A.-C. Ehlis

Event-related functional near-infrared spectroscopy (fNIRS): are the measurements reliable?

The purpose of the present study was to investigate the retest reliability of event-related functional near-infrared spectroscopy (fNIRS). Therefore, isolated functional activation was evoked in the occipital cortex by a periodic checkerboard stimulation. During a 52-channel fNIRS recording, 12 subjects underwent 60 trials of visual stimulation in two sessions. The retest interval was set to 3 weeks. Linear correlations of the contrast t values supplemented by scatter plots, channel-wise intraclass correlation coefficients (ICC) as well as reproducibility indices for the quantity of activated channels (RQUANTITY) and the location (ROVERLAP) of the detected activation were calculated. The results at the group level showed good reliability in terms of the single measure ICCs (up to 0.84) and excellent reproducibility quantified by RQUANTITY and ROVERLAP (up to 96% of the quantity and the location were reproducible), whereas the results at the single subjects level were mediocre. Furthermore, the reliability assessed by single measurement ICCs improved if regarded at a cluster level.

Model-based analysis of rapid event-related functional near-infrared spectroscopy (NIRS) data: A parametric validation study

To validate the usefulness of a model-based analysis approach according to the general linear model (GLM) for functional near-infrared spectroscopy (fNIRS) data, a rapid event-related paradigm with an unpredictable stimulus sequence was applied to 15 healthy subjects. A parametric design was chosen wherein four differently graded contrasts of a flickering checkerboard were presented, allowing directed hypotheses about the rank order of the evoked hemodynamic response amplitudes. The results indicate the validity of amplitude estimation by three main findings (a) the GLM approach for fNIRS data is capable to identify human brain activation in the visual cortex with inter-stimulus intervals of 4-9 s (6.5 s average) whereas in non-visual areas no systematic activation was detectable; (b) the different contrast level intensities lead to the hypothesized rank order of the GLM amplitude parameters: visual cortex activation evoked by highest contrast>moderate contrast>lowest contrast>no stimulation; (c) analysis of null-events (no stimulation) did not produce any significant activation in the visual cortex or in other brain areas. We conclude that a model-based GLM approach delivers valid fNIRS amplitude estimations and enables the analysis of rapid event-related fNIRS data series, which is highly relevant in particular for cognitive fNIRS studies.

A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function

Nitric oxide (NO) is a gaseous neurotransmitter thought to play important roles in several behavioral domains. On a neurobiological level, NO acts as the second messenger of the N-methyl-D-aspartate receptor and interacts with both the dopaminergic as well as the serotonergic system. Thus, NO is a promising candidate molecule in the pathogenesis of endogenous psychoses and a potential target in their treatment. Furthermore, the chromosomal locus of the gene for the NO-producing enzyme NOS-I, 12q24.2, represents a major linkage hot spot for schizophrenic and bipolar disorder. To investigate whether the gene encoding NOS-I (NOS1) conveys to the genetic risk for those diseases, five NOS1 polymorphisms as well as a NOS1 mini-haplotype, consisting of two functional polymorphisms located in the transcriptional control region of NOS1, were examined in 195 chronic schizophrenic, 72 bipolar-I patients and 286 controls. Single-marker association analysis showed that the exon 1c promoter polymorphism was linked to schizophrenia (SCZ), whereas synonymous coding region polymorphisms were not associated with disease. Long promoter alleles of the repeat polymorphism were associated with less severe psychopathology. Analysis of the mini-haplotype also revealed a significant association with SCZ. Mutational screening did not detect novel exonic polymorphisms in patients, suggesting that regulatory rather than coding variants convey the genetic risk on psychosis. Finally, promoter polymorphisms impacted on prefrontal functioning as assessed by neuropsychological testing and electrophysiological parameters elicited by a Go-Nogo paradigm in 48 patients (continuous performance test). Collectively these findings suggest that regulatory polymorphisms of NOS1 contribute to the genetic risk for SCZ, and modulate prefrontal brain functioning.

Frontal activation during a verbal-fluency task as measured by near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is an optical method which allows non-invasive in vivo measurements of concentration changes of oxygenated hemoglobin (O(2)Hb) and deoxygenated hemoglobin (HHb) in brain tissue. The present study investigated the blood oxygenation changes that were associated with the execution of the Verbal-Fluency Test (VFT) in left and right prefrontal brain areas of 14 healthy subjects by means of NIRS. During the VFT, subjects were required to pronounce as many nouns as possible beginning with the letters A, F, and S. Compared to a baseline resting condition, we found a significant increase of O2Hb (left hemisphere: baseline, 1.2+/-1.1microm; VFT(letterS), 3.56+/-2.02microm; right hemisphere: baseline, 1.26+/-1.08microm; VFT(letterS), 3.67+/-2.03microm) and a significant decrease of HHb (left hemisphere: baseline, -0.21+/-0.59microm; VFT(letterS), -0.67+/-0.60microm; right hemisphere: baseline, -0.29+/-0.53microm; VFT(letterS), -0.68+/-0.44microm) during the execution of the VFT over both hemispheres. No lateralization effects were observed. The results confirm that NIRS is suitable for the measurement of blood oxygenation changes in frontal brain areas that are associated with cognitive tasks.

Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys

OBJECTIVEnTo investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD).nnnMETHODnSixteen boys with ADHD and 19 healthy controls were investigated electrophysiologically during performance of a visual Go-Nogo task (Continuous Performance Test, CPT). An electrophysiological source localization method was employed to further analyze the data.nnnRESULTSnThe ADHD boys showed a significantly diminished central Nogo-P3, due to a lack of Nogo-related frontalization of the positive brain electrical field in this group. This two-dimensional effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC) in the ADHD boys in the Nogo condition of the CPT. Both groups did not significantly differ regarding the amplitude of the Nogo-N2.nnnCONCLUSIONSnThe results indicate deficits in prefrontal response control in unmedicated ADHD boys that do not seem to be specifically inhibitory in nature. A supposed dysfunction of the ACC in ADHD was confirmed.

Functional near-infrared spectroscopy: A long-term reliable tool for measuring brain activity during verbal fluency

The present study investigated the short- and long-term retest reliability of brain activity measured with functional near-infrared spectroscopy (fNIRS) during verbal fluency, the most published cognitive task within fNIRS literature. We examined 15 healthy right handed subjects in a block design task with retest intervals of three weeks and one year. Performance was constant over time. Amplitude of brain activation, as indicated by increases of oxygenated (O(2)Hb) and total (totHb) and decreases of deoxygenated haemoglobin (HHb), was reduced at session two and reversed at the third session for the fluency related region of interest (ROI). Small decreases for session two and three were found outside the ROI. These changes in amplitude may contribute to variability of reproducibility as measured with intraclass correlation coefficients (ICCs) within the ROI. Acceptable reliability for all chromophores and comparisons was reached for the mean of repeated measures at cluster level. Spatial (size and localisation), temporal and whole probe set activity was completely acceptable without exception. Retest reliability was not satisfactory at single subject and single channel level. Amplitude decreases over time outside the ROI suggest higher physiological or arousal effects for session one. Amplitude recovery in the ROI in session three argues for a psychological effect. Overall our findings indicate that fNIRS analyses at single subject and single channel level should be interpreted cautiously, while group and cluster analyses have sufficient test retest reliability.

Reduced lateral prefrontal activation in adult patients with attention-deficit/hyperactivity disorder (ADHD) during a working memory task: a functional near-infrared spectroscopy (fNIRS) study.

Near-infrared spectroscopy (NIRS) is an optical imaging method, which allows non-invasive in vivo measurements of changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin in cortical tissue. For the present study, we examined 13 adult ADHD patients and 13 age- and gender-matched healthy controls by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of a working memory (n-back) paradigm. Compared to the healthy control group, ADHD patients showed reduced task-related increases in the concentration of O2Hb in NIRS channels located over the ventro-lateral prefrontal cortex, indicating reduced activation during performance of the n-back task in this part of the brain. This finding was particularly apparent for the task condition with high working memory load (2-back), and was accompanied by a statistical trend towards an increased number of omission errors in the patient group. The data confirm previous findings of working memory deficits and prefrontal cortex dysfunction in patients suffering from ADHD, and are discussed in the light of imaging findings and theoretical models of working memory function.

Cerebral oxygenation changes in the prefrontal cortex: effects of age and gender.

Multi-channel near-infrared spectroscopy (NIRS) is an optical method, which allows non-invasive in vivo measurements of changes in the concentration of oxygenated (O(2)Hb) and deoxygenated (HHb) hemoglobin in living brain tissue, simultaneously from multiple measurement points. In the present study, 44 young and 42 elderly subjects were investigated by means of multi-channel NIRS (optical topography) during performance of the verbal fluency task (VFT). The aim of the study was to analyze the effects of the subjects age and gender on functional brain activation during this cognitive task. In summary, the results clearly show that the VFT activated the left and right dorsolateral prefrontal cortex (increases in O(2)Hb and more localized decreases in HHb), with an obvious left-hemispheric dominance. The elderly subjects generally exhibited less activation and no left hemispheric lateralization effect. In contrast to a previous study, we did not find a clear influence of the subjects gender on the brain activation pattern.

Early stages (P100) of face perception in humans as measured with event-related potentials (ERPs)

Summary.According to current ERP literature, face specific activity is reflected by a negative component over the inferior occipito-temporal cortex between 140 and 180u2009ms after stimulus onset (N170). A recently published study (Liu et al., 2002) using magnetoencephalography (MEG) clearly indicated that a face-selective component can be observed at 100u2009ms (M100) which is about 70u2009ms earlier than reported in most previous studies. Here we report these early differences at 107u2009ms between the ERPs of faces and buildings over the occipito-temporal cortex using electroencephalography. To exclude contrast differences as the main factor for this P100 differences we replicated this study using pictures of faces and scrambled faces. Both studies indicated that face processing starts already at ∼100u2009ms with an initial stage which can be measured not only with MEG but also with ERPs.

Multi-channel near-infrared spectroscopy detects specific inferior-frontal activation during incongruent Stroop trials

Near-infrared spectroscopy (NIRS) is an optical method, which allows non-invasive in vivo measurements of changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin in brain tissue. In the present study we investigated 10 healthy subjects by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of congruent and incongruent trials of the Stroop color word task. With a similar pattern of activation for both congruent and incongruent Stroop trials in the NIRS channels located left superior-frontally, the results for O2Hb and the total amount of hemoglobin (Hb-tot) indicate specific activation for interference trials in inferior-frontal areas of the left hemisphere. This result is in line with several neuroimaging studies (fMRI, PET) that have already investigated the frontal activation related to Stroop interference, which further supports the assumption that multi-channel NIRS is sensitive enough to detect spatially specific activation during the performance of cognitive tasks.