抑郁症患者情绪图片反应特征及杏仁核反应模式的研究

目的 探讨抑郁症患者对情感刺激的行为学反应模式及其相关的杏仁核时程反应过程.方法 12例首次发病、未经治疗的抑郁症患者(抑郁症组)和13名健康个体(健康对照组)对观看正性、中性和负性情绪图片的愉悦度等评分;并在被动注视任务下行功能磁共振成像,采用感兴趣区分析方法,比较两组杏仁核在不同情绪图片任务组块间的血氧水平依赖(BOLD)信号时间反应特征.结果 (1)抑郁症组情绪图片愉悦度评分[正性:(6.6 ±0.2)分;中性:(4.7 ±0.1)分]低于健康对照组[分别为(7.7 ±0.2)分和(5.1 ±0.1)分],负性情绪图片评分[(3.4 ±0.3)分]高于健康对照组[(2.2 ±0.2)分;P<0.01].(2)对正性情绪图片任务,两组间右侧杏仁核存在"组×时间"交互作用(P=0.002);抑郁症组杏仁核BOLD信号变化率为(0.02±0.09)%,激活时间后移至Block 2.对负性情绪图片任务,两组间左侧杏仁核有"组×时间"交互作用(P=0.008),右侧杏仁核存在组主效应(P=0.007)和时间主效应(P=0.016),抑郁症组BOLD信号变化率低于(-0.06 ±0.14)%.结论 杏仁核是抑郁症患者丧失愉悦体验和情绪低落的神经基础之一.     

Attentional modulation of emotional stimulus processing: an fMRI study using emotional expectancy

We used emotional expectancy to study attentional modulation in the processing of emotional stimuli. During functional magnetic resonance imaging (fMRI), volunteers saw emotional and neutral expectancy cues signaling the subsequent presentation of corresponding emotional or neutral pictorial stimuli. As a control, emotional and neutral pictures were presented without preceding expectancy cue, resulting in a 2 x 2 factorial design with the factors "expectancy" and "emotion." Statistical analysis revealed a significant positive interaction effect between these factors in the medial prefrontal cortex (MPFC, Brodmann area [BA] 9/10), amygdala, and dorsal midbrain. In all these regions, expectancy augmented the neural response to emotional but not to neutral pictures. Time course analysis of raw data suggests that this augmented activation was not preceded by baseline increases in MPFC and amygdala during the period of emotional expectancy. In a post-scanning session, the paradigm was presented for a second time to allow emotional intensity rating. Again, a significant interaction between expectancy and emotion was observed, with intensity ratings specifically enhanced in emotional photographs preceded by expectancy. There was a positive correlation between intensity ratings and blood oxygenation level-dependent (BOLD) signals in the left amygdala. We conclude that specific components of the emotion network show enhanced activation in response to emotional stimuli when these are preceded by expectancy. This enhancement effect is not present in neutral pictures and might parallel accentuated subjective feeling states.     

Stimulus novelty and emotion perception: the near absence of habituation in the visual cortex

In rapid serial visual presentation of pictures, an early event-related brain potential component shows enlarged negativity over occipital regions for emotional pictures compared with neutral pictures. The present study examined whether the processing of emotional target pictures varies as a function of stimulus repetition. Accordingly, pictures of erotica, neutral contents, and mutilations were repeatedly presented (90 times) while the electroencephalogram was recorded with a 129 dense sensor array. As in previous studies, emotional pictures were associated with a larger posterior negativity than neutral pictures. Furthermore, differential emotion processing did not vary as a function of stimulus repetition and was similarly expressed across blocks of picture presentation. These findings suggest the near absence of habituation in differential emotion processing during perceptual processing.     

Amygdalar activation associated with positive and negative facial expressions

Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.     

Startle reflex hyporeactivity in Parkinson's disease: An emotion-specific or arousal-modulated deficit?

We previously reported that patients with Parkinson's disease (PD) demonstrate reduced psychophysiologic reactivity to unpleasant pictures as indexed by diminished startle eyeblink magnitude [Bowers, D., Miller, K., Bosch, W., Gokcay, D., Pedraza, O., Springer, U., et al. (2006). Faces of emotion in Parkinsons disease: Micro-expressivity and bradykinesia during voluntary facial expressions. Journal of the International Neuropsychological Society, 12(6), 765–773; Bowers, D., Miller, K., Mikos, A., Kirsch-Darrow, L., Springer, U., Fernandez, H., et al. (2006). Startling facts about emotion in Parkinson's disease: Blunted reactivity to aversive stimuli. Brain, 129(Pt 12), 3356–3365]. In the present study, we tested the hypothesis that this hyporeactivity was primarily driven by diminished reactivity to fear-eliciting stimuli as opposed to other types of aversive pictures. This hypothesis was based on previous evidence suggesting amygdalar abnormalities in PD patients, coupled with the known role of the amygdala in fear processing. To test this hypothesis, 24 patients with Parkinson's disease and 24 controls viewed standardized sets of emotional pictures that depicted fear, disgust (mutilations, contaminations), pleasant, and neutral contents. Startle eyeblinks were elicited while subjects viewed these emotional pictures. Results did not support the hypothesis of a specific emotional reactivity deficit to fear pictures. Instead, the PD patients showed reduced reactivity to mutilation pictures relative to other types of negative pictures in the context of normal subjective ratings. Further analyses revealed that controls displayed a pattern of increased startle eyeblink magnitude for “high arousal” versus “low arousal” negative pictures, regardless of picture category, whereas startle eyeblink magnitude in the PD group did not vary by arousal level. These results suggest that previous findings of decreased aversion-modulated startle is driven by reduced reactivity to highly arousing negative stimuli rather than to a specific category (i.e., fear or disgust) of emotion stimuli.     

Amygdala response to both positively and negatively valenced stimuli

Human lesion and functional imaging data suggest a central role for the amygdala in the processing of negative stimuli. To determine whether the amygdala's role in affective processing extends beyond negative stimuli, subjects viewed pictures that varied in emotional content (positive vs negative valence) and arousal level (high vs low) while undergoing functional magnetic resonance imaging. Amygdala activation, relative to a low arousal and neutral valence picture baseline, was significantly increased for both positively and negatively valenced stimuli and did not differ for the two valences. There were no laterality effects. Whereas arousal level appeared to modulate the amygdala response for negative stimuli, all positively valenced pictures (both high and low in arousal) produced significant amygdala responses. These results clearly demonstrate a role for the amygdala in processing emotional stimuli that extends beyond negative and fearful stimuli.     

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.     

Amygdalar function reflects common individual differences in emotion and pain regulation success

Although the co-occurrence of negative affect and pain is well recognized, the mechanism underlying their association is unclear. To examine whether a common self-regulatory ability impacts the experience of both emotion and pain, we integrated neuroimaging, behavioral, and physiological measures obtained from three assessments separated by substantial temporal intervals. Our results demonstrated that individual differences in emotion regulation ability, as indexed by an objective measure of emotional state, corrugator electromyography, predicted self-reported success while regulating pain. In both emotion and pain paradigms, the amygdala reflected regulatory success. Notably, we found that greater emotion regulation success was associated with greater change of amygdalar activity following pain regulation. Furthermore, individual differences in degree of amygdalar change following emotion regulation were a strong predictor of pain regulation success, as well as of the degree of amygdalar engagement following pain regulation. These findings suggest that common individual differences in emotion and pain regulatory success are reflected in a neural structure known to contribute to appraisal processes.     

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.     

Abnormal neural responses to emotional visual stimuli in adolescents with conduct disorder.

BACKGROUND: It is widely held that aggression and antisocial behavior arise as a consequence of a deficiency in responding to emotional cues in the social environment. We asked whether neural responses evoked by affect-laden pictures would be abnormal in adolescents with conduct disorder (CD). METHODS: Functional magnetic resonance imaging during passive viewing of pictures with neutral or strong negative affective valence was performed in 13 male adolescents with severe CD aged 9 to 15 years and in 14 healthy age-matched control subjects. RESULTS: Main effects for negative-neutral affective valence included activations in the amygdala and hippocampus, ventral extrastriate visual cortex, and intraparietal sulcus bilaterally. There was a significant group-by-condition interaction in the right dorsal anterior cingulate cortex that was due to a pronounced deactivation in the patient group during viewing of negative pictures. When correcting for anxiety and depressive symptoms, we additionally found a reduced responsiveness of the left amygdala to negative pictures in patients compared with control subjects. CONCLUSIONS: We suggest that these findings reflect an impairment of both the recognition of emotional stimuli and the cognitive control of emotional behavior in patients with CD, resulting in a propensity for aggressive behavior.     

A preliminary study of increased amygdala activation to positive affective stimuli in mania

Objectives:  The present study in hypomanic and manic patients explored how amygdala responses to affective stimuli depend on the valence of the stimuli presented.
Methods:  We compared 10 patients with 10 matched healthy control subjects. We measured blood oxygen level-dependent (BOLD) responses in the amygdala while subjects passively viewed photographs taken from the International Affective Picture System. After the fMRI session, subjects saw the pictures again and subjectively rated the emotional valence and intensity of each picture.
Results:  Compared to healthy individuals, hypomanic or manic patients showed higher valence ratings in positive pictures and associated larger BOLD responses in the left amygdala during positive versus neutral picture viewing. This enhanced amygdala activation was correlated with Young Mania Rating Scale scores and with euphoric as opposed to irritable symptom presentation.
Conclusions:  Increased valence ratings and amygdala responses to positive affective stimuli may reflect a positive processing bias contributing to elevated mood states characteristic for euphoric mania.     

Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety

Background

Previous functional imaging studies demonstrating amygdala response to happy facial expressions have all included the presentation of negatively valenced primary comparison expressions within the experimental context. This study assessed amygdala response to happy and neutral facial expressions in an experimental paradigm devoid of primary negatively valenced comparison expressions.

Methods

Sixteen human subjects (eight female) viewed 16-sec blocks of alternating happy and neutral faces interleaved with a baseline fixation condition during two functional magnetic resonance imaging scans.

Results

Within the ventral amygdala, a negative correlation between happy versus neutral signal changes and state anxiety was observed. The majority of the variability associated with this effect was explained by a positive relationship between state anxiety and signal change to neutral faces.

Conclusions

Interpretation of amygdala responses to facial expressions of emotion will be influenced by considering the contribution of each constituent condition within a greater subtractive finding, as well as 1) their spatial location within the amygdaloid complex; and 2) the experimental context in which they were observed. Here, an observed relationship between state anxiety and ventral amygdala response to happy versus neutral faces was explained by response to neutral faces.     

Neural correlates of positive and negative emotion regulation

The ability to cope adaptively with emotional events by volitionally altering one's emotional reactions is important for psychological and physical health as well as social interaction. Cognitive regulation of emotional responses to aversive events engages prefrontal regions that modulate activity in emotion-processing regions such as the amygdala. However, the neural correlates of the regulation of positive emotions remain largely unexplored. We used event-related functional magnetic resonance imaging to examine the neural correlates of cognitively increasing and decreasing emotional reactions to positive and negative stimuli. Participants viewed negative, positive, and neutral pictures while attempting to increase, decrease, or not alter their emotional reactions. Subjective reactions were assessed via on-line ratings. Consistent with previous studies, increasing negative and positive emotion engaged primarily left-lateralized prefrontal regions, whereas decreasing emotion activated bilateral prefrontal regions. Different activations unique to increasing versus decreasing emotion were observed for positive and negative stimuli: Unique increase-related activations were observed only for positive stimuli, whereas unique decrease-related activations were observed only for negative stimuli. Regulation also modulated activity in the amygdala, a key emotion-processing region. Regulation effects on amygdala activity were larger for positive than for negative stimuli, potentially reflecting a greater malleability of positive emotional reactions. Increasing and decreasing positive and negative emotion can thus increase and decrease subjective reactions and associated amygdala activity in line with regulatory goals, and is associated with different patterns of prefrontal activation as a function of emotional valence and regulatory goal.     

Eye-catching: right hemisphere attentional bias for emotional pictures

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

Eye-catching: Right hemisphere attentional bias for emotional pictures

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

Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study

Disruption of facial emotion perception occurs in neuropsychiatric disorders where the expression of emotion is dulled or blunted, for example depersonalization disorder and schizophrenia. It has been suggested that, in the clinical context of emotional blunting, there is a shift in the relative contribution of brain regions subserving cognitive and emotional processing. The non-competitive glutamate receptor antagonist ketamine produces such emotional blunting in healthy subjects. Therefore, we hypothesised that in healthy subjects ketamine would elicit neural responses to emotional stimuli which mimicked those reported in depersonalization disorder and schizophrenia. Thus, we predicted that ketamine would produce reduced activity in limbic and visual brain regions involved in emotion processing, and increased activity in dorsal regions of the prefrontal cortex and cingulate gyrus, both associated with cognitive processing and, putatively, with emotion regulation. Measuring BOLD signal change in fMRI, we examined the neural correlates of ketamine-induced emotional blunting in eight young right-handed healthy men receiving an infusion of ketamine or saline placebo while viewing alternating 30 s blocks of faces displaying fear versus neutral expressions. The normal pattern of neural response occurred in limbic and visual cortex to fearful faces during the placebo infusion. Ketamine abolished this: significant BOLD signal change was demonstrated only in left visual cortex. However, with ketamine, neural responses were demonstrated to neutral expressions in visual cortex, cerebellum and left posterior cingulate gyrus. Emotional blunting may be associated with reduced limbic responses to emotional stimuli and a relative increase in the visual cortical response to neutral stimuli.     

Negative content enhances stimulus‐specific cerebral activity during free viewing of pictures,faces, and words

Negative visual stimuli have been found to elicit stronger brain activation than do neutral stimuli. Such emotion effects have been shown for pictures, faces, and words alike, but the literature suggests stimulus‐specific differences regarding locus and lateralization of the activity. In the current functional magnetic resonance imaging study, we directly compared brain responses to passively viewed negative and neutral pictures of complex scenes, faces, and words (nouns) in 43 healthy participants (21 males) varying in age and demographic background. Both negative pictures and faces activated the extrastriate visual cortices of both hemispheres more strongly than neutral ones, but effects were larger and extended more dorsally for pictures, whereas negative faces additionally activated the superior temporal sulci. Negative words differentially activated typical higher‐level language processing areas such as the left inferior frontal and angular gyrus. There were small emotion effects in the amygdala for faces and words, which were both lateralized to the left hemisphere. Although pictures elicited overall the strongest amygdala activity, amygdala response to negative pictures was not significantly stronger than to neutral ones. Across stimulus types, emotion effects converged in the left anterior insula. No gender effects were apparent, but age had a small, stimulus‐specific impact on emotion processing. Our study specifies similarities and differences in effects of negative emotional content on the processing of different types of stimuli, indicating that brain response to negative stimuli is specifically enhanced in areas involved in processing of the respective stimulus type in general and converges across stimuli in the left anterior insula.     

Age-related differences in the medial temporal lobe responses to emotional faces as revealed by fMRI

Age-related differences involved in the neural substrates of emotional face perception were investigated in young and old healthy volunteers. The subjects were scanned using functional magnetic resonance imaging while they were judging the gender of faces with negative, positive, or neutral emotional valence. The results showed that both the predominant activation in young subjects and reduced activity in old subjects contributed to a significant age difference in the left amygdala during the perception of negative faces. Activity in the right parahippocampal gyrus during the perception of positive faces diminished with advancing age. Neural activity in the angular gyrus and lingual gyrus of the right hemisphere was reduced in the old subjects during the perception of positive faces. There was no region where old subjects had greater activity than young subjects during the task. In old subjects, the overall activity in the right hippocampus during the task correlated negatively with age, whereas the activity in the right parahippocampal gyrus correlated positively with neuropsychological performance. There was no significant correlation between subjects' characteristics and signal change in young subjects. These results indicate the age-associated vulnerability of the medial temporal lobe structures including the amygdala, hippocampus, and parahippocampal gyrus during face perception. The dissociation with reduced activity in the left amygdala and the right parahippocampal gyrus may suggest that aging differentially affects neural responses to faces with negative or positive emotional valence. The parieto-occipital lobe, which has been found to be involved in face processing, also showed a functional decline associated with aging.     

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.