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Introduction: Cognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear., Methods: To further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based event-related potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory theta-burst stimulation-a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)-over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices., Results: The results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials ("Gratton effect") that was only accomplished with an intact DLPFC (i.e., following placebo stimulation)., Discussion: Because non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ehlis, Zarantonello, Haeussinger, Rohe, Rosenbaum, Fallgatter and Maier.)

Objective: Addictive behavior is characterized by fast automatic responses to drug-related cues (termed cue reactivity ) and deficient cognitive control. The ability to detect errors is a prerequisite for an adaptive increase of cognitive control to prevent further errors. In the current study, cue-reactivity effects on cognitive control were assessed via hemodynamic activity within the dorsolateral prefrontal cortex (dlPFC) using functional near-infrared spectroscopy (fNIRS) and simultaneous electroencephalography (EEG), assessing error monitoring (error-related negativity/error negativity, ERN/Ne) and error adaption in subsequent trials (N2). Nondependent social drinkers were the focus in this multimodal approach., Method: Effects of alcohol consumption patterns and the personality trait of impulsivity were assessed in n = 55 social drinkers. Hemodynamic activity within the dlPFC (cognitive control), error monitoring (ERN/Ne), post-error conflict monitoring (N2), error rates, and post-error slowing (PES) were measured during a modified Eriksen flanker task cued by beverage pictures., Results: ERN/Ne amplitudes were reduced during alcohol-cued trials. Post-error adaption was reflected in increased dlPFC activity after errors, whereas N2 amplitudes were reduced. There was a correlation of impulsivity and alcohol-cued ERN/Ne amplitude that was mediated by alcohol consumption pattern., Conclusions: Impulsivity-related decreases in error monitoring during cue reactivity were mediated by alcohol consumption pattern. However, cognitive control was not affected by cue reactivity, suggesting more complex interactions than previously assumed.

Auditory verbal hallucinations (AVH) are a characteristic symptom of psychosis. An influential cognitive model accounting for the mechanisms in the generation of AVHs describes a defective monitoring of inner speech, leading to the misidentification of internally generated thoughts as externally generated events. In this study, we utilized an inner speech paradigm during a simultaneous measurement with functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI), in order to replicate the findings of neural correlates of inner speech and auditory verbal imagery (AVI) in healthy subjects, reported in earlier studies, and to provide the first validation of the paradigm for fNIRS measurements. To this end, 20 healthy subjects were required to generate and silently recite first and second person sentences in their own voice (inner speech) and imagine the same sentences in a different, alien voice (AVI). Furthermore, questionnaires were deployed to assess the predisposition to acoustic hallucinations and schizotypal traits to investigate their connection to activation patterns associated with inner speech and monitoring processes. The results showed that both methods, fNIRS and fMRI, exhibited congruent activations in key brain areas, claimed to be associated with monitoring processes, indicating that the paradigm seems to be applicable using fNIRS alone. Furthermore, the results showed similar brain areas activated during inner speech and monitoring processes to those from earlier studies. However, our results indicate that the activations were dependent more on the sentence form and less on the imaging condition, showing more active brain areas associated with second person sentences. Integration of the sentence construction into the model of inner speech and deficient monitoring processes as the basis for the formation of AVHs should be considered in further studies. Furthermore, negative correlations between questionnaires' scores and activations in precentral gyrus and premotor cortex indicate a relationship of schizotypal characteristics and a deficient activation pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Storchak, Hudak, Dresler, Haeussinger, Fallgatter and Ehlis.)

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset disorder persisting into adulthood for a large proportion of cases. Neurofeedback (NF) has shown promising results in children with ADHD, but randomized controlled trials in adults with ADHD are scarce. We aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. Patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at 6-months follow-up (FU) including 3 booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. We conclude that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. We did not find any significant differences in outcome between groups when looking at the whole sample. When evaluating learners only, they demonstrate superior effects as compared to non-learners, which suggests specific effects in addition to non-specific effects of NF when learning occurs., (© 2021. The Author(s).)

Objectives: Excessive bodybuilding as a pathological syndrome has been classified based on two different theories: bodybuilding as dependency or as muscle dysmorphic disorder (MDD). This study is a first attempt to find psychophysiological data supporting one of these classifications. Methods: Twenty-four participants (bodybuilders vs healthy controls) were presented with pictures of bodies, exercise equipment or general reward stimuli in a control or experimental condition, and were measured with functional near-infrared spectroscopy (fNIRS). Higher activation in the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) while watching bodies and training equipment in the experimental condition (muscular bodies and bodybuilding-typical equipment) would be an indicator for the addiction theory. Higher activation in motion-related areas would be an indicator for the MDD theory. Results: We found no task-related differences between the groups in the DLPFC and OFC, but a significantly higher activation in bodybuilders in the primary somatosensory cortex (PSC) and left-hemispheric supplementary motor area (SMA) while watching body pictures (across conditions) as compared to the control group. Conclusions: These neurophysiological results could be interpreted as a first evidence for the MDD theory of excessive bodybuilding.

The ability to reconcile is a key factor for a cooperative and successful life. Among the many factors that have an impact on how people negotiate social contracts, poor cognitive control (which is inversely linked to impulsivity) may exert negative effects on forgiveness. To investigate the neurobiological basis of this proposition, subjects with high vs. low impulsivity scores completed an ultimatum game (UG) and a dictator game (DG). First, the participants played an UG where they had to accept or reject offers from fair or unfair opponents. Afterward, the roles changed, and a DG was played. Here, subjects had the opportunity to forgive or take revenge on unfair opponents by the allocation of a fair/unfair amount of money. During this task, activity of the dorsolateral prefrontal cortex (DLPFC) was assessed via functional near-infrared spectroscopy (fNIRS). Highly impulsive subjects were significantly more revenge-seeking than individuals with a low impulsivity. This behavioral difference was reflected in the activation pattern of the left DLPFC, where higher activation in trials with unfair opponents was found, but only in the highly impulsive group. This result is discussed as an indicator of more revenge-driven behavior in highly impulsive individuals, since activity in the left DLPFC is associated with retaliation., (Copyright © 2019 Maier, Rosenbaum, Haeussinger, Brüne, Fallgatter and Ehlis.)

Attention biases towards threat signals have been linked to the etiology and symptomatology of social anxiety disorder (SAD). Dysfunction of the dorsolateral prefrontal cortex (dlPFC) may contribute to attention biases in anxious individuals. The aim of this study was to investigate the feasibility of near-infrared spectroscopy (NIRS) neurofeedback (NF) training-targeting the dlPFC-and its effects on threat-related attention biases of individuals with SAD. 12 individuals with SAD participated in the NIRS-NF training lasting 6-8 weeks and including a total of 15 sessions. NF performance increased significantly, while the attention bias towards threat-related stimuli and SAD symptom severity decreased after the training. The individual increase in neurofeedback performance as well as the individual decrease in SAD symptom severity was correlated with decreased responses to social threat signals in the cerebral attention system. Thus, this pilot study does not only demonstrate that NIRS-based NF is feasible in SAD patients, but also may be a promising method to investigate the causal role of the dlPFC in attention biases in SAD. Its effectiveness as a treatment tool might be examined in future studies.

Spontaneous low frequency oscillations (LFO) in functional imaging data have gained increased interest in the study of cognitive decline. Persons diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display alterations in their amount of LFO in various brain regions. This is commonly interpreted as disruptions in the autoregulation of the cerebral microvascular system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54 MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during rest over the frontal and the parietal cortex. Both MCI and healthy elderly controls showed less LFO in the frontal cortex as compared to young subjects. For the parietal cortex a decrease in LFO could be observed for the MCI group in comparison to healthy elderly subjects. Correlations of more LFO with worse performance in neuropsychological tests point to compensatory processes. LFO measured with NIRS might be especially suited for longitudinal studies aiming at predicting cognitive decline.

In order to act in a socially acceptable way, the ability to forgive is indispensable. It has been suggested that forgiveness relies on cognitive control, more specifically inhibition. In this study, we combined an ultimatum game (UG) and a dictator game (DG) with inhibitory, continuous theta-burst stimulation (cTBS; verum vs. placebo, within-subjects design) of the right dorsolateral prefrontal cortex (DLPFC) to investigate the effect of reduced cognitive control on forgiveness. To this end, participants played an UG against fair and unfair opponents, where they had to accept or reject (fair and unfair) monetary offers, and then received a cTBS prior to playing a DG against the same opponents with reversed roles. The participants now had the possibility to forgive the unfair opponents (allocation of a fair amount of money) or to take revenge whereby the cTBS effects were assessed with functional near-infrared spectroscopy. Following verum cTBS, participants allocated significantly less money to their unfair opponents than in the placebo cTBS condition. Also, reaction times (RTs) differed significantly between verum and placebo cTBS for unfair opponents (higher RTs following verum stimulation) but not for fair opponents. These results strongly indicate that cognitive control is a fundamental requirement for overcoming unwanted emotional responses., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rumination is a perseverative thinking style that is associated with adverse mental and physical health. Stressful situations have been considered as a trigger for this kind of thinking. Until today, there are mixed findings with respect to the relations of functional connectivity (FC) and rumination. The study at hand aimed to investigate, in how far high and low ruminators would show elevated levels of state rumination after a stress induction and if these changes would show corresponding changes in FC in the cognitive control network (CCN) and dorsal attention network (DAN). 23 high and 22 low trait ruminators underwent resting-state measurements before and after a stress induction with the Trier Social Stress Test (TSST). Changes in rsFC through the TSST were measured with functional near-infrared spectroscopy within and between regions of the CCN. Stress successfully induced state rumination in both groups but stronger in the high trait ruminators. High trait ruminators showed elevated FC within the CCN at baseline, but attenuated increase in FC following the TSST. Increases in FC correlated negatively with state rumination. A lack of FC reactivity within the CCN in high ruminators might reflect reduced network integration between brain regions necessary for emotion regulation and cognitive control.

The study of the stress response has been of great interest in the last decades due to its relationship to physical and mental health. Along with the technological progress in the neurosciences, different methods of stress induction have been developed for the special requirements regarding the acquisition of neuroimaging data. However, these paradigms often differ from ecologically valid stress inductions such as the Trier Social Stress Test (TSST) in substantial ways. In the study at hand, we used the rather robust optical imaging method of functional Near-infrared Spectroscopy (fNIRS) to assess brain activation during the TSST and two non-stressful control conditions. Additionally, we measured other stress parameters including the cortisol response and subjective stress ratings. As expected we found significant increases in subjective and physiological stress measures during the TSST in comparison to the baseline and control conditions. We found higher activation in parts of the cognitive control network (CCN) and dorsal attention network (DAN) - comprising the dorsolateral prefrontal cortex, the inferior frontal gyrus and superior parietal cortex - during the performance of the TSST in comparison to the control conditions. Further, calculation errors during the TSST as well as subjective and physiological stress parameters correlated significantly with the activation in the CCN. Our study confirms the validity of previous neuroimaging data obtained from adapted stress procedures by providing cortical activation data during a classical stress induction paradigm (i.e., the TSST) for the first time., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Repetitive thinking styles such as rumination are considered to be a key factor in the development and maintenance of mental disorders. Different situational triggers (e.g., social stressors) have been shown to elicit rumination in subjects exhibiting such habitual thinking styles. At the same time, the process of rumination influences the adaption to stressful situations. The study at hand aims to investigate the effect of trait rumination on neuronal activation patterns during the Trier Social Stress Test (TSST) as well as the physiological and affective adaptation to this high-stress situation., Methods: A sample of 23 high and 22 low ruminators underwent the TSST and two control conditions while their cortical hemodynamic reactions were measured with functional near-infrared spectroscopy (fNIRS). Additional behavioral, physiological and endocrinological measures of the stress response were assessed., Results: Subjects showed a linear increase from non-stressful control conditions to the TSST in cortical activity of the cognitive control network (CCN) and dorsal attention network (DAN), comprising the bilateral dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG) and superior parietal cortex/somatosensory association cortex (SAC). During stress, high ruminators showed attenuated cortical activity in the right IFG, whereby deficits in IFG activation mediated group differences in post-stress state rumination and negative affect., Conclusions: Aberrant activation of the CCN and DAN during social stress likely reflects deficits in inhibition and attention with corresponding negative emotional and cognitive consequences. The results shed light on possible neuronal underpinnings by which high trait rumination may act as a risk factor for the development of clinical syndromes.

Mindfulness meditation as a therapeutic intervention has been shown to have positive effects on psychological problems such as depression, pain or anxiety disorders. In this study, we used functional near-infrared spectroscopy (fNIRS) to detect differences in hemodynamic responses of meditation experts (14 participants) and a control group (16 participants) in a resting and a mindfulness condition. In both conditions, the sound of a meditation bowl was used to find group differences in the auditory system and adjacent cortical areas. Different lateralization patterns of the brain were found in expert meditators while being in a resting state (amplified left hemisphere) or being in mindfulness state (amplified right hemisphere). Compared to the control group, meditation experts had a more widespread pattern of activation in the auditory cortex, while resting. In the mindfulness condition, the control group showed a decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the meditation experts had a significant increase in those areas. In addition, meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond the meditative task itself, indicating possible long-term changes in the brain and their positive effects on empathy, meta cognitive skills and health., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Cue reactivity is an automatic reaction to alcohol-related cues, contributing to the maintenance of drinking behavior and relapse in alcohol dependency. The identification of valid cue-reactivity features is a prerequisite for its clinical application. We were interested in the effects of visual features of alcohol cues (e.g., color) on cue reactivity. Assuming its development at a pre-pathological stage, we analyzed cue reactivity in heavy social drinkers, with light social drinkers as controls. We investigated whether cue reactivity was independent of visual features at an attentional (P100) and a motivational level (late positive potential, LPP)., Method: Event-related potentials (ERPs; P100, LPP) were analyzed during a visual beverage classification task in heavy social drinkers and light social drinkers (N = 34 university students). Photographs of beverages were classified as alcoholic or nonalcoholic. Two additional stimulus sets depicted unrecognizable scrambled visual information and recognizable black silhouettes of the original beverages. Analysis of contrast waves inferred content (unrecognized scrambled trials subtracted from original) and color information (recognized shape trials subtracted from original) during visual processing. Linear regression was used to predict Alcohol Use Disorders Identification Test (AUDIT) scores from ERPs., Results: In heavy social drinkers, alcoholic-content LPP was increased and P100 latency was shorter compared with nonalcoholic cues. Linear regression for alcohol content condition in the overall sample revealed shorter P100 latency and increased LPP amplitude predicting AUDIT scores. None of those effects were significant in the visual-feature control condition., Conclusions: Alcohol cue reactivity in heavy social drinkers was related to faster early attentional processes and motivational salience. The effect occurred independently of visual features in the pictures.

Background: A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD., Methods: In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls., Results: In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group., Limitations: Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT., Conclusion: Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

Background: Extracranial signals are the main source of noise in functional near-infrared spectroscopy (fNIRS) as light is penetrating the cortex but also skin and muscles of the head. Aim: Here we performed three experiments to investigate the contamination of fNIRS measurements by temporal muscle activity. Material and methods: For experiment 1, we provoked temporal muscle activity by instructing 31 healthy subjects to clench their teeth three times. We measured fNIRS signals over left temporal and frontal channels with an interoptode distance of 3 cm, in one short optode distance (SOD) channel (1 cm) and electromyography (EMG) over the edge of the temporal muscle. In experiment 2, we screened resting state fNIRS-fMRI (functional magnetic resonance imaging) data of one healthy subject for temporal muscle artifacts. In experiment 3, we screened a dataset of sound-evoked activity ( n = 33) using bi-temporal probe-sets and systematically contrasted subjects presenting vs. not presenting artifacts and blocks/events contaminated or not contaminated with artifacts. Results: In experiment 1, we could demonstrate a hemodynamic-response-like increase in oxygenated (O 2 Hb) and decrease in deoxygenated (HHb) hemoglobin with a large amplitude and large spatial extent highly exceeding normal cortical activity. Correlations between EMG, SOD, and fNIRS artifact activity showed only limited evidence for associations on a group level with rather clear associations in a sub-group of subjects. The fNIRS-fMRI experiment showed that during the temporal muscle artifact, fNIRS is completely saturated by muscle oxygenation. Experiment 3 showed hints for contamination of sound-evoked oxygenation by the temporal muscle artifact. This was of low relevance in analyzing the whole sample. Discussion: Temporal muscle activity e.g., by clenching the teeth induces a large hemodynamic-like artifact in fNIRS measurements which should be avoided by specific subject instructions. Data should be screened for this artifact might be corrected by exclusion of contaminated blocks/events. The usefulness of established artifact correction methods should be evaluated in future studies. Conclusion: Temporal muscle activity, e.g., by clenching the teeth is one major source of noise in fNIRS measurements.

Based on neurofeedback (NF) training as a neurocognitive treatment in attention-deficit/hyperactivity disorder (ADHD), we designed a randomized, controlled functional near-infrared spectroscopy (fNIRS) NF intervention embedded in an immersive virtual reality classroom in which participants learned to control overhead lighting with their dorsolateral prefrontal brain activation. We tested the efficacy of the intervention on healthy adults displaying high impulsivity as a sub-clinical population sharing common features with ADHD. Twenty participants, 10 in an experimental and 10 in a shoulder muscle-based electromyography control group, underwent eight training sessions across 2 weeks. Training was bookended by a pre- and post-test including go/no-go, n-back, and stop-signal tasks (SST). Results indicated a significant reduction in commission errors on the no-go task with a simultaneous increase in prefrontal oxygenated hemoglobin concentration for the experimental group, but not for the control group. Furthermore, the ability of the subjects to gain control over the feedback parameter correlated strongly with the reduction in commission errors for the experimental, but not for the control group, indicating the potential importance of learning feedback control in moderating behavioral outcomes. In addition, participants of the fNIRS group showed a reduction in reaction time variability on the SST. Results indicate a clear effect of our NF intervention in reducing impulsive behavior possibly via a strengthening of frontal lobe functioning. Virtual reality additions to conventional NF may be one way to improve the ecological validity and symptom-relevance of the training situation, hence positively affecting transfer of acquired skills to real life.

The investigation of the neural underpinnings of increased arithmetic complexity in children is essential for developing educational and therapeutic approaches and might provide novel measures to assess the effects of interventions. Although a few studies in adults and children have revealed the activation of bilateral brain regions during more complex calculations, little is known about children. We investigated 24 children undergoing one-digit and two-digit multiplication tasks while simultaneously recording functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) data. FNIRS data indicated that one-digit multiplication was associated with brain activity in the left superior parietal lobule (SPL) and intraparietal sulcus (IPS) extending to the left motor area, and two-digit multiplication was associated with activity in bilateral SPL, IPS, middle frontal gyrus (MFG), left inferior parietal lobule (IPL), and motor areas. Oscillatory EEG data indicated theta increase and alpha decrease in parieto-occipital sites for both one-digit and two-digit multiplication. The contrast of two-digit versus one-digit multiplication yielded greater activity in right MFG and greater theta increase in frontocentral sites. Activation in frontal areas and theta band data jointly indicate additional domain-general cognitive control and working memory demands for heightened arithmetic complexity in children. The similarity in parietal activation between conditions suggests that children rely on domain-specific magnitude processing not only for two-digit but-in contrast to adults-also for one-digit multiplication problem solving. We conclude that in children, increased arithmetic complexity tested in an ecologically valid setting is associated with domain-general processes but not with alteration of domain-specific magnitude processing.

Depression has been shown to be related to a variety of aberrant brain functions and structures. Particularly the investigation of alterations in functional connectivity (FC) in major depressive disorder (MDD) has been a promising endeavor, since a better understanding of pathological brain networks may foster our understanding of the disease. However, the underling mechanisms of aberrant FC in MDD are largely unclear. Using functional near-infrared spectroscopy (fNIRS) we investigated FC in the cortical parts of the default mode network (DMN) during resting-state in patients with current MDD. Additionally, we used qualitative and quantitative measures of psychological processes (e.g., state/trait rumination, mind-wandering) to investigate their contribution to differences in FC between depressed and non-depressed subjects. Our results indicate that 40% of the patients report spontaneous rumination during resting-state. Depressed subjects showed reduced FC in parts of the DMN compared to healthy controls. This finding was linked to the process of state/trait rumination. While rumination was negatively correlated with FC in the cortical parts of the DMN, mind-wandering showed positive associations.

Cue reactivity (CR) is an important concept for relapse in substance use disorders (SUD). Although cue exposure (CE) therapy is discussed as relapse prevention, current approaches still need improvement considering its efficacy. From a neurobiological perspective, CR is related to an over-activation in sensitized subcortical structures, their projections to motivationally relevant cortical structures (e.g. orbitofrontal cortex, OFC) and deficient prefrontal inhibitory control. Therefore, we analyzed prefrontal cortical activation and its relation to craving during smoking CE. We focused on the OFC-as a projection area of sensitized subcortical structures-due its importance in the processing of reinforcement value and the dorsolateral prefrontal cortex (dlPFC) based on its importance for behavioral inhibition. Functional near-infrared spectroscopy (fNIRS) was used to assess hemodynamics in prefrontal regions during smoking CE in 24 subjects (n = 12 occasional smokers, n = 12 controls). Subjective craving intensity (minimum craving as marker of baseline inhibition, range as marker of inhibition time course) was additionally assessed. Craving ratings indicated that CR was elicited solely in smokers, not controls. Those subjective ratings correlated with hemodynamic activity in OFC (craving range) and dlPFC (minimum craving). OFC activation was found earlier throughout the CE in smokers compared to controls. Connectivity (seed-based correlation) between OFC and dlPFC was increased in smokers. fNIRS can capture prefrontal hemodynamic activity involved in CR elicited during CE and is therefore a promising method to investigate CR and its implications for relapse prevention in SUD., (© 2015 Society for the Study of Addiction.)

Since functional imaging of whole body movements is not feasible with functional magnetic resonance imaging (fMRI), the present study presents in vivo functional near-infrared spectroscopy (fNIRS) as a suitable technique to measure body movement effects on fronto-temporo-parietal cortical activation in single- and dual-task paradigms. Previous fNIRS applications in studies addressing whole body movements were typically limited to the assessment of prefrontal brain areas. The current study investigated brain activation in the frontal, temporal and parietal cortex of both hemispheres using functional near-infrared spectroscopy (fNIRS) with two large 4×4 probe-sets with 24 channels each during single and dual gait tasks. 12 young healthy adults were measured using fNIRS walking on a treadmill: the participants performed two single-task (ST) paradigms (walking at different speeds, i.e. 3 and 5km/h) and a dual task (DT) paradigm where a verbal fluency task (VFT) had to be executed while walking at 3km/h. The results show an increase of activation in Broca's area during the more advanced conditions (ST 5km/h vs. ST 3km/h, DT vs. ST 3km/h, DT vs. 5km/h), while the corresponding area on the right hemisphere was also activated. DT paradigms including a cognitive task in conjunction with whole body movements elicit wide-spread cortical activation patterns across fronto-temporo-parietal areas. An elaborate assessment of these activation patterns requires more extensive fNIRS assessments than the traditional prefrontal investigations, e.g. as performed with portable fNIRS devices., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Frontotemporal dementia is an increasingly studied disease, the underlying functional impairments on a neurobiological level of which have not been fully understood. Patients with the behavioral-subtype frontotemporal dementia (bvFTD) are particularly challenging for clinical measurements such as functional imaging due to their behavioral symptoms. Here, an alternative imaging method, functional near-infrared spectroscopy (fNIRS), is introduced to measure task-related cortical brain activation based on blood oxygenation. The current study investigated differences in cortical activation patterns of patients with bvFTD, Alzheimer's dementia (AD), and healthy elderly subjects measured by fNIRS., Method: Eight probable bvFTD patients completed the semantic, phonological, and control conditions of a verbal fluency task. Eight AD patients and eight healthy controls were compared on the same task. Simultaneously, an fNIRS measurement was conducted and analyzed using a correction method based on the expected negative correlation between oxygenated and deoxygenated hemoglobin., Results: Healthy controls show an increase in cortical activation measured in frontoparietal areas such as the dorsolateral prefrontal cortex. The activation pattern of patients with AD is similar, but weaker. In contrast, bvFTD patients show a more frontopolar pattern, with activation of Broca's area, instead of the dorsolateral prefrontal cortex and the superior temporal gyrus. The frontoparietal compensation mechanisms, seen in the healthy elderly, were missing in bvFTD patients., Conclusion: Different frontoparietal cortical activation patterns may indicate a correlate of diverse pathophysiological mechanisms of AD and bvFTD during verbal fluency processing. The AD pattern is weaker and more similar to the healthy pattern, whereas the bvFTD pattern is qualitatively different, namely more frontopolar and without frontoparietal compensation activation. It adheres to a change of cortical activation during the course of the disease.

Targeted modulation of cortical functions by non-invasive brain stimulation is widely used for the investigation of the neurophysiological signatures of executive functions and put forward as a potential specific treatment for its disorders. To further investigate the underlying mechanisms, we performed two experiments involving 46 subjects that performed a semantic and a phonological verbal fluency task (VFT) as well as a simple speech-production task after application of 1mA anodal or cathodal transcranial direct current stimulation (tDCS) to the left inferior frontal gyrus (IFG). Brain activation was measured by functional near-infrared spectroscopy (fNIRS) during task performance. Neither preceding anodal nor cathodal tDCS was found to modulate VFT performance of either difficulty. However, preconditioning with anodal tDCS increased brain activity during the VFT whereas a trendwise decrease of activation was found after cathodal stimulation. Notably, this difference was not found with simple speech production. These findings support the notion of a polarity-specific malleability of neuronal network activity underlying speech production by tDCS. Most importantly, the task-specificity of the modulatory effect observed after the end of stimulation demonstrates lasting neurophysiological effects of tDCS that are reflected in modifications of cortical excitability by challenging cognitive tasks., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is a large body of evidence showing a substantial relationship between depression and deficits in cognitive functioning. Especially in late-life depression, cognitive impairments are associated with worse treatment progress and are considered a risk factor for neurodegenerative disorders. However, little is known about the differences in neural processing and coupling during rest and cognitive functions in patients with late-life depression compared to healthy elderly individuals. The study at hand aims to investigate the cognitive control network in late-life depression during a cognitive task and at rest by means of functional near-infrared spectroscopy. Hemodynamic responses were measured at rest and during the Trail Making Test using functional near-infrared spectroscopy in a matched sample of 49 depressed and 51 nondepressed elderly subjects (age range: 51-83 years; 64.1 ± 6.58 [mean ± standard deviation]). Functional connectivity (FC) and network metrics were derived from the data and analyzed with respect to differences between the subject groups. Depressed and nondepressed subjects showed significant differences in FC both at rest and during task performance. Depressed subjects showed reduced FC in a left frontopolar cortical network during task performance and increased FC in a left frontoparietal cortical network at rest. Depressed elderly subjects showed altered FC and network organization during different mental states. Higher FC at rest may be an indicator of self-referential processes such as rumination that may reduce FC during task performance due to an overtaxed executive control system., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rationale: Neurobiological effects of neuropsychiatric medication can contribute to the understanding of mechanisms of action and to the evaluation of target medication effects. Cholinesterase inhibitors (ChEI) have been used in patients with Alzheimer's disease (AD) for years with only small knowledge about the underlying neurobiological effects. The measurement of brain activation links neurobiological and functional aspects but is challenging in the group of demented patients; here, an alternative method, functional near-infrared spectroscopy (fNIRS), is introduced to measure those medication effects., Objectives: The current study investigated the influence of ChEI on cortical activation of patients with AD measured using fNIRS during a verbal fluency task (VFT)., Methods: In this study, 24 probable AD patients were investigated three times using fNIRS: before medication with rivastigmine was given (t0), when the medication was at the target dose after 4 weeks (t1), and after the target dose was kept constant for a further 8 weeks (t2)., Results: The results show a concentration increase of oxygenated hemoglobin as measured with fNIRS from t0 to t2 in speech relevant areas and a general decrease in prefrontal areas. Behaviorally, an improvement was found for the VFT used to measure cortical activation during fNIRS. In the neuropsychological test battery, no significant changes were found, yet high effect sizes for the mini mental status examination, immediate and delayed word list recall were found., Conclusions: The results indicate a positive effect of ChEI on cognitive function. The underlying cortical changes can be imaged using fNIRS.

Background: Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands., Methods: Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated., Results: Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics., Conclusion: Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

Objectives: The present study aimed at investigating neurophysiological markers of language perception in schizophrenia using simultaneous near-infrared spectroscopy (NIRS) and event-related potentials (ERPs), which have been proven to be useful for studying language processing abilities in psychiatric patients. The study shall help to integrate previous findings from ERP and fMRI studies on figurative language comprehension in schizophrenia and elucidate how electrophysiological and haemodynamic markers of language processing are related., Methods: Twenty-two healthy subjects and 22 schizophrenia patients judged 120 sentences regarding their meaningfulness. Phrases were literal, metaphoric, or meaningless. EEG-fNIRS signals were recorded throughout the entire experiment., Results: Schizophrenia patients showed deficient and delayed sentence comprehension. Both the early N400 and left-hemispheric activation during language comprehension were altered in patients. Correlation analyses showed that metaphor-related ERPs were strongly linked to haemodynamic cortical activity in healthy subjects, but not in patients., Conclusions: Our results indicate group differences in cortical electrophysiological and haemodynamic activation that represent rather general impairments in the processing of complex language. Simultaneous EEG/NIRS applications are useful to depict these neural markers and to investigate their relationship. Future studies are needed to clarify the nature of respective anomalies and their potential as putative neural markers in schizophrenia research.

Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with Alzheimer's disease and subjects with mild cognitive impairment compared to age-matched healthy controls. In this study, the association of VSEP with subjective memory impairment (SMI), a potential risk or prodromal marker for Alzheimer's disease, was examined. The association of VSEP latencies and SMI was studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders. The results show increased VSEP latencies for peak P2 at Fz-F4 in subjects who report SMI and are worried about it as compared to subjects who report memory impairment, but are not concerned and subjects without complaints. The results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer's disease.

Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging method that detects temporal concentration changes of oxygenated and deoxygenated hemoglobin within the cortex, so that neural activation can be inferred. However, even though fNIRS is a very practical and well-tolerated method with several advantages particularly in methodically challenging measurement situations (e.g., during tasks involving movement or open speech), it has been shown to be confounded by systemic compounds of non-cerebral, extra-cranial origin (e.g. changes in blood pressure, heart rate). Especially event-related signal patterns induced by dilation or constriction of superficial forehead and temple veins impair the detection of frontal brain activation elicited by cognitive tasks. To further investigate this phenomenon, we conducted a simultaneous fNIRS-fMRI study applying a working memory paradigm (n-back). Extra-cranial signals were obtained by extracting the BOLD signal from fMRI voxels within the skin. To develop a filter method that corrects for extra-cranial skin blood flow, particularly intended for fNIRS data sets recorded by widely used continuous wave systems with fixed optode distances, we identified channels over the forehead with probable major extra-cranial signal contributions. The averaged signal from these channels was then subtracted from all fNIRS channels of the probe set. Additionally, the data were corrected for motion and non-evoked systemic artifacts. Applying these filters, we can show that measuring brain activation in frontal brain areas with fNIRS was substantially improved. The resulting signal resembled the fMRI parameters more closely than before the correction. Future fNIRS studies measuring functional brain activation in the forehead region need to consider the use of different filter options to correct for interfering extra-cranial signals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

An approach bias for alcohol stimuli (i.e. faster approach than avoidance reactions) might facilitate relapses in alcohol dependence. Neurobiological models suggest hypersensitivity in the reward system [inter alia nucleus accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced approach impulses towards alcohol stimuli. At the same time, in alcohol dependence, these structures are only insufficiently controlled by a hypoactive dorsolateral prefrontal cortex (DLPFC). The present study investigated the cortical aspects of this model with functional near-infrared spectroscopy in 21 alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age, gender and education) during performance of the Approach-Avoidance Task (AAT) for the first time. Complementing previous findings, in reaction times (RTs), patients showed stronger approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in HC. Group differences in activity of the OFC were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures. Probable awareness of the behavioural hypotheses due to explicit task instructions and patients' deficient prefrontal function might account for this equally aligned pattern. Results are discussed with regard to recent findings revealing a reduced behavioural approach bias and risk for relapse by applying a retraining version of the AAT. Functional measurements might serve as a method for monitoring the corresponding neurobiological changes and-possibly-predicting the success of such a training., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Vagus somatosensory evoked potentials are a method for assessing the function of the vagus nerve, which were shown to be altered in neurodegenerative diseases like Alzheimer's and Parkinson's disease. Various parameters of the stimulation such as the electrode position and the stimulus intensity have already been investigated. In this study, the focus is on the systematic examination of the other parameters of the stimulation of the vagus somatosensory evoked potentials: stimulus duration, interstimulus interval, and, again, the stimulation intensity. Thirty young and healthy subjects were examined using five different sets of stimulation parameters, and 24 were included in the further analysis. The results show that a reduction of the stimulus duration and a decrease in stimulus intensity have a significant effect on the amplitudes. A shortening of the interstimulus interval does not seem to have such an effect, but this stimulation is rated more painful and unpleasant than the standard stimulation. Overall, the standard stimulation used so far seems to be the most preferable condition.

The simultaneous application of different neuroimaging methods combining high temporal and spatial resolution can uniquely contribute to current issues and open questions in the field of pragmatic language perception. In the present study, comprehension of novel metaphors was investigated using near-infrared spectroscopy (NIRS) combined with the simultaneous acquisition of electroencephalography (EEG)/event-related potentials (ERPs). For the first time, we investigated the effects of figurative language on early electrophysiological markers (P200, N400) and their functional relationship to cortical haemodynamic responses within the language network (Broca's area, Wernicke's area). To this end, 20 healthy subjects judged 120 sentences with respect to their meaningfulness, whereby phrases were either literal, metaphoric, or meaningless. Our results indicated a metaphor-specific P200 reduction and a linear increase of N400 amplitudes from literal over metaphoric to meaningless sentences. Moreover, there were metaphor related effects on haemodynamic responses accessed with NIRS, especially within the left lateral frontal cortex (Broca's area). Significant correlations between electrophysiological and haemodynamic responses indicated that P200 reductions during metaphor comprehension were associated with an increased recruitment of neural activity within left Wernicke's area, indicating a link between variations in neural activity and haemodynamic changes within Wernicke's area. This link may reflect processes related to interindividual differences regarding the ability to classify novel metaphors. The present study underlines the usefulness of simultaneous NIRS measurements in language paradigms - especially for investigating the functional significance of neurophysiological markers that have so far been rarely examined - as these measurements are easily and efficiently realizable and allow for a complementary examination of neural activity and associated metabolic changes in cortical areas., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Previous studies have suggested complex interactions of mood and cognition in the lateral prefrontal cortex (PFC). Although such interactions might be influenced by various factors such as personality and cultural background, their reproducibility and generalizability have hardly been explored. In the present study, we focused on a previously found correlation between negative mood states and PFC activity during a verbal working memory (WM) task, which had been demonstrated by using near-infrared spectroscopy (NIRS) in a Japanese sample. To confirm and extend the generalizability of this finding, we conducted a similar experiment in a German sample, i.e., participants with a different language background. Here, PFC activity during verbal and spatial WM tasks was measured by NIRS using a delayed match-to-sample paradigm after the participants' natural mood states had been evaluated by a mood questionnaire (Profiles of Mood States: POMS). We also included control tasks to consider the general effect of visual/auditory inputs and motor responses. For the verbal WM task, the POMS total mood disturbance (TMD) score was negatively correlated with baseline-corrected NIRS data mainly over the left dorsolateral PFC (i.e., higher TMD scores were associated with reduced activation), which is consistent with previous studies. Moreover, this relationship was also present when verbal WM activation was contrasted with the control task. These results suggest that the mood-cognition interaction within the PFC is reproducible in a sample with a different language background and represents a general phenomenon.

Cognitive decline is very common in age and particularly in subjects with neurodegenerative conditions. Besides memory and language, executive functions are very often affected in elderly and patients with Alzheimer's disease or Parkinson's disease. However, the neural alterations associated with these executive deficits are still not fully understood. Therefore, we measured cortical activation using functional near-infrared spectroscopy (fNIRS) in 16 healthy elderly subjects (50-75 years) performing the Trail Making Test (TMT), a widely used neuropsychological instrument measuring executive function. In line with previous studies focusing on younger subjects, the results showed frontal activation during the TMT A and the TMT B in the dorsolateral prefrontal cortex, the frontopolar area and also Broca's area. Furthermore, significant activation in the left motor, somatosensory cortices and somatosensory association cortices was demonstrated. Additionally, after a median split the differences between younger (<58 years) and older (>58 years) subjects were analyzed with the older subjects showing a less focused prefrontal activation. Altogether, fNIRS was found to be suitable to detect cortical activation in elderly subjects during performance of the TMT as well as aging-related differences in prefrontal activation topography. These neural correlates of executive functions should be further investigated as a potential prodromal neural marker of executive deficits and neurodegenerative processes., (© 2013.)

Objectives: Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation., Methods: Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC., Results: At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found., Conclusion: Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

Neural processing inferred from hemodynamic responses measured with functional near infrared spectroscopy (fNIRS) may be confounded with individual anatomical or systemic physiological sources of variance. This may hamper the validity of fNIRS signal interpretations and associations between individual traits and brain activation, such as the link between impulsivity-related personality traits and decreased prefrontal cognitive control during reward-based decision making. Hemodynamic responses elicited by an intertemporal choice reward task in 20 healthy subjects were investigated for multimodal correlations of simultaneous fNIRS-fMRI and for an impact of anatomy and scalp fMRI signal fluctuations on fNIRS signals. Moreover, correlations of prefrontal activation with trait "sensitivity to reward" (SR) were investigated for differences between methods. While showing substantial individual variability, temporal fNIRS-fMRI correlations increased with the activation, which both methods consistently detected within right inferior/middle frontal gyrus. Here, up to 41% of fNIRS channel activation variance was explained by individual gray matter volume simulated to be reached by near-infrared light, and up to 20% by scalp-cortex distance. Extracranial fMRI and fNIRS time series showed significant temporal correlations in the temple region. SR was negatively correlated with fMRI but not fNIRS activation elicited by immediate rewards of choice within right inferior/middle frontal gyrus. Higher SR increased the correlation between extracranial fMRI and fNIRS signals and decreased fNIRS-fMRI correlations. Task-related fNIRS signals might be impacted by regionally and individually weighted sources of anatomical and systemic physiological error variance. Trait-activation correlations might be affected or biased by systemic physiological responses, which should be accounted for in future fNIRS studies of interindividual differences., (Copyright © 2013 Elsevier Inc. All rights reserved.)

While progressive neurocognitive impairments are associated with aging and Alzheimer's disease (AD), cortical reorganization might delay difficulties in effortful word retrieval, which represent one of the earliest cognitive signs of AD. Using functional near-infrared spectroscopy (fNIRS), we investigated cortical hemodynamic responses elicited by phonological and semantic verbal fluency in non-demented, healthy subjects (n = 325; age: 51-82 years). Age predicted bilaterally reduced inferior frontal junction (IFJ) and increased middle frontal and supramarginal gyri activity in both task conditions using multiple regressions. Compared with age the years of education as well as sex (IFJ activation in females > males) partly predicted opposite effects on activation, while task performance was not significant predictor. All predictors showed small effect sizes. IFJ activation was more pronounced during phonological compared with semantic fluency, and higher in the left hemisphere. Age only marginally predicted relative lateralization. Middle frontal and supramarginal gyri activity may compensate for an aging-related decrease in IFJ recruitment during verbal fluency. Longitudinal observations will further investigate these neural changes regarding an early AD prediction, while individuals are still cognitively healthy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: 25.0±2.8 years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6±0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4±9.7)% and V(gray) absorbed (3.1±1.8)% of the energy. The mean V(gray) volume (1.1±0.4) cm3 was negatively correlated (r=-.76) with the SCD and frontal sinus volume (r=-.57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r=.46) and the traversed frontal sinus volume (r=.43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.