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In this study, the neural correlates of error processing in adult patients with attention deficit hyperactivity disorder (ADHD) are to be investigated for the first time. Recent studies in children with ADHD suggested, with some inconsistencies, deficits in error processing. Based on an analogue study with students, we hypothesized that ADHD patients show reduced amplitudes in the event-related potential (ERP) of the Pe (error positivity) but normal amplitudes of the ERN (error-related negativity) after incorrect responses.In this study we investigated 34 adult ADHD patients and 34 healthy controls with a modified version of the Eriksen flanker task while recording the neural activity with 26 scalp EEG electrodes. Patients discontinued all medication at least 3 days prior to investigation. Age was included as a control variable for the statistical analyses.As hypothesized, we found reduced Pe amplitudes, but also reduced ERN values, in ADHD patients. Importantly, theses differences as well as the deficits in behavioural performance were mainly detectable in the younger subsample, but not in the elderly subsample. Our results indicate that adult ADHD patients are characterized by deficits in error processing, which vanish with age.

Solving arithmetical problems is a core skill which is learned starting early in childhood and has been shown to involve a temporo-parietal network. In this study, we investigated hemodynamic concentration changes in oxygenated (O(2)Hb) and deoxygenated hemoglobin (HHb) within cortical brain regions by means of near-infrared spectroscopy (NIRS). Ten healthy subjects had to calculate or just read two-digit addition tasks that were either presented as numeric formulas or embedded in text. We found higher increases for O(2)Hb in parietal brain regions of both hemispheres for the calculation compared to the reading-only condition. Furthermore, these increases were more pronounced during text-embedded tasks than during numeric tasks. Corresponding decreases of HHb could also be detected. These first NIRS findings on that topic confirm that parietal regions are involved in the processing of arithmetic tasks while the amount of activation seems to depend on task modalities like difficulty or complexity.

Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is associated with deficits in executive functions such as verbal fluency. Functional near-infrared spectroscopy offers the possibility to measure brain activity during verbal fluency in psychiatric patients due to low susceptibility to movements artefacts. Fourteen patients with mainly combined ADHD subtype and 14 healthy controls matched for age, gender, handedness, education level, and intelligence showed equal performance in phonological verbal fluency and higher performance in semantical verbal fluency in comparison to the controls. On the level of brain function indicated by concentration changes of oxygenated and deoxygenated haemoglobin, both groups showed inferior frontal brain activity during both tasks. ADHD patients had a lower magnitude of oxygenation and a significant negative correlation of brain activity with performance, i.e. higher brain activity was associated with lower performance. These results might be interpreted as a lack of disease related deficits, as an economical recruitment of cognitive resources, or - more likely - as an expression of a benefit in the patient group. High verbal competence in our samples could contribute to these findings. One speculative and post hoc explanation aims at the clinically well-known phenomenon of hyperfocusing in patients with ADHD.

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.

Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), have been associated with ADHD. The rs4570625 G-allele polymorphisms of the TPH2 gene have already been related to altered reactivity of the brain during perception tasks with emotional stimuli in healthy adults. Here we investigated the influence of the ADHD related risk alleles for rs4570625 and for rs11178997 on prefrontal brain function during cognitive response control in large samples of adult ADHD patients (n=124) and healthy controls (n=84). Response control was elicited with a Go-NoGo task (continuous performance test; CPT) performed during recording of an ongoing EEG. From the resulting event-related potentials in the Go- and NoGo conditions of the CPT, the NoGo-anteriorization (NGA) has been calculated as a valid neurophysiological parameter for prefrontal brain function. In the current study, ADHD risk alleles of both polymorphisms were found to be associated with a reduction in the NGA in both healthy controls and ADHD patients. These findings are in line with the notion that genetic variations associated with altered serotonergic neurotransmission are also associated with the function of the prefrontal cortex during response inhibition. This mechanism might also be relevant in the pathophysiology of ADHD.

Despite prominent prefrontal deficits and alterations in anatomy, neurophysiology, and neuropsychology after long-term alcohol consumption in alcohol dependent patients, only a few investigations of functional brain activity have been published. Using functional near-infrared spectroscopy (fNIRS), we examined the concentration changes in oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin in 17 right-handed alcohol dependent patients after detoxification and 17 matched healthy controls during a verbal fluency task. Alcohol dependent patients were characterized by normal behavioural performance (number of words produced) and physiological activation patterns (increase of O(2)Hb and decrease of HHb) over frontotemporal regions during phonological and semantical verbal fluency. However, the degree of activation was diminished (lower magnitude of oxygenation) and the localization of the activation was more restricted to inferior frontal areas as compared with the healthy participants. fNIRS is a sensitive and valid method, to detect alterations in brain functioning in clinical groups like alcohol dependent patients. Altered prefrontal functional brain activation during verbal fluency in alcohol dependent patients in a detoxified state may precede behavioural or cognitive alterations with a later onset.

It has been shown that dopamine (DA) influences performance on neurocognitive tests, which are thought to rely on prefrontal activity. The purpose of this study was to explore the effects of gene polymorphisms related to DA activity, namely the D4 DA receptor (DRD4) gene exon III polymorphisms, on prefrontal cortex (PFC) activation. In this study we measured the brain oxygenation of the PFC during an n-back task with near-infrared spectroscopy (NIRS). We investigated 40 young healthy subjects, 12 of which carried the DRD4 exon III 7-repeat allele (group 7). These were compared with subjects without a 7-repeat allele (n=28, group 4). Additionally, we compared good and bad performers with respect to brain activation. As expected, we found significant increases in the concentration of oxygenated haemoglobin [O2Hb] during the 1-back and 2-back condition compared with baseline, and a corresponding significant decrease of deoxyhaemoglobin concentration. As a main result of this study we also found an interaction effect between task condition and DRD4 genotype with higher increases of [O2Hb] during the 2-back version compared with the 1-back version for the subjects of the 7-repeat allele group only. The same effect was seen as a statistical trend, when we compared bad performers with good performers. Therefore, we interpret the effects of the 7-repeat allele group of DRD4 as a sign of ineffective brain activity, perhaps even as a sign of prefrontal noise.

Near-infrared spectroscopy (NIRS) is an optical imaging method that allows non-invasive in-vivo measurements of changes in the concentration of oxygenated (O 2 Hb) and deoxygenated (HHb) hemoglobin in brain tissue. For the present study, we examined 12 schizophrenic patients and 12 age- and gender-matched healthy controls by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of two versions of the Verbal Fluency Test (VFT; letter and category version). The results indicate that the verbal fluency tasks generally led to clear frontal activation in healthy controls, which was significantly reduced in schizophrenic patients. The letter version of the VFT induced overall stronger activation than the category version, the group difference being particularly pronounced for phonological fluency. Moreover, significant positive correlations between task-related activation effects in prefrontal and temporal NIRS channels were found in both schizophrenic patients and healthy controls. The results confirm functional deficits within the frontal lobe in patients suffering from schizophrenic illnesses, but do not confirm previous findings on abnormal fronto-temporal correlations or increased temporal activation in this group of patients. The data furthermore underline the usefulness of functional NIRS in monitoring hemodynamic responses associated with cognitive processes in healthy controls and patients with neuro-psychiatric disorders.

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.

Patients suffering from dementia show altered functional brain activation patterns especially in prefrontal brain regions, as research suggests. The present study follows three aims: to replicate these findings, to investigate treatment effects when administering galantamine, and to put gender differences in focus. We compared 12 patients with dementia to 12 age- and gender-matched healthy subjects regarding changes in haemoglobin concentration in brain tissue while performing a verbal fluency task (VFT). Concentration changes of oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin were measured by multi-channel near-infrared spectroscopy (NIRS), an easily applicable and non-invasive method of optical topography. In the patient group, measurement was repeated 4 and 8 weeks after starting treatment with galantamine. The results showed a reduced increase in O(2)Hb during task performance for patients compared to healthy controls. Furthermore, female subjects showed more pronounced activation in O(2)Hb as well as HHb compared to male subjects. Regarding treatment effects, no clear results could be obtained. In HHb, evidence for an entrainment effect was found. In the light of existing literature, the present study suggests an interaction of gender and age regarding brain activation patterns which should be aimed at in future investigations.

Prefrontal electric stimulation has been demonstrated to effectively modulate cognitive processing. Specifically, the amelioration of cognitive control (CC) over emotional distraction by transcranial direct current stimulation (tDCS) points toward targeted therapeutic applications in various psychiatric disorders. In addition to behavioral measures, autonomous nervous system (ANS) responses are fundamental bodily signatures of emotional information processing. However, interactions between the modulation of CC by tDCS and ANS responses have received limited attention. We here report on ANS data gathered in healthy subjects that performed an emotional CC task parallel to the modulation of left prefrontal cortical activity by 1 mA anodal or sham tDCS. Skin conductance responses (SCRs) to negative and neutral pictures of human scenes were reduced by anodal as compared to sham tDCS. Individual SCR amplitude variations were associated with the amount of distraction. Moreover, the stimulation-driven performance- and SCR-modulations were related in form of a quadratic, inverse-U function. Thus, our results indicate that non-invasive brain stimulation (i.e., anodal tDCS) can modulate autonomous responses synchronous to behavioral improvements, but the range of possible concurrent improvements from prefrontal stimulation is limited. Interactions between cognitive, affective, neurophysiological, and vegetative responses to emotional content can shape brain stimulation effectiveness and require theory-driven integration in potential treatment protocols.

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.

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.

Preliminary evidence suggests beneficial effects of transcranial magnetic stimulation (TMS) on anxiety. The objective of this study was to investigate the effects of intermittent theta burst stimulation (iTBS) as a form of TMS on acute anxiety provoked by a virtual reality (VR) scenario. Participants with spider phobia (n=41) and healthy controls (n=42) were exposed to a spider scenario in VR after one session of iTBS over the prefrontal cortex or sham treatment. Participants with spider phobia reacted with more anxiety compared to healthy controls. Their heart rate and skin conductance increased compared to baseline. Contrary to expectations, iTBS did not influence these reactions, but modulated heart rate variability (HRV). Sympathetic influence on HRV showed an increase in the active iTBS group only. This study does not support the idea of beneficial effects of a single session of iTBS on anxiety, although other protocols or repeated sessions might be effective.

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.

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.

The purpose of this study was to investigate the regional specificity of multi-channel functional near-infrared spectroscopy (fNIRS) in the detection of cortical activation in humans. Therefore, brain activation evoked by a visual as well as a motor task was examined using 52-channel fNIRS. Analyses demonstrated an isolated activation in the occipital area during visual stimulation, whereas other regions exhibited little or no activation. Analyses of the motor task data clearly identified a differential activation pattern. The observation of an extensive cortical area by multi-channel measurement during two different tasks made it possible to examine the extent to which fNIRS measurements detect regional specific activations. We conclude that fNIRS measurements can detect regionally isolated cortical activation.

ZusammenfassungDie Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) wird in den letzten Jahren immer stärker als Erkrankung betrachtet, die auch im Erwachsenenalter eine relevante Rolle spielt. Vor allem das Symptom der Hyperaktivität wird in neueren Arbeiten mit defizitären Inhibitionsprozessen in kortikalen Hirnregionen in Zusammenhang gebracht. Mit der transkraniellen Magnetstimulation (TMS) ist es sehr gut möglich, Inhibitionsprozesse im Kortex zu messen. In dieser Arbeit wird ein kurzer Überblick über Messmethoden inhibitorischer Hirnfunktionen mittels TMS gegeben, die bereits bei Kindern mit ADHS angewendet wurden. Des Weiteren wird deren Reliabilität diskutiert. Im Anschluss werden bisherige Ergebnisse dieser Messungen dargestellt sowie erste Ergebnisse bei erwachsenen ADHSPatienten vorgestellt und diskutiert. Sich daraus ergebende Fragen und Perspektiven werden abschließend erörtert.

ZusammenfassungBei der elektrischen Stimulation des N. vagus über einen sensiblen Hautast am äußeren Ohr lassen sich spezifische neuronale Antworten als bipolar evozierte Fernfeldpotenziale an der Schädelkalotte abgreifen, die als Vagus-evozierte Potenziale bezeichnet werden. Latenzen im Bereich weniger Millisekunden wie bei akustisch Evozierten Potenzialen (AEP) und Veränderungen nach Lokalanästhesie im Stimulationsgebiet, sind Hinweise für ihre neurogene Entstehung im Bereich der Vagus-Kerngebiete im Hirnstamm. Wir präsentieren die Daten von fünf Einzelfalluntersuchungen von verschiedenen neuropsychiatrischen Erkrankungen und diskutieren sie hinsichtlich der betroffenen neuroanatomischen Strukturen. Diese neue Methode wäre gerade im Hinblick auf eine Früherkennung neurodegenerativer Erkrankungen wie M. Parkinson oder Alzheimer-Erkrankung von großem Nutzen für den frühzeitigen und zielgerichteten Einsatz neuroprotektiver Behandlungsmöglichkeiten. Im Vergleich zur bisherigen operativen Vorgehensweise bei der Stimulation des Vagus-Hauptstammes wäre eine nebenwirkungsfreie und minimalinvasive Stimulationsweise auch ein bedeutender Fortschritt im Hinblick auf den therapeutischen Einsatz bei therapieresistenten Epilepsien und Depressionen.

Recent studies using ERPs in face recognition revealed that face processing starts around 100 ms after stimulus onset, 70 ms earlier than suggested before. While the neural sources of the N 170 component have repeatedly been found to be localized in the gyrus fusiformis and the inferior occipital cortex, sources have not yet been investigated for the P100 component during face processing. Therefore, we measured the ERPs elicited by faces and control stimuli in 72 subjects in order to localize the neural sources of both the P100 and the N 170 component. We observed significantly higher P100 and N 170 amplitudes to faces compared to control stimuli. LORETA source localization revealed significantly higher brain activity in the left and right gyrus fusiformis for the N 170 component, with additional regions of increased brain activation in a parieto-temporal-occipital network. For the P100, faces activated the left and right gyrus fusiformis significantly stronger than control stimuli. This study reveals that the first step of face processing (about 100 ms after stimulus presentation) is localized in the gyrus fusiformis. The second step of face processing around 170 ms involves the gyrus fusiformis, with additional activation in a more distributed network, including the occipital cortex.

In this study we investigated the functional brain activation during response inhibition by means of concentration changes in oxygenated [O 2 Hb] and deoxygenated [HHb] hemoglobin. 9 subjects were measured with multi-channel near-infrared spectroscopy (NIRS) over the left and right lateral prefrontal cortex. The activation task consisted of three blocks of cued Go–NoGo conditions, which were contrasted with three blocks of cued Go conditions. The Go- and Go–NoGo blocks lasted 30 s each, were presented in alternating order, and were preceded by a 30 s resting period. The results clearly show that both conditions induced a brain activation consisting of significant increases of [O 2 Hb] and decreases of [HHb]. These effects indicate that an active control condition is necessary for the adequate interpretation of the results. Most importantly, we found significantly higher increases of [O 2 Hb] and decreases of [HHb] during the inhibition phase as compared to the simple motor response in bilateral inferior frontal regions of the brain, which is in accordance with other brain imaging studies. With the introduction of an active control condition in this study, we improved the methodology of a previous investigation. We conclude that multi-channel NIRS is suitable for the functional identification of the inferior prefrontal brain area activated during response inhibition.

Recently, a new electrophysiological method for the assessment of vagus nerve function in the brainstem has been proposed in healthy participants. Before this procedure may be applied to patients with neurodegenerative diseases, its feasibility in elderly healthy participants and a possible age effect on the measurement have to be investigated. The vagus sensory evoked potentials (VSEP) after transcutaneous electric stimulation of the sensory auricular branch of the vagus nerve have been assessed in healthy younger and elderly participants. VSEP measured as far field potentials probably originating in vagus nuclei in the brainstem were recorded in 20 of 22 younger as well as in 39 of 43 elderly healthy participants. Latencies were significantly longer in the elderly as compared to the younger participants, while no clear age effects on amplitudes were identified. These results indicate that the assessment of VSEP is feasible also in elderly healthy participants. This is a prerequisite for testing this method in elderly patients with neurodegenerative diseases like Alzheimer and Parkinson disease as a noninvasive tool to detect an affection of the brainstem nuclei of the vagus nerve early in their course.

Abstract: In the present study, a modified version of the Eriksen Flanker Task has been used to study event-related potentials (ERPs) elicited by correct responses, response errors, and invalid negative response feedback following correct button presses (“PC-error trials”). Conventional error potentials (error related negativity [ERN/Ne]; error-positivity [Pe]) were observed after incorrect button presses but not following negative response feedback in PC-error trials. Furthermore, a late positive deflection occurred specifically after PC-errors (Late positivity [PL]), which might reflect a conscious processing of these unexpected events. The results imply some restrictions for the notion that the ERN/Ne reflects the activity of a general and “generic” neural error-detection system in the human brain. Furthermore, the existence of an “event-detection system” is indicated, which might be involved in the processing of events that violate learned expectations.

Abstract: In this study we investigated the changes in brain oxygenation in 22 subjects during a verbal fluency task (VFT) using multichannel near-infrared spectroscopy (NIRS). To assess topographical effects in more detail we measured over bilateral prefrontal and over the left frontolateral cortex in 11 subjects. We found significantly higher increases in O2HB, as a sign of cerebral activation, during the VFT compared to a verbal repetition control task over the left prefrontal and the inferior left lateral brain areas. These results underscore the value of NIRS to assess functional brain activation during cognitive tasks. Furthermore, it shows the advantage of multichannel compared to previously used single channel NIRS measurements.

Multi-channel near-infrared spectroscopy (NIRS) is a relatively new method to investigate the brain activation, based on changes in oxygenated haemoglobin (O2Hb) and deoxygenated haemoglobin (HHb). Recently, it has been shown that NIRS seems to be able to detect even small changes in O2Hb and HHb concentration due to cognitive demands. This study aimed at investigating the changes in O2Hb and HHb concentrations of the parietal cortex during a spatial task, a modified version of the Benton Line Orientation Task [Gur, R. C., Alsop, D., Glahn, D., Petty, R., Swanson, C. L., Maldjian, J. A., et al. (2000). An fMRI study of sex differences in regional activation to a verbal and a spatial task. Brain & Language, 74(2), 157–170.]. Twenty-four subjects were measured with NIRS while they had to estimate the orientation of a given line or to name the colour of the line in the control condition. Both conditions consisted of three activation phases each lasting 30 s, with a 10 s baseline and a 20 s post resting period. For assessing the changes in O2Hb and HHb concentrations, we measured with 24 NIRS channels over the parietal cortex using the NIRS apparatus ETG-100 (Hitachi Medical Ltd.). O2Hb concentration significantly increased during the active phase compared to the baseline for both conditions, but was significantly higher in the active phase for the line orientation condition compared to the colour naming condition bilaterally parieto-occipital. For the HHb concentrations, we only found significant decreases for both conditions but no differences between the conditions. The results of our study underscore the value of multi-channel NIRS for assessing cortical activation during cognitive tasks.

According to current ERP literature, face specific activity is reflected by a negative component over the inferior occipito-temporal cortex between 140 and 180 ms 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 100 ms (M100) which is about 70 ms earlier than reported in most previous studies. Here we report these early differences at 107 ms 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 approximately 100 ms with an initial stage which can be measured not only with MEG but also with ERPs.

The 22q11 microdeletion syndrome (22q11-DS) is strongly associated with schizophreniform disorders and, in turn, the 22q11 deletion region harbours several candidate genes for schizophrenia. Here, we present the case of an adolescent female patient with 22q11-DS associated with impaired cognitive abilities and behavioural abnormalities. The patient was studied with magnetic resonance imaging (MRI) and positron emission tomography (PET) as well as extensive neurophysiological investigations. Although no structural or functional abnormalities were found in MRI and PET, assessment of event-related potentials elicited during the Continuous Performance Test revealed a lack of NoGo anteriorisation. The latter was replicated in a second case of 22q11-DS with schizoaffective disorder but devoid of a severe somatic syndrome. This electrophysiological finding, which indicates modified functioning of the cingulate gyrus, has previously been demonstrated only in patients suffering from schizophrenia and attention deficit/hyperactivity disorder, two psychopathological conditions frequently associated with 22q11-DS. We conclude that more extensive study of NoGo anteriorisation as a potential endophenotype of 22q11-DS patients at risk for 22q11-associated psychiatric conditions is warranted.

We investigated error processing of 39 subjects engaging the Eriksen flanker task. In all 39 subjects a pronounced negative deflection (ERN/Ne) and a later positive component (Pe) were observed after incorrect as compared to correct responses. The neural sources of both components were analyzed using LORETA source localization. For the negative component (ERN/Ne) we found significantly higher brain electrical activity in medial prefrontal areas for incorrect responses, whereas the positive component (Pe) was localized nearby but more rostral within the anterior cingulate cortex (ACC). Thus, different neural generators were found for the ERN/Ne and the Pe, which further supports the notion that both error-related components represent different aspects of error processing.

A functional length variation in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) influences brain function, personality traits, and susceptibility to psychiatric disorders. Here we measured prefrontal brain function by means of event-related potentials during an error processing paradigm. Physiologically, occurrence of an error elicits two specific electrical responses in the prefrontal cortex, the early error related negativity (Ne/ERN) and the later occurring error positivity (Pe), reflecting different components of error processing. Healthy subjects with one or two copies of the low-activity 5-HTTLPR short variant showed significantly higher amplitudes of the Ne/ERN and a trend to higher amplitudes of the Pe as compared to age- and gender-matched individuals homozygous for the long allele. Performance measures and latencies of these ERP-components did not differ between groups. These results indicate that the 5-HTTLPR short variant is associated with enhanced responsiveness of the brain and further supports the notion that prefrontal brain function is influenced by allelic variation in serotonin transporter function.

Objective : To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD). Method : Sixteen 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. Results : The 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. Conclusions : The 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.

The medial prefrontal cortex is believed to be involved in emotional experiences, but also in situations in which attention and self-monitoring is required. Therefore, it might be that the medial prefrontal cortex is not only activated by the emotional state per se, but rather through the task requirements that were used to induce emotions in the laboratory. The present study investigated the change of oxygenation in the left and right prefrontal cortex measured with near-infrared spectroscopy (NIRS) from 14 subjects during two kinds of emotional induction, which differed in the self-monitoring requirements. The task with the higher self-monitoring requirements resulted in an increased concentration of oxygenated hemoglobin (O 2 HB). This activation pattern was not observed during the emotional induction with the fewer self-monitoring requirements, although the subjective ratings indicated that both tasks induced comparable emotional states. The results indicate that task requirements should be taken into account when investigating the neural substrate of emotions.

Background Neurofeedback has been applied effectively in various areas, especially in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This study protocol is designed to investigate the effect of slow cortical potential (SCP) feedback and a new form of neurofeedback using near-infrared spectroscopy (NIRS) on symptomatology and neurophysiological parameters in an adult ADHD population. A comparison of SCP and NIRS feedback therapy methods has not been previously conducted and may yield valuable findings about alternative treatments for adult ADHD. Methods/Design The outcome of both neurofeedback techniques will be assessed over 30 treatment sessions and after a 6-month follow-up period, and then will be compared to a nonspecific biofeedback treatment. Furthermore, to investigate if treatment effects in this proof-of-principle study can be predicted by specific neurophysiological baseline parameters, regression models will be applied. Finally, a comparison with healthy controls will be conducted to evaluate deviant pretraining neurophysiological parameters, stability of assessment measures, and treatment outcome. Discussion To date, an investigation and comparison of SCP and NIRS feedback training to an active control has not been conducted; therefore, we hope to gain valuable insights in effects and differences of these types of treatment for ADHD in adults. Trial registration This study is registered with the German Registry of Clinical Trials: DRKS00006767, date of registration: 8 October 2014.

In this pilot study near-infrared spectroscopy (NIRS) neurofeedback was investigated as a new method for the treatment of Attention Deficit-/Hyperactivity Disorder (ADHD). Oxygenated hemoglobin in the prefrontal cortex of children with ADHD was measured and fed back. 12 sessions of NIRS-neurofeedback were compared to the intermediate outcome after 12 sessions of EEG-neurofeedback (slow cortical potentials, SCP) and 12 sessions of EMG-feedback (muscular activity of left and right musculus supraspinatus). The task was either to increase or decrease hemodynamic activity in the prefrontal cortex (NIRS), to produce positive or negative shifts of SCP (EEG) or to increase or decrease muscular activity (EMG). In each group nine children with ADHD, aged 7–10 years, took part. Changes in parents’ ratings of ADHD symptoms were assessed before and after the 12 sessions and compared within and between groups. For the NIRS-group additional teachers’ ratings of ADHD symptoms, parents’ and teachers’ ratings of associated behavioral symptoms, childrens’ self reports on quality of life and a computer based attention task were conducted before, 4 weeks and 6 months after training. As primary outcome, ADHD symptoms decreased significantly 4 weeks and 6 months after the NIRS training, according to parents’ ratings. In teachers’ ratings of ADHD symptoms there was a significant reduction 4 weeks after the training. The performance in the computer based attention test improved significantly. Within-group comparisons after 12 sessions of NIRS-, EEG- and EMG-training revealed a significant reduction in ADHD symptoms in the NIRS-group and a trend for EEG- and EMG-groups. No significant differences for symptom reduction were found between the groups. Despite the limitations of small groups and the comparison of a completed with two uncompleted interventions, the results of this pilot study are promising. NIRS-neurofeedback could be a time-effective treatment for ADHD and an interesting new option to consider in the treatment of ADHD.

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.

Serial position performance was measured with the Buschke selective reminding test (BSRT). Hippocampal size was automatically measured via MRI using high-dimensional spatial transformation and a predefined hippocampus mask. We conducted regression analyses with delayed primacy, delayed recency and total delayed recall performance as outcome variables; predictors were age, family history of Alzheimer’s disease (AD), APOE e4 status, sex, level of education, total intracranial volume, and left and right hippocampal size. Results: The size of both the left and right hippocampus was positively correlated with delayed primacy performance, although left hippocampal size was a slightly better predictor of performance. In contrast, hippocampal size did not predict total delayed recall or recency performance. Conclusions:These findings are consistent with the hypothesis that the hippocampus is involved in delayed primacy consolidation. To our knowledge, this is the first time this has been reported in cognitively-intact older individuals, using in-vivo imaging. Our results shed some light on the relationship between delayed primacy performance and generalised cognitive decline. Since delayed primacy consolidation relies on a healthy hippocampus, and the hippocampus is affected early in AD, it is possible that failure to consolidate delayed primacy items might indirectly signal the incipient emergence of the disease.

The central representation of numeri- cal cognition is commonly considered an abstract magnitude representation serving as one key precursor for higher mathe- matical thinking. However, recent research indicates that the representation might not be purely abstract. In fact, accumulating evidence suggests that numerical represen- tations are rooted in and shaped by spe- cific motor activities and sensory-bodily experiences and, therefore, are influenced by so-called embodied numerical repre- sentations. If we want to understand how numerical understanding develops, it is crucial to elucidate the basic cognitive tools with which we develop a sense of number. We argue that it is necessary to address this issue on both a behavioral and an eural level. Contrasting the view of functional magnetic resonance imaging (fMRI) being the generally preferable neuroimaging technique, we argue that particularly in embodied cognition, restrictions and ben- efits of different imaging methods should guide the chosen research question. In our opinion, near-infrared spectroscopy (NIRS) is optimally suited to investi- gate embodied cognition paradigms that explicitly involve motion. In the follow- ing, recent research will be outlined show- ing that numerical cognition is not purely abstract, but influenced by embodied rep- resentations. NIRS will then be introduced as a feasible technique for the investigation of embodied cognitions. Since research in this domain is largely restricted to the perception of embodied experiences, but fails to address motion itself, we willfinally argue that NIRS offers a good opportunity to fill this research gap.

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and associated neurochemical reactions, following glucocorticoid release from the adrenal glands, accompanied by rapid physiological responses. Stimulation of this pathway results in the activation of specific brain regions, including the hippocampus, amygdala and prefrontal cortex which are enriched with glucocorticoid receptors (GRs). Recent findings indicate that the activation of GRs mediates the regulation of the brain-derived neurotrophic factor (BDNF). BDNF is crucial for neural plasticity, as it promotes cellular growth and synaptic changes. Hence stress-induced activation of these pathways leads to neuroplastic changes, including the formation of long-lasting memories of the experiences. As a consequence, organisms can learn from stressful events and respond in an adaptive manner to similar demands in the future. Whereas an optimal stress level leads to enhancement of memory performance, the exposure to extreme, traumatic or chronic stressors is a risk factor for psychopathologies which are associated with memory impairment and cognitive deficits such as posttraumatic stress disorder (PTSD). In this review article, we will outline the implications of stress exposure on memory formation involving the role of glucocorticoids and BDNF. Within this context, potential adverse effects of neuroplastic alterations will be discussed using the example of PTSD.

Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and enduring developmental disorder whose underlying etiological and neurobiological processes are the current focus of major research. Research strategies have made considerable effort in elucidating the complex genetic architecture of ADHD and indicate various pathways from genotype to phenotype. Understanding ADHD as a neuropsychiatric disorder enabled to investigate markers of neural activity as endophenotypes to better explain the link from gene to symptomatology (the so-called imaging genetics approach). Overcoming the originally rather restrictive requirements for an endophenotype, imaging genetics studies are supposed to offer a much more flexible and hypothesis-driven approach towards the etiology of ADHD. Although 1) ADHD often persists into adulthood, thus remaining a prevalent disorder, and 2) imaging genetics provides a promising research approach, a review on imaging genetics in adult ADHD – as available for childhood ADHD (Durston 2010) – is lacking. In this review, therefore, findings from the few available imaging genetics studies in adult ADHD will be summarized and complemented by relevant findings from healthy controls and children with ADHD that are considered important for the adult ADHD imaging genetics approach. The studies will be reviewed regarding implications for basic research and possible practical applications. Imaging genetics studies in adult ADHD have the potential to further clarify pathophysiological pathways and mechanisms, to derive new testable hypotheses, to investigate genetic interaction effects and to partly influence practical applications. In combination with other research strategies, they can incrementally foster the understanding of relevant processes in a more comprehensive way. Current limitations comprise the incapability to discover new genes, a high genetic load in patients potentially obscuring the effect of single candidate genes, the mostly unknown heritability of the endophenotype and the heterogeneous manifestation of ADHD.

During the last years diverging results concerning the effects of repetitive transcranial magnetic stimulation (rTMS) have been reported. In this context, especially its application as a therapeutic tool by means of increasing the activation of specific cortical neuronal networks which are known to be impaired in particular disorders has been in the focus of attention. However, a number of studies could not confirm its role as a modulator of neuronal activation and associated clinical symptoms.In our study we, therefore, aimed at investigating its effect on emotion regulation in a distinctly defined setting using a single session of intermittent theta burst stimulation (iTBS), a modern form of rTMS, on the left prefrontal cortex. To do so, 40 subjects with spider phobia were treated with either sham or verum rTMS prior to a confrontation with spiders in a virtual reality (VR) challenge. With a lifetime prevalance of 6%, spider phobia is the most common phobia of the animal type while at the same it is known for its relatively low comorbidity with other psychiatric disorders. It therefore serves well as a modell disorder to study the effects of dysfunctional emotion regulation in response to fear-relevant stimuli without too many confounding effects. During VR, subjective ratings of anxiety and disgust as well as objective markers of fear processing (electrodermal activity (EDA), hear rate) were recorded. Moreover, prefrontal activation patterns by means of functional near-infrared spectroscopy during an emotional stroop task were assessed prior to as well as after the VR challenge. Further, the results were compared to the ones of 40 healthy control subjects which received an equivalent treatment. First results could confirm a specific effect of the VR challenge on the electrophysiological parameters as well as subjective ratings in spider phobics. Anxiety and disgust a well as heart rate and EDA increased significantly after the confrontation with the virtual spiders and showed a trend towards a decrease at the end of the challenge in terms of habituation processes. Interestingly, however, heart rate variability which is know to be influenced by both sympathetic as well as parasympathetic activation, was altered not only in spider phobics that received a verum rTMS treatment but also in the healthy controls. In this regard the direction of the results pointed to an increased influence of the sympathetic systems while the influence of the parasympathetic system was decreased in both groups. Possible underlying mechanisms which might explain this finding as well as implications on the opportunities and difficulties concerning the potential of iTBS as an intervention method are discussed.

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.

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.

The ability to recognize and adequately interpret emotional states in others plays a fundamental role in regulating social interaction. Body language presents an essential element of nonverbal communication which is often perceived prior to mimic expression. However, the neural networks that underlie the processing of emotionally expressive body movement and body posture are poorly understood. 33 healthy subjects have been investigated using the optically based imaging method functional near-infrared spectroscopy (fNIRS) during the performance of a newly developed emotion discrimination paradigm consisting of faceless avatars expressing fearful, angry, sad, happy or neutral gait patterns. Participants were instructed to judge (a) the presented emotional state (emotion task) and (b) the observed walking speed of the respective avatar (speed task). We measured increases in cortical oxygenated haemoglobin (O2HB) in response to visual stimulation during emotion discrimination. These O2HB concentration changes were enhanced for negative emotions in contrast to neutral gait sequences in right occipito-temporal and left temporal and temporo-parietal brain regions. Moreover, fearful and angry bodies elicited higher activation increases during the emotion task compared to the speed task. Haemodynamic responses were correlated with a number of behavioural measures, whereby a positive relationship between emotion regulation strategy preference and O2HB concentration increases after sad walks was mediated by the ability to accurately categorize sad walks. Our results support the idea of a distributed brain network involved in the recognition of bodily emotion expression that comprises visual association areas as well as body/movement perception specific cortical regions that are also sensitive to emotion. This network is activated less when the emotion is not intentionally processed (i.e. during the speed task). Furthermore, activity of this perceptive network is, mediated by the ability to correctly recognize emotions, indirectly connected to active emotion regulation processes. We conclude that a full understanding of emotion perception and its neural substrate requires the investigation of dynamic representations and means of expression other than the face.

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.

Two decades ago, the introduction of functional near-infrared spectroscopy (fNIRS) into the field of neuroscience created new opportunities for investigating neural processes within the human cerebral cortex. Since then, fNIRS has been increasingly used to conduct functional activation studies in different neuropsychiatric disorders, most prominently schizophrenic illnesses, affective disorders and developmental syndromes, such as attention-deficit/hyperactivity disorder as well as normal and pathological aging. This review article provides a comprehensive overview of state of the art fNIRS research in psychiatry covering a wide range of applications, including studies on the phenomenological characterization of psychiatric disorders, descriptions of life-time developmental aspects, treatment effects, and genetic influences on neuroimaging data. Finally, methodological shortcomings as well as current research perspectives and promising future applications of fNIRS in psychiatry are discussed. We conclude that fNIRS is a valid addition to the range of neuroscientific methods available to assess neural mechanisms underlying neuropsychiatric disorders. Future research should particularly focus on expanding the presently used activation paradigms and cortical regions of interest, while additionally fostering technical and methodological advances particularly concerning the identification and removal of extracranial influences on fNIRS data as well as systematic artifact correction. Eventually, fNIRS might be a useful tool in practical psychiatric settings involving both diagnostics and the complementary treatment of psychological disorders using, for example, neurofeedback applications.

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.

Current research strategies have made great efforts to further elucidate the complex genetic architecture of attention-deficit hyperactivity disorder (ADHD). The present study examined the impact of an LPHN3 haplotype that has recently been associated with ADHD (Arcos-Burgos et al., 2010) on neural activity in a visual Go-NoGo task. Two hundred sixteen adult ADHD patients completed a Continuous Performance Test (CPT) while the ongoing EEG was simultaneously recorded. Results showed that patients carrying two copies of the LPHN3 risk haplotype (n=114) made more omission errors and had a more anterior Go-centroid of the P300 than patients carrying at least one LPHN3 non-risk haplotype (n=102). Accordingly, the NoGo-Anteriorization (NGA; topographical ERP difference of the Go- and NoGo-condition), a neurophysiological marker of prefrontal functioning, was reduced in the LPHN3 high risk group. However, in the NoGo-condition itself no marked differences attributable to the LPHN3 haplotype could be found. Our findings indicate that, within a sample of ADHD patients, the LPHN3 gene impacts behavioral and neurophysiological measures of cognitive response control. The results of our study further strengthen the concept of an LPHN3 risk haplotype for ADHD and support the usefulness of the endophenotype approach in psychiatric and psychological research. Published by Elsevier B.V.

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.

The Approach–Avoidance Task (AAT) measures automatic approach–avoidance tendencies and their regulation: compatible reactions (approach positive, avoid negative) are faster than incompatible ones (approach negative, avoid positive). The present study assessed event-related potentials (ERPs) in 15 healthy persons for depicting neuropsychological sub-processes of such stimulus-response compatibility (SRC) effects. Early attention allocation preparing efficient stimulus classification (N1 ERP) and response inhibition on the level of response representations (N2 ERP) were found to underlie the solution of the AAT-conflict. For positive stimuli, these processes were enhanced during the incompatible condition avoid positive compared to the compatible condition approach positive. Source localization analysis revealed activity in right occipital areas (N1 ERP), and in left DLPFC and insula (N2 ERP) to be neuronal generators of these electrophysiological SRC effects. This neuronal regulation resulted in no influence of incompatibility at the behavioural level. For negative pictures, we found the reversed pattern: there were no electrophysiological SRC effects, but clear behavioural SRC effects in both RTs and error frequency, i.e. participants were faster and made fewer errors during avoiding than approaching negative pictures. These valence-specific differences are in line with previous studies indicating negative stimuli – probably due to higher importance for survival – to more strongly influence behaviour.