Amygdala responsiveness to emotional words is modulated by subclinical anxiety and depression

Several neuroimaging studies underlined the importance of the amygdala and prefrontal brain structures (e.g. dorsolateral prefrontal cortex [DLPFC]) for the processing of emotional stimuli and for emotion regulation. Many studies used visual scenes or faces as emotion-inducing material, and there is evidence that negative or positive words activate emotion-processing brain regions in the same way. However, no study so far focused on the influence of subclinical measures of anxiety or depression on the neural processing of emotional words. In this fMRI-study, we therefore investigated brain activation to emotional words in relation to subclinical measures of trait anxiety and depression in a sample of 21 healthy subjects. We also assessed effects of subclinical anxiety and depression on amygdala-prefrontal coupling during negative (versus neutral) word reading. Both negative and positive words activated the amygdala, and negative-word processing revealed a positive correlation between amygdala activity and scores of trait anxiety and subclinical depression. During negative versus neutral word reading, subjects with high trait anxiety also showed a stronger functional coupling between left amygdala and left DLPFC. These results suggest a modulation of negative-word processing by subclinical depression and anxiety, as well as possible prefrontal compensatory processes during unintentional emotion regulation in subjects with higher trait anxiety.     

Emotion processing in words: a test of the neural re-use hypothesis using surface and intracranial EEG

This study investigates the spatiotemporal brain dynamics of emotional information processing during reading using a combination of surface and intracranial electroencephalography (EEG). Two different theoretical views were opposed. According to the standard psycholinguistic perspective, emotional responses to words are generated within the reading network itself subsequent to semantic activation. According to the neural re-use perspective, brain regions that are involved in processing emotional information contained in other stimuli (faces, pictures, smells) might be in charge of the processing of emotional information in words as well. We focused on a specific emotion—disgust—which has a clear locus in the brain, the anterior insula. Surface EEG showed differences between disgust and neutral words as early as 200 ms. Source localization suggested a cortical generator of the emotion effect in the left anterior insula. These findings were corroborated through the intracranial recordings of two epileptic patients with depth electrodes in insular and orbitofrontal areas. Both electrodes showed effects of disgust in reading as early as 200 ms. The early emotion effect in a brain region (insula) that responds to specific emotions in a variety of situations and stimuli clearly challenges classic sequential theories of reading in favor of the neural re-use perspective.     

The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder

Previous studies examining neural responses to emotional stimuli in individuals with major depressive disorder (MDD) have indicated increased responses within the left amygdala to sad faces, and increased activity within the visual cortex and striatum to expressions of happiness. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, positive and negative pictures of the International Affective Picture System in 15 healthy individuals and 15 patients with MDD. Depressed individuals demonstrated lower activity in the right hippocampus and the right insula to negative affective pictures, whereas they showed lower activity in the right anterior cingulate cortex and the left insula to positive pictures. However, within the MDD group, the severity of depression correlated with the activity of the left amygdala, bilateral inferior orbitofrontal areas, and the left insula to negative pictures, whereas there were no clear indications of association between specific cerebral regions and positive pictures. Our findings indicate that preferential decreases in the left amygdala in response to negative pictures might be involved in the processing of emotional stimuli in depressed individuals. Also, these findings suggest that the bilateral inferior orbitofrontal cortices and left amygdala may be preferentially recruited in MDD patients, but not in healthy individuals.     

Emotion perception and executive control interact in the salience network during emotionally charged working memory processing

Processing of emotional stimuli can either hinder or facilitate ongoing working memory (WM); however, the neural basis of these effects remains largely unknown. Here we examined the neural mechanisms of these paradoxical effects by implementing a novel emotional WM task in an fMRI study. Twenty‐five young healthy participants performed an N‐back task with fearful and neutral faces as stimuli. Participants made more errors when performing 0‐back task with fearful versus neutral faces, whereas they made fewer errors when performing 2‐back task with fearful versus neutral faces. These emotional impairment and enhancement on behavioral performance paralleled significant interactions in distributed regions in the salience network including anterior insula (AI) and dorsal cingulate cortex (dACC), as well as in emotion perception network including amygdala and temporal‐occipital association cortex (TOC). The dorsal AI (dAI) and dACC were more activated when comparing fearful with neutral faces in 0‐back task. Contrarily, dAI showed reduced activation, while TOC and amygdala showed stronger responses to fearful as compared to neutral faces in the 2‐back task. These findings provide direct neural evidence to the emerging dual competition model suggesting that the salience network plays a critical role in mediating interaction between emotion perception and executive control when facing ever‐changing behavioral demands. Hum Brain Mapp 35:5606–5616, 2014. © 2014 Wiley Periodicals, Inc.     

Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia.

BACKGROUND: The study aimed to identify brain activation during direct and automatic processing of phobogenic stimuli in specific phobia. METHODS: Responses to phobia-related and neutral pictures (spiders and mushrooms) were measured by means of event-related functional magnetic resonance imaging during two different tasks. In the identification task, subjects were asked to identify the object (spider or mushroom). In a demanding distraction task, subjects had to match geometric figures displayed in the foreground of the pictures. RESULTS: Phobics showed greater responses to spiders versus mushrooms in the left amygdala, left insula, left anterior cingulate gyrus (ACC), and left dorsomedial prefrontal cortex (DMPFC) during the identification task and in the left and right amygdala during the distraction task. All of these activations were also significantly increased compared to control subjects who did not show stronger brain activation to spiders versus mushrooms under any task condition. CONCLUSIONS: Our findings propose specific neural correlates of automatic versus direct evaluation of phobia-relevant threat. While the amygdala, especially the right amygdala, seems to be crucially involved in automatic stimuli processing, activation of areas such as the insula, ACC and DMPFC is rather associated with direct threat evaluation and requires sufficient attentional resources.     

Effects of left and right medial temporal lobe resections on hemodynamic correlates of negative and neutral scene processing

Enhanced visual cortex activation by negative compared to neutral stimuli is often attributed to modulating feedback from the amygdala, but evidence from lesion studies is scarce, particularly regarding differential effects of left and right amygdala lesions. Therefore, we compared visual cortex activation by negative and neutral complex scenes in an event‐related fMRI study between 40 patients with unilateral temporal lobe resection (TLR; 19 left [lTLR], 21 right [rTLR]), including the amygdala, and 20 healthy controls. We found preserved hemodynamic emotion modulation of visual cortex in rTLR patients and only subtle reductions in lTLR patients. In contrast, rTLR patients showed a significant decrease in visual cortex activation irrespective of picture content. In line with this, healthy controls showed small emotional modulation of the left amygdala only, while their right amygdala was activated equally by negative and neutral pictures. Correlations of activation in amygdala and visual cortex were observed for both negative and neutral pictures in the controls. In both patient groups, this relationship was attenuated ipsilateral to the TLR. Our results support the notion of reentrant mechanisms between amygdala and visual cortex and suggest laterality differences in their emotion‐specificity. While right medial temporal lobe structures including the amygdala seem to influence visual processing in general, the left medial temporal lobe appears to contribute specifically to emotion processing. Still, effects of left TLR on visual emotion processing were relatively subtle. Therefore, hemodynamic correlates of visual emotion processing are likely supported by a distributed cerebral network, challenging an amygdalocentric view of emotion processing.     

The role of the amygdala in human fear: automatic detection of threat

Behavioral data suggest that fear stimuli automatically activate fear and capture attention. This effect is likely to be mediated by a subcortical brain network centered on the amygdala. Consistent with this view, brain imaging studies show that masked facial stimuli activate the amygdala as do masked pictures of threatening animals such as snakes and spiders. When the stimulus conditions allow conscious processing, the amygdala response to feared stimuli is enhanced and a cortical network that includes the anterior cingulate cortex and the anterior insula is activated. However, the initial amygdala response to a fear-relevant but non-feared stimulus (e.g. pictures of spiders for a snake phobic) disappears with conscious processing and the cortical network is not recruited. Instead there is activation of the dorsolateral and orbitofrontal cortices that appears to inhibit the amygdala response. The data suggest that activation of the amygdala is mediated by a subcortical pathway, which passes through the superior colliculi and the pulvinar nucleus of the thalamus before accessing the amygdala, and which operates on low spatial frequency information.     

Saying it with feeling: neural responses to emotional vocalizations.

To determine how vocally expressed emotion is processed in the brain, we measured neural activity in healthy volunteers listening to fearful, sad, happy and neutral non-verbal vocalizations. Enhanced responses to emotional vocalizations were seen in the caudate nucleus, as well as anterior insular, temporal and prefrontal cortices. The right amygdala exhibited decreased responses to fearful vocalizations as well as fear-specific inhibitory interactions with left anterior insula. A region of the pons, implicated in acoustic startle responses also showed fear-specific interactions with the amygdala. The data demonstrate: firstly, that processing of vocal emotion involves a bilaterally distributed network of brain regions; and secondly, that processing of fear-related auditory stimuli involves context-specific interactions between the amygdala and other cortical and brainstem regions implicated in fear processing.     

Brain activation during direct and indirect processing of positive and negative words

The effects of task conditions on brain activation to emotional stimuli are poorly understood. In this event-related fMRI study, brain activation to negative and positive words (matched for arousal) and neutral words was investigated under two task conditions. Subjects either had to attend to the emotional meaning (direct task) or to non-emotional features of the words (indirect task). Regardless of task, positive vs. negative words led to increased activation in the ventral medial prefrontal cortex, while negative vs. positive words induced increased activation of the insula. Compared to neutral words, all emotional words were associated with increased activation of the amygdala. Finally, the direct condition, as compared to the indirect condition, led to enhanced activation to emotional vs. neutral words in the dorsomedial prefrontal cortex and the anterior cingulate cortex. These results suggest valence and arousal dependent brain activation patterns that are partially modulated by participants’ processing mode of the emotional stimuli.     

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.     

Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data

A meta‐analysis of 140 neuroimaging studies was performed using the activation‐likelihood‐estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus‐specific likelihood of being activated. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Differential influences of emotion, task, and novelty on brain regions underlying the processing of speech melody

We investigated the functional characteristics of brain regions implicated in processing of speech melody by presenting words spoken in either neutral or angry prosody during a functional magnetic resonance imaging experiment using a factorial habituation design. Subjects judged either affective prosody or word class for these vocal stimuli, which could be heard for either the first, second, or third time. Voice-sensitive temporal cortices, as well as the amygdala, insula, and mediodorsal thalami, reacted stronger to angry than to neutral prosody. These stimulus-driven effects were not influenced by the task, suggesting that these brain structures are automatically engaged during processing of emotional information in the voice and operate relatively independent of cognitive demands. By contrast, the right middle temporal gyrus and the bilateral orbito-frontal cortices (OFC) responded stronger during emotion than word classification, but were also sensitive to anger expressed by the voices, suggesting that some perceptual aspects of prosody are also encoded within these regions subserving explicit processing of vocal emotion. The bilateral OFC showed a selective modulation by emotion and repetition, with particularly pronounced responses to angry prosody during the first presentation only, indicating a critical role of the OFC in detection of vocal information that is both novel and behaviorally relevant. These results converge with previous findings obtained for angry faces and suggest a general involvement of the OFC for recognition of anger irrespective of the sensory modality. Taken together, our study reveals that different aspects of voice stimuli and perceptual demands modulate distinct areas involved in the processing of emotional prosody.     

Towards a functional neuroanatomy of self processing: effects of faces and words

We studied the neural correlates of self vs. non-self judgements using functional magnetic resonance imaging (fMRI). Individually tailored faces and personality trait words were used as stimuli in three experiments (exp.). In the first two experiments, brain activation was measured while subjects viewed morphed versions of either their own (self face exp.) or their partner's face (partner's face exp.), alternating in blocks with presentation of an unknown face. In the self face exp. right limbic areas (hippocampal formation, insula, anterior cingulate), the right middle temporal lobe, left inferior parietal and left prefrontal regions showed signal changes. In the partner's face exp., only the right insula was activated. In the third exp., subjects made decisions about psychological trait adjectives previously categorized as describing their own attributes. Activation was present in the precuneus, the left parietal lobe, left insula/inferior frontal gyrus and the left anterior cingulate. A reaction time advantage was present when subjects responded to self-relevant words. The main area with signal changes during self-reference processing, regardless of the type of stimulus, was the left fusiform gyrus. The self-relevant stimuli engaged to a differential extent long term and working memory, semantic and emotional processes. We suggest that regions activated by these stimuli are engaged in self-processing.     

Emotional self-reference: brain structures involved in the processing of words describing one's own emotions

The present functional magnetic resonance imaging study investigated the role of emotion-related (e.g., amygdala) and self-related brain structures (MPFC in particular) in the processing of emotional words varying in stimulus reference. Healthy subjects (N = 22) were presented with emotional (pleasant or unpleasant) or neutral words in three different conditions: (1) self (e.g., my fear), (2) other (e.g., his fear) and (3) no reference (e.g., the fear). Processing of unpleasant words was associated with increased amygdala and also insula activation across all conditions. Pleasant stimuli were specifically associated with increased activation of amygdala and insula when related to the self (vs. other and no reference). Activity in the MPFC (vMPFC in particular) and anterior cingulate cortex (ACC) was preferentially increased during processing of self-related emotional words (vs. other and no reference). These results demonstrate that amygdala activation in response to emotional stimuli is modulated by stimulus reference and that brain structures implicated in emotional and self-related processing might be important for the subjective experience of one's own emotions.     

Individual differences in alexithymia and brain response to masked emotion faces

Alexithymia is considered a dimensional personality trait that refers to a cluster of deficits in the recognition, differentiation, and verbalization of emotions. Research on the neurobiology of alexithymia has focused hitherto on impairments in the controlled processing of emotional information. In the present study automatic brain reactivity to facial emotion was investigated as a function of alexithymia (as assessed by the 20-Item Toronto Alexithymia Scale - TAS-20). During 3 T fMRI scanning, pictures of sad, happy, and neutral facial expression masked by neutral faces were presented to 33 healthy women. A priori regions of interest in the whole brain analysis were cerebral structures that are known to be crucially involved in the emotion perception from the face. Independently from trait anxiety and depression TAS-20 alexithymia was negatively correlated with activation to masked sad and happy faces in several regions of interest (in particular, insula, superior temporal gyrus, middle occipital and parahippocampal gyrus). In addition, the TAS-20 score was negatively correlated with response of the left amygdala to masked sad faces. A reduced automatic reactivity of the amygdala and visual occipito-temporal areas could implicate less automated engagement in the encoding of emotional stimuli in high alexithymia. In addition, a low spontaneous insular and amygdalar responsivity in high alexithymia individuals could be related to an attenuation of basic emotional experiences which may contribute to problems in identifying and differentiating one's feelings.     

Differential amygdala activation to negative and positive emotional pictures during an indirect task

The role of the amygdala for the processing of valence and arousal is a matter of debate. Using event-related functional magnetic resonance imaging, we tested valence-specific amygdala effects during attentional distraction. Subjects attended to a matching task in the foreground of neutral pictures, and of negative and positive pictures matched for arousal. Negative pictures elicited stronger amygdala activation than neutral or positive pictures, suggesting valence-specific amygdala responses under attentional load.     

Neural correlates of alexithymia: A meta-analysis of emotion processing studies

Alexithymia is a personality trait characterized by difficulties in the experience and cognitive processing of emotions. It is considered a risk factor for a range of psychiatric and neurological disorders. Functional neuroimaging studies investigating the neural correlates of alexithymia have reported inconsistent results. To integrate previous findings, we conducted a parametric coordinate-based meta-analysis including fifteen neuroimaging studies on emotion processing in alexithymia. During the processing of negative emotional stimuli, alexithymia was associated with a diminished response of the amygdala, suggesting decreased attention to such stimuli. Negative stimuli additionally elicited decreased activation in supplementary motor and premotor brain areas and in the dorsomedial prefrontal cortex, possibly underlying poor empathic abilities and difficulties in emotion regulation associated with alexithymia. Positive stimuli elicited decreased activation in the right insula and precuneus, suggesting reduced emotional awareness in alexithymia regarding positive affect. Independent of valence, higher (presumably compensatory) activation was found in the dorsal anterior cingulate possibly indicating increased cognitive demand. These results suggest valence-specific as well as valence-independent effects of alexithymia on the neural processing of emotions.     

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.     

Questioning the role of amygdala and insula in an attentional capture by emotional stimuli task

Our senses are constantly monitoring the environment for emotionally salient stimuli that are potentially relevant for survival. Because of our limited cognitive resources, emotionally salient distractors prolong reaction times (RTs) as compared to neutral distractors. In addition, many studies have reported fMRI blood oxygen level‐dependent (BOLD) activation of both the amygdala and the anterior insula for similar valence contrasts. However, a direct correlation of trail‐by‐trial BOLD activity with RTs has not been shown, yet, which would be a crucial piece of evidence to relate the two observations. To investigate the role of the above two regions in the context of emotional distractor effects, we study here the correlation between BOLD activity and RTs for a simple attentional capture by emotional stimuli (ACES) choice reaction time task using a general linear subject‐level model with a parametric RT regressor. We found significant regression coefficients in the anterior insula, supplementary motor cortex, medial precentral regions, sensory‐motor areas and others, but not in the amygdala, despite activation of both insula and amygdala in the traditional valence contrast across trials (i.e., negative vs. neutral pictures). In addition, we found that subjects that exhibit a stronger RT distractor effect across trials also show a stronger BOLD valence contrast in the right anterior insula but not in the amygdala. Our results indicate that the current neuroimaging‐based evidence for the involvement of the amygdala in RT slowing is limited. We advocate that models of emotional capture should incorporate both the amygdala and the anterior insula as separate entities.     

Age-related differences in brain regions supporting successful encoding of emotional faces

In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.