Task-dependent neural correlates of the processing of verbal threat-related stimuli in social phobia

The neural basis of abnormal processing of phobia-related linguistic cues in individuals suffering from social phobia is unknown, particularly in respect to different task conditions. Using event-related functional magnetic resonance imaging, this study investigated brain activation to phobia-related and phobia-unrelated words in 19 socially phobic patients and 18 healthy control subjects (HC) while subjects had to attend either to social meaning or to grammatical category of words (direct or indirect task). During the indirect task, patients, compared to HC, showed an increased activation of the amygdala and orbitofrontal cortex (OFC) in response to phobia-related vs. phobia-unrelated words. Activation of the insula was positively correlated with patients’ symptom severity during the direct task. The results suggest a specific role of the amygdala and OFC during the processing of verbal phobia-relevant distracting information. In contrast, insula activation seems to be more important for direct processing of disorder-related words, especially in more severe cases of social phobia.     

The interaction of anticipatory anxiety and emotional picture processing: An event‐related brain potential study

The present study examined the interaction of anticipatory anxiety and selective emotion processing. Toward this end, a rapid stream of pleasant, neutral, and unpleasant pictures was presented in alternating blocks of threat‐of‐shock or safety, which were signaled by colored picture frames. The main finding is that pleasant pictures elicited a sustained negative difference potential over occipital regions during threat as compared to safety periods. In contrast, unpleasant and neutral picture processing did not vary as a function of threat‐of‐shock. Furthermore, in both the safety and threat‐of‐shock conditions, emotional pictures elicited an enlarged early posterior negativity and late positive potential. These data show that the activation of the fear/anxiety network exerts valence‐specific effects on affective picture processing. Pleasant stimuli mismatching the current state of anticipatory anxiety apparently draw more attentional resources.     

Neurocognitive effects of HF-rTMS over the dorsolateral prefrontal cortex on the attentional processing of emotional information in healthy women: an event-related fMRI study

Current evidence concerning the neurocircuitry underlying the interplay between attention and emotion is mainly correlational. We used high-frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) to experimentally manipulate activity within the right or left dorsolateral prefrontal cortex (DLPFC) of healthy women and examined changes in attentional processing of emotional information using an emotional modification of the exogenous cueing task during event-related fMRI. Right prefrontal HF-rTMS resulted in impaired disengagement from angry faces, associated with decreased activation within the right DLPFC, dorsal anterior cingulate cortex (dACC) and left superior parietal gyrus, combined with increased activity within the right amygdala. Left prefrontal HF-rTMS resulted in diminished attentional engagement by angry faces and was associated with increased activity within the right DLPFC, dACC, right superior parietal gyrus and left orbitofrontal cortex. The present observations are in line with reports of a functionally interactive network of cortical-limbic pathways that play a central role in emotion regulation.     

Attentional modulation of emotional stimulus processing in patients with major depression—Alterations in prefrontal cortical regions

Patients with depression show an impaired ability to modulate emotional states and to process positive emotional information. Here we examined expectancy-induced modulation of emotional picture processing in major depression. We hypothesized alterations in the medial prefrontal cortex. During fMRI, 15 depressed and 21 healthy control subjects passively viewed affective photographs. Half of the pictures were preceded by an expectancy cue signaling whether an emotionally salient or neutral picture would follow. The contrast ‘cued versus uncued emotional picture viewing’ was used to study modulation of emotional picture processing by preceding attention. Healthy individuals showed enhanced activation in the dorsomedial prefrontal cortex and decreased activation in the dorsolateral prefrontal cortex during cued compared to uncued emotional picture perception. The group comparison revealed that these modulatory effects were significantly attenuated in depressed patients. This attenuation was particularly observed in the positive compared to the negative picture condition and tended to normalize in the dorsomedial prefrontal cortex after remission of symptoms. Altered prefrontal modulation in depression may contribute to impaired affect modulation and related clinical symptoms, such as anhedonia.     

The neural processing of fearful faces without attention and consciousness: an event-related potential study

To investigate whether the non-conscious processing of fearful faces exist in unattended condition, event-related potentials (ERPs) were recorded in a facial expression detection task. Participants were asked to discriminate the facial expressions (fearful or neutral) at the attended location. Unattended faces were associated with a response that was either congruent or in conflict with the response to the attended face. ERP results showed that the trials with response conflict between attended and unattended faces enhanced the amplitude of the P3 component when the neutral face was presented at attended location and the fearful face was presented at the unattended location. Our findings imply that the non-conscious fearful faces can be processed in the unattended condition.     

Healthy aging is associated with increased neural processing of positive valence but attenuated processing of emotional arousal: an fMRI study

Arousal and valence play key roles in emotional perception, with normal aging leading to changes in the neural substrates supporting valence processing. The objective of this study was to investigate normal age-related changes in the neural substrates of emotional arousal processing. Twenty-three young and 23 older, healthy women underwent functional magnetic resonance imaging as they viewed images which were neutral or positive in valence and which varied in arousal level from low to high. Using a parametric modulation approach, we examined how the blood oxygen-level dependent signal varied with single trial subjective ratings of valence and arousal, and whether this differed with age. In accordance with previous studies we found that the older group showed greater activation in response to positive valence, in the left amygdala, left middle temporal gyrus and right lingual gyrus. In contrast however, they showed reduced reactivity to emotional arousal, in occipital and temporal visual cortices bilaterally, the left inferior parietal cortex, and the supplementary motor area bilaterally. This study represents the first of its kind to clearly dissociate how aging affects the neural correlates of emotional arousal and valence. The changes in arousal processing may in part be mediated by the functional reorganization evident in the aging brain, such as reduced activation of the posterior cortices as described by the posterior-anterior shift in ageing (PASA) effect.     

Phase re-setting of gamma neural oscillations during novelty processing in an appetitive context

Based on the previous study where phase-synchronization (PS) of gamma-band responses (GBRs) proved a reliable cerebral correlate of involuntary attention and its enhancement under threat, we measured gamma-PS elicited by novel sounds from human electroencephalogram (EEG) scalp-recordings when participants responded to visual stimuli displaying either highly motivational or neutral sceneries. We then tested the modulatory effect of the emotional conditions on auditory responses. Novel distractor sounds did not affect behavioural accuracy on subjects' visual task performance in neutral context but markedly decreased hit rate in the appetitive one. Similarly, gamma-PS to novel sounds remained intact in neutral context, whereas it showed an increase, within the 35-Hz sub-range, in the appetitive context. These results suggest that a context of processing positive emotional stimuli results into an enhanced processing of task-irrelevant novel auditory events, and, furthermore, that gamma-PS is tuned under conditions that could promote long-term survival.     

Masked fear words produce increased SCRs: an anomaly for Ohman's theory of pre-attentive processing in anxiety

A. Ohman and J.J.F. Soares (1994) demonstrated that masked presentation of phobic pictures produces increased skin conductance responses (SCRs) in phobic subjects. A. Ohman (1993) explained this phenomenon in terms of a hypothetical "feature detector" that identifies physical characteristics of stimuli and activates the arousal system without involving significance evaluation or consciousness. By exposing spider phobics to spider words, general threat words, and neutral words instead of pictures, this explanation was tested. Words were presented both masked and unmasked while electrodermal activity was measured. Under unmasked conditions, SCRs were largest for spider words followed by general threat words, then neutral words. When masked, the difference between spider words and general threat words disappeared but SCRs remained significantly smaller for neutral words. It is concluded that activation of the arousal system by masked threat cues does not necessarily depend on their perceptual characteristics.     

Emotional perception: Correspondence of early and late event-related potentials with cortical and subcortical functional MRI

This research examines the relationship between brain activity recorded with functional magnetic resonance imaging (fMRI) and event related potentials (ERP) as these responses varied over a series of emotionally evocative and neutral pictures. We investigate the relationship of early occipitotemporal and later centroparietal emotion-modulated ERPs in one sample to fMRI estimates of neural activity in another sample in a replicated experiment. Using this approach, we aimed to link effects found in time-resolved electrocortical measures to specific neural structures across individual emotional and nonemotional picture stimuli. The centroparietal late positive potential (LPP) showed covariation with emotion-modulated regions of hemodynamic activation across multiple dorsal and ventral visual cortical structures, while the early occipitotemporal potential was not reliably associated. Subcortical and corticolimbic structures involved in the perception of motivationally relevant stimuli also related to modulation of the LPP, and were modestly associated to the amplitude of the early occipitotemporal potential. These data suggest that early occipitotemporal potentials may reflect multiple sources of modulation including motivational relevance, and supports the perspective that the slow-wave LPP represents aggregate cortical and subcortical structures involved in emotional discrimination.     

Emotional arousal and activation of the visual cortex: An fMRI analysis

Functional activity in the visual cortex was assessed using functional magnetic resonance imaging technology while participants viewed a series of pleasant, neutral, or unpleasant pictures. Coronal images at four different locations in the occipital cortex were acquired during each of eight 12-s picture presentation periods (on) and 12-s interpicture interval (off). The extent of functional activation was larger in the right than the left hemisphere and larger in the occipital than in the occipitoparietal regions during processing of all picture contents compared with the interpicture intervals. More importantly, functional activity was significantly greater in all sampled brain regions when processing emotional (pleasant or unpleasant) pictures than when processing neutral stimuli. In Experiment 2, a hypothesis that these differences were an artifact of differential eye movements was ruled out. Whereas both emotional and neutral pictures produced activity centered on the calcarine fissure (Area 17), only emotional pictures also produced sizable clusters bilaterally in the occipital gyrus, in the right fusiform gyrus, and in the right inferior and superior parietal lobules.     

Cortisol-induced enhancement of emotional face processing in social phobia depends on symptom severity and motivational context

We investigated the effects of cortisol administration on approach and avoidance tendencies in 20 patients with social anxiety disorder (SAD). Event-related brain potentials (ERPs) were measured during a reaction time task, in which patients evaluated the emotional expression of photographs of happy and angry faces by making an approaching (flexion) or avoiding (extension) arm movement. Patients showed significant avoidance tendencies for angry but not for happy faces, both in the placebo and cortisol condition. Moreover, ERP analyses showed a significant interaction of condition by severity of social anxiety on early positive (P150) amplitudes during avoidance compared to approach, indicating that cortisol increases early processing of social stimuli (in particular angry faces) during avoidance. This result replicates previous findings from a non-clinical sample of high anxious individuals and demonstrates their relevance for clinical SAD. Apparently the cortisol-induced increase in processing of angry faces in SAD depends on symptom severity and motivational context.     

Insula reactivity and connectivity to anterior cingulate cortex when processing threat in generalized social anxiety disorder

Aberrant subcortical-prefrontal connectivity may contribute to insula hyper-reactivity to threat in generalized social anxiety disorder (gSAD). A novel PsychoPhysiological Interaction (PPI) analysis was used to examine functional ‘coupling’ between the insula and prefrontal cortex in gSAD patients and healthy controls (HCs). During fMRI, 29 gSAD and 26 HC volunteers performed an Emotional Face Matching Task, involving the processing of fear, angry, and happy expressions. As expected, compared with HCs, gSAD patients exhibited greater bilateral anterior insula (aINS) reactivity for fear vs. happy faces; this group difference was less robust for angry vs. happy faces. PPI of insula connectivity when processing fearful faces revealed the gSAD group had less right aINS-dorsal anterior cingulate coupling compared to HCs. Findings indicate that aINS hyper-reactivity for fear faces in gSAD, compared to controls, involves reduced connectivity with a prefrontal region implicated in cognitive control and emotion regulation.     

Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing

Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n=13 and n=8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed.     

The role of somatic threat feature detectors in the attentional bias toward pain: Effects of spatial attention

Our previous work suggests that somatic threat feature detectors indexed by a pain‐evoked midlatency negative scalp potential play an important role in the attentional bias toward pain. In these studies the somatic threat feature detectors facilitated the shift in attention to a somatic threat when attention was focused on another stimulus modality but not when it was focused on another spatial location. This experiment used the Posner cuing paradigm to investigate possible explanations for this discrepancy. The results demonstrate that the different somatic threat effects observed in previous modal and spatial cuing studies are not due to attentional set. Rather, this discrepancy may be related to differences in contingent attention capture. This study also verifies earlier findings suggesting that some of the pain‐related P2 component generators are involved in stimulus‐driven shifts in spatial attention toward task‐relevant stimuli.     

An artificial neural network model of orienting attention toward threatening somatosensory stimuli

An artificial neural network model was designed to test the threat detection hypothesis developed in our experimental studies, where threat detector activity in the somatosensory association areas is monitored by the medial prefrontal cortex, which signals the lateral prefrontal cortex to redirect attention to the threat. As in our experimental studies, simulated threat-evoked activations of all three brain areas were larger when the somatosensory target stimulus was unattended than attended, and the increase in behavioral reaction times when the target stimulus was unattended was smaller for threatening than nonthreatening stimuli. The model also generated a number of novel predictions, for example, the effect of threat on reaction time only occurs when the target stimulus is unattended, and the P3a indexes prefrontal cortex activity involved in redirecting attention toward response processes on that trial and sensory processes on subsequent trials.     

Shifting the focus of attention modulates amygdala and anterior cingulate cortex reactivity to emotional faces

Functional neuroimaging studies have largely established the prominence of amygdala during emotion processing and prefrontal areas such as anterior cingulate cortex (ACC) during attentional modulation. In general, emotion processing paradigms known to probe amygdala have not been adapted to recruit prefrontal areas. In this study we used a well-known perceptual face matching paradigm, designed to elicit amygdala response, and asked volunteers to shift their focus in order to recruit regions responsible for attentional control. Stimuli comprised a trio of geometric shapes (circles, rectangles, triangles) presented alongside a trio of emotional faces (angry, fear, or happy) within the same field of view, and subjects were instructed to Match Faces or Match Shapes, as a means of attending to and away from the emotional content, respectively. We observed greater amygdala reactivity to Match Faces (>Match Shapes), and greater rostral ACC response to Match Shapes (>Match Faces). Results indicate that simply and volitionally directing attention toward or away from emotional content correspondingly modulates amygdala and ACC activity.     

Enhanced neural reactivity and selective attention to threat in anxiety

Attentional bias towards threat is implicated in the etiology and maintenance of anxiety disorders. We examined the neural correlates of threat bias in anxious and nonanxious participants to shed light on the neural chronometry of this cognitive bias. In this study, event-related potentials (ERPs) were recorded while anxious (n = 23) and nonanxious (n = 23) young adults performed a probe-discrimination task measuring attentional bias towards threat (angry) and positive (happy) face stimuli. Results showed an attention bias towards threat among anxious participants, but not among nonanxious participants. No bias to positive faces was found. ERP data revealed enhanced C1 amplitude (∼80 ms following threat onset) in anxious relative to nonanxious participants when cue displays contained threat faces. Additionally, P2 amplitude to the faces display was higher in the anxious relative to the nonanxious group regardless of emotion condition (angry/happy/neutral). None of the ERP analyses associated with target processing were significant. In conclusion, our data suggest that a core feature of threat processing in anxiety lies in functional perturbations of a brain circuitry that reacts rapidly and vigorously to threat. It is this over-activation that may set the stage for the attention bias towards threat observed in anxious individuals.     

Sex differences in the neural correlates of emotion: evidence from neuroimaging

Sex differences in emotional processes represent some of the most robust sex stereotypes worldwide. However, empirical support for these stereotypes is lacking, especially from research utilizing objective measures, such as neuroimaging methodologies. We conducted a selective review of functional neuroimaging studies that have empirically tested for sex differences in the association between brain function and emotional processes (including perception, reactivity, regulation and experience). Evidence was found for marked sex differences in the neural mechanisms underlying emotional processes, and in most cases suggested that males and females use different strategies during emotional processing, which may lead to sex differences in the observed (or subjectively reported) emotional process. We discuss how these findings may offer insight into the mechanisms underlying sex differences in emotional behaviors, and outline a number of methodological considerations for future research. Importantly, results suggest that sex differences should not be ignored in research investigating the neurobiology of emotion.     

Evidence-based treatment of anxiety and phobia in children and adolescents: current status and effects on the emotional response

Research on treatments for childhood anxiety disorders has increased greatly in recent decades. As a result, it has become increasingly necessary to synthesize the findings of these treatment studies into reviews in order to draw wider conclusions on the efficacy of treatments for childhood anxiety. Previous reviews of this literature have used varying criteria to determine the evidence base. For the current review, stricter criteria consistent with the original Task Force (1995) guidelines were used to select and evaluate studies. Studies were divided by anxiety disorder; however, many studies combine various anxiety disorders in their samples. As a result, these were included in a combined anxiety disorder group. Using more traditional guidelines, studies were assigned a status of well-established, probably efficacious, or experimental based on the available literature and the quality of the studies. While some treatments do meet the criteria for well-established status, it is clear from this examination that gaps remain and replication is necessary to establish many of these treatments as efficacious. In addition, there still appears to be a lack of research on the effects of treatment on the physiological and cognitive aspects of fear and anxiety.     

Neural correlates of attention bias to threat in post-traumatic stress disorder

Attentional biases have been proposed to contribute to symptom maintenance in posttraumatic stress disorder (PTSD), although the neural correlates of these processes have not been well defined; this was the goal of the present study. We administered an attention bias task, the dot probe, to a sample of 37 (19 control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to controls, PTSD+ participants demonstrated increased activation in the dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In addition, attentional avoidance of threat corresponded with increased ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder.