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.     

Alexithymia influences brain activation during emotion perception but not regulation

Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.     

Anodal Transcranial Direct-Current Stimulation Over the Right Dorsolateral Prefrontal Cortex Influences Emotional Face Perception

The dorsolateral prefrontal cortex (DLPFC) is considered to play a crucial role in many high-level functions, such as cognitive control and emotional regulation. Many studies have reported that the DLPFC can be activated during the processing of emotional information in tasks requiring working memory. However, it is still not clear whether modulating the activity of the DLPFC influences emotional perception in a detection task. In the present study, using transcranial direct-current stimulation (tDCS), we investigated (1) whether modulating the right DLPFC influences emotional face processing in a detection task, and (2) whether the DLPFC plays equal roles in processing positive and negative emotional faces. The results showed that anodal tDCS over the right DLPFC specifically facilitated the perception of positive faces, but did not influence the processing of negative faces. In addition, anodal tDCS over the right primary visual cortex enhanced performance in the detection task regardless of emotional valence. Our findings suggest, for the first time, that modulating the right DLPFC influences emotional face perception, especially faces showing positive emotion.     

Serotonin transporter genotype modulates cognitive reappraisal of negative emotions: a functional magnetic resonance imaging study

A functional polymorphism within the serotonin transporter gene (5-HTTLPR) has been reported to modulate emotionality and risk for affective disorders. The short (S) allele has less functional efficacy than the long (L) allele and has been associated with enhanced emotional reactivity. One possible contributing factor to the high emotionality in S carriers may be inefficient use of cognitive strategies such as reappraisal to regulate emotional responses. The aim of the present study was to test whether the 5-HTTLPR genotype modulates the neural correlates of emotion regulation. To determine neural differences between S and L allele carriers during reappraisal of negative emotions, 15 homozygous S (S′/S′) and 15 homozygous L (L′/L′) carriers underwent functional magnetic resonance imaging (fMRI), while performing an instructed emotion regulation task including downregulation, upregulation and passive viewing of negative emotional pictures. Compared to L′/L′ allele carriers, subjects who carry the S′/S′ allele responded with lower posterior insula and prefrontal brain activation during passive perception of negative emotional information but showed greater prefrontal activation and anterior insula activation during down- and upregulation of negative emotional responses. The current results support and extend previous findings of enhanced emotionality in S carriers by providing additional evidence of 5-HTTLPR modulation of volitional emotion regulation.     

Posterior cingulate activation during moral dilemma in adolescents

Neuroimaging research examining correlates of adolescent behavioral maturation has focused largely on issues related to higher cognitive development. Currently few studies have explored neural correlates of emotional reactivity in adolescent groups. In this study, we sought to examine the nature of posterior cingulate activation during situations of moral dilemma in normal adolescents. We focused on this region because of emerging evidence that suggests its role in emotionally self-relevant mental processing. Ten healthy teenagers, aged from 14 to 16 years, underwent three fMRI sequences designed to examine (i) brain responses during moral dilemma; (ii) brain responses during passive viewing of the moral dilemma outcome; and (iii); "deactivation" during a simple cognitive task compared with resting-state activity. Our main finding was that during moral dilemma, all subjects showed significant activation of the posterior cingulate cortex, and more variable activation of the medial frontal cortex and angular gyrus. Interestingly, these findings were replicated in each subject using the passive viewing task, suggesting that the previous pattern was not specific to moral reasoning or decision making. Finally, six of the ten subjects showed deactivation of the same posterior cingulate region during the cognitive task, indicating some commonality of function between posterior cingulate activity during moral dilemmas and rest. We propose that these posterior cingulate changes may relate to basic neuronal activities associated with processing self-relevant emotional stimuli. Given the high single-subject reproducibility of posterior cingulate activations, our findings may contribute to further characterize adolescent emotional reactivity in developmental neuroimaging studies.     

In search of convergent regional brain abnormality in cognitive emotion regulation: A transdiagnostic neuroimaging meta‐analysis

Ineffective use of adaptive cognitive strategies (e.g., reappraisal) to regulate emotional states is often reported in a wide variety of psychiatric disorders, suggesting a common characteristic across different diagnostic categories. However, the extent of shared neurobiological impairments is incompletely understood. This study, therefore, aimed to identify the transdiagnostic neural signature of disturbed reappraisal using the coordinate‐based meta‐analysis (CBMA) approach. Following the best‐practice guidelines for conducting neuroimaging meta‐analyses, we systematically searched PubMed, ScienceDirect, and Web of Science databases and tracked the references. Out of 1,608 identified publications, 32 whole‐brain neuroimaging studies were retrieved that compared brain activation in patients with psychiatric disorders and healthy controls during a reappraisal task. Then, the reported peak coordinates of group comparisons were extracted and several activation likelihood estimation (ALE) analyses were performed at three hierarchical levels to identify the potential spatial convergence: the global level (i.e., the pooled analysis and the analyses of increased/decreased activations), the experimental‐contrast level (i.e., the analyses of grouped data based on the regulation goal, stimulus valence, and instruction rule) and the disorder‐group level (i.e., the analyses across the experimental‐contrast level focused on increasing homogeneity of disorders). Surprisingly, none of our analyses provided significant convergent findings. This CBMA indicates a lack of transdiagnostic convergent regional abnormality related to reappraisal task, probably due to the complex nature of cognitive emotion regulation, heterogeneity of clinical populations, and/or experimental and statistical flexibility of individual studies.     

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.     

Hyperactivation balances sensory processing deficits during mood induction in schizophrenia

While impairments in emotion recognition are consistently reported in schizophrenia, there is some debate on the experience of emotion. Only few studies investigated neural correlates of emotional experience in schizophrenia. The present functional magnetic resonance imaging study compared a standard visual mood induction paradigm with an audiovisual method aimed at eliciting emotions more automatically. To investigate the interplay of sensory, cognitive and emotional mechanisms during emotion experience, we examined connectivity patterns between brain areas. Sixteen schizophrenia patients and sixteen healthy subjects participated in two different mood inductions (visual and audiovisual) that were administered for different emotions (happiness, sadness and neutral). Confirming the dissociation of behavioral and neural correlates of emotion experience, patients rated their mood similarly to healthy subjects but showed differences in neural activations. Sensory brain areas were activated less, increased activity emerged in higher cortical areas, particularly during audiovisual stimulation. Connectivity was increased between primary and secondary sensory processing areas in schizophrenia. These findings support the hypothesis of a deficit in filtering and processing sensory information alongside increased higher-order cognitive effort compensating for perception deficits in the affective domain. This may suffice to recover emotion experience in ratings of clinically stable patients but may fail during acute psychosis.     

Influence of Emotional Processing on Working Memory in Schizophrenia

Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli “in the moment.” However, neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia. We asked whether given a more vulnerable cognitive system in schizophrenia, individuals with this disorder would show increased or decreased modulation of working memory (WM) as a function of the emotional content of stimuli compared with healthy control subjects. In addition, we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses. In the present study, 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session. Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli (happy or fearful faces), randomly intermixed and occurring both as targets and non-targets. Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli. Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli, but demonstrated altered dorsolateral prefrontal cortex (DLPFC) and hippocampal activity while performing an emotionally loaded WM-task. Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia. Emotional arousal may challenge dorsal-frontal control systems, which may have both beneficial and detrimental influences. Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se.     

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.     

Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy

Clinical research has demonstrated differential efficacy of selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which may relate to differential acute effects these medications have on emotional brain processes. Here we present findings from a Multi-Level Kernel Density Analysis meta-analysis that integrates and contrasts activations from disparate fMRI studies in order to examine whether single dose SSRIs and NRIs have different effects on emotion processing tasks in healthy participants. Seven SSRI and four NRI studies were eligible for inclusion. SSRIs decreased amygdala responses, suggesting reduced emotional reactivity to emotional stimuli, whereas NRIs increased frontal and medial activation, suggesting increased emotion regulation. As hypothesised, an interaction of antidepressant and task type was found, such that SSRIs modulated amygdaloid-hippocampal, medial and frontal activity during both the presentation of faces and pictures, whereas NRIs only modulated the activation in medial and frontal regions during the presentation of pictures. Findings are interpreted within a novel model of the differential effects of SSRIs and NRIs on emotion processing.     

Emotion and Theory of Mind in Schizophrenia—Investigating the Role of the Cerebellum

Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks.     

Neural long-term effects of emotion regulation on episodic memory processes

Emotions can enhance memory which is on the one hand advantageous, but on the other hand may be detrimental in the long term, for example in the case of traumatic events. Although cognitive emotion regulation may reduce emotion experience and corresponding neural activation, at present little is known about its influence on long-term memory. We investigated memory for emotional pictures in healthy female subjects 1 year after voluntary emotion regulation using fMRI. Whereas memory performance was not affected by regulation, our data revealed a dissociation of brain regions involved in memory encoding and recognition depending on whether emotional engagement during encoding had been downregulated. Emotional engagement during encoding resulted in a long-term subsequent memory effect in mesolimbic brain regions and hippocampus, and in recognition-related activation in the amygdala. In contrast, when negative emotions had been downregulated during encoding memory performance was predicted by prefrontal activation. Our data suggest that memory for emotionally encoded stimuli is supported by emotional re-activation, whereas memory for successfully encoded items during emotion regulation is rather supported by recognition of features and cognitive contents. These results contribute to research on long-term effects of emotion regulation in everyday life and open new avenues to understand and possibly influence traumatic memory traces.     

Modulation of amygdalar activity by the conscious regulation of negative emotion

Lesion and neuroimaging studies suggest the amygdala is important in the perception and production of negative emotion; however, the effects of emotion regulation on the amygdalar response to negative stimuli remain unknown. Using event-related fMRI, we tested the hypothesis that voluntary modulation of negative emotion is associated with changes in neural activity within the amygdala. Negative and neutral pictures were presented with instructions to either "maintain" the emotional response or "passively view" the picture without regulating the emotion. Each picture presentation was followed by a delay, after which subjects indicated how they currently felt via a response keypad. Consistent with previous reports, greater signal change was observed in the amygdala during the presentation of negative compared to neutral pictures. No significant effect of instruction was found during the picture presentation component of the trial. However, a prolonged increase in signal change was observed in the amygdala when subjects maintained the negative emotional response during the delay following negative picture offset. This increase in amygdalar signal due to the active maintenance of negative emotion was significantly correlated with subjects' self-reported dispositional levels of negative affect. These results suggest that consciously evoked cognitive mechanisms that alter the emotional response of the subject operate, at least in part, by altering the degree of neural activity within the amygdala.     

Sex differences in brain activation to emotional stimuli: a meta-analysis of neuroimaging studies

Substantial sex differences in emotional responses and perception have been reported in previous psychological and psychophysiological studies. For example, women have been found to respond more strongly to negative emotional stimuli, a sex difference that has been linked to an increased risk of depression and anxiety disorders. The extent to which such sex differences are reflected in corresponding differences in regional brain activation remains a largely unresolved issue, however, in part because relatively few neuroimaging studies have addressed this issue. Here, by conducting a quantitative meta-analysis of neuroimaging studies, we were able to substantially increase statistical power to detect sex differences relative to prior studies, by combining emotion studies which explicitly examined sex differences with the much larger number of studies that examined only women or men. We used an activation likelihood estimation approach to characterize sex differences in the likelihood of regional brain activation elicited by emotional stimuli relative to non-emotional stimuli. We examined sex differences separately for negative and positive emotions, in addition to examining all emotions combined. Sex differences varied markedly between negative and positive emotion studies. The majority of sex differences favoring women were observed for negative emotion, whereas the majority of the sex differences favoring men were observed for positive emotion. This valence-specificity was particularly evident for the amygdala. For negative emotion, women exhibited greater activation than men in the left amygdala, as well as in other regions including the left thalamus, hypothalamus, mammillary bodies, left caudate, and medial prefrontal cortex. In contrast, for positive emotion, men exhibited greater activation than women in the left amygdala, as well as greater activation in other regions including the bilateral inferior frontal gyrus and right fusiform gyrus. These meta-analysis findings indicate that the amygdala, a key region for emotion processing, exhibits valence-dependent sex differences in activation to emotional stimuli. The greater left amygdala response to negative emotion for women accords with previous reports that women respond more strongly to negative emotional stimuli, as well as with hypothesized links between increased neurobiological reactivity to negative emotion and increased prevalence of depression and anxiety disorders in women. The finding of greater left amygdala activation for positive emotional stimuli in men suggests that greater amygdala responses reported previously for men for specific types of positive stimuli may also extend to positive stimuli more generally. In summary, this study extends efforts to characterize sex differences in brain activation during emotion processing by providing the largest and most comprehensive quantitative meta-analysis to date, and for the first time examining sex differences as a function of positive vs. negative emotional valence. The current findings highlight the importance of considering sex as a potential factor modulating emotional processing and its underlying neural mechanisms, and more broadly, the need to consider individual differences in understanding the neurobiology of emotion.     

Implicit emotion regulation affects outcome evaluation

Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes.     

Right brain,left brain in depressive disorders: Clinical and theoretical implications of behavioral,electrophysiological and neuroimaging findings

The right and left side of the brain are asymmetric in anatomy and function. We review electrophysiological (EEG and event-related potential), behavioral (dichotic and visual perceptual asymmetry), and neuroimaging (PET, MRI, NIRS) evidence of right-left asymmetry in depressive disorders. Recent electrophysiological and fMRI studies of emotional processing have provided new evidence of altered laterality in depressive disorders. EEG alpha asymmetry and neuroimaging findings at rest and during cognitive or emotional tasks are consistent with reduced left prefrontal activity in depressed patients, which may impair downregulation of amygdala response to negative emotional information. Dichotic listening and visual hemifield findings for non-verbal or emotional processing have revealed abnormal perceptual asymmetry in depressive disorders, and electrophysiological findings have shown reduced right-lateralized responsivity to emotional stimuli in occipitotemporal or parietotemporal cortex. We discuss models of neural networks underlying these alterations. Of clinical relevance, individual differences among depressed patients on measures of right-left brain function are related to diagnostic subtype of depression, comorbidity with anxiety disorders, and clinical response to antidepressants or cognitive behavioral therapy.     

Fronto-limbic function in unaffected offspring at familial risk for bipolar disorder during an emotional working memory paradigm

Evidence from neuroimaging studies indicate that individuals with bipolar disorder (BD) exhibit altered functioning of fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for BD exhibit such alterations. Using an fMRI emotional working memory paradigm, we investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8–17 years old) with at least one parent diagnosed with BD (HBO), and 16 age-matched healthy control (HC) participants. Neural activity and functional connectivity analyses focused on a priori neural regions supporting emotion processing (amygdala and ventral striatum) and voluntary emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC)). Relative to HC, HBO exhibited greater right VLPFC (BA47) activation in response to positive emotional distracters and reduced VLPFC modulation of the amygdala to both the positive and negative emotional distracters; there were no group differences in connectivity for the neutral distracters. These findings suggest that alterations in the functioning of fronto-limbic systems implicated in voluntary emotion regulation are present in unaffected bipolar offspring. Future longitudinal studies are needed to determine the extent to which such alterations represent neurodevelopmental markers of risk for future onset of BD.     

Decreased prefrontal activation during letter fluency task in adults with pervasive developmental disorders: a near-infrared spectroscopy study

Functional neuroimaging studies have suggested that dysfunction of prefrontal cortex (PFC) is present in persons with pervasive developmental disorders (PDD). Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive bedside measurement of regional cerebral blood volume. Although NIRS enables the noninvasive clarification of brain functions in many psychiatric disorders, it has not yet been used to examine subjects with PDD. The aim of our study was to conduct an NIRS cognitive activation study to verify PFC dysfunction in PDD. The subjects were 10 adults with PDD and 10 age- and gender-matched healthy subjects. Hemoglobin concentration changes were measured with a 24-channel NIRS machine during the letter fluency task. While the number of words generated during the letter fluency task did not differ significantly between groups, the analysis of covariance including IQ as a confounding covariate showed that the PDD group was associated with bilateral reduction in oxy-hemoglobin concentration change as compared with the control group. The statistical results did not change when only IQ-matched high-functioning subjects (N=7) were included. Moreover, reduced oxy-hemoglobin concentration change for the right PFC was significantly correlated with verbal communication deficits within the PDD group. The present findings are consistent with proposed prefrontal dysfunction in PDD subjects identified by other neuroimaging modalities. The present results may be also potentially useful for applying NIRS to clinical settings of child psychiatry.     

Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study.

BACKGROUND: Successful control of affect partly depends on the capacity to modulate negative emotional responses through the use of cognitive strategies. Although the capacity to regulate emotions is critical to mental well-being, its neural substrates remain unclear. METHODS: We used functional magnetic resonance imaging to ascertain brain regions involved in the voluntary regulation of emotion and whether dynamic changes in negative emotional experience can modulate their activation. Fourteen healthy subjects were scanned while they either maintained the negative affect evoked by highly arousing and aversive pictures (e.g., experience naturally) or suppressed their affect using cognitive reappraisal. In addition to a condition-based analysis, online subjective ratings of intensity of negative affect were used as covariates of brain activity. RESULTS: Inhibition of negative affect was associated with activation of dorsal anterior cingulate, dorsal medial prefrontal, and lateral prefrontal cortices, and attenuation of brain activity within limbic regions (e.g., nucleus accumbens/extended amygdala). Furthermore, activity within dorsal anterior cingulate was inversely related to intensity of negative affect, whereas activation of the amygdala was positively covaried with increasing negative affect. CONCLUSIONS: These findings highlight a functional dissociation of corticolimbic brain responses, involving enhanced activation of prefrontal cortex and attenuation of limbic areas, during volitional suppression of negative emotion.