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1.  Prefrontal cortex and executive function in young children: a review of NIRS studies 
Executive function (EF) refers to the higher-order cognitive control process for the attainment of a specific goal. There are several subcomponents of EF, such as inhibition, cognitive shifting, and working memory. Extensive neuroimaging research in adults has revealed that the lateral prefrontal cortex plays an important role in EF. Developmental studies have reported behavioral evidence showing that EF changes significantly during preschool years. However, the neural mechanism of EF in young children is still unclear. This article reviews recent near-infrared spectroscopy (NIRS) research that examined the relationship between the development of EF and the lateral prefrontal cortex. Specifically, this review focuses on inhibitory control, cognitive shifting, and working memory in young children. Research has consistently shown significant prefrontal activation during tasks in typically developed children, but this activation may be abnormal in children with developmental disorders. Finally, methodological issues and future directions are discussed.
PMCID: PMC3865781  PMID: 24381551
prefrontal cortex; executive function; young children; NIRS; developmental disorders
2.  Psychosomatic problems and countermeasures in Japanese children and adolescents 
In Japan there are a number of children and adolescents with emotion-related disorders including psychosomatic diseases (orthostatic dysregulation, anorexia nervosa, recurrent pains), behavior problems and school absenteeism. According to our previous report, the Japanese children had significantly higher score of physical symptoms and psychiatric complaints than did the Swedish children, and these were more strongly influenced by school-related stress than by home-related stress. To enforce countermeasures for psychosomatic problems in children, the Japanese Society of Psychosomatic Pediatrics (established in 1982) have started several new projects including multi-center psychosomatic researches and society-based activities. In this article, we present an outline of our study on mental health in Japanese children in comparison with Swedish children. Countermeasures including clinical guidelines for child psychosomatic diseases are reviewed and discussed.
PMCID: PMC3362750  PMID: 22433184
Psychosomatic disease; Orthostatic dysregulation; Anorexia nervosa; School absenteeism; Migraine
3.  Sensitivity of fNIRS to cognitive state and load 
Functional near-infrared spectroscopy (fNIRS) is an emerging low-cost noninvasive neuroimaging technique that measures cortical bloodflow. While fNIRS has gained interest as a potential alternative to fMRI for use with clinical and pediatric populations, it remains unclear whether fNIRS has the necessary sensitivity to serve as a replacement for fMRI. The present study set out to examine whether fNIRS has the sensitivity to detect linear changes in activation and functional connectivity in response to cognitive load, and functional connectivity changes when transitioning from a task-free resting state to a task. Sixteen young adult subjects were scanned with a continuous-wave fNIRS system during a 10-min resting-state scan followed by a letter n-back task with three load conditions. Five optical probes were placed over frontal and parietal cortices, covering bilateral dorsolateral PFC (dlPFC), bilateral ventrolateral PFC (vlPFC), frontopolar cortex (FP), and bilateral parietal cortex. Activation was found to scale linearly with working memory load in bilateral prefrontal cortex. Functional connectivity increased with increasing n-back loads for fronto-parietal, interhemispheric dlPFC, and local connections. Functional connectivity differed between the resting state scan and the n-back scan, with fronto-parietal connectivity greater during the n-back, and interhemispheric vlPFC connectivity greater during rest. These results demonstrate that fNIRS is sensitive to both cognitive load and state, suggesting that fNIRS is well-suited to explore the full complement of neuroimaging research questions and will serve as a viable alternative to fMRI.
PMCID: PMC3930096  PMID: 24600374
working memory; n-back; functional connectivity; resting state; fronto-parietal
California Medicine  1952;76(1):23-26.
The intimate relationship between the urinary and genital systems permits stimuli in one system to influence the other. At least 15 per cent of women with symptoms of cystitis have no organic basis for their complaints. In psychiatric studies it has been noted that sexual conflict is the primary etiological factor in these patients. In some cases, continuance of the disorder leads to irreversible organic change. Urinary symptoms such as frequency, urgency, burning or retention are most common in women and become an automatic response to anxiety-provoking or sexual stimuli.
In men, functional urinary symptoms are relatively infrequent. Often they indicate problems of genital dysfunction. Complaints of impotence, penile pain, testicular pain, or non-specific urethritis stem back to difficulties in their sexual lives. Many of the patients have symptoms of a generalized anxiety tension state due to sexual problems.
A purely organic consideration of genitourinary disorders will lead to erroneous conclusions and unsatisfactory therapeutic results. The psychosomatic approach—that is, considering both physical and psychological aspects—will explain many hitherto difficult cases.
PMCID: PMC1521180  PMID: 14886756
5.  Using MazeSuite and Functional Near Infrared Spectroscopy to Study Learning in Spatial Navigation 
MazeSuite is a complete toolset to prepare, present and analyze navigational and spatial experiments1. MazeSuite can be used to design and edit adapted virtual 3D environments, track a participants' behavioral performance within the virtual environment and synchronize with external devices for physiological and neuroimaging measures, including electroencephalogram and eye tracking.
Functional near-infrared spectroscopy (fNIR) is an optical brain imaging technique that enables continuous, noninvasive, and portable monitoring of changes in cerebral blood oxygenation related to human brain functions2-7. Over the last decade fNIR is used to effectively monitor cognitive tasks such as attention, working memory and problem solving7-11. fNIR can be implemented in the form of a wearable and minimally intrusive device; it has the capacity to monitor brain activity in ecologically valid environments.
Cognitive functions assessed through task performance involve patterns of brain activation of the prefrontal cortex (PFC) that vary from the initial novel task performance, after practice and during retention12. Using positron emission tomography (PET), Van Horn and colleagues found that regional cerebral blood flow was activated in the right frontal lobe during the encoding (i.e., initial naïve performance) of spatial navigation of virtual mazes while there was little to no activation of the frontal regions after practice and during retention tests. Furthermore, the effects of contextual interference, a learning phenomenon related to organization of practice, are evident when individuals acquire multiple tasks under different practice schedules13,14. High contextual interference (random practice schedule) is created when the tasks to be learned are presented in a non-sequential, unpredictable order. Low contextual interference (blocked practice schedule) is created when the tasks to be learned are presented in a predictable order.
Our goal here is twofold: first to illustrate the experimental protocol design process and the use of MazeSuite, and second, to demonstrate the setup and deployment of the fNIR brain activity monitoring system using Cognitive Optical Brain Imaging (COBI) Studio software15. To illustrate our goals, a subsample from a study is reported to show the use of both MazeSuite and COBI Studio in a single experiment. The study involves the assessment of cognitive activity of the PFC during the acquisition and learning of computer maze tasks for blocked and random orders. Two right-handed adults (one male, one female) performed 315 acquisition, 30 retention and 20 transfer trials across four days. Design, implementation, data acquisition and analysis phases of the study were explained with the intention to provide a guideline for future studies.
PMCID: PMC3227178  PMID: 22005455
6.  Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in Schizophrenia 
Biological Psychiatry  2011;70(1):19-27.
Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this paper is to examine the utility of TMS as a means of measuring neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. When incorporating TMS paradigms in research studies, methodological considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), functional MRI (fMRI), functional near infrared spectroscopy (fNIRS), magnetoencephalography (MEG), and electroencephalography (EEG), to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate different neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiological modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the CNTRICS armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.
PMCID: PMC3270326  PMID: 21571254
Transcranial magnetic stimulation; TMS; schizophrenia; CNTRICS; cortical function; biological marker
7.  Lifestyles and psychosomatic symptoms among elementary school students and junior high school students 
To examine the relationship between lifestyles and psychosomatic symptoms in children, we conducted a self-administered questionnaire survey of elementary school students and junior high school students in Japan.
We designed an original questionnaire to investigate the lifestyles and psychosomatic symptoms of children. In 1997, responses to the questionnaires were elicited from public elementary school fourth grade students (then aged 9–10) and public junior high school seventh grade students (then aged 12–13). The survey was repeated annually for three years as the students advanced through school.
For both boys and girls, each cross-sectional analysis revealed a strong relationship between lifestyle behaviors and psychosomatic symptoms. Psychosomatic, symptoms scores varied according to daily hours of sleep, eating of breakfast, having strong likes and dislikes of food, bowel habits, and daily hours of television watching. Both boys and girls with “good” lifestyle, behaviors evaluated by the HPI (Health Practice Index) showed lower scores for psychosomatic symptoms.
These findings show that the lifestyle behaviors of children are significantly associated with psychosomatic symptoms and suggest that poor lifestyle behaviors are likely to increase physical and psychological health risks.
PMCID: PMC2723516  PMID: 21432317
lifestyles; psychosomatic symptoms; elementary school; junior high school; health practice index
8.  Reduced dorsolateral prefrontal cortical hemodynamic response in adult obsessive-compulsive disorder as measured by near-infrared spectroscopy during the verbal fluency task 
Near-infrared spectroscopy has helped our understanding of the neurobiological mechanisms of psychiatric disorders and has advantages including noninvasiveness, lower cost, and ease of use compared with other imaging techniques, like functional magnetic resonance imaging. The verbal fluency task is the most common and well established task used to assess cognitive activation during near-infrared spectroscopy. Recent functional neuroimaging studies have shown that the orbitofrontal cortex and other brain regions, including the dorsolateral prefrontal cortex, may play important roles in the pathophysiology of obsessive-compulsive disorder (OCD). This study aimed to evaluate hemodynamic responses in the dorsolateral prefrontal cortex in patients with OCD using near-infrared spectroscopy during the verbal fluency task and to compare these with dorsolateral prefrontal cortex responses in healthy controls.
Twenty patients with OCD and 20 controls matched for age, gender, handedness, and estimated intelligence quotient participated in this study. The verbal fluency task was used to elicit near-infrared spectroscopic activation and consisted of a 30-second pre-task, followed by three repetitions of a 20-second verbal fluency task (total 60 seconds), followed by a 70-second post-task period. The near-infrared spectroscopy experiment was conducted on the same day as surveys of obsessive-compulsive symptoms, depression, and anxiety. Z-scores for changes in the concentration of oxygenated hemoglobin were compared between the OCD patients and controls in 14 channels set over the left and right dorsolateral prefrontal cortex and frontopolar areas.
During the verbal fluency task, significant task-related activation was detected in both the OCD group and the controls. Changes in oxygenated hemoglobin concentration in the right dorsolateral prefrontal cortex were significantly smaller in the OCD group than in the controls, but were not statistically significant after correction for multiple comparisons.
Patients with OCD have reduced prefrontal, especially right dorsolateral prefrontal, cortical hemodynamic responses as measured by near-infrared spectroscopy during the verbal fluency task. These results support the hypothesis that the dorsolateral prefrontal cortex plays a role in the pathophysiology of OCD.
PMCID: PMC3713899  PMID: 23874098
functional neuroimaging; near-infrared spectroscopy; obsessive-compulsive disorder; prefrontal hemodynamic response; verbal fluency task; dorsolateral prefrontal cortex
9.  The critical role of psychosomatics in promoting a new perspective upon health and disease 
Journal of Medicine and Life  2009;2(4):343-349.
In an evolutionary model, health and disease are regarded as successful and respectively failed adaptation to the demands of the environment. The social factors are critical for a successful adaptation, while emotions are means of both signaling the organism's state and of adapting the physiological responses to environmental challenges. Hence the importance of a biopsychosocial model of health and disease. Psychoemotional distress generates and/or amplifies somatic symptoms. Somatization may be viewed as an altered cognitive process, inclining the individual to an augmented perception of bodily sensations and to an increased degree of complexity in reporting negative experiences (hence the greater cognitive effort allocated thereto). Somatosensory amplification and alexithymia are key elements in this process. The brain's right hemisphere is more involved in the generation of emotionally conditioned somatization symptoms. Somatic symptoms have various psychological and social functions and are strongly influenced by the particular belief system of the individual. Inappropriately perceiving the environment as an aggressor and excessively responding to it (by activating the cytokine system in correlation with the arousal of the psychic, nervous, and endocrine systems) may be a key element in the altered cognition conducive to ill health.
PMCID: PMC3019025  PMID: 20108747
somatoform disorders; unexplained physical symptoms; somatization; amplification; alexithymia; cognitive model; cytokine
10.  Psychosomatic complaints and sense of coherence among adolescents in a county in Sweden: a cross-sectional school survey 
Over the last five to ten years there has been an increase in psychosomatic complaints (PSC) in Swedish children. The objective of the study was to examine the relation between PSC and sense of coherence (SOC).
A cross-sectional school survey in the county of Västmanland, Sweden. All 16- and 19-year old adolescents present at school on the day of the survey were asked to complete a questionnaire in their classrooms during a one-lesson hour session under the supervision of their teachers. Totally 3,998 students in both private and public schools, studying in ninth grade elementary school or third grade secondary school participated.
The results from our study show that there is a statistically significant relation between PSC and SOC among adolescents. It also shows that adolescents with a weak SOC score have more symptoms of PSC.
Our study indicates that SOC can help the adolescents to choose a coping strategy that is appropriate for the situation and thereby may prevent them from developing PSC. However, additional studies are needed to confirm our findings.
PMCID: PMC2265297  PMID: 18261203
11.  Neuroimaging with Near-Infrared Spectroscopy Demonstrates Speech-Evoked Activity in the Auditory Cortex of Deaf Children Following Cochlear Implantation 
Hearing research  2010;270(1-2):39-47.
Cochlear implants (CI) are commonly used to treat deafness in young children. While many factors influence the ability of a deaf child who is hearing through a CI to develop speech and language skills, an important factor is that the CI has to stimulate the auditory cortex. Obtaining behavioral measurements from young children with CIs can often be unreliable. While a variety of noninvasive techniques can be used for detecting cortical activity in response to auditory stimuli, many have critical limitations when applied to the pediatric CI population. We tested the ability of near-infrared spectroscopy (NIRS) to detect cortical responses to speech stimuli in pediatric CI users. Neuronal activity leads to changes in blood oxy- and de-oxyhemoglobin concentrations that can be detected by measuring the transmission of near-infrared light through the tissue. To verify the efficacy of NIRS, we first compared auditory cortex responses measured with NIRS and fMRI in normal-hearing adults. We then examined four different participant cohorts with NIRS alone. Speech-evoked cortical activity was observed in 100% of normal-hearing adults (11 of 11), 82% of normal-hearing children (9 of 11), 78% of deaf children who have used a CI >4 months (28 of 36), and 78% of deaf children who completed NIRS testing on the day of CI initial activation (7 of 9). Therefore, NIRS can measure cortical responses in pediatric CI users, and has the potential to be a powerful adjunct to current CI assessment tools.
PMCID: PMC2997935  PMID: 20888894
Cochlear implant; NIRS; fMRI; hearing; brain; auditory cortex; speech detection
12.  The Developmental Trajectory of Brain-Scalp Distance from Birth through Childhood: Implications for Functional Neuroimaging 
PLoS ONE  2011;6(9):e24981.
Measurements of human brain function in children are of increasing interest in cognitive neuroscience. Many techniques for brain mapping used in children, including functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS), use probes placed on or near the scalp. The distance between the scalp and the brain is a key variable for these techniques because optical, electrical and magnetic signals are attenuated by distance. However, little is known about how scalp-brain distance differs between different cortical regions in children or how it changes with development. We investigated scalp-brain distance in 71 children, from newborn to age 12 years, using structural T1-weighted MRI scans of the whole head. Three-dimensional reconstructions were created from the scalp surface to allow for accurate calculation of brain-scalp distance. Nine brain landmarks in different cortical regions were manually selected in each subject based on the published fNIRS literature. Significant effects were found for age, cortical region and hemisphere. Brain-scalp distances were lowest in young children, and increased with age to up to double the newborn distance. There were also dramatic differences between brain regions, with up to 50% differences between landmarks. In frontal and temporal regions, scalp-brain distances were significantly greater in the right hemisphere than in the left hemisphere. The largest contributors to developmental changes in brain-scalp distance were increases in the corticospinal fluid (CSF) and inner table of the cranium. These results have important implications for functional imaging studies of children: age and brain-region related differences in fNIRS signals could be due to the confounding factor of brain-scalp distance and not true differences in brain activity.
PMCID: PMC3177859  PMID: 21957470
13.  Reduced brain activation during imitation and observation of others in children with pervasive developmental disorder: a pilot study 
Children with pervasive developmental disorder (PDD) are thought to have poor imitation abilities. Recently, this characteristic has been suggested to reflect impairments in mirror neuron systems (MNS). We used near-infrared spectroscopy (NIRS) to examine the brain activity of children with PDD during tasks involving imitation and observations of others.
The subjects were 6 male children with PDD (8–14 years old) and 6 age- and gender-matched normal subjects (9–13 years old). A video in which a woman was opening and closing a bottle cap was used as a stimulus. Hemoglobin concentration changes around the posterior part of the inferior frontal gyrus and the adjacent ventral premotor cortex were measured with a 24-channel NIRS machine during action observation and action imitation tasks. Regional oxygenated hemoglobin concentration changes were significantly smaller in the PDD group than in the control group. Moreover, these differences were clearer in the action observation task than in the action imitation task.
Dysfunction in the MNS in children with PDD was suggested by the reduced activation in key MNS regions during tasks involving observations and imitations of others. These preliminary results suggest that further studies are needed to verify MNS dysfunction in children with PDD.
PMCID: PMC3673857  PMID: 23718943
Pervasive developmental disorder; Imitation; Mirror neuron systems; Near-infrared spectroscopy
14.  Motion artifact cancellation in NIR spectroscopy using discrete Kalman filtering 
As a continuation of our earlier work, we present in this study a Kalman filtering based algorithm for the elimination of motion artifacts present in Near Infrared spectroscopy (NIR) measurements. Functional NIR measurements suffer from head motion especially in real world applications where movement cannot be restricted such as studies involving pilots, children, etc. Since head movement can cause fluctuations unrelated to metabolic changes in the blood due to the cognitive activity, removal of these artifacts from NIR signal is necessary for reliable assessment of cognitive activity in the brain for real life applications.
Previously, we had worked on adaptive and Wiener filtering for the cancellation of motion artifacts in NIR studies. Using the same NIR data set we have collected in our previous work where different speed motion artifacts were induced on the NIR measurements we compared the results of the newly proposed Kalman filtering approach with the results of previously studied adaptive and Wiener filtering methods in terms of gains in signal to noise ratio. Here, comparisons are based on paired t-tests where data from eleven subjects are used.
The preliminary results in this current study revealed that the proposed Kalman filtering method provides better estimates in terms of the gain in signal to noise ratio than the classical adaptive filtering approach without the need for additional sensor measurements and results comparable to Wiener filtering but better suitable for real-time applications.
This paper presented a novel approach based on Kalman filtering for motion artifact removal in NIR recordings. The proposed approach provides a suitable solution to the motion artifact removal problem in NIR studies by combining the advantages of the existing adaptive and Wiener filtering methods in one algorithm which allows efficient real time application with no requirement on additional sensor measurements.
PMCID: PMC2846950  PMID: 20214809
15.  Comparison of alterations in cerebral hemoglobin oxygenation in late life depression and Alzheimer’s disease as assessed by near-infrared spectroscopy 
Patients with Alzheimer’s disease (AD) often present with apathy symptoms resembling the decreased motivation observed in depressed patients. Therefore, differentiating the initial phase of AD from late life depression may be difficult in some cases. Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that uses near-infrared light to measure changes in hemoglobin concentration on the cortical surface during activation tasks. The objective of this study was to investigate differences in brain activation associated with late life depression and with AD by means of NIRS.
NIRS was performed in 30 patients with depression, 28 patients with AD, and 33 healthy controls, all aged 60 years or older. During two tasks, a verbal fluency task and a visuospatial task, changes in oxygenated hemoglobin concentration in the frontal and parietal cortices were investigated.
In the visuospatial task, cortical activation was lower in the depressed group than in the AD group, and significant differences were observed in the parietal cortex.
NIRS can detect differences in brain activation between patients with late life depression and those with AD. NIRS is a promising tool for the differential diagnosis of late life depression and AD.
PMCID: PMC3995325  PMID: 24636630
Near-infrared spectroscopy; Brain activation; Alzheimer’s disease; Depression
16.  Cerebral perfusion and oxygenation are impaired by folate deficiency in rat: absolute measurements with noninvasive near-infrared spectroscopy 
Brain microvascular pathology is a common finding in Alzheimer's disease and other dementias. However, the extent to which microvascular abnormalities cause or contribute to cognitive impairment is unclear. Noninvasive near-infrared spectroscopy (NIRS) can address this question, but its use for clarifying the role of microvascular dysfunction in dementia has been limited due to theoretical and practical considerations. We developed a new noninvasive NIRS method to obtain quantitative, dynamic measurements of absolute brain hemoglobin concentration and oxygen saturation and used it to show significant cerebrovascular impairments in a rat model of diet-induced vascular cognitive impairment. We fed young rats folate-deficient (FD) and control diets and measured absolute brain hemoglobin and hemodynamic parameters at rest and during transient mild hypoxia and hypercapnia. With respect to control animals, FD rats featured significantly lower brain hemoglobin concentration (72±4 μmol/L versus 95±6 μmol/L) and oxygen saturation (54%±3% versus 65%±2%). By contrast, resting arterial oxygen saturation was the same for both groups (96%±4%), indicating that decrements in brain hemoglobin oxygenation were independent of blood oxygen carrying capacity. Vasomotor reactivity in response to hypercapnia was also impaired in FD rats. Our results implicate microvascular abnormality and diminished oxygen delivery as a mechanism of cognitive impairment.
PMCID: PMC3130317  PMID: 21386853
aging; capillaries; CBF; NIRS; nutrition; VCI
17.  Quantification of functional near infrared spectroscopy to assess cortical reorganization in children with cerebral palsy 
Optics express  2010;18(25):25973-25986.
Cerebral palsy (CP) is the most common motor disorder in children. Currently available neuroimaging techniques require complete body confinement and steadiness and thus are extremely difficult for pediatric patients. Here, we report the use and quantification of functional near infrared spectroscopy (fNIRS) to investigate the functional reorganization of the sensorimotor cortex in children with hemiparetic CP. Ten of sixteen children with congenital hemiparesis were measured during finger tapping tasks and compared with eight of sixteen age-matched healthy children, with an overall measurement success rate of 60%. Spatiotemporal analysis was introduced to quantify the motor activation and brain laterality. Such a quantitative approach reveals a consistent, contralateral motor activation in healthy children at 7 years of age or older. In sharp contrast, children with congenital hemiparesis exhibit all three of contralateral, bilateral and ipsilateral motor activations, depending on specific ages of the pediatric subjects. This study clearly demonstrates the feasibility of fNIRS to be utilized for investigating cortical reorganization in children with CP or other cortical disorders.
PMCID: PMC3568529  PMID: 21164944
18.  Pre-Task Prefrontal Activation during Cognitive Processes in Aging: A Near-Infrared Spectroscopy Study 
PLoS ONE  2014;9(6):e98779.
Cognitive processing generally deteriorates as people age. Recent neuroimaging studies have shown that the prefrontal cortex (PFC) is involved in human-specific behavior, such as preparing for future actions and prospective memory; hence, the PFC may be voluntarily activated even during the “resting” condition that precedes task execution. The purpose of the present study was to investigate changes in voluntary pre-task activation as a result of aging using a paradigm that includes a longer intertrial interval (e.g., 30 sec) than has been used in previous studies.
A total of 120 cognitively normal adults (young: 60, old: 60) participated in this near-infrared spectroscopy (NIRS) study. All subjects performed 6 repetitions of the working memory task, which included a 30 sec resting period and a 28.8 sec task period. The resting period was divided into baseline and pre-task (preT) periods, and the task period was divided into early easy task (eT) and late difficult task (dT) periods. We then normalized the data, analyzed the magnitude of task-related NIRS responses in each period and compared the results between groups using an analysis of variance test.
Statistical analyses revealed a significant interaction between group × optode location × period, in which hemodynamic responses in the PFC during the preT period were smaller in the elderly in than young adults. By contrast, during the task period, the hemodynamic responses were higher in the lateral PFC in the elderly than in young adults. Spearman's rank correlation analysis showed a positive correlation between hemodynamic changes during the preT period in the PFC and correct answer ratios in both groups.
These findings suggest that more pre-task activation in the anterior PFC is related to better cognitive performance in humans. Thus, a reduction in this activation might partly explain cognitive decline in the elderly.
PMCID: PMC4045856  PMID: 24897305
19.  Reduced interhemispheric functional connectivity of children with autism spectrum disorder: evidence from functional near infrared spectroscopy studies 
Biomedical Optics Express  2014;5(4):1262-1274.
Autism spectrum disorder (ASD) is a neuro-developmental disorder, which has been associated with atypical neural synchronization. In this study, functional near infrared spectroscopy (fNIRS) was used to study the differences in functional connectivity in bilateral inferior frontal cortices (IFC) and bilateral temporal cortices (TC) between ASD and typically developing (TD) children between 8 and 11 years of age. As the first report of fNIRS study on the resting state functional connectivity (RSFC) in children with ASD, ten children with ASD and ten TD children were recruited in this study for 8 minute resting state measurement. Compared to TD children, children with ASD showed reduced interhemispheric connectivity in TC. Children with ASD also showed significantly lower local connectivity in bilateral temporal cortices. In contrast to TD children, children with ASD did not show typical patterns of symmetry in functional connectivity in temporal cortex. These results support the feasibility of using the fNIRS method to assess atypical functional connectivity of cortical responses of ASD and its potential application in diagnosis.
PMCID: PMC3985986  PMID: 24761305
(170.2655) Functional monitoring and imaging; (170.5380) Physiology; (170.3880) Medical and biological imaging
20.  Near-Infrared Spectroscopy in Schizophrenia: A Possible Biomarker for Predicting Clinical Outcome and Treatment Response 
Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that can measure hemoglobin changes in brain tissues, and its use in psychiatry has been progressing rapidly. Although it has several disadvantages (e.g., relatively low spatial resolution and the possibility of shallow coverage in the depth of brain regions) compared with other functional neuroimaging techniques (e.g., functional magnetic resonance imaging and positron emission tomography), fNIRS may be a candidate instrument for clinical use in psychiatry, as it can measure brain activity in naturalistic position easily and non-invasively. fNIRS instruments are also small and work silently, and can be moved almost everywhere including schools and care units. Previous fNIRS studies have shown that patients with schizophrenia have impaired activity and characteristic waveform patterns in the prefrontal cortex during the letter version of the verbal fluency task, and part of these results have been approved as one of the Advanced Medical Technologies as an aid for the differential diagnosis of depressive symptoms by the Ministry of Health, Labor and Welfare of Japan in 2009, which was the first such approval in the field of psychiatry. Moreover, previous studies suggest that the activity in the frontopolar prefrontal cortex is associated with their functions in chronic schizophrenia and is its next candidate biomarker. Future studies aimed at exploring fNIRS differences in various clinical stages, longitudinal changes, drug effects, and variations during different task paradigms will be needed to develop more accurate biomarkers that can be used to aid differential diagnosis, the comprehension of the present condition, the prediction of outcome, and the decision regarding treatment options in schizophrenia. Future fNIRS researches will require standardized measurement procedures, probe settings, analytical methods and tools, manuscript description, and database systems in an fNIRS community.
PMCID: PMC3827961  PMID: 24294205
near-infrared spectroscopy; verbal fluency task; biological markers; early intervention; clinical outcome
21.  Associations between scores of psychosomatic health symptoms and health-related quality of life in children and adolescents 
The aims of the present study are to investigate whether there are differences in health-related quality of life (HRQoL) between girls and boys in two different age groups, to study how much of children’s variance in HRQoL can be explained by common psychosomatic health symptoms, and to examine whether the same set of psychosomatic symptoms can explain differences in HRQoL, both between girls and boys and between older and younger school children.
A cross-sectional study was conducted of 253 children, 99 of ages 11–12 years (n=51 girls, n=48 boys) and 154 of ages 15–16 years (n=82 girls, n=72 boys), in Swedish schools. The KIDSCREEN-52 instrument, which covers 10 dimensions of HRQoL and additional questions about psychosomatic health symptoms, were used. Analyses of variance were conducted to investigate differences between the genders and age groups, and in interaction effects on the KIDSCREEN-52 dimensions. Regression analyses were used to investigate the impacts of psychosomatic symptoms on gender and age group differences in HRQoL.
Boys rated themselves higher than girls on the KIDSCREEN dimensions: physical and psychological well-being, moods and emotions, self-perception, and autonomy. Main effects of age group were found for physical well-being, psychological well-being, moods and emotions, self-perception, autonomy, and school environment, where younger children rated their HRQoL more highly than those aged 15–16 years. Girls rated their moods and emotions dramatically lower than boys in the older age group, but the ratings of emotional status were more similar between genders at younger ages. Psychosomatic symptoms explained between 27% and 50% of the variance in the children’s HRQoL. Sleeping difficulties were a common problem for both girls and boys. Depression and concentration difficulties were particularly associated with HRQoL among girls whereas stomach aches were associated with HRQoL among boys.
Girls and adolescents experience poorer HRQoL than boys and younger children, but having psychosomatic symptoms seem to explain a substantial part of the variation. Strategies to promote health among school children, in particular to alleviate sleep problems among all children, depression and concentration difficulties among girls, and stomach aches among boys, are of great importance.
PMCID: PMC3831247  PMID: 24148880
Health; Quality of life; Gender; School; Children; Adolescents; Psychosomatic symptoms; Sleep problems; KIDSCREEN
22.  Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study 
Background: Autism spectrum disorder (ASD) has been called a “developmental disconnection syndrome,” however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life.
Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner.
Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants.
Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD.
PMCID: PMC3734360  PMID: 23964223
autism; functional connectivity; near-infrared spectroscopy; endophenotype; infancy
23.  The Psychosomatic Emergency 
California Medicine  1966;105(4):276-280.
Many psychiatric problems present themselves under the guise of physical rather than mental symptoms.
These occur in several categories: (1) Psychological problems which work in conjunction with definitive organic pathology, such as the fear of death. (2) Symptoms produced by altered physiology or biochemistry resultant from an acute orchronic stress state. (3) A combination of A and B above. (4) Patients with an intense disease, such as hypochondriasis. (5) Psychiatric symptoms, such as depression, anxiety or apathy which develop antecedent or subsequent to a fearfully anticipated illness or procedure.
These patients have certain characteristics in common. (1) They manifest a disproportionate concern over symptoms. (2) The symptoms are inconsistent with the usual pattern of organic disease. (3) The onset is concurrent with states of conflict. (4) There is usually a personal and family history of psychic and psychosomatic disorders. (5) Other psychiatric disorders are usually present. (6) Secondary gain is usually evident.
These patients can be successfully treated within the hospital setting and within the framework of psychiatric consultation and psychotherapy.
PMCID: PMC1516487  PMID: 5976883
24.  The Role of Orbitofrontal Cortex in Processing Empathy Stories in 4- to 8-Year-Old Children 
This study investigates the neuronal correlates of empathic processing in children aged 4–8 years, an age range discussed to be crucial for the development of empathy. Empathy, defined as the ability to understand and share another person's inner life, consists of two components: affective (emotion-sharing) and cognitive empathy (Theory of Mind). We examined the hemodynamic responses of preschool and school children (N = 48), while they processed verbal (auditory) and non-verbal (cartoons) empathy stories in a passive following paradigm, using functional Near-Infrared Spectroscopy. To control for the two types of empathy, children were presented blocks of stories eliciting either affective or cognitive empathy, or neutral scenes which relied on the understanding of physical causalities. By contrasting the activations of the younger and older children, we expected to observe developmental changes in brain activations when children process stories eliciting empathy in either stimulus modality toward a greater involvement of anterior frontal brain regions. Our results indicate that children's processing of stories eliciting affective and cognitive empathy is associated with medial and bilateral orbitofrontal cortex (OFC) activation. In contrast to what is known from studies using adult participants, no additional recruitment of posterior brain regions was observed, often associated with the processing of stories eliciting empathy. Developmental changes were found only for stories eliciting affective empathy with increased activation, in older children, in medial OFC, left inferior frontal gyrus, and the left dorsolateral prefrontal cortex. Activations for the two modalities differ only little, with non-verbal presentation of the stimuli having a greater impact on empathy processing in children, showing more similarities to adult processing than the verbal one. This might be caused by the fact that non-verbal processing develops earlier in life and is more familiar.
PMCID: PMC3110480  PMID: 21687450
OFC; cognitive empathy; affective empathy; children; fNIRS; verbal; non-verbal
25.  Effects of Physical Activity on Children’s Executive Function: Contributions of Experimental Research on Aerobic Exercise 
Developmental review : DR  2010;30(4):331-551.
Executive function refers to the cognitive processes necessary for goal-directed cognition and behavior, which develop across childhood and adolescence. Recent experimental research indicates that both acute and chronic aerobic exercise promote children’s executive function. Furthermore, there is tentative evidence that not all forms of aerobic exercise benefit executive function equally: Cognitively-engaging exercise appears to have a stronger effect than non-engaging exercise on children’s executive function. This review discusses this evidence as well as the mechanisms that may underlie the association between exercise and executive function. Research from a variety of disciplines is covered, including developmental psychology, kinesiology, cognitive neuroscience, and biopsychology. Finally, these experimental findings are placed within the larger context of known links between action and cognition in infancy and early childhood, and the clinical and practical implications of this research are discussed.
PMCID: PMC3147174  PMID: 21818169
Aerobic Exercise; Physical Activity; Executive Function; Cognition; Infancy/Childhood

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