The role of the medial frontal cortex in the maintenance of emotional states

Evidence is accruing that people can maintain their emotional states, but how they do it and which brain regions are responsible still remains unclear. We examined whether people maintain emotional states ‘actively’, with explicit elaboration of the emotion, or ‘passively’, without elaboration. Twenty-four participants completed an emotion maintenance task in which they either maintained the emotional intensity from the first picture of a pair to compare to that of the second picture (‘maintain’ condition), or only rated their emotional response to the second picture (‘non-maintain’ condition). Supporting the ‘active’ maintenance hypothesis, when maintaining vs not maintaining emotion, participants exhibited increased height and width of activation in the dorsal medial frontal cortex (MFC) and lateral prefrontal cortex, regions associated with explicit emotion generation and manipulation of contents in working memory, respectively. Supporting the ‘passive’ maintenance hypothesis, however, when viewing negative emotional pictures (vs neutral pictures) that were not explicitly maintained, participants exhibited greater duration of activity in the rostral MFC, a region associated with implicit emotion generation. Supported by behavioral findings, this evidence that people maintain emotional states both naturally in the rMFC and strategically in the dMFC may be critical for understanding normal as well as disordered emotion regulation.     

Brain dynamics of visual attention during anticipation and encoding of threat- and safe-cues in spider-phobic individuals

This study systematically investigated the sensitivity of the phobic attention system by measuring event-related potentials (ERPs) in spider-phobic and non-phobic volunteers in a context where spider and neutral pictures were presented (phobic threat condition) and in contexts where no phobic but unpleasant and neutral or only neutral pictures were displayed (phobia-irrelevant conditions). In a between-group study, participants were assigned to phobia-irrelevant conditions either before or after the exposure to spider pictures (pre-exposure vs post-exposure participants). Additionally, each picture was preceded by a fixation cross presented in one of three different colors that were informative about the category of an upcoming picture. In the phobic threat condition, spider-phobic participants showed a larger P1 than controls for all pictures and signal cues. Moreover, individuals with spider phobia who were sensitized by the exposure to phobic stimuli (i.e. post-exposure participants) responded with an increased P1 also in phobia-irrelevant conditions. In contrast, no group differences between spider-phobic and non-phobic individuals were observed in the P1-amplitudes during viewing of phobia-irrelevant stimuli in the pre-exposure group. In addition, cues signaling neutral pictures elicited decreased stimulus-preceding negativity (SPN) compared with cues signaling emotional pictures. Moreover, emotional pictures and cues signaling emotional pictures evoked larger early posterior negativity (EPN) and late positive potential (LPP) than neutral stimuli. Spider phobics showed greater selective attention effects than controls for phobia-relevant pictures (increased EPN and LPP) and cues (increased LPP and SPN). Increased sensitization of the attention system observed in spider-phobic individuals might facilitate fear conditioning and promote generalization of fear playing an important role in the maintenance of anxiety disorders.     

Depersonalization disorder: thinking without feeling

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive–compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization — absent subjective experience of emotion — is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.     

ERP dynamics underlying successful directed forgetting of neutral but not negative pictures

Subjective experience suggests that negatively arousing memories are harder to control than neutral ones. Here, we investigate this issue in an item-cued directed forgetting experiment. Electroencephalogram event-related potentials (ERPs) were recorded as participants viewed un-arousing neutral and highly arousing negative photographs, each followed by a cue to remember or forget it. Directed forgetting, that is reduced recognition of ‘to-be-forgotten’ items, occurred for neutral but not negative pictures. ERPs revealed three underlying effects: first, during picture viewing a late parietal positive potential (LPP) was more pronounced for negative than for neutral pictures. Second, ‘remember’ cues were associated with larger LPPs than ‘forget’ cues. Third, an enhanced frontal positivity appeared for ‘forget’ cues. This frontal positivity was generated in right dorso-lateral prefrontal regions following neutral pictures and in medial frontal cortex following negative pictures. LPP magnitude when viewing negative pictures was correlated with reduced directed forgetting, whereas both the enhanced frontal positivity for forget cues and the larger parietal positivity for remember cues predicted more directed forgetting. This study indicates that both processes of selective rehearsal (parietal positivities) and frontally controlled inhibition contribute to successful directed forgetting. However, due to their deeper incidental processing, highly arousing negative pictures are exempt from directed forgetting.     

Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates

The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, ‘uncertain’ (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of ‘uncertain’ clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive.     

Cortical reactions to verbal abuse: event-related brain potentials reflecting the processing of socially threatening words

Human information processing is sensitive to aversive stimuli, in particular to negative cues that indicate a threat to physical integrity. We investigated the extent to which these findings can be transferred to stimuli that are associated with a social rather than a physical threat. Event-related potentials were recorded during silent reading of neutral, positive, physically threatening, and socially threatening words, whereby socially threatening words were represented by swear words. We found facilitated processing of positive and physically threatening words in contrast to both neutral and socially threatening words at a first potential that emerged at about 120 ms after stimulus onset. At a semantic processing stage reflected by the N400, processing of all classes of affective words, including socially threatening words, differed from neutral words. We conclude that socially threatening words as well as neutral words capture more attentional resources than positive and physically threatening words at early stages. However, social threatening words are processed in a manner similar to other emotional words and different from neutral words at higher levels.     

Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study.

BACKGROUND: The aim of this study was to identify brain activation to socially threatening stimuli in social phobic subjects during different experimental conditions. METHODS: With event-related functional magnetic resonance imaging, brain activation to photographs and schematic pictures depicting angry or neutral facial expressions was measured in social phobic subjects and healthy control subjects, while subjects assessed either emotional expression (angry vs. neutral; explicit task) or picture type (photographic vs. schematic; implicit task). RESULTS: Compared with control subjects, phobics showed greater responses to angry than to neutral photographic faces in the insula regardless of task, whereas amygdala, parahippocampal gyrus, and extrastriate visual cortex were more strongly activated only during the implicit task. Phobics, in contrast to control subjects, showed similar activation patterns during both tasks. For schematic angry versus neutral faces, activation of insula and extrastriate visual cortex was found in phobics, but not in control subjects, during both tasks. CONCLUSIONS: Differences between social phobics and control subjects in brain responses to socially threatening faces are most pronounced when facial expression is task-irrelevant. Phobics intensively process angry (photographic as well as schematic) facial expressions, regardless of whether this is required. The insula plays a unique role in the processing of threat signals by social phobics.     

Depersonalization disorder: thinking without feeling.

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive-compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization--absent subjective experience of emotion--is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.     

Pictures cueing threat: brain dynamics in viewing explicitly instructed danger cues

Recent event-related brain potential studies revealed the selective processing of emotional and threatening pictures. Integrating the picture viewing and threat-of-shock paradigm, the present study examined the processing of emotional pictures while they were explicitly instructed to cue threat of real world danger (i.e. electric shocks). Toward this end, 60 pleasant, neutral and unpleasant IAPS-pictures were presented (1 s) as a continuous random stream while high-density EEG and self-reported threat were assessed. In three experimental runs, each picture category was used once as a threat-cue, whereas in the other conditions the same category served as safety-cue. An additional passive viewing run served as a no-threat condition, thus, establishing a threat-safety continuum (threat-cue-safety-cue-no-threat) for each picture category. Threat-of-shock modulated P1, P2 and parieto-occipital LPP amplitudes. While the P1 component differentiated among threat- and no-threat conditions, the P2 and LPP effects were specific to pictures signaling threat-of-shock. Thus, stimulus processing progressively gained more accurate information about environmental threat conditions. Interestingly, the finding of increased EPN and centro-parietal LPP amplitudes to emotional pictures was independent from threat-of-shock manipulation. Accordingly, the results indicate distinct effects associated with the intrinsic significance of emotional pictures and explicitly instructed threat contingencies.     

Pervasive competition between threat and reward in the brain

In the current functional MRI study, we investigated interactions between reward and threat processing. Visual cues at the start of each trial informed participants about the chance of winning monetary reward and/or receiving a mild aversive shock. We tested two competing hypothesis: according to the ‘salience hypothesis’, in the condition involving both reward and threat, enhanced activation would be observed because of increased salience; according to the ‘competition hypothesis’, the processing of reward and threat would trade-off against each other, leading to reduced activation. Analysis of skin conductance data during a delay phase revealed an interaction between reward and threat processing, such that the effect of reward was reduced during threat and the effect of threat was reduced during reward. Analysis of imaging data during the same task phase revealed interactions between reward and threat processing in several regions, including the midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and dorsal anterior cingulate cortex. Taken together, our findings reveal conditions during which reward and threat trade-off against each other across multiple sites. Such interactions are suggestive of competitive processes and may reflect the organization of opponent systems in the brain.     

‘Ecstasy’ as a social drug: MDMA preferentially affects responses to emotional stimuli with social content

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is used recreationally to improve mood and sociability, and has generated clinical interest as a possible adjunct to psychotherapy. One way that MDMA may produce positive ‘prosocial’ effects is by changing responses to emotional stimuli, especially stimuli with social content. Here, we examined for the first time how MDMA affects subjective responses to positive, negative and neutral emotional pictures with and without social content. We hypothesized that MDMA would dose-dependently increase reactivity to positive emotional stimuli and dampen reactivity to negative stimuli, and that these effects would be most pronounced for pictures with people in them. The data were obtained from two studies using similar designs with healthy occasional MDMA users (total N = 101). During each session, participants received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and negative responses to standardized positive, negative and neutral pictures with and without social content. MDMA increased positive ratings of positive social pictures, but reduced positive ratings of non-social positive pictures. We speculate this ‘socially selective’ effect contributes to the prosocial effects of MDMA by increasing the comparative value of social contact and closeness with others. This effect may also contribute to its attractiveness to recreational users.     

Defensive startle response to emotional social cues in social anxiety

Potentiation of fear-related defense behaviours coordinated by the amygdala in response to environmental threat characterizes several anxiety disorders. We compared eye-blink startle responses to startle probes delivered during the presentation of emotional and neutral social cues in high and low generalized social anxiety. Socially anxious individuals exhibited larger startle responses to emotional (positive and negative) relative to neutral social cues, compared to non-anxious individuals.     

Cognitive and neural contributors to emotion regulation in aging

Older adults, compared to younger adults, focus on emotional well-being. While the lifespan trajectory of emotional processing and its regulation has been characterized behaviorally, few studies have investigated the underlying neural mechanisms. Here, older adults (range: 59–73 years) and younger adults (range: 19–33 years) participated in a cognitive reappraisal task during functional magnetic resonance imaging (fMRI) scanning. On each trial, participants viewed positive, negative or neutral pictures and either naturally experienced the image (‘Experience’ condition) or attempted to detach themselves from the image (‘Reappraise’ condition). Across both age groups, cognitive reappraisal activated prefrontal regions similar to those reported in prior studies of emotion regulation, while emotional experience activated the bilateral amygdala. Psychophysiological interaction analyses revealed that the left inferior frontal gyrus (IFG) and amygdala demonstrated greater inverse connectivity during the ‘Reappraise’ condition relative to the ‘Experience’ condition. The only regions exhibiting significant age differences were the left IFG and the left superior temporal gyrus, for which greater regulation-related activation was observed in younger adults. Controlling for age, increased performance on measures of cognition predicted greater regulation-related decreases in amygdala activation. Thus, while older and younger adults use similar brain structures for emotion regulation and experience, the functional efficacy of those structures depends on underlying cognitive ability.     

Multiple-cue probabilistic learning in spider-fearful and in panic-prone individuals

Probabilistic learning was studied in spider-fearful and in panic-prone individuals. Participants learned to predict the occurrence of aversive outcomes on the basis of relevant and irrelevant stimuli. The salience of irrelevant stimuli was manipulated by the use of threat-related objects, i.e. pictures of spiders and pictures of emergency situations. In spider-fearful individuals, the presence of irrelevant pictures of spiders interfered with the adequate acquisition of the association between neutral relevant stimuli and aversive outcomes. Salient, i.e. threat-related, irrelevant stimuli exerted competitive effects on the accruing of associative strengths between neutral stimuli and aversive outcomes in spider-fearful, but not in panic-prone, individuals.     

Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation

Several lines of evidence suggest that the amygdala and the bed nucleus of the stria terminalis (BNST) are differentially involved in phasic and sustained fear. Even though, results from neuroimaging studies support this distinction, a specific effect of a temporal dissociation with phasic responses to onset versus sustained responses during prolonged states of threat anticipation has not been shown yet. To explore this issue, we investigated brain activation during anticipation of threat in 38 healthy participants by means of functional magnetic resonance imaging. Participants were presented different visual cues indicated the temporally unpredictable occurrence of a subsequent aversive or neutral stimulus. During the onset of aversive versus neutral anticipatory cues, results showed a differential phasic activation of amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (PFC). In contrast, activation in the BNST and other brain regions, including insula, dorsolateral PFC, ACC, cuneus, posterior cingulate cortex, and periaqueductal grey was characterized by a sustained response during the threat versus neutral anticipation period. Analyses of functional connectivity showed phasic amygdala response as positively associated with activation, mainly in sensory cortex areas whereas sustained BNST activation was negatively associated with activation in visual cortex and positively correlated with activation in the insula and thalamus. These findings suggest that the amygdala is responsive to the onset of cues signaling the unpredictable occurrence of a potential threat while the BNST in concert with other areas is involved in sustained anxiety. Furthermore, the amygdala and BNST are characterized by distinctive connectivity patterns during threat anticipation. Hum Brain Mapp 37:1091–1102, 2016. © 2015 Wiley Periodicals, Inc .     

Defensive engagement and perceptual enhancement

We tested whether visual cortical sensitivity to external cues in the context of an acute defensive reaction is heightened or attenuated. A strong cardiac defense (fear) response was elicited by presenting an abrupt, loud acoustic stimulus following a 10-min period of quiescence. Electrocortical responses to aversive and neutral pictures following defensive stimulus onset were measured using dense-array EEG. Pictures were flickered at 12.5 Hz to evoke steady-state visual evoked potentials (ssVEP), which can be reliably extracted on the basis of single trials. Visual cortical activity indexing perceptual processing was substantially heightened when pictures were shown in temporal proximity to (i.e., 5 s after) the defense stimulus. Replicating previous studies, aversive visual stimuli were associated with enhanced ssVEP amplitude, compared to neutral stimuli. Acute defense facilitates visual perception of external cues and preserves accurate discrimination between threatening and safe cues.     

Eye-catching: right hemisphere attentional bias for emotional pictures

To examine whether healthy individuals spontaneously direct attention to emotional pictures, eye movements were monitored continuously during the presentation of pairs of emotional and neutral pictures. A right hemisphere advantage was expected for initial orienting to emotional pictures. When an emotionally arousing picture was presented in the left visual hemifield, i.e., to the right hemisphere, the initial saccade was more often issued towards it, irrespective of valence. Negative pictures did not lead to avoidance throughout the 8-second trials; rather, both positive and negative valence held attention. This study adds to the evidence that overt attention to visual stimuli is boosted by emotion and that there is a right hemisphere advantage for orienting to emotional cues.     

Eye-catching: Right hemisphere attentional bias for emotional pictures

To examine whether healthy individuals spontaneously direct attention to emotional pictures, eye movements were monitored continuously during the presentation of pairs of emotional and neutral pictures. A right hemisphere advantage was expected for initial orienting to emotional pictures. When an emotionally arousing picture was presented in the left visual hemifield, i.e., to the right hemisphere, the initial saccade was more often issued towards it, irrespective of valence. Negative pictures did not lead to avoidance throughout the 8-second trials; rather, both positive and negative valence held attention. This study adds to the evidence that overt attention to visual stimuli is boosted by emotion and that there is a right hemisphere advantage for orienting to emotional cues.     

Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.     

Paranoid thinking as a heuristic

Paranoid thinking can be viewed as a human heuristic used by individuals to deal with uncertainty during stressful situations. Under stress, individuals are likely to emphasize the threatening value of neutral stimuli and increase the reliance on paranoia-based heuristic to interpreter events and guide their decisions. Paranoid thinking can also be activated by stress arising from the possibility of losing a good opportunity; this may result in an abnormal allocation of attentional resources to social agents. A better understanding of the interplay between cognitive heuristics and emotional processes may help to detect situations in which paranoid thinking is likely to exacerbate and improve intervention for individuals with delusional disorders.