Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI.

Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields.

Centromedial amygdala is more relevant for phobic confrontation relative to the bed nucleus of stria terminalis in patients with spider phobia.

Recent studies indicate differential involvement of the centromedial amygdala (CM) and the bed nucleus of the stria terminalis (BNST) during processing (anticipation and confrontation) of threat stimuli. Here, temporal predictability was shown to be a relevant factor. In this study, we want to investigate the relevance of these effects, which were found in healthy subjects, for anxiety disorders. Therefore, we investigated the differential involvement of CM and BNST in the anticipation and confrontation of phobic stimuli under variation of temporal predictability in spider phobia. 21 patients with spider phobia and 21 healthy controls underwent a temporally predictable/unpredictable phobic and neutral anticipation and confrontation paradigm using functional magnetic resonance imaging (fMRI) and ROI analyses. During the anticipation phase, healthy controls showed higher CM and BNST activity during the predictable compared with the unpredictable condition compared with the anxiety patients. During a confrontation phase that followed the anticipation phase, CM was more activated than BNST during the phobic compared with the neutral confrontation. While this effect was independent of threat predictability in patients, healthy controls showed higher activation in the CM compared with the BNST only during the predictable spider confrontation compared with the predictable bird confrontation. The results contribute to a better understanding of the separate roles of the CM and BNST during phobic processes. The CM was found to be more relevant to phobic confrontation in patients with spider phobia compared with the BNST.

BNST and amygdala activation to threat: Effects of temporal predictability and threat mode.

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder.

BACKGROUND: Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD. METHODS: Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations. RESULTS: PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks. CONCLUSIONS: We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

Serotonin transporter polymorphism modulates neural correlates of real-life joint action. An investigation with functional near-infrared spectroscopy (fNIRS).

A functional polymorphism (5-HTTLPR) within the serotonin transporter gene (SERT) has been associated with personality dimensions such as neuroticism, with emotional reactivity to negative events, and with an increased risk of affective disorders. More specifically, the short (S) allele of 5-HTTLPR has been linked to increased amygdala activity and has been identified as a risk allele for depressive disorders. Recently, Homberg and Lesch (2011) urged for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR S-allele and argued that the S-allele could be considered adaptive in certain contexts. They postulated that S-allele carriers show hypervigilant behavior in social situations and should thus show increased social conformity. Therefore, we tested whether 5-HTTLPR modulates the neural correlates of real-life social joint action through functional near-infrared spectroscopy (fNIRS). Thirty participants, homozygote for 5-HTTLPR, were measured and analyzed while they were involved in a previously published joint-action paradigm, which reliably leads to an activation of the left parietal cortex. We found that homozygote S-allele carriers showed increased inferior parietal lobe activation, compared to the LL-allele carriers for the contrast "joint action greater solo action". Therefore, our results provide evidence for beneficial effects of the S-allele on the neural correlates of social interactions.

Voluntary suppression of thoughts is influenced by anxious and ruminative tendencies in healthy volunteers.

Replicating thought suppression effects with the Think/No-Think paradigm (TNT) has failed in some studies investigating the phenomenon of below-baseline recall of suppressed stimuli. Attempts have been made to isolate factors that might explain inter-individual differences in suppression performance. Certain personality traits, whether associated with a pathological state or investigated in a community sample, have been shown to interfere with successful thought suppression and might be responsible for some of the negative results obtained in TNT studies. In the present study we investigate the influence of psychometric measures of depression and anxiety in a fairly large sample of healthy volunteers. We show that high brooding and anxious tendencies predict worse suppression performance. While no suppression was shown when investigating the TNT not taking the psychometric measures into account, including these two traits in the analysis resulted in a pattern of below-baseline recall only for low brooders and low anxious participants. We argue that inclusion of variables measuring personality traits is warranted using the TNT and that these variables already exert their influence at minimal levels of variance, significantly improving the interpretability of the results. Future research should therefore cautiously investigate potential confounding personality characteristics before analysing their data.

ADHD related behaviors are associated with brain activation in the reward system.

Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) suggest dysfunctional reward processing, with hypo-responsiveness during reward anticipation in the reward system including the nucleus accumbens (NAcc). In this study, we investigated the association between ADHD related behaviors and the reward system using functional magnetic resonance imaging in a non-clinical sample. Participants were 31 healthy, female undergraduate students with varying levels of self-reported ADHD related behaviors measured by the adult ADHD self-report scale. The anticipation of different types of reward was investigated: monetary reward, punishment avoidance, and verbal feedback. All three reward anticipation conditions were found to be associated with increased brain activation in the reward system, with the highest activation in the monetary reward anticipation condition, followed by the punishment avoidance anticipation condition, and the lowest activation in the verbal feedback anticipation condition. Most interestingly, in all three conditions, NAcc activation was negatively correlated with ADHD related behaviors. In conclusion, our results from a non-clinical sample are in accordance with reported deficits in the reward system in ADHD patients: the higher the number and severity of ADHD related behaviors, the lower the neural responses in the dopaminergic driven reward anticipation task. Thus, our data support current aetiological models of ADHD which assume that deficits in the reward system might be responsible for many of the ADHD related behaviors.

DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in schizophrenic patients--support for the glutamate hypothesis of schizophrenias.

Dysbindin (DTNBP1) is a recently characterized protein that seems to be involved in the modulation of glutamatergic neurotransmission in the human brain, thereby influencing prefrontal cortex function and associated cognitive processes. While association, neuroanatomical and cellular studies indicate that DTNBP1 might be one of several susceptibility genes for schizophrenia, the effect of dysbindin on prefrontal brain function at an underlying neurophysiological level has not yet been explored for these patients. The NoGo-anteriorization (NGA) is a topographical event-related potential measure, which has been established as a valid neurophysiological marker of prefrontal brain function. In the present study, we investigated the influence of seven dysbindin gene variants on the NGA in a group of 44 schizophrenic patients. In line with our a priori hypothesis, one DTNBP1 polymorphism previously linked to schizophrenia (rs2619528) was found to be associated with changes in the NGA; however, the direction of this association directly contrasts with our previous findings in a healthy control sample. This differential impact of DTNBP1 gene variation on prefrontal functioning in schizophrenic patients vs. healthy controls is discussed in terms of abnormal glutamatergic baseline levels in patients suffering from schizophrenic illnesses. This is the first report on a role of DTNBP1 gene variation for prefrontal functioning at a basic neurophysiological level in schizophrenic patients. An impact on fundamental processes of cognitive response control may be one mechanism by which DTNBP1 gene variants via glutamatergic transmission contribute to the pathophysiology underlying schizophrenic illnesses.

Cortical correlates of auditory sensory gating: a simultaneous near-infrared spectroscopy event-related potential study.

Sensory gating refers to the ability of cerebral networks to inhibit responding to irrelevant environmental stimuli, a mechanism that protects the brain from information overflow. The reduction of the P50 amplitude (an early component of the event-related potential/ERP in electrophysiological recordings) after repeated occurrence of a particular acoustic stimulus is one means to quantitatively assess gating mechanisms. Even though P50 suppression has been extensively investigated, neuroimaging studies on the cortical correlates of auditory sensory gating are so far very sparse. Near-infrared spectroscopy (NIRS) is an optical imaging technique perfectly suitable for the investigation of auditory paradigms, since it involves virtually no noise. We conducted a simultaneous NIRS-ERP measurement to assess cortical correlates of auditory sensory gating in humans. The multi-channel NIRS recording indicated a specific activation of prefrontal and temporo-parietal cortices during conditions of increased sensory gating (dual-click trials). Combining the hemodynamic data with an electrophysiological index of the "gating quality" (gating quotient Q) revealed a positive correlation between the amount of sensory gating and the strength of the hemodynamic response during dual-clicks in the left prefrontal and temporal cortices. The results are in line with previous findings and confirm a possible inhibitory influence of the prefrontal cortex on primary auditory cortices.

Increased EEG power density in alpha and theta bands in adult ADHD patients.

This study examined EEG abnormalities in adults with attention deficit hyperactivity disorder (ADHD). We investigated EEG frequencies in 34 adults with ADHD and 34 control subjects. Two EEG readings were taken over 5 min intervals during an eyes-closed resting period with 21 electrodes placed in accordance with the international 10-20 system. Fourier transformation was performed to obtain absolute power density in delta, theta, alpha and beta frequency bands. The ADHD patients showed a significant increase of absolute power density in alpha and theta bands. No differences were found for beta activity. Our findings indicate that abnormalities in the EEG power spectrum of adults with ADHD are different than those described in children. Reliable discriminators between patients and healthy subjects in adulthood could be alpha and theta power density. Based on our results, we suggest further research involving longitudinal studies in ADHD patients to investigate the changes of EEG abnormalities with age.

The impact of prefrontal cortex for selective attention in a visual working memory task.

In this study, a variant of the n-back task was used to investigate electrophysiological correlates of top-down processes in visual-object working memory. Event-related potentials were used to replicate results concerning an attention related modulation of neural processes and to investigate the involvement of prefrontal cortex in this modulation. 16 healthy subjects executed an n-back task with sequentially presented faces and scenes. Attention was selectively directed to only one stimulus category. We found an enhancement of the N170 amplitudes for relevant stimuli compared to irrelevant or neutral stimuli. Late frontal amplitudes were stronger positive for relevant compared to neutral stimuli indicating selective attention processes of working memory. Evidence for selective inhibition was not found.

D4 receptor gene variation modulates activation of prefrontal cortex during working memory.

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.

The other-race effect for face perception: an event-related potential study.

It is well known that a recognition bias can be observed whenever subjects have to decide whether they have seen a person before that belongs to a different ethnical group. Although this "other-race effect" is well documented on a behavioural level, its underlying mechanisms remain unclear. One plausible explanation might be that cortical areas involved in face processing are not as effective for other-race faces due to a missing experience with individuals from other ethnical groups. This interpretation is strongly supported by a functional magnetic resonance imaging study showing decreased brain activity on other-race faces. Furthermore, two event-related potential studies revealed differences in brain activity in the first 250 ms after face presentation, but with inconsistent results. Therefore, we investigated 12 Caucasian subjects, showing them faces of Asian and Caucasian subjects in a perceptual priming paradigm and measured the event-related brain potentials. On a behavioural level we found slower reaction times to Asian faces compared to Caucasian faces in the unprimed condition, reflecting a deficit for Caucasian subjects to process other-race faces. In accordance with these behavioural data we see a significantly reduced late N250r amplitude in the unprimed condition to the Asian faces compared to the Caucasian faces. These results clearly indicate that the other-race effect was present in our sample and very specific only in the unprimed condition around 350-450 ms after stimulus onset.

Event-related functional near-infrared spectroscopy (fNIRS) based on craniocerebral correlations: reproducibility of activation?

The purpose of the present study was to assess the retest reliability of cortical activation detected by event-related functional near-infrared spectroscopy (fNIRS) based on craniocerebral correlations. Isolated functional activation was evoked in the motor cortex by a periodically performed finger-tapping task. During 44-channel fNIRS recording, 12 subjects performed 30 trials of right and left index finger tapping in two sessions. The retest interval was set to 3 weeks. Simple correlations of the contrast t-values supplemented by scatterplots, channel-wise intraclass correlation coefficients (ICC), as well as reproducibility indices for the size and the location of the detected activation were calculated. The results at the group level showed sufficient single measure ICCs (up to 0.80) and excellent reproducibility of the size and the location (up to 89% were reproducible). Comparisons of the intersession group amplitudes demonstrate that the fNIRS signals were stable across time in a retest study design: the number of significant differences was less than randomly occurring false-positive activated channels if an alpha level of 5% is chosen. Effect size analyses indicated that the intersession amplitude differences are small (mean < 0.25). For deoxyhemoglobin and oxyhemoglobin distinct statistical power profiles were revealed regarding the activation vs. baseline contrast as well as the intersession amplitude differences, indicating a higher sensitivity of deoxyhemoglobin for local hemodynamic changes. The results suggest that sensorimotor activation assessed by event-related fNIRS based on craniocerebral correlations is sufficiently reproducible at the group level.

Event-related visual versus blocked motor task: detection of specific cortical activation patterns with functional near-infrared spectroscopy.

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.

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

The purpose of the present study was to investigate the retest reliability of event-related functional near-infrared spectroscopy (fNIRS). Therefore, isolated functional activation was evoked in the occipital cortex by a periodic checkerboard stimulation. During a 52-channel fNIRS recording, 12 subjects underwent 60 trials of visual stimulation in two sessions. The retest interval was set to 3 weeks. Linear correlations of the contrast t values supplemented by scatter plots, channel-wise intraclass correlation coefficients (ICC) as well as reproducibility indices for the quantity of activated channels (RQUANTITY) and the location (ROVERLAP) of the detected activation were calculated. The results at the group level showed good reliability in terms of the single measure ICCs (up to 0.84) and excellent reproducibility quantified by RQUANTITY and ROVERLAP (up to 96% of the quantity and the location were reproducible), whereas the results at the single subjects' level were mediocre. Furthermore, the reliability assessed by single measurement ICCs improved if regarded at a cluster level.

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

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

Near-infrared optical topography to assess activation of the parietal cortex during a visuo-spatial task.

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.

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

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