Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies.
ABSTRACT Although amygdala activity has been purported to be modulated by affective and non-affective factors, considerable controversy remains on its precise functional nature. We conducted a meta-analysis of 385 functional neuroimaging studies of emotional processing, examining the effects of experimental characteristics on the probability of detecting amygdala activity. All emotional stimuli were associated with higher probability of amygdala activity than neutral stimuli. Comparable effects were observed for most negative and positive emotions, however there was a higher probability of activation for fear and disgust relative to happiness. The level of attentional processing affected amygdala activity, as passive processing was associated with a higher probability of activation than active task instructions. Gustatory-olfactory and visual stimulus modalities increased the probability of activation relative to internal stimuli. Aversive learning increased the probability of amygdala activation as well. There was some evidence of hemispheric specialization with a relative left-lateralization for stimuli containing language and a relative right-lateralization for masked stimuli. Methodological variables, such as type of analysis and magnet strength, were also independent predictors of amygdala activation.
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ABSTRACT: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI. A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response. Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation. Registered at clinicaltrials.gov ( NCT01051466 ).BMC Psychiatry 04/2015; 15(1):82. DOI:10.1186/s12888-015-0457-2 · 2.24 Impact Factor
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ABSTRACT: Although the cost of poor treatment outcomes of depression is staggering we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in MDD and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with major depressive disorder (MDD) in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. 80 MDD outpatients were scanned pre-treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin- norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level–dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by >=50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (cohen’s d effect size .63 to .77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward “normalization” post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (cohen’s d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity which progressed to hypo-reactivity rather than normalization post-treatment and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general versus differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin- norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.Neuropsychopharmacology 03/2015; DOI:10.1038 /npp.2015.89 · 7.83 Impact Factor
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ABSTRACT: Reading is a complex higher-order cognitive activity unique to human beings, which transmits the sense, feeling, tone, and intention of the writer and brings pleasures. However, the neurocognitive aspects of emotion processing in literary reading are still hardly understood. This dissertation aims to investigate the affective processing mechanisms during literary reading. The neurocognitive poetics model of literary reading by Jacobs (2011, 2014) is referred to as guidance for the author to pose relevant research questions and to test key assumptions of the model. The foci of this dissertation include the lexical, inter-lexical level, and supra-lexical level. For this dissertation, an fMRI experiments were conducted, in which 120 text passages from the Harry Potter book series were presented. The passages presented contained three orthogonal factorial dimensions: Emotion, Supra-naturalness, and Language (L1 vs. L2). Chapter 2 investigates the emotion potential of single words in reading. Results showed significant correlations between affective lexical variables, passage ratings, as well as activity in regions associated with emotion, situation model building, multi-modal semantic integration, and Theory of Mind, suggesting that the emotion potential of texts can be predicted by lexical and inter-lexical affective variables. Chapter 3 investigates the neural correlates of the immersion reading experience. Immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than neutral pas-sages. The results suggest that negatively valenced contents activate the affective empathy network and facilitate the immersive reading experience. Chapter 4 investigates the effect of world-knowledge violation during situation model construction. Readers assigned passages in the supra-natural condition significantly higher scores on dimensions of supra-naturalness, surprise, and reading pleasure. Neural correlates of reading supra-natural vs. neutral contents include neural correlates associated with world-knowledge integration, the salience network, emotion processing, and attention. Finally, the author investigated whether there is any quantitative or qualitative difference in emotion processing when reading in L1 vs. L2 at the neuronal level. At the behavioral and factorial fMRI results showed stronger perceived emotionality in L1 than in L2. Furthermore, MVPA results reading literature in L1 seems to provide a more differentiated emotional experience. Results of the present thesis supported the emotion potential of word recognition, fiction feelings, and the world knowledge violation in the neurocognitive poetics model. Furthermore, the salience, extended language, and ToM networks are extensively involved in the emotion processing in literary reading. Future studies on emotion processing in literary reading will benefit from this dissertation to develop more specific neuroscientific hypotheses on the causal relationships and interactions between different neural networks with more sophisticated methods, potentially applying such approaches to cross-linguistic/cultural studies.01/2015, Degree: Dr. phil. in Psychology, Supervisor: Arthur Jacobs