, NS) selected from the International Affective Digitized Sounds-2 on physiological and physiological responses, including PFC activity in normal participants. We studied the effect of both stimuli using 12 normal subjects (mean age 26.8 years) on cerebral blood oxygenation in the bilateral PFC by a multi-channel NIRS, alpha wave appearance rate in theta, alpha, beta by EEG, autonomic nervous function by heart rate, and emotional conditions by the State-Trait Anxiety Inventory (STAI) and the visual analogue scale (VAS). PS was selected over 7.00 and NS were fewer than 3.00 in the Pleasure values. Sounds were recorded during 3 s and reproduced at random using software. Every task session was designed in a block manner: seven rests with Brown Noise (30 s) and six tasks (30 s) blocks. All participants performed each session in random order with eyes closed. A paired Student's t-test was used for comparisons (P<0.05). PFC activity showed increases bilaterally during both stimuli with a greater activation of the left side in PS and a tendency of more activation by NS in the right PFC. Significantly greater alpha wave intensity was obtained in PS. Heart rate tended to show smaller values in PS. The STAI level tended to show smaller values in PS, and a significantly greater VAS score was obtained in PS which indicated 'pleasant'. Despite the limitations of this study such as the low numbers of the subjects, the present study indicated that PS provided pleasant psychological and physiological responses and NS unpleasant responses. The PFC was activated bilaterally, implying a valence effect with the possibility of a dominant side.

Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

In order to clarify the central mechanism controlling respiratory rate during mental stress, we examined the relation between prefrontal cortex (PFC) activity and respiratory rate during mental arithmetic (MA) tasks. Employing two-channel near-infrared spectroscopy (NIRS), we measured hemoglobin (Hb) concentration changes in the bilateral PFC during MA tasks in normal adults. To evaluate asymmetry of the PFC activity, we calculated the laterality index (LI); (R-L)/(R + L) of oxy-Hb concentration changes (R = right, L = left); positive LI scores indicate right-dominant activity, while negative scores indicate left-dominant activity. For measurements of respiratory rate, we employed a Kinect motion sensor (Microsoft). The MA tasks increased both oxy-Hb in the bilateral PFC and respiratory rate (p < 0.001). In addition, there was a significant correlation between LI and respiratory rate (r = 0.582, p < 0.02). These results indicate that the MA-induced activity in the right PFC was greater than that in the left PFC in subjects with large increases of respiratory rate, suggesting that the right PFC has a greater role in cerebral regulation of respiratory rate during mental stress.

It remains unclear whether language tasks in one's first (L1) or second (L2) language can cause stress responses and whether frontal, autonomic and behavioral responses to stressful tasks are correlated. In this study, we studied 22 Chinese subjects whose L2 was English and measured the cerebral blood oxygenation in their frontal lobe by using functional near-infrared spectroscopy (fNIRS) as participants engaged in a mental arithmetic task (MAT) and verbal fluency tasks (VFTs) in L1 (Chinese) and L2 (English). To examine the activated cortical areas, we estimated the channel location based on Montreal Neurological Institute (MNI) standard brain space by using a probabilistic estimation method. We evaluated heart rate (HR) changes to analyze autonomic nervous system (ANS) functioning. We found that the MAT and VFTs induced greater increases in HR than did the control (Ctrl) task. Furthermore, subjects developed greater increases in HR in the MAT and VFTL2 than they did in the VFTL1. Compared with the Ctrl task, the MAT and both VFTL1 and VFTL2 produced robust and widespread bilateral activation of the frontal cortex. Interestingly, partial correlation analysis indicated that the activity in the left inferior frontal gyrus (LIFG) [Brodmann's area (BA) 47] was consistently correlated with the increases in HR across the three tasks (MAT, VFTL2, and VFTL1), after controlling for the performance data. The present results suggested that a VFT in L2 may be more stressful than in L1. The LIFG may affect the activation of the sympathetic system induced by stressful tasks, including MATs and VFTs.

We aimed to evaluate the usefulness of a newly developed, near-infrared spectroscopy (NIRS) device for monitoring hemodynamic changes during carotid artery stenting (CAS), as a means to detect filter obstruction due to distal embolism. We evaluated 16 patients with internal carotid artery (ICA) stenosis during the CAS procedure, using a NIRS system that can monitor not only changes in oxygenation of hemoglobin (Hb), but also the fluctuation of oxyhemoglobin (oxy-Hb) synchronized with heartbeat. The NIRS system detected a marked decrease of oxy-Hb and an increase of deoxyhemoglobin (deoxy-Hb) during ICA occlusion in patients without anterior cross circulation (ACC). Patients with ACC showed much smaller changes. The analysis of oxy-Hb fluctuation made it possible to detect occurrence of no-flow in the absence of Hb concentration changes. The amplitude of oxy-Hb fluctuation in the no/slow-flow group was significantly smaller than that in the normal-flow group. Our results indicate that the present high time-resolution NIRS device, which can measure oxy-Hb fluctuation, is superior to conventional NIRS for detecting filter obstruction.

Near-infrared spectroscopy enables recognition of various brain conditions based on certain factors, such as oxygenated hemoglobin (oxy-Hb). Since July 2012, we have been trying to determine the mechanisms of autonomic function in Japanese children with orthostatic intolerance (also called orthostatic dysregulation) in Nihon University Itabashi Hospital in Tokyo, Japan. A total of 23 children aged 7-16 years diagnosed with postural tachycardia syndrome (POTS), a subtype of orthostatic dysregulation, were enrolled in the study. We evaluated the relation between asymmetry in frontal cortex activity and the automatic nervous system and compared oxy-Hb changes in the right and left frontal cortices during an active standing test. We observed that during active standing oxy-Hb decreased in the frontal cortex. The oxy-Hb changes were asymmetrical, with a significantly larger decrease in the left frontal cortex than in the right frontal cortex, suggesting that tachycardia during active standing in POTS patients might be caused by activation of the right frontal cortex, which induces sympathetic nervous system activity.

In order to clarify the mechanism through which extract of Ginkgo biloba leaves (EGb) improves cognitive function, we examined the effects of EGb on cerebral blood oxygenation in the prefrontal cortex (PFC) and on performance during a working memory task, using near-infrared spectrometry (NIRS). First, we evaluated differences in behavioral performance of the Sternberg working memory test (ST) and in the activation pattern of the PFC during ST between 15 young and 19 middle-aged healthy women. Then, we examined the effect of EGb (120 mg/day for 6 weeks) on ST performance and PFC activation pattern in the middle-aged group. The middle-aged group exhibited a longer reaction time (RT) in ST than the young group and showed a different PFC activation pattern during ST, i.e., the middle-aged group showed bilateral activation while the young group showed right-dominant activation. In the middle-aged group, administration of EGb for 6 weeks shortened the RT of ST and changed the PFC activation pattern to right-dominant, like that in the young group. The results indicate the PFC plays a role in the physiological cognitive function-enhancing effect of EGb. EGb might improve working memory function in middle-aged individuals by counteracting the occurrence of aging-related hemispheric asymmetry reduction.

Patients with cerebral ischemia or brain tumor have been reported to exhibit an increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying this hemodynamic response pattern are unclear. In this study, we performed a simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864, 1998). We hypothesized that the oxygen extraction rate during the rest period (E 0) in the patients is larger than in normal subjects, because the cerebral blood flow and the speed at which the blood passes through the brain tissues are lower in the patients. The simulation result showed an increase of deoxy-Hb as well as oxy-Hb, especially when E 0 is extremely high. Thus, the results of our simulation suggest that the increase of deoxy-Hb during activation in patients with ischemia or brain tumor is caused by an increased oxygen extraction rate at rest, compared with that of healthy adults.

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.

The aim of this study was to predict mental stress levels of aged people at rest from two-channel near-infrared spectroscopy (NIRS) data from the prefrontal cortex (PFC). We used the State-Trait Anxiety Inventory (STAI) for the mental stress index.We previously constructed a machine learning algorithm to predict mental stress level using two-channel NIRS data from the PFC in 19 subjects aged 20-24 years at rest (Sato et al., Adv Exp Med Biol 765:251-256, 2013). In the present study, we attempted the same prediction for aged subjects aged 61-79 years (10 women; 7 men). The mental stress index was again STAI. After subjects answered the STAI questionnaire, the NIRS device measured oxy- and deoxy-hemoglobin concentration changes during a 3-min resting state. The algorithm was formulated within a Bayesian machine learning framework and implemented by Markov Chain Monte Carlo. Leave-one-subject-out cross-validation was performed.Average prediction error between the actual and predicted STAI values was 5.27. Prediction errors of 12 subjects were lower than 5.0. Since the STAI score ranged from 20 to 80, the algorithm appeared functional for aged subjects also.

The effects of artificial occlusal disharmony (AOD) on working memory function and prefrontal cortex (PFC) activity in the elderly were examined. We evaluated working memory function using the modified Sternberg test (ST). We measured activity in the bilateral PFC during ST using near-infrared spectroscopy (NIRS) before and after AOD: the mandibular position was displaced by a splint for 10 min. AOD caused a gradual increase of oxyhemoglobin (oxy-Hb) in the bilateral PFC. The response time of ST (six digits) after AOD was longer than that before AOD. The oxy-Hb increase during ST after AOD was smaller than that before AOD. These results indicate that short-term physical stress caused by AOD decreased working memory function in elderly subjects, associated with a decrease of the evoked PFC activity during working memory function.

The purpose of this study was to investigate the effects of stress on -prefrontal cortex (PFC), emotion (using visual analogue scale, VAS, and State-Trait Anxiety Inventory, STAI), and the autonomic nervous system (ANS). Two types of stress were applied: (1) malocclusion-induced physical stress and (2) mental stress induced by an arithmetic task. Malocclusion was induced using an experimentally deviated mandibular device (EDMD) to obtain an experimentally deviated mandibular position (EDMP). A total of 11 healthy volunteers participated in the study. On day 1 they performed a pretrial arithmetic task followed by a 10-min rest, after which they performed a posttrial EDMD + arithmetic task or rest device + arithmetic task. These two tasks were selected at random and assigned at the rate of one per day. Activity in the PFC tended to show an increase in the pretrial arithmetic tasks and rest device + arithmetic task, but a decrease in the EDMD + arithmetic task compared with the rest device + arithmetic task. Heart rate significantly increased during the rest device + arithmetic task, whereas no significant difference was observed during the EDMD + arithmetic task. The EDMD + arithmetic task significantly increased STAI scores (p = 0.0047), and the significant decrease in VAS indicated "unpleasant" (p = 0.035). These findings suggest that EDMP-induced reduction in the level of PFC activity was a response to discomfort, indicating that EDMP affects systemic function such as that of the ANS as an unpleasant stressor.

We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.

Background: Psychological distress is a risk factor of stroke in humans and worsens the behavioral and neurological outcomes. In rats, acute stress exposure preceding ischemic events attenuates learning and memory. The retrosplenial cortex (RS) plays an important role in these functions, and global brain ischemia (GBI) or acute stress exposure can induce a decrease in expression of the immature neuronal marker, doublecortin (DCX), in the RS. However, little is known about the DCX expression in the RS after stress exposure prior to GBI., Methods: Eighteen male Sprague-Dawley rats were used. Acute stress exposure was applied as the forced swim paradigm and GBI was induced by bilateral common carotid arterial occlusion for 10 min. The rats were divided into three groups: GBI model preconditioned by stress (n = 6, Group P), GBI model preconditioned by non-stress (n = 6, Group G), and controls (n = 6, Group C). We performed immunohistochemistry to observe and analyze the DCX-expressing cells and Fluoro-Jade B (FJB) staining to detect cell death in the RS after GBI in each group., Results: The total number of DCX-expressing cells was 1,032, 1,219, and 1,904 in Group P, Group G, and Group C, respectively. The mean number of DCX-expressing cells per unit area was significantly lower in Group P and Group G than in Group C (P < 0.001). Moreover, the number was significantly lower in Group P than in Group G (P < 0.05). In each group, no FJB positive cells were observed., Conclusion: DCX plays an important role in various cytoskeletal changes. Preconditioning by acute stress exposure accelerated the decrease in DCX expression in the RS after GBI.

The aim of this study was to develop a simple technique for objective assessment of mental stress levels by measuring hemoglobin concentration changes in the bilateral prefrontal cortex (PFC) at rest, employing two-channel near-infrared spectroscopy (NIRS). Each subject was instructed to think about nothing in particular for 3 min and then to complete the State-Trait Anxiety Inventory (STAI) test. Next, NIRS measurements were taken and the left/right asymmetry of PFC activity at rest was evaluated by calculating the proposed Laterality Index at Rest (LIR). There was a significant positive correlation between the LIR and STAI score in 39 subjects. The present method allowed evaluation of mental stress level from NIRS data in the PFC at rest.

Transient ischemic attack (TIA) is a major complication in patients with carotid artery stenosis. Patients with severe stenosis sometimes complain of orthostatic dizziness, such as syncope. The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for evaluating cerebral circulation in patients with carotid artery stenosis during head-up tilt test (HUTT). Fourteen patients with carotid artery stenosis and nine normal control subjects participated. In addition to blood pressure monitoring, hemoglobin (Hb) values (oxy-Hb, deoxy-Hb, and total Hb) were recorded by a wearable NIRS instrument with a high time resolution during HUTT. Oxy-Hb, which decreased initially when the test table was elevated, subsequently increased in normal volunteers and patients with carotid artery stenosis and did not differ significantly between the two groups. However, the oxy-Hb reduction in the carotid artery stenosis group (-0.02 ± 0.03 a.u.) at 30 s after elevation of the table was significantly larger than in the normal group (0.02 ± 0.02 a.u., P < 0.01). Our results indicate that oxy-Hb reduction in patients with carotid artery stenosis may be related to orthostatic dizziness. We concluded that NIRS monitoring is useful for evaluating cerebral autoregulation in patients with severe carotid artery stenosis.

Several distinctive activity patterns have been observed in the brain at rest. The aim of this study was to determine whether the STAI index can be predicted from changes in the oxy- and deoxy-hemoglobin (Hb) concentrations by using two-channel prefrontal cortex (PFC) NIRS data for the resting state. The study population comprised 19 subjects. Each subject performed four trials, each of which consisted of resting with no task for 3 min. Data were acquired using a portable NIRS device equipped with two channels. The prediction algorithm was derived within a Bayesian machine learning framework. The prediction errors for seven subjects were not greater than 5.0. Because the STAI index varied between 20 and 80, these predictions appeared reasonable. The present method allowed prediction of mental status based on the NIRS data at resting condition obtained in the PFC.

The aim of this study was to develop a NIRS-based neurofeedback system to modulate activity in the prefrontal cortex (PFC). We evaluated the effectiveness of the system in terms of separability of changes in oxy-Hb and its derivative. Training with neurofeedback resulted in higher separability than training without neurofeedback or no training, suggesting that the neurofeedback system could enhance self-control of PFC activity. Interestingly, the dorsolateral PFC exhibited enhanced activity and high separability after neurofeedback training. These observations suggest that the neurofeedback system might be useful for training subjects to regulate emotions by self-control of dorsolateral PFC activity.

Many studies have demonstrated cognitive function disorders including space learning disorders after global brain ischemia (GBI). Previous research on space perception and learning has indicated that the retrosplenial cortex (RS) is strongly involved. We performed immunostaining with doublecortin (DCX) for neurons with plasticity potential in the RS and investigated the neuronal numbers to assess the changes of plasticity in the RS following GBI. We employed male Sprague-Dawley rats and carried out bilateral carotid arterial occlusion for 10 min as a GBI model (control, n = 5; GBI model, n = 5). We counted the right and left hemispheres separately on two serial sections, for a total of four regions per animal to examine the differences in expression related to GBI. Additionally, we performed Fluoro-Jade B (FJB) staining to investigate the cause of any DCX-expressing neuron decrease. The total number of DCX-expressing neurons was 1,652 and 912 in the controls and GBI model, respectively. The mean number of DCX-expressing neurons per unit area was significantly lower in the GBI model than in the controls. FJB positive neurons were not found in the RS, while many were present in the -hippocampus CA1 after GBI. The decrease of DCX-expressing neurons in the RS indicated a plasticity decrease following GBI. The lack of FJB positive neurons in the RS after GBI suggested that the decrease of DCX-expressing neurons in the RS was not due to neuronal cell death in contrast to the hippocampus CA1, while the FJB positive neurons in the hippocampus indicated a delayed neuronal cell death as observed in many previous studies.

We examined the acute effect of physical exercise on prefrontal cortex activity in older adults using functional near-infrared spectroscopy (NIRS). Fourteen older adults visited our laboratory twice: once for exercise and once for the control condition. On each visit, subjects performed working memory tasks before and after moderate intensity exercise with a cycling ergo-meter. We measured the NIRS response at the prefrontal cortex during the working memory task. We found that physical exercise improved behavioral performance of the working memory task compared with the control condition. Moreover, NIRS analysis showed that physical exercise enhanced the prefrontal cortex activity, especially in the left hemisphere, during the working memory task. These findings suggest that the moderate intensity exercise enhanced the prefrontal cortex activity associated with working memory performance in older adults.

Background: The 2010 CPR Guidelines recommend that extracorporeal cardiopulmonary resuscitation (ECPR) using an emergency cardiopulmonary bypass (CPB) should be considered for patients with cardiac arrest. However, it is not yet clear whether this therapy can improve cerebral circulation and oxygenation in these patients. To clarify this issue, we evaluated changes of cerebral blood oxygenation (CBO) during ECPR using near-infrared spectroscopy (NIRS)., Methods: We employed NIRS to measure CBO in the bilateral frontal lobe in patients transported to the emergency room (ER) after out-of-hospital cardiac arrest between November 2009 and June 2011., Results: Fifteen patients met the above criteria. The tissue oxygenation index (TOI) on arrival at the ER was 36.5 %. This increased to 67.8 % during ECPR (P < 0.001). The one patient whose TOI subsequently decreased had a favorable neurological outcome., Conclusion: Increase of TOI during ECPR might reflect an improvement in cerebral blood flow, while decrease of TOI after ECPR might reflect oxygen utilization by the brain tissue as a result of neuronal cell survival. NIRS may be useful for monitoring cerebral hemodynamics and oxygen metabolism during CPR.

Rationale: Successful response inhibition is associated with right-lateralized inferior frontal cortex (IFC) activity, and alcohol impairs this inhibitory control, thereby enhancing false-alarm responses in the Go/No-Go task. However, the neural correlates of effect of alcohol on response inhibition remain unclear., Objective: This study characterized the acute effects of alcohol on IFC activity during Go/No-Go tasks using near-infrared spectroscopy (NIRS)., Methods: Thirty-two subjects visited our laboratory twice: once for alcohol intake and once for placebo intake. On each visit, subjects performed Go/No-Go tasks immediately before and 10 min after intake of the alcohol or placebo. NIRS was used to evaluate IFC activity measured during Go/No-Go tasks., Results: Alcohol significantly enhanced false-alarm responses in No-Go trials. NIRS analysis showed that IFC activity was greater in the right hemisphere than in the left hemisphere prior to alcohol or placebo intake. This right hemispheric superiority was eliminated in response to alcohol but not in response to placebo. Correlation analysis showed that subjects with right-lateralized IFC activity made fewer false-alarm responses in No-Go trials and that alcohol-induced inhibition of hemispheric IFC asymmetry resulted in higher false-alarm rates., Conclusion: These findings suggest that the right IFC may mediate the acute effects of alcohol on inhibitory control. When the alcohol impairs the right IFC activity, subjects cannot inhibit the pre-potent responses for No-Go trials, resulting in enhanced false-alarm responses. Thus, this study successfully demonstrated the neural correlates of the alcohol effect in the right IFC activity during inhibitory control processes.

This study used off-line repetitive transcranial magnetic stimulation (rTMS) to examine the roles of the superior parietal lobule (SPL) and inferior frontal gyrus (IFG) in a deductive reasoning task. Subjects performed a categorical syllogistic reasoning task involving congruent, incongruent, and abstract trials. Twenty four subjects received magnetic stimulation to the SPL region prior to the task. In the other 24 subjects, TMS was administered to the IFG region before the task. Stimulation lasted for 10min, with an inter-pulse frequency of 1Hz. We found that bilateral SPL (Brodmann area (BA) 7) stimulation disrupted performance on abstract and incongruent reasoning. Left IFG (BA 45) stimulation impaired congruent reasoning performance while paradoxically facilitating incongruent reasoning performance. This resulted in the elimination of the belief-bias. In contrast, right IFG stimulation only impaired incongruent reasoning performance, thus enhancing the belief-bias effect. These findings are largely consistent with the dual-process theory of reasoning, which proposes the existence of two different human reasoning systems: a belief-based heuristic system; and a logic-based analytic system. The present findings suggest that the left language-related IFG (BA 45) may correspond to the heuristic system, while bilateral SPL may underlie the analytic system. The right IFG may play a role in blocking the belief-based heuristic system for solving incongruent reasoning trials. This study could offer an insight about functional roles of distributed brain systems in human deductive reasoning by utilizing the rTMS approach., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Various studies have demonstrated the usefulness of near infrared spectroscopy (NIRS) for detecting cerebral ischemia during a carotid endarterectomy; however, it is difficult to apply NIRS to the diagnosis of ischemic stroke, since commercially available NIRS, which uses continuous-wave light, does not provide quantitative values of baseline hemoglobin (Hb) concentrations. In contrast, time-resolved near-infrared spectroscopy (TRS) permits quantitative measurement of Hb concentrations. We applied TRS to detection of cerebra vasospasm after subarachnoid hemorrhage (SAH). We investigated 11 age-matched controls and 14 aneurysmal SAH patients that comprised 10 patients with World Federation of Neurological Societies (WFNS) grade V and 4 patients with WFNS grade II. Employing TR-NIRS, we measured the cortical oxygen saturation (CoSO2) and baseline Hb concentrations in the middle cerebral artery territory. The CoSO2 and Hb concentrations remained stable after SAH in 6 patients; digital subtraction angiography (DSA) did not reveal vasospasm in these patients. In 8 patients, however, CoSO2 and total Hb decreased abruptly between 5 and 9 days after SAH. DSA revealed diffuse vasospasms in 6 of 8 patients. The reduction of CoSO2 predicted occurrence of vasospasm at a cutoff value of 3.9%-6.4% with 100% sensitivity and 85.7% specificity. Trans cranial Doppler (TCD) failed to detect vasospasm in 4 cases, whereas TR-NIRS could. Finally, TRS performed on day 1 after SAH revealed significantly higher CoSO2 than that of the controls (p = 0.048), but there was no significant difference in total Hb. TRS detected vasospasm by evaluating the CBO in the cortex and may be more sensitive than TCD, which assesses the blood flow velocity in the M1 portion. TRS may be useful for the diagnosis of ischemic events in stroke patients.

Objective: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has been used in moyamoya disease (MD) and non-moyamoya ischemic stroke (non-MD). It is important to monitor hemodynamic changes caused by bypass surgery for postoperative management. We evaluated the bypass blood flow during STA-MCA anastomosis by using indocyanine green (ICG) fluorescence angiography., Methods: We evaluated the bypass blood flow in 13 MD and 21 non-MD patients during STA-MCA anastomosis by means of ICG angiography with injection of ICG into the anastomosed STA. The ICG perfusion area was calculated when the ICG fluorescence intensity reached maximum. We measured cortical oxygen saturation before anastomosis by means of visual light spectroscopy., Results: ICG angiography demonstrated bypass blood flow from the anastomosed STA to the cortical vessels in all patients. The ICG perfusion area in MD (20.7 ± 6.6 cm(2)) was significantly larger than that in non-MD (8.4 ± 9.1 cm(2), P < 0.05). The cortical oxygen saturation (58.9% ± 8.3%) in MD was significantly lower than that in non-MD (73.4% ± 9.5%, P < 0.05)., Conclusions: ICG angiography with injection of ICG into the bypass artery allowed quantitative assessment of bypass blood flow. The bypass supplies blood flow to a greater extent in MD than in non-MD during surgery. This might be caused by a larger pressure gradient between the anastomosed STA and recipient vessels in MD. These observations indicate that MD requires careful control of systemic blood pressure after surgery to avoid cerebral hyperperfusion syndrome. ICG angiography is considered useful for facilitating safe and accurate bypass surgery and providing information for postoperative management., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Early detection of vasospasm is essential for the treatment of delayed ischemic neurological deficits in subarachnoid hemorrhage (SAH). We evaluated cerebral blood oxygenation (CBO) changes after SAH employing quantitative time-resolved near-infrared spectroscopy (TR-NIRS) for this purpose., Methods: We investigated 11 age-matched controls and 14 aneurysmal SAH patients, including 10 patients with WFNS grade V and 4 patients with grade II. Employing TR-NIRS, we measured the cortical oxygen saturation (CoSO(2)) and baseline hemoglobin concentrations in the middle cerebral artery territory. Measurements of TR-NIRS and transcranial Doppler sonography (TCD) were performed repeatedly after SAH., Results: In six patients, the CoSO(2) and hemoglobin concentrations remained stable after SAH; digital subtraction angiography (DSA) did not reveal vasospasm in these patients. In eight patients, however, CoSO(2) and total hemoglobin decreased abruptly between 5 and 9 days after SAH. DSA revealed diffuse vasospasms in six of eight patients. The reduction of CoSO(2) predicted occurrence of vasospasm at a cutoff value of 3.9%-6.4% with 100% of sensitivity and 85.7% of specificity. TCD failed to detect the vasospasm in four cases, which TR-NIRS could detect. Finally, TR-NIRS performed on Day 1 after SAH revealed significantly higher CoSO(2) than that of controls (p = .048), but there was no significant difference in total hemoglobin., Conclusion: TR-NIRS detected vasospasm by evaluating the CBO in the cortex and may be more sensitive than TCD, which assesses the blood flow velocity in the M1 portion. The cerebral oxygen metabolism in SAH might be reduced by brain damage due to aneurysmal rupture., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Although endovascular treatment has a high success rate, it is not clear how endovascular treatment affects cerebral perfusion and hemodynamics during the perioperative period. We evaluated changes in cerebral blood oxygenation (CBO) repeatedly after endovascular treatment employing time-resolved spectroscopy (TRS). We investigated a patient (10 months old, female) who suffered cerebral arteriovenous fistula. Cerebral angiography demonstrated a pial arteriovenous fistula with three feeders (left PICA, SCA, and AICA). TRS demonstrated a decrease of oxyhemoglobin, total hemoglobin, and oxygen saturation associated with an increase of deoxyhemoglobin in all of the regions measured just after embolization, indicating that embolization improved hyperemia caused by the AV shunt. Interestingly, progressive improvement of hyperemia was observed 3 and 8 days after embolization of the feeders. The present study demonstrated that embolization of the feeders caused progressive changes in CBO and hemodynamics during the perioperative period. TRS may be a useful tool for monitoring cerebral blood perfusion changes after endovascular surgery.

We evaluated the effect of aging on the prefrontal cortex (PFC) activity and heart rate during the task. Employing near infrared spectroscopy (NIRS), we measured hemoglobin concentration changes in the bilateral PFC during a mental arithmetic task in young and older females. We selected the subjects who exhibited an increase in oxyhemoglobin with a decrease in deoxyhemoglobin during the task. We observed that right PFC activity predominantly modulates sympathetic effects during the task in both groups. However, the changes of oxyhemoglobin and heart rate during the task in older subjects were significantly smaller than those in young subjects. These results indicate that aging affects evoked cerebral blood oxygenation (CBO) response patterns of the PFC during a mental stress task. Aging did not affect the laterality of PFC activity in modulation of ANS function in the subjects who exhibited increases of oxyhemoglobin and deoxyhemoglobin associated with a decrease of deoxyhemoglobin during the task. However, aging reduced the heart rate increase during the task.

We demonstrated that ischemic strokes exhibit an increase of deoxyhemoglobin during activation. We evaluated the effect of revascu-larization on the abnormal evoked cerebral blood oxygenation (CBO) re-sponses in these patients, employing near-infrared spectroscopy (NIRS). We selected five patients who exhibited an increase of deoxyhemoglobin associated with increases of oxyhemoglobin and total hemoglobin during activation for this study. These patients showed marked reductions of base-line regional cerebral blood flow and cerebrovascular reserve capacity, which were improved 1 week after revascularization. Postoperative NIRS demonstrated that the increase of deoxyhemoglobin during activa-tion was not observed after revascularization. This preliminary study demonstrated that the abnormal evoked-CBO response in ischemic stroke patients could be improved by revascularization.

Indocyanine green (ICG) emits near-infrared fluorescence when it is excited by near-infrared light. The near infrared fluorescence of ICG was applied to the imaging of cerebral vessels during neurosurgical operations such as clipping of aneurysms. In this study, ICG angiography was applied to extracranial-intracranial (EC-IC) bypass surgery to evaluate the hemodynamic changes induced by bypass in moyamoya disease (MD) and non-moyamoya ischemic diseases (non-MD). These patients underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We compared the cortical areas where the bypass supplied blood flow between MD and non-MD. ICG angiography clearly demonstrated the bypass blood flow from the anastomosed STA to the cortical vessels including arteries, capillaries, and veins in both MD and non-MD. Interestingly, the anastomosed STA supplied blood flow to a larger cortical area in MD than non-MD. The bypass supplied greater extent of blood flow to the ischemic brain in MD than in non-MD. This difference might be caused by the fact that the perfusion pressure was lower in MD than in non-MD.

We examined the usefulness of near infrared time-resolved spectroscopy (TRS) for detection of vasospasm in subarachnoid hemorrhage (SAH). We investigated seven aneurysmal SAH patients with poor clinical conditions (WFNS grade V) who underwent endovascular coil embolization. Employing TRS, we measured the oxygen saturation (SO(2)) and baseline hemoglobin concentrations in the cortices. Measurements of TRS and transcranial Doppler sonography (TCD) were performed repeatedly for 14 days after SAH. In four of the seven patients, the SO(2) and hemoglobin concentrations measured in the brain tissue of the middle cerebral artery territory remained stable after SAH. However, in three patients, TRS revealed abrupt decreases in SO(2) and total hemoglobin between 5 and 9 days after SAH. Cerebral angiography performed on the same day revealed severe vasospasms in these patients. Although TCD detected the vasospasm in two of three cases, it failed to do so in one case. TRS could detect vasospasms after SAH by evaluating the cortical blood oxygenation.

The sensitivity of the near-infrared spectroscopy signal to the brain activation depends on the thickness and structure of the superficial tissues. The influence of the frontal sinus, which is void region in the skull, on the sensitivity to the brain activation is investigated by the time-resolved experiments and the theoretical modelling of the light propagation in the head. In the time-resolved experiments, the mean-time of flight for the forehead scarcely depends upon the existence of the frontal sinus when probe spacing was shorter than 30 mm. The partial optical path length in the brain, which indicates the sensitivity of the near-infrared spectroscopy signal to the brain activation, in a simplified head model is predicted by Monte Carlo simulation. The influence of the frontal sinus on the sensitivity of the signal depends on the thickness of the skull and the depth of the frontal sinus.

Measurement of multichannel continuous-wave near-infrared spectroscopy (CW-NIRS) is dependent on the modified Beer-Lambert law, which includes optical pathlength (PL) as an essential parameter. PLs are known to differ across different head regions and different individuals, but the distribution of PLs for the whole head has not been evaluated so far. Thus, using time-resolved near-infrared spectroscopy (TR-NIRS), we measured the optical characteristics including PL, scattering coefficients (mu'(s)), and absorption coefficients (mu(a)) at three wavelengths (760, 800, 830 nm). Then, we constructed maps of these parameters on the subjects' head surface. While the PLs in nearby channels are similar, they differ depending on the regions of the head. The PLs in the region above the Sylvian fissure tended to be shorter than those in the other regions at all of the wavelengths. The difference in the distribution of PLs may be attributed to differences in tissue absorption and scattering properties. The current study suggests the importance of considering PL differences in interpreting functional data obtained by CW-NIRS.

We describe the set-up for an electrical muscle stimulation device based on near-infrared spectroscopy (NIRS), designed for use as a brain-computer interface (BCI). Employing multi-channel NIRS, we measured evoked cerebral blood oxygenation (CBO) responses during real motor tasks and motor-imagery tasks. When a supra-threshold increase in oxyhemoglobin concentration was detected, electrical stimulation (50 Hz) of the biceps brachii muscle was applied to the side contralateral to the hand grasping task or ipsilateral to the motor-imagery task. We observed relatively stable and reproducible CBO responses during real motor tasks with an average accuracy of 100%, and during motor imagery tasks with an average accuracy of 61.5%. Flexion movement of the arm was evoked in all volunteers in association with electrical muscle stimulation and no adverse effects were noted. These findings suggest that application of the electrical muscle stimulation system based on a NIRS-BCI is non-invasive and safe, and may be useful for the physical training of disabled patients.

The purpose of this study was to compare the influence of biting and finger clenching intensity on the concentration of oxygenated hemoglobin (OxyHb) in regional cerebral blood flow (rCBF) as an indicator of brain activity in the primary motor (MI) and somatosensory (SI) cortices. Functional near-infrared spectroscopy (fNIRS) was used in 8 healthy subjects. Subjects were required to do biting (bite) and finger clenching (fclench) at 20, 50 and 80% of maximum force. To minimize the effect of temporal muscle activity on the working side of the jaw, the fNIRS probes were positioned contralaterally, in the left temporal region. Activation of MI and SI cortices with bite and fclench was noted in all subjects, irrespective of the intensity of bite and fclench. A significant increase was observed in OxyHb in MI and SI between 20% and both 50 and 80% intensity. In MI cortex, OxyHb showed a significant increase between 80% and both 20 and 50% fclench intensity. The results suggest that intensity of bite and fclench influences activation levels in MI and SI. Further, an activation was more obvious with bite than fclench.

The purpose of this study was to elucidate the influence of bite force control on oxygenated hemoglobin (OxyHb) levels in regional cerebral blood flow as an indicator of brain activity in the premotor area. Healthy right-handed volunteers with no subjective or objective symptoms of problems of the stomatognathic system or cervicofacial region were included. Functional near-infrared spectroscopy (fNIRS) was used to determine OxyHb levels in the premotor area during bite force control. A bite block equipped with an occlusal force sensor was prepared to measure clenching at the position where the right upper and lower canine cusps come into contact. Intensity of clenching was shown on a display and feedback was provided to the subjects. Intensity was set at 20, 50 and 80% of maximum voluntary teeth clenching force. To minimize the effect of the temporal muscle on the working side of the jaw, the fNIRS probes were positioned contralaterally, in the left region. The findings of this study are: activation of the premotor area with bite force control was noted in all subjects, and in the group analysis OxyHb in the premotor cortex was significantly increased as the clenching strengthened at 20, 50 and 80% of maximum voluntary clenching force. These results suggest there is a possibility that the premotor area is involved in bite force control.

The relationship between changes in cerebral blood oxygenation and neuronal activity remains to be fully established. We compared somatosensory evoked potentials (SEP) and evoked cerebral blood oxygenation (CBO) changes in the sensorimotor cortex of the rat. In rats anesthetized with urethane and alpha-chloralose, we measured SEP and CBO using visible light spectroscopy (VLS) during neuronal activity. Increase of stimulus frequency caused a decrease of SEP amplitude, but an increase in concentration changes of deoxy-Hb and oxygen saturation. The difference in frequency responses between SEP and CBO might be caused by activation of inhibitory neurons, which could suppress excitatory neurons at high stimulus frequencies; activation of inhibitory neurons could reduce SEP amplitude, and increase oxygen saturation due to an increase of evoked cerebral blood flow.

In order to evaluate the effect of cerebral ischemia on the flavoprotein fluorescence (FPF), we compared the changes in the FPF and somatosensory evoked potential (SEP) during transient cerebral ischemia in the rat. We measured the FPF and SEP simultaneously via a cranial window made over the right sensorimotor cortex during the left median nerve stimulation in F344 rats. We compared change in FPF and SEP during cerebral ischemia for 60 min. The rCBF were rapidly recovered after reperfusion. However, the recovery rates of the FPF were significantly faster than those of the SEP after reperfusion. These findings indicate that activity-dependent changes of the FPF do not necessarily correlate with the electrical activity after transient cerebral ischemia.

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) in the frontal lobe during language tasks, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) in the right and left frontal lobes in normal adults (n = 9, mean age = 29.6 +/- 4.8 years). We employed a newly developed 8-channel time-resolved near-infrared spectroscopy (TRS) instrument. The results demonstrated differences in MOP in the fronto-temporal areas with subject and wavelength; however, there was no significant difference between the right and left sides (p > 0.05). Also, the VFT did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In all of the recording regions, the VFT caused increases in concentration of oxyhemoglobin and total hemoglobin associated with a decrease in deoxyhemoglobin concentration, indicating that these cortical areas were activated by the VFT. However, the mean concentration changes of oxyhemoglobin and total hemoglobin on the left side were larger than those on the right side. In addition, functional MRI demonstrated that the inferior frontal gyrus on the left side was activated in the subjects who exhibited increases in oxyhemoglobin concentration in these areas. These results suggest that TRS may be useful to study language function and to assess hemispheric dominance for language.

Acupuncture is helpful in treating various diseases, including autonomic nervous system (ANS) dysfunction caused by mental stress. On the other hand, the frontal lobe is suggested to play an important role in stress responses by modulating the ANS. The aim of the study was to evaluate the effects of acupuncture on ANS and frontal lobe activities. We investigated 18 normal adults. We measured the activity of prefrontal cortex (PFC) caused by real acupuncture (WHO-LI4) and sham acupuncture, employing optical topography. To evaluate ANS function, we analyzed heart rate variability (HRV). Analysis of HRV revealed a decrease of the LF/HF ratio, and an increase of the HF power by real acupuncture, indicating a shift to parasympathetic dominancy. Acupuncture also caused cerebral blood oxygenation changes in both directions, that is, an increase and/or a decrease of oxyhemoglobin (Oxy-Hb) in the bilateral PFC. However, the Oxy-Hb change was not correlated with HRV parameters in the majority of cases. One of the possible explanations of the poor correlations might be that the PFC activity induced by acupuncture is not closely linked with ANS function.

Blood-oxygen-level-dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been used to perform functional imaging in brain disorders such as stroke and brain tumors. However, recent studies have revealed that BOLD-fMRI does not image activation areas correctly in such patients. To clarify the characteristics of the evoked cerebral blood oxygenation (CBO) changes occurring in stroke and brain tumors, we have been comparing near-infrared spectroscopy (NIRS) and BOLD-fMRI recording during functional brain activation in these patients. We review our recent studies and related functional imaging studies on the brain disorders. In the primary sensorimotor cortex (PSMC) on the nonlesion side, the motor task consistently caused a decrease of deoxyhemoglobin (deoxy-Hb) with increases of oxyhemoglobin (oxy-Hb) and total hemoglobin (t-Hb), which is consistent with the evoked CBO response observed in normal adults. BOLD-fMRI demonstrated robust activation areas on the nonlesion side. In stroke patients, severe cerebral ischemia (i.e., misery perfusion) caused an increase of deoxy-Hb during the task, associated with increases of oxy-Hb and t-Hb, in the PSMC on the lesion side. In addition, the activation volume of BOLD-fMRI was significantly reduced on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side, but it tended to decrease in other areas during the tasks. In brain tumors, BOLD-fMRI clearly demonstrated activation areas in the PSMC on the lesion side in patients who displayed a normal evoked CBO response. However, the activation volume on the lesion side was significantly reduced in patients who exhibited an increase of deoxy-Hb during the task. In both stroke and brain tumors, false-negative activations (i.e., marked reductions of activation volumes) in BOLD imaging were associated with increases of deoxy-Hb, which could cause a reduction in BOLD signal. BOLD-fMRI investigations of patients with brain disorders should be performed while giving consideration to atypical evoked CBO changes.

Background and Purpose: To evaluate the mechanisms of failure of blood oxygenation level-dependent (BOLD) imaging in stroke, we compared the evoked cerebral blood oxygenation (CBO) responses and activation volumes (AVs) of BOLD functional MRI (fMRI) in chronic stroke patients with moderate and severe cerebral ischemia., Methods: We measured the evoked CBO responses in the primary sensorimotor cortex (PSMC) by means of near-infrared spectroscopy during contralateral motor tasks. We compared the AV of BOLD-functional MRI in the PSMC on the nonlesion and lesion sides. Single-photon emission computed tomography was used to classify ischemic status as moderate (slight reduction of regional cerebral blood flow and cerebrovascular reserve capacity [CVRC]) or severe (marked reduction of regional cerebral blood flow and CVRC; ie, misery perfusion)., Results: In age-matched controls, deoxyhemoglobin concentration decreased with concomitant increases in oxyhemoglobin and total hemoglobin concentrations during activation. The PSMC on the nonlesion side exhibited a normal CBO response pattern. On the lesion side, moderate cerebral ischemia did not affect the CBO response pattern, but severe cerebral ischemia caused an increase of deoxyhemoglobin during the task, associated with increases of oxyhemoglobin and total hemoglobin. Moderate cerebral ischemia induced only a slight reduction of the AV on the lesion side; however, severe cerebral ischemia markedly reduced the AV on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side in severe cerebral ischemia, whereas it tended to decrease in other areas during the tasks., Conclusions: Misery perfusion caused a marked reduction of the AV on BOLD imaging, associated with an increase of deoxyhemoglobin concentration during activation. BOLD-fMRI investigations of stroke patients should be performed while giving consideration to baseline circulatory status. Functional near-infrared spectroscopy could be an alternative means to assess the CVRC.

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) during activation and deactivation, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) and driving simulation in the right and left prefrontal cortex (PFC), employing a newly developed time-resolved near infrared spectroscopy, which allows quantitative measurements of the evoked-CBO changes by determining the MOP with a sampling time of 1 s. The results demonstrated differences in MOP in the foreheads with the subjects and wavelength; however, there was no significant difference between the right and left foreheads (p > 0.05). Also, both the VFT and driving simulation task did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In the bilateral PFCs, the VFT caused increases of oxyhemoglobin and total hemoglobin associated with a decrease of deoxyhemoglobin, while the driving simulation task caused decreases of oxyhemoglobin and total hemoglobin associated with an increase of deoxyhemoglobin; there were no significant differences in evoked-CBO changes between the right and left PFC. The present results will be useful for quantitative measurement of hemodynamic changes during activation and deactivation in the adults by near infrared spectroscopy.

Background: Cortical stimulation via a subdural grid electrode (SGE) is one of the most reliable methods for identifying eloquent areas before surgery. However, the physiological conditions of the cortex during stimulation cannot be monitored electrophysiologically because of electrical artifacts. In the present case, we tested whether or not multichannel near-infrared spectroscopy (NIRS) topography, a noninvasive optical imaging technique, is applicable for monitoring the physiological conditions of the stimulated cortex., Case Description: The patient (a 27-year-old right-handed man) suffered from glioma in the left frontal lobe. For preoperative cortical mapping, SGEs were implanted over the left motor cortex before tumor resection. Employing NIRS topography, we undertook 2 dimensional imaging of the changes in oxyhemoglobin (Oxy-Hb) and deoxyhemoglobin (Deoxy-Hb) concentration during electrical stimulation. Five-hertz stimulation with 5 mA at the left-hand area produced a localized increase in Oxy-Hb and a decrease in Deoxy-Hb, associated with slight twitching of the right hand. In contrast, 50-Hz stimulation produced significant increases in both Oxy-Hb and Deoxy-Hb at the stimulation site, and the area with such cerebral blood oxygenation (CBO) changes propagated beyond the hand area associated with prominent muscle contractions of the right upper extremity, suggesting that 50-Hz stimulation caused epileptic discharge., Conclusion: Near-infrared spectroscopy topography may represent a useful tool for imaging the degree and extent of the physiological effects of electrical stimulation on the cortex, and permits safe and accurate cortical mapping.

The present case demonstrates that the blood oxygenation level-dependent (BOLD) signal intensity can decrease in the activated motor cortex on the lesion side (left) of a patient with a left frontal glioma during functional recovery after surgery. Near-infrared spectroscopy revealed that the decrease of BOLD signal was associated with increases of cerebral blood volume and deoxyhemoglobin concentrations in the cerebral vessels. This implies that the interpretation of results obtained by functional MR imaging in patients with brain disorders must take into consideration such atypically evoked cerebral blood oxygenation changes, which do not increase the BOLD signals.