Diffusion tensor imaging revealed that trait anxiety predicts the microstructural properties of a prespecified fiber tract between the amygdala and the perigenual anterior cingulate cortex. Besides this particular pathway, it is likely that other pathways are also affected. We investigated white matter differences in persons featuring an anxious or a nonanxious personality, taking into account all potential pathway connections between amygdala and anxiety-related regions of the prefrontal cortex (PFC). Diffusion-weighted images, measures of trait anxiety and of reappraisal use (an effective emotion-regulation style), were collected in 48 females. With probabilistic tractography, pathways between the amygdala and the dorsolateral PFC, dorsomedial PFC, ventromedial PFC, and orbitofrontal cortex (OFC) were delineated. The resulting network showed a direct ventral connection between amygdala and PFC and a second limbic connection following the fornix and the anterior limb of the internal capsule. Reappraisal use predicted the microstructure of pathways to all calculated PFC regions in the left hemisphere, indicating stronger pathways for persons with high reappraisal use. Trait anxiety predicted the microstructure in pathways to the ventromedial PFC and OFC, indexing weaker connections in trait-anxious persons. These effects appeared in the right hemisphere, supporting lateralization and top-down inhibition theories of emotion processing. Whereas a specific microstructure is associated with an anxious personality, a different structure subserves emotion regulation. Both are part of a broad fiber tract network between amygdala and PFC.

Emotional words--as symbols for biologically relevant concepts--are preferentially processed in brain regions including the visual cortex, frontal and parietal regions, and a corticolimbic circuit including the amygdala. Some of the brain structures found in functional magnetic resonance imaging are not readily apparent in electro- and magnetoencephalographic (EEG; MEG) measures. By means of a combined EEG/MEG source localization procedure to fully exploit the available information, we sought to reduce these discrepancies and gain a better understanding of spatiotemporal brain dynamics underlying emotional-word processing. Eighteen participants read high-arousing positive and negative, and low-arousing neutral nouns, while EEG and MEG were recorded simultaneously. Combined current-density reconstructions (L2-minimum norm least squares) for two early emotion-sensitive time intervals, the P1 (80-120 ms) and the early posterior negativity (EPN, 200-300 ms), were computed using realistic individual head models with a cortical constraint. The P1 time window uncovered an emotion effect peaking in the left middle temporal gyrus. In the EPN time window, processing of emotional words was associated with enhanced activity encompassing parietal and occipital areas, and posterior limbic structures. We suggest that lexical access, being underway within 100 ms, is speeded and/or favored for emotional words, possibly on the basis of an "emotional tagging" of the word form during acquisition. This gives rise to their differential processing in the EPN time window. The EPN, as an index of natural selective attention, appears to reflect an elaborate interplay of distributed structures, related to cognitive functions, such as memory, attention, and evaluation of emotional stimuli.

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The hedonic meaning of words affects word recognition, as shown by behavioral, functional imaging, and event-related potential (ERP) studies. However, the spatiotemporal dynamics and cognitive functions behind are elusive, partly due to methodological limitations of previous studies. Here, we account for these difficulties by computing combined electro-magnetoencephalographic (EEG/MEG) source localization techniques. Participants covertly read emotionally high-arousing positive and negative nouns, while EEG and MEG were recorded simultaneously. Combined EEG/MEG current-density reconstructions for the P1 (80–120 ms), P2 (150–190 ms) and EPN component (200–300 ms) were computed using realistic individual head models, with a cortical constraint. Relative to negative words, the P1 to positive words predominantly involved language-related structures (left middle temporal and inferior frontal regions), and posterior structures related to directed attention (occipital and parietal regions). Effects shifted to the right hemisphere in the P2 component. By contrast, negative words received more activation in the P1 time-range only, recruiting prefrontal regions, including the anterior cingulate cortex (ACC). Effects in the EPN were not statistically significant. These findings show that different neuronal networks are active when positive versus negative words are processed. We account for these effects in terms of an “emotional tagging” of word forms during language acquisition. These tags then give rise to different processing strategies, including enhanced lexical processing of positive words and a very fast language-independent alert response to negative words. The valence-specific recruitment of different networks might underlie fast adaptive responses to both approach- and withdrawal-related stimuli, be they acquired or biological.

The well-established memory bias for arousing-negative stimuli seems to be enhanced in high trait-anxious persons and persons suffering from anxiety disorders. We monitored the emergence and development of such a bias during and after learning, in high and low trait anxious participants. A word-learning paradigm was applied, consisting of spoken pseudowords paired either with arousing-negative or neutral pictures. Learning performance during training evidenced a short-lived advantage for arousing-negative associated words, which was not present at the end of training. Cued recall and valence ratings revealed a memory bias for pseudowords that had been paired with arousing-negative pictures, immediately after learning and two weeks later. This held even for items that were not explicitly remembered. High anxious individuals evidenced a stronger memory bias in the cued-recall test, and their ratings were also more negative overall compared to low anxious persons. Both effects were evident, even when explicit recall was controlled for. Regarding the memory bias in anxiety prone persons, explicit memory seems to play a more crucial role than implicit memory. The study stresses the need for several time points of bias measurement during the course of learning and retrieval, as well as the employment of different measures for learning success.

Relative to healthy controls, anxiety-disorder patients show anomalies in classical conditioning that may either result from, or provide a risk factor for, clinically relevant anxiety. Here, we investigated whether healthy participants with enhanced anxiety vulnerability show abnormalities in a challenging affective-conditioning paradigm, in which many stimulus-reinforcer associations had to be acquired with only few learning trials. Forty-seven high and low trait-anxious females underwent MultiCS conditioning, in which 52 different neutral faces (CS+) were paired with an aversive noise (US), while further 52 faces (CS−) remained unpaired. Emotional learning was assessed by evaluative (rating), behavioral (dot-probe, contingency report), and neurophysiological (magnetoencephalography) measures before, during, and after learning. High and low trait-anxious groups did not differ in evaluative ratings or response priming before or after conditioning. High trait-anxious women, however, were better than low trait-anxious women at reporting CS+/US contingencies after conditioning, and showed an enhanced prefrontal cortex (PFC) activation towards CS+ in the M1 (i.e., 80–117 ms) and M170 time intervals (i.e., 140–160 ms) during acquisition. These effects in MultiCS conditioning observed in individuals with elevated trait anxiety are consistent with theories of enhanced conditionability in anxiety vulnerability. Furthermore, they point towards increased threat monitoring and detection in highly trait-anxious females, possibly mediated by alterations in visual working memory.

Persons suffering from anxiety disorders display facilitated processing of arousing and negative stimuli, such as negative words. This memory bias is reflected in better recall and increased amygdala activity in response to such stimuli. However, individual learning histories were not considered in most studies, a concern that we meet here. Thirty-four female persons (half with high-, half with low trait anxiety) participated in a criterion-based associative word-learning paradigm, in which neutral pseudowords were paired with aversive or neutral pictures, which should lead to a valence change for the negatively paired pseudowords. After learning, pseudowords were tested with fMRI to investigate differential brain activation of the amygdala evoked by the newly acquired valence. Explicit and implicit memory was assessed directly after training and in three follow-ups at 4-day intervals. The behavioral results demonstrate that associative word-learning leads to an explicit (but no implicit) memory bias for negatively linked pseudowords, relative to neutral ones, which confirms earlier studies. Bilateral amygdala activation underlines the behavioral effect: Higher trait anxiety is correlated with stronger amygdala activation for negatively linked pseudowords than for neutrally linked ones. Most interestingly, this effect is also present for negatively paired pseudowords that participants could not remember well. Moreover, neutrally paired pseudowords evoked higher amygdala reactivity than completely novel ones in highly anxious persons, which can be taken as evidence for generalization. These findings demonstrate that few word-learning trials generate a memory bias for emotional stimuli, indexed both behaviorally and neurophysiologically. Importantly, the typical memory bias for emotional stimuli and the generalization to neutral ones is larger in high anxious persons.

Limbic hyperactivation and an impaired functional interplay between the amygdala and the prefrontal cortex are discussed to go along with, or even cause, pathological anxiety. Within the multi-faceted group of anxiety disorders, the highly prevalent social phobia (SP) is characterized by excessive fear of being negatively evaluated. Although there is widespread evidence for amygdala hypersensitivity to emotional faces in SP, verbal material has rarely been used in imaging studies, in particular with an eye on disorder-specificity. Using functional magnetic resonance imaging (fMRI) and a block design consisting of (1) overall negative, (2) social-phobia related, (3) positive, and (4) neutral words, we studied 25 female patients with social phobia and 25 healthy female control subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant but not to generally negative words in SP patients, with a positive correlation to symptom severity. A functional connectivity analysis revealed a weaker coupling between the amygdala and the left middle frontal gyrus in patients. Symptom severity was negatively related to connectivity strength between the amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area 10 and 11). The findings clearly support the view of a hypersensitive threat-detection system, combined with disorder-related alterations in amygdala-prefrontal cortex connectivity in pathological anxiety.