Beyond the N400: complementary access to early neural correlates of novel metaphor comprehension using combined electrophysiological and haemodynamic measurements.

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.

Prefrontal correlates of approach preferences for alcohol stimuli in alcohol dependence.

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.

Genetic variation in MAOA modulates prefrontal cortical regulation of approach-avoidance reactions.

BACKGROUND: Regulation of automatic approach and avoidance behavior requires affective and cognitive control, which are both influenced by a genetic variation in the gene encoding Monoamine Oxidase A (termed MAOA-uVNTR). METHODS: The current study investigated MAOA genotype as a moderator of prefrontal cortical activation measured with functional near-infrared spectroscopy (fNIRS) in 37 healthy young adults during performance of the approach-avoidance task with positive and negative pictures. RESULTS: Carriers of the low- compared to the high-expressing genetic variant (MAOA-L vs. MAOA-H) showed increasing regulatory activity in the right dorsolateral prefrontal cortex (DLPFC) during incompatible conditions (approach negative, avoid positive). This might have been a compensatory mechanism for stronger emotional reactions as shown in previous studies and might have prevented any influence of incompatibility on behavior. In contrast, fewer errors but also lower activity in the right DLPFC during processing of negative compared to positive stimuli indicated MAOA-H carriers to have used other regulatory areas. This resulted in slower reaction times in incompatible conditions, but--in line with the known better cognitive regulation efficiency--allowed them to perform incompatible reactions without activating the DLPFC as the highest control instance. Carriers of one low- and one high-expressing allele lay as an intermediate group between the reactions of the low- and high-expressing groups. CONCLUSIONS: The relatively small sample size and restriction to fNIRS for assessment of cortical activity limit our findings. Nevertheless, these first results suggest monoam-inergic mechanisms to contribute to interindividual differences in the two basic behavioral principles of approach and avoidance and their neuronal correlates.

N1 and N2 ERPs reflect the regulation of automatic approach tendencies to positive stimuli.

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.

Prefrontal activation patterns of automatic and regulated approach-avoidance reactions - a functional near-infrared spectroscopy (fNIRS) study.

INTRODUCTION: The present pilot study investigated cortical processes during automatic and regulated approach-avoidance reactions for the first time. METHODS 1: In 15 healthy volunteers, prefrontal activity was measured with functional near-infrared spectroscopy (fNIRS) during performance of a joystick version of the Approach-Avoidance Task (AAT). In experiment 1, participants approached (pulled towards their body) and avoided (pushed away from their body) positive and negative pictures. RESULTS 1: Incompatible, regulated reactions (avoid positive, approach negative) compared to compatible, automatic reactions (approach positive, avoid negative) caused stronger activation in terms of a decrease of deoxygenated haemoglobin (HHb) in right dorsolateral prefrontal cortex (DLPFC) (i.e., in one of the main instances for behavioural control in humans). METHODS 2: In the context of pathologically enhanced approach tendencies in addiction disorders and of planned future studies, we presented alcohol and non-alcohol pictures in experiment 2. RESULTS 2: Here, left anterior lateral orbitofrontal cortex as part of the general reward system processing secondary rewards showed stronger activation in terms of increased oxygenated haemoglobin (O(2)Hb) during approaching compared to avoiding alcohol pictures. This difference was positively correlated with participants' expectation about beneficial effects of alcohol in terms of emotional regulation. DISCUSSION: Despite some limitations due to the pilot character of the study, our results suggest that further combinations of the AAT and functional imaging methods will reveal detailed insight into neuronal mechanisms constituting approach-avoidance as basic behavioural principles and into specifically altered sub-processes in alcohol dependence.

Inhibitory transcranial magnetic theta burst stimulation attenuates prefrontal cortex oxygenation.

Recent studies highlighted the great potential of newly established theta burst stimulation (TBS) protocols for non-invasive human brain stimulation studies using transcranial magnetic stimulation (TMS). While intermittent TBS over the primary motor cortex was found to potentiate motor evoked potentials, continuous TBS led to profound attenuations. Although numerous studies investigated the impact of TBS on motor cortex function, yet, only few imaging studies focused on its effects in other brain areas. Particularly for the prefrontal cortex, it is unclear whether TBS has similar effects compared to application over motor areas. In the current study continuous TBS was applied to either the left or right dorsolateral prefrontal cortex in a sample of healthy subjects. Changes in prefrontal oxygenation were measured during an emotional Stroop task by means of functional multi-channel near-infrared spectroscopy (fNIRS) before and after stimulation. Results showed bilaterally decreased prefrontal oxygenation following inhibitory stimulation of the left prefrontal cortex but no behavioral effect. No such alterations were observed following right-hemispheric or sham stimulation. The results of the current study are in line with earlier findings and additionally demonstrate that also prefrontal oxygenation can be impaired by continuous TBS.

Controlled attention allocation mediates the relation between goal-oriented pursuit and approach-avoidance reactions to negative stimuli.

Approach and avoidance are two basic behavioural principles. The current study investigated neuropsychological mechanisms underlying the influence of the personality characteristic goal-oriented pursuit on the efficiency of regulating such approach-avoidance reactions. Therefore, the P3 event-related potential (ERP) reflecting controlled attention allocation was assessed during the Approach-Avoidance Task (AAT) with positive and negative pictures in 36 healthy participants. For negative pictures, analyses revealed the neuropsychological mechanism of controlled attention allocation to mediate the relation between personality and behaviour: Stronger goal-oriented pursuit was associated with higher controlled attention allocation to the incompatible compared to the compatible condition and--thereby--with less automatic avoidance tendencies in response to negative pictures, i.e., with higher efficiency of regulation. Results are discussed in terms of their implications for future studies on mechanisms determining the influence of personality traits, situational factors and their interaction on approach-avoidance behaviour.

Differential prefrontal and frontotemporal oxygenation patterns during phonemic and semantic verbal fluency.

Movement artifacts are still considered a problematic issue for imaging research on overt language production. This motion-sensitivity can be overcome by functional near-infrared spectroscopy (fNIRS). In the present study, 50 healthy subjects performed a combined phonemic and semantic overt verbal fluency task while frontal and temporal cortex oxygenation was recorded using multi-channel fNIRS. Results showed a partial dissociation for phonemic and semantic word generation with equally increased oxygenation in frontotemporal cortices for both types of tasks whereas anterior and superior prefrontal areas were exclusively activated during phonemic fluency. Also, a general left-lateralization was found being more pronounced during semantic processing. These findings line up with earlier imaging and lesion studies emphasizing a crucial role of the temporal lobe for semantic word production, whereas phonemic processing seems to depend on intact frontal lobe function.

Recovery of cortical functioning in abstinent alcohol-dependent patients: prefrontal brain oxygenation during verbal fluency at different phases during withdrawal.

OBJECTIVES: Neurotoxic effects of alcohol consumption are well-known. There is plenty of literature on frontal lobe impairment on the behavioural and structural brain imaging level. However, only few functional imaging studies investigated altered neural patterns and even less abstinence-related neural recovery. METHODS: In a cross-sectional design three patient groups (acute withdrawal, detoxified, abstinent) and healthy controls (each n = 20) performed a phonological and semantic verbal fluency task (VFT) while brain activity was measured with near-infrared spectroscopy (NIRS). RESULTS: First, for the phonological condition withdrawal patients and detoxified patients showed less fluency-related frontal lobe activation compared to controls despite equal performance. Second, significant linear trend effects from withdrawal patients over detoxified and abstinent patients up to healthy controls indicated more normal activation patterns in the abstinent group that did not differ significantly from the controls. In the detoxified group brain activation increased with time since detoxification. CONCLUSIONS: Our results are compatible with an increase in frontal brain activity from alcohol dependence over abstinence up to normal functioning. However, as cross-sectional designs do not allow to assess causal relations, results have to be considered preliminary and longitudinal studies are needed to further elucidate recovery processes in alcohol dependence.

Neural correlates of spontaneous panic attacks.

In this report, we present two anxiety disorder patients who spontaneously experienced a panic attack during an fMRI examination and subsequently aborted the measurement. We analyzed the functional data gathered up to that point in relation to the patients' subsequent verbal reports of the course of the panic attacks. Within prominent structures of the fear network (amygdala, insula, prefrontal cortex) neural dynamics mirrored the description of the attack very well for one of the patients. For the other patient who experienced a less intense attack and who was treated pharmacologically at the time of measurement, the relation was limited to the prefrontal cortex. Investigating the temporal dynamics of neural activation in an ecologically valid situation may point to the potentially different roles of the amygdala and the insula as well as the prefrontal cortex prior to and during a panic attack.

Functional amygdala-hippocampus connectivity during anticipation of aversive events is associated with Gray's trait "sensitivity to punishment".

BACKGROUND: The reinforcement sensitivity theory postulates a behavioral inhibition system that modulates reaction to stimuli indicating aversive events. Gray's dimension of anxiety, reflecting human trait sensitivity to aversive events, determines the extent to which stimuli activate the behavioral inhibition system. Although structural brain imaging has previously identified the amygdala and the hippocampus as two major components related to the behavioral inhibition system, the functional dynamics of the responses in these structures remain unclear. METHODS: In this study, we examined the event-related functional magnetic resonance imaging blood oxygen level-dependent response in the hippocampus and amygdala as well as the functional connectivity of the two regions during anticipation of monetary loss in 45 healthy human subjects. RESULTS: Anticipation of loss elicited activation in the hippocampus as well as in the amygdala. Additionally, substantial functional connectivity between the two areas was observed. Furthermore, this functional connectivity was significantly correlated with individual differences in Gray's trait sensitivity to aversive events. Specifically, higher trait sensitivity to aversive events was associated with increased functional connectivity following cues indicating potential loss. CONCLUSIONS: In summary, we show that individual differences regarding Gray's trait sensitivity to aversive events as defined by the reinforcement sensitivity theory are associated with the neural dynamics of the amygdala-hippocampal circuit during anticipation of aversive events. In particular, evidence is provided for a relationship between functional brain imaging data and a psychometric approach specifically measuring Gray's trait sensitivity to aversive events, thereby potentially identifying the neural substrate of the behavioral inhibition system.