Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task

Functional imaging studies consistently find that emotional stimuli activate the posterior cingulate cortex, a region that appears to have memory-related functions. However, prior imaging studies have not controlled for non-emotional stimulus features that might activate this region by engaging memory processes unrelated to emotion. This study examined whether emotional words activated the posterior cingulate cortex when these potentially confounding factors were controlled. Sixty-four pleasant and 64 unpleasant words were matched with neutral words on non-emotional features known to influence memory. Eight subjects underwent block-designed functional magnetic resonance imaging scans while evaluating the valence of these words. The posterior cingulate cortex was significantly activated bilaterally during both unpleasant and pleasant compared to neutral words. The strongest activation peak with both unpleasant and pleasant words was observed in the left subgenual cingulate cortex. Anteromedial orbital and left inferior and middle frontal cortices were also activated by both pleasant and unpleasant words. Right amygdala and auditory cortex were activated only by unpleasant words, while left frontal pole was activated only by pleasant words. The results show that activation of the posterior cingulate cortex by emotional stimuli cannot be attributed to the memory-enhancing effects of non-emotional stimulus features. The findings are consistent with the suggestion that this region may mediate interactions of emotional and memory-related processes. The results also extend prior findings that evaluating emotional words consistently activates the subgenual cingulate cortex, and suggest a means of probing this region in patients with mood disorders.     

Cerebral blood flow changes associated with attribution of emotional valence to pleasant, unpleasant, and neutral visual stimuli in a PET study of normal subjects.

OBJECTIVE: To assist in the development of a model for the psychopathology of emotions, the present study sought to identify the neural circuits associated with the evaluation of visual stimuli for emotional valence. METHOD: Seventeen healthy individuals were shown three sets of emotionally laden pictures carrying pleasant, unpleasant, and neutral content. While subjects evaluated the picture set for emotional valence, regional cerebral blood flow was measured with the use of [15O] water positron emission tomography. Subjective ratings of the emotional valence of the picture sets were recorded. Data were analyzed by comparing the images acquired during the neutral condition with the unpleasant and pleasant image sets and the unpleasant and pleasant conditions with each other. RESULTS: Processing of pleasant stimuli was associated with increased blood flow in the dorsal-lateral, orbital, and medial frontal cortex relative to the unpleasant condition and in the cingulate, precuneus, and visual cortex relative to the neutral condition. Evaluation of unpleasant stimuli activated the amygdala, visual cortex, and cerebellum relative to the pleasant condition and the nucleus accumbens, precuneus, and visual cortex relative to the neutral condition. CONCLUSIONS: Observing and assigning emotional value to unpleasant stimuli produced activations in subcortical limbic regions, whereas evaluation of pleasant stimuli produced activations in cortical limbic areas. These findings are consistent with the notion of a subcortical and archaic danger recognition system and a system detecting pleasantness in events and situations that is phylogenetically younger, involving primarily the prefrontal cortex.     

The cerebellum and emotional experience

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.     

Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus

It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes.     

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND: Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS: Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS: These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.     

An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder

The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.     

Specific brain activation in Japanese and Caucasian people to fearful faces

Different regions of brain activation, as measured by fMRI, were evident in Japanese and Caucasian individuals observing facial expressions categorized as fearful according to Ekman criteria. Activation was evident in the posterior cingulate, supplementary motor cortex and the amygdala in Caucasians, while activation was evident in the right inferior frontal, premotor cortex and left insula and in Japanese individuals. The results suggest that Caucasians respond to fearful faces in a more direct, emotional way, whereas Japanese do not attach an emotional valence to the faces and therefore activate a template matching system to identify facial expressions. The faces widely used as emotional stimuli therefore are not universally perceived, and cultural specificity should be taken into consideration in designing facial tasks.     

Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli

Repeated presentations of emotional facial expressions were used to assess habituation in the human brain using fMRI. Significant fMRI signal decrement was present in the left dorsolateral prefrontal and premotor cortex, and right amygdala. Within the left prefrontal cortex greater habituation to happy vs fearful stimuli was evident, suggesting devotion of sustained neural resources for processing of threat vs safety signals. In the amygdala, significantly greater habituation was observed on the right compared to the left. In contrast, the left amygdala was significantly more activated than the right to the contrast of fear vs happy. We speculate that the right amygdala is part of a dynamic emotional stimulus detection system, while the left is specialized for sustained stimulus evaluations.     

Color Stroop and negative priming in schizophrenia: An fMRI study

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention—the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions–medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls–but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.     

The neural substrates of social emotion perception and regulation are modulated by adult attachment style

Adult attachment style (AAS) refers to individual differences in the way people experience and regulate their social relationships and corresponding emotions. Based on developmental and psychological research, it has been hypothesized that avoidant attachment style (AV) entails deactivating strategies in social contexts, whereas anxious attachment style (AX) involves hyper vigilance and up-regulation mechanisms. However, the neural substrates of differences in social emotion regulation associated with AAS have not been systematically investigated. Here we used fMRI in 19 healthy adults to investigate the effect of AAS on the processing of pleasant or unpleasant social and nonsocial scenes. Participants were asked either to naturally attend (NAT), cognitively reappraise (REAP), or behaviorally suppress (ESUP) their emotional responses. Avoidantly attached participants showed increased prefrontal and anterior cingulate activation to social negative scenes when making spontaneous emotion judgments. They also exhibited persistent increases in dorsolateral prefrontal cortex and left amygdala activity for the same stimuli during reappraisal, as well as additional activation in supplementary motor area and ventral caudate during the suppression of social positive emotions. These results suggest that AV may imply less efficient reappraisal strategies to regulate social negative emotions, and lead to higher conflict or effortful control when suppression cannot be employed. In contrast, anxiously attached participants showed differential increases in the right amygdala and left parahippocampal cortex for social negative and positive stimuli, respectively, but only when making spontaneous emotion judgments. No effect of AX was found during down-regulation conditions. This suggests heightened arousal to negative information without difficulty in down-regulating emotions through cognitive re-evaluation or suppression. Taken together, these findings reveal for the first time the neural underpinnings of attachment-related differences in social emotion regulation.     

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.     

Amygdala activation during reading of emotional adjectives--an advantage for pleasant content

This event-related functional magnetic resonance imaging (fMRI)study investigated brain activity elicited by emotional adjectivesduring silent reading without specific processing instructions.Fifteen healthy volunteers were asked to read a set of randomlypresented high-arousing emotional (pleasant and unpleasant)and low-arousing neutral adjectives. Silent reading of emotionalin contrast to neutral adjectives evoked enhanced activationsin visual, limbic and prefrontal brain regions. In particular,reading pleasant adjectives produced a more robust activationpattern in the left amygdala and the left extrastriate visualcortex than did reading unpleasant or neutral adjectives. Moreover,extrastriate visual cortex and amygdala activity were significantlycorrelated during reading of pleasant adjectives. Furthermore,pleasant adjectives were better remembered than unpleasant andneutral adjectives in a surprise free recall test conductedafter scanning. Thus, visual processing was biased towards pleasantwords and involved the amygdala, underscoring recent theoreticalviews of a general role of the human amygdala in relevance detectionfor both pleasant and unpleasant stimuli. Results indicate preferentialprocessing of pleasant information in healthy young adults andcan be accounted for within the framework of appraisal theory.     

The neural substrates of social emotion perception and regulation are modulated by adult attachment style

Adult attachment style (AAS) refers to individual differences in the way people experience and regulate their social relationships and corresponding emotions. Based on developmental and psychological research, it has been hypothesized that avoidant attachment style (AV) entails deactivating strategies in social contexts, whereas anxious attachment style (AX) involves hyper vigilance and up-regulation mechanisms. However, the neural substrates of differences in social emotion regulation associated with AAS have not been systematically investigated. Here we used fMRI in 19 healthy adults to investigate the effect of AAS on the processing of pleasant or unpleasant social and nonsocial scenes. Participants were asked either to naturally attend (NAT), cognitively reappraise (REAP), or behaviorally suppress (ESUP) their emotional responses. Avoidantly attached participants showed increased prefrontal and anterior cingulate activation to social negative scenes when making spontaneous emotion judgments. They also exhibited persistent increases in dorsolateral prefrontal cortex and left amygdala activity for the same stimuli during reappraisal, as well as additional activation in supplementary motor area and ventral caudate during the suppression of social positive emotions. These results suggest that AV may imply less efficient reappraisal strategies to regulate social negative emotions, and lead to higher conflict or effortful control when suppression cannot be employed. In contrast, anxiously attached participants showed differential increases in the right amygdala and left parahippocampal cortex for social negative and positive stimuli, respectively, but only when making spontaneous emotion judgments. No effect of AX was found during down-regulation conditions. This suggests heightened arousal to negative information without difficulty in down-regulating emotions through cognitive re-evaluation or suppression. Taken together, these findings reveal for the first time the neural underpinnings of attachment-related differences in social emotion regulation.     

Activity and functional connectivity of inferior frontal cortex associated with response conflict

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.     

An fMRI Study of the Neural Correlates of Incidental Versus Directed Emotion Processing in Pediatric Bipolar Disorder

ObjectiveTo use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD).MethodEqual numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years.ResultsRelative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus).ConclusionsIncreased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD.     

Default mode network activity in schizophrenia studied at resting state using probabilistic ICA

Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.     

The effect of one left-sided dorsolateral prefrontal sham-controlled HF-rTMS session on approach and withdrawal related emotional neuronal processes

Objective

Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion.

Methods

In this sham-controlled, single-blind crossover study using fMRI, we examined in 20 right-handed healthy females whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces.

Results

While positive information was being processed, we observed after one active HF-rTMS session enhanced neuronal activity in the left superior frontal cortex and right inferior parietal cortex. After sham HF-rTMS, we found significant decreases in neuronal activity in the left superior frontal cortex, the left inferior prefrontal cortex, as well as in the right posterior cingulate gyrus. When negative information was processed, one active stimulation attenuated neuronal activity in the right insula only.

Conclusions

Our findings suggest that during the processing of positive information one active session enhanced the ability to empathize with the depicted emotional stimuli, while during the processing of negative information it resulted in decreased psychophysiological reactions.

Significance

These results provide new information on the working mechanism of left-sided HF-rTMS.     

Short Term Exposure to a Violent Video Game Induces Changes in Frontolimbic Circuitry in Adolescents

Despite evidence of effects of violent video game play on behavior, the underlying neuronal mechanisms involved in these effects remain poorly understood. We report a functional MRI (fMRI) study during two modified Stroop tasks performed immediately after playing a violent or nonviolent video game. Compared with the violent video game group, the nonviolent video game group demonstrated more activation in some regions of the prefrontal cortex during the Counting Stroop task. In contrast to the violent video game group, significantly stronger functional connectivity between left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) was identified in the nonviolent video game group. During an Emotional Stroop task, the violent video game group showed more activity in the right amygdala and less activation in regions of the medial prefrontal cortex (MPFC). Furthermore, functional connectivity analysis revealed the negative coupling between right amygdala and MPFC in the nonviolent video game group. By contrast, no significant functional connectivity between right amygdala and MPFC was found in the violent video game group. These results suggest differential engagement of neural circuitry in response to short term exposure to a violent video game as compared to a nonviolent video game.     

In search of the emotional self: an fMRI study using positive and negative emotional words

OBJECTIVE: The authors used functional magnetic resonance imaging (fMRI) to define the neural regions mediating self-referential processing of emotional stimuli and to explore how these regions are influenced by the emotional valence of the stimulus. METHOD: Ten healthy subjects were presented with words describing positive and negative personality traits during fMRI scanning in three different conditions. In the self-referential processing condition, subjects judged whether they thought each trait described them. In the other-referential processing condition, subjects judged whether the stimulus described a generally desirable trait. In the letter-recognition control condition, subjects indicated whether the word contained a specific target letter. RESULTS: The self-referential condition induced bilateral activation in the dorsomedial prefrontal cortex, whereas the other-referential condition induced activation in lateral prefrontal areas. Activation in the right dorsomedial prefrontal cortex was unique to the self-referential condition regardless of the valence of the words, although positive words produced a more robust activation than did negative words. In the self-referential condition, differences between the processing of positive and negative words were seen in regions outside the medial frontal cortex, with reductions in the insula, temporal and occipital regions, and inferior parietal regions associated with negative words. CONCLUSIONS: A widely distributed network of brain areas contributes to emotional processing. Among these regions, the right dorsomedial prefrontal cortex is one main area mediating self-reference. By providing a personal perspective in the evaluation of emotional stimuli, the right dorsomedial prefrontal cortex may mediate cognitive processes, such as those involved in psychotherapy, that guide self-regulation of emotional experience.     

Brain regions showing increased activation by threat-related words in panic disorder

Threat-related stimuli consistently activate the posterior cingulate cortex in normal subjects and have exaggerated effects on memory in patients with panic disorder. We hypothesized that panic patients would show increased response to threat-related stimuli in the posterior cingulate cortex. While undergoing fMRI, six panic patients and eight healthy volunteers made valence judgements of threat-related and neutral words. Both groups showed threat-related activation in the left posterior cingulate and left middle frontal cortices, but the activation was significantly greater in panic patients. Panic patients also had more right>left asymmetry of activation in the mid-parahippocampal region. The increased responsivity observed in the posterior cingulate and dorsolateral prefrontal cortices is consistent with the hypothesis that panic disorder patients engage in more extensive memory processing of threat-related stimuli.