The impact of self-distancing on emotion explosiveness and accumulation: An fMRI study.

Emotions unfold over time with episodes differing in explosiveness (i.e., profiles having a steep vs. a gentle start) and accumulation (i.e., profiles increasing over time vs. going back to baseline). In the present fMRI study, we wanted to replicate and extend previous findings on the psychological and neural mechanisms underlying emotion explosiveness and accumulation. Specifically, we aimed to: (a) replicate the finding that different neural mechanisms are associated with emotion explosiveness and accumulation, (b) replicate the finding that adopting a self-distanced (vs. self-immersed) perspective decreases emotion explosiveness and accumulation at the level of self-report, and (c) examine whether adopting a self-distanced (vs. self-immersed) perspective similarly modulates activity in the brain regions associated with emotion explosiveness and accumulation. Participants in an fMRI scanner were asked to adopt a self-immersed or self-distanced perspective while reading and thinking about negative social feedback, and to report on felt changes in negative affect during that period using an emotion intensity profile tracking approach. We replicated previous findings showing that emotion explosiveness and accumulation were related to activity in regions involved in self-referential processing (such as the medial prefrontal cortex) and sustained visceral arousal (such as the posterior insula), respectively. The finding that adopting a self-distanced (vs. self-immersed) perspective lowers emotion explosiveness and accumulation was also replicated at a self-report level. However, perspective taking did not impact activity in the neural correlates of emotion explosiveness and accumulation.

The neural basis of emotions varies over time: different regions go with onset- and offset-bound processes underlying emotion intensity.

According to theories of emotion dynamics, emotions unfold across two phases in which different types of processes come to the fore: emotion onset and emotion offset. Differences in onset-bound processes are reflected by the degree of explosiveness or steepness of the response at onset, and differences in offset-bound processes by the degree of accumulation or intensification of the subsequent response. Whether onset- and offset-bound processes have distinctive neural correlates and, hence, whether the neural basis of emotions varies over time, still remains unknown. In the present fMRI study, we address this question using a recently developed paradigm that allows to disentangle explosiveness and accumulation. Thirty-one participants were exposed to neutral and negative social feedback, and asked to reflect on its contents. Emotional intensity while reading and thinking about the feedback was measured with an intensity profile tracking approach. Using non-negative matrix factorization, the resulting profile data were decomposed in explosiveness and accumulation components, which were subsequently entered as continuous regressors of the BOLD response. It was found that the neural basis of emotion intensity shifts as emotions unfold over time with emotion explosiveness and accumulation having distinctive neural correlates.

Default mode and task-positive networks connectivity during the N-Back task in remitted depressed patients with or without emotional residual symptoms.

Clinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N-Back task. Twenty-six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N-Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N-Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N-Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3-Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491-3501, 2017. © 2017 Wiley Periodicals, Inc.

Antidepressant short-term and long-term brain effects during self-referential processing in major depression.

Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.

The eye of the self: precuneus volume and visual perspective during autobiographical memory retrieval.

Visual perspective (i.e. first-person versus third-person perspective) during autobiographical memory (AM) retrieval plays a role in both emotional regulation and self-related processes. However, its neural underpinnings remain mostly unexplored. Visual perspective during AM retrieval was assessed in two independent datasets of 45 and 20 healthy young adults with two different AM retrieval tasks. Diffeomorphic anatomical registration using exponentiated lie algebra and voxel-based morphometry were used to assess individual differences in the precuneus grey matter volume. The spontaneous tendency to recall memories from a first-person perspective was positively correlated with the right precuneus volume among the two independent datasets. Whole-brain analyses revealed that these results were relatively specific to the anterior part of the right precuneus. Our results provide first evidence for the role of the precuneus in egocentric spatial processing in the context of AM retrieval among healthy subjects.

The dark side of self-focus: brain activity during self-focus in low and high brooders.

There are two distinct modes of self-focus: analytical self-focus is abstract, general and evaluative whereas experiential self-focus is concrete, specific and non-evaluative. Using functional magnetic resonance imaging (fMRI), we investigated the neural bases of these two modes of self-focus in relation with brooding, the maladaptive form of rumination. Forty-one French-speaking right-handed healthy young adults (10 men, mean age ± s.d.: 21.8 ± 2.3 years) engaged in analytical and experiential self-focus triggered by verbal stimuli during fMRI. Brooding was measured with the 22-item Rumination Response Style scale. Individuals with lower brooding scores showed greater activation of the posterior cingulate cortex/precuneus during analytical than experiential self-focus, whereas individuals with higher brooding scores did not. This is consistent with the hypothesis that brooding is associated with less control over the nature of the self-focus engaged. These findings may help to refine our understanding of how rumination promotes depression through maladaptive self-focus.

Medial prefrontal cortex and the self in major depression.

Self-focus (i.e. the process by which one engages oneself in self-referential processing) is a core issue in the psychopathology of major depression. The cortical midline structures, including the medial prefrontal cortex (MPFC), play a key role in self-referential processing in healthy subjects. Four functional magnetic resonance imaging studies recently found either an increased or a decreased MPFC activation during self-referential processing in depressed patients compared to healthy controls. Building on critical differences in experimental settings, we argue that these conflicting results are indeed consistent with two modes of elevated MPFC activation in major depression. An elevated tonic ventral MPFC activation, as uncovered by an event-related design, may embody automatic aspects of depressive self-focus, such as attracting attention to self-relevant incoming information. An elevated phasic dorsal MPFC activation, as uncovered by a block-based design, may embody more strategic aspects of depressive self-focus, such as comparing the self with inner standards. Additionally, strategic self-focus in depression may recruit the anterior cingulate cortex and more lateral regions of the prefrontal cortex. An aberrant functional connectivity of the dorsal MPFC may underlie this lack of reciprocal inhibition between the cognitive control network and the default mode network. Altogether, these results suggest that self-focus in depression may emerge as a process competing for brain resources due to a lack of inhibition of the default mode network, resulting in detrimental effects on externally-oriented cognitive processes. Follow-up studies are warranted to determine the trait vs. state nature of these biomarkers and their ability to predict treatment outcome.

Reciprocal imitation: toward a neural basis of social interaction.

Social interaction is a coregulated coupling activity that involves at least 2 autonomous agents. Numerous methodological and technical challenges impede the production of natural social interaction within an Magnetic Resonance Imaging environment under controlled conditions. To overcome the obstacle, we chose a simple format of social interaction, namely "interactive imitation" through a double-video system. We registered blood oxygen level-dependent activity of 23 participants during 2 imitative conditions: free (F) and instructed (I) episodes of imitating (i) and of being imitated (bi). In addition to the areas classically reported in instructed imitation tasks, 2 activation patterns were found, which differentiate the subconditions. Firstly, brain areas involved during decisional and attentional processes (dorsolateral prefrontal cortex , dorsal part of anterior cingulate gyrus [dACC], pre-SMA) were activated during all conditions except for instructed imitation-classically used in neuroimaging studies of imitation. Second, a greater activation in dACC and insula combined with an increased deactivation in the default mode network was observed when subjects were imitated compared with when they imitated. We suggest that these 2 patterns reflect the anticipation of the other's behavior and the engagement with others required by social interaction.

Different brain structures related to self- and external-agency attribution: a brief review and meta-analysis.

Several neuroimaging studies have consistently shown activations of areas surrounding the temporo-parietal junction (TPJ) during tasks exploring the sense of agency. Beyond TPJ, activations in different structures, such as the dorsolateral prefrontal cortex (dLPFC), the pre-supplementary motor area (pre-SMA), the insula and the precuneus have been reported. Moreover, a possible dissociation between self- and external-agency attribution has been suggested. To test the hypothesis of distinct neural correlates for self- and external-agency attribution a quantitative meta-analysis, based on activation likelihood estimation (ALE) method, across 15 PET and fMRI studies (228 subjects) was conducted. Results show converging activations including the TPJ, pre-SMA, precuneus and dorsomedial prefrontal cortex (dMPFC) in external-agency, while insula activation was related to self-agency. We discuss these findings, highlighting the role of the insula, and calling for the use of alternative paradigms such as intentional binding and interactive imitation to study agency.

Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies.

BACKGROUND: A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). METHODS: A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. RESULTS: Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. LIMITATIONS: The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. CONCLUSIONS: The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks.

Dopaminergic modulation of the default mode network in Parkinson's disease.

Default mode network (DMN) is characterized by a deactivation of several cortical areas (including medial prefrontal cortex and posterior cingulate cortex) during goal-directed experimental tasks. Few findings are reported on DMN and the involvement of dopaminergic medication on this network in Parkinson's disease (PD). To evaluate the effect of levodopa on DMN deactivation, we conducted a randomized, crossover, placebo-controlled experiment consisting of two fMRI assessments in fourteen non-demented, non-depressed PD patients compared to thirteen healthy volunteers. They received either acute doses of levodopa or placebo in two fMRI sessions. Brain deactivation was evaluated during a facial emotion recognition task. While the control subjects showed a classical brain deactivation pattern during the emotional task, the PD patients taking placebo only deactivated the ventral medial prefrontal cortex. Patients failed to deactivate the posterior midline and lateral parts of DMN network. After levodopa administration, this network was restored conjointly with the improvement of motor dysfunction in PD patients. The levodopa effect on DMN is probably the consequence of a beneficial dopamine (DA) medication effect which leads to a fine tuning of the dopamine level in the motor part of striatum, resulting to a global improvement of physical state of PD patients and consequently an increased attentional resource to external stimuli. The absence of medial prefrontal deactivation impairment may suggest a preserved mesocortical DA system in these patients.

Self-referential processing and the prefrontal cortex over the course of depression: a pilot study.

BACKGROUND: Depressed patients exhibit cognitive biases, including maladaptive self-focus. In a previous functional magnetic resonance imaging (fMRI) study, the dorsal medial prefrontal cortex (MPFC) activation during self-referential versus semantic processing was unique to patients, as was the left dorsolateral prefrontal cortex (DLPFC) activation. The aim of this pilot study was to examine whether this pattern was stable over the course of depression. METHODS: Sixteen participants (8 depressed inpatients, 8 healthy controls) viewed personality traits during fMRI and judged whether each trait described them or not ('self' condition), or whether it described a socially desirable trait or not ('general' condition). There were 2 scanning sessions with an interval of at least 6weeks, in which patients received an antidepressant treatment. RESULTS: After a mean duration of 9 weeks, depressed patients displayed a more balanced activation of the left DLPFC but a greater activation of the dorsal MPFC in 'self' versus 'general' condition remained. LIMITATIONS: The small sample size and heterogeneous clinical features prevented subgroups analyses between responders and non-responders. CONCLUSIONS: The change of the left DLPFC activation suggests that antidepressants are associated with a more balanced allocation of cognitive control across self-referential and non-self-referential processes. The apparent lack of effect on the dorsal MPFC activity is consistent with the specific effects of antidepressants versus cognitive behavior therapy (CBT) previously demonstrated in depression. Future studies could examine the relationships between the dorsal MPFC activity in depressed patients and the need to reduce self-focus through CBT to achieve remission and prevent relapse.

Differential patterns of initial and sustained responses in amygdala and cortical regions to emotional stimuli in schizophrenia patients and healthy participants.

BACKGROUND: We sought to investigate the altered brain responses to emotional stimuli in patients with schizophrenia. METHODS: We analyzed data from 14 patients with schizophrenia and 14 healthy controls who performed an emotional face matching task. We evaluated brain activity and connectivity in the amygdala and cortical regions during the initial (first 21 seconds of each stimulation block) and sustained (last 21 seconds) stages of an emotional processing task, and we determined changes in amygdala activity across the emotional processing task. RESULTS: The patients with schizophrenia showed similar amygdala activation to the controls during the initial stage of processing, but their activation decreased during the sustained stage. The controls showed increasing amygdala activity across the emotional blocks, whereas activity progressively decreased in the schizophrenia group. The patients with schizophrenia showed increased cortical activity and interconnectivity in the medial frontal and inferior parietal cortex in the initial stage of emotional processing.There was increased activity in the superior temporal cortex and greater connectivity with the inferior parietal cortex in the sustained stage. Performance accuracy was lower in the schizophrenia group in the first part of the block, while their reaction time was longer in the latter part of the block. LIMITATIONS: It was not possible to specify the moment at which the switch in amygdala response occurred. CONCLUSION: Our findings suggest that patients with schizophrenia have an initial automatic emotional response but that they need to switch to a compensatory cognitive strategy to solve the task.

Dopaminergic modulation of amygdala activity during emotion recognition in patients with Parkinson disease.

Variable findings have been reported for emotional processing in patients with Parkinson disease (PD). These contradictions could be due to differences in the progression of dopamine (DA) depletion. Levodopa treatment could have either beneficial or detrimental effects on brain functions modulated by DA according to disease progression. In healthy subjects, levodopa administration leads to a decreased amygdala activation in response to emotional tasks. Because it is known that there is a link between DA loss in mesolimbic system and depression, we hypothesized that PD patients without depression would have spared limbic DA projections. Consequently, levodopa medication could overdose limbic regions relative to severe dorsal striatal denervation. To evaluate the effect of levodopa on amygdala activation, we conducted a functional magnetic resonance imaging study in nondemented, nondepressed PD patients compared with healthy volunteers. Patients with PD and healthy subjects received either levodopa or placebo in 2 functional magnetic resonance imaging sessions. Amygdala activation was evaluated during a facial emotion recognition task. A similar right-amygdala activity was seen in both healthy subjects and PD patients in the placebo session. After levodopa administration, activity was reduced in both groups. In the patients, the levodopa dose used significantly improved motor dysfunction. Nondemented, nondepressed PD patients thus seem to have relatively preserved DA mesolimbic projections, and consequently, the same dose of levodopa needed to correct the lack of DA in the severely depleted putamen (motor part of striatum) would incidentally overdose the mesolimbic projections toward the amygdala.

Neural bases of different cognitive strategies for facial affect processing in schizophrenia.

OBJECTIVE: To examine the neural basis and dynamics of facial affect processing in schizophrenic patients as compared to healthy controls. METHOD: Fourteen schizophrenic patients and fourteen matched controls performed a facial affect identification task during fMRI acquisition. The emotional task included an intuitive emotional condition (matching emotional faces) and a more cognitively demanding condition (labeling emotional faces). Individual analysis for each emotional condition, and second-level t-tests examining both within-, and between-group differences, were carried out using a random effects approach. Psychophysiological interactions (PPI) were tested for variations in functional connectivity between amygdala and other brain regions as a function of changes in experimental conditions (labeling versus matching). RESULTS: During the labeling condition, both groups engaged similar networks. During the matching condition, schizophrenics failed to activate regions of the limbic system implicated in the automatic processing of emotions. PPI revealed an inverse functional connectivity between prefrontal regions and the left amygdala in healthy volunteers but there was no such change in patients. Furthermore, during the matching condition, and compared to controls, patients showed decreased activation of regions involved in holistic face processing (fusiform gyrus) and increased activation of regions associated with feature analysis (inferior parietal cortex, left middle temporal lobe, right precuneus). CONCLUSIONS: Our findings suggest that schizophrenic patients invariably adopt a cognitive approach when identifying facial affect. The distributed neocortical network observed during the intuitive condition indicates that patients may resort to feature-based, rather than configuration-based, processing and may constitute a compensatory strategy for limbic dysfunction.

Amygdala activation modulated by levodopa during emotional recognition processing in healthy volunteers: a double-blind, placebo-controlled study.

A critical role of dopaminergic systems in emotional processing has been revealed by several animal and clinical studies in Parkinson disease and schizophrenia. We conducted a study with functional magnetic resonance imaging (fMRI) in 13 healthy volunteers to test the dopaminergic modulation on amygdala response to emotional processing and to evaluate if it was the result of a direct action on amygdalar nuclei or indirect modulation via medial prefrontal cortex projecting on amygdala.A placebo-controlled crossover experimental design was used. Subjects received either levodopa (100 mg) or placebo in 2 fMRI sessions. Amygdala activation was evaluated during a facial emotion recognition test.The statistical comparison between placebo versus levodopa situations revealed a significant reduction in activation of right amygdala during the levodopa fMRI session. The functional connectivity analysis revealed only a change of correlated activations between right and left amygdala, and not medial prefrontal cortex, after levodopa administration. Our results suggest that administration of levodopa to healthy volunteers impairs the amygdalar activation. It supports the hypothesis that amygdala activation follows an inverted U-shaped curve in relation to dopamine (DA) concentration. The results of the functional connectivity seem to suggest a dopaminergic action on amygdalar nuclei rather than a modulation of medial prefrontal cortex on amygdala.

Brain T1 intensity changes after levodopa administration in healthy subjects: a voxel-based morphometry study.

AIM: To test T1 intensity variations induced by levodopa administration in the regional fixation area in the human brain. METHOD: Using non-invasive magnetic resonance imaging (MRI) technique [T1-weighted sequence MPRAGE; TE/TR/TI = 5/25/800 ms; impulsion angle = 15 degrees; field of view = 256 x 230 x 180 mm3; acquisition matrix = 256 x 192 x 104; reconstruction matrix = 256 x 256 x 128), we tested changes in the T1 MRI signal intensity resulting in changes in the grey matter automatic classification after administration of a single dose of 100 mg of levodopa by a voxel-based morphometry method (VBM) in 12 healthy subjects. RESULTS: The VBM analysis demonstrated an increased number of voxels attributed to grey matter after levodopa administration in an anatomical cluster which included substantia nigra, tegmental ventral area and subthalamic nucleus bilaterally, the principal origin and first relay nuclei of projections in brain dopaminergic systems (t = 8.61; corrected for all grey matter volume P < 0.001). CONCLUSION: Our results suggest that levodopa administration could induce an MRI T1 signal intensity variation that is not evident to the naked eye, but is detectable by measuring local signal intensities. Possible clinical applications are discussed.

Effects of antidepressant drugs on emotion.

Until recently, scant attention has been paid to the effect of antidepressant drugs on emotion, and we have little knowledge about the way antidepressant drugs modulate neural processing of emotional and affective information, or their relationship to mood changes. Numerous behavioral studies have examined the impact of depression on the recognition of facial expressions. Although conflicting results have been obtained, depressive patients seem to attribute a different emotional valence to these stimuli than do control subjects. Recent studies have shown that a single dose of an antidepressant can increase the processing of positively versus negatively valenced material in nondepressed volunteers. Such psychopharmacological effects may ameliorate the negative biases that characterize mood disorders. Antidepressants may therefore work in a manner comparable with that of psychologic treatments that aim to redress negative biases in information processing. Studies with functional neuroimaging also show that emotional processes are dependent upon a variety of structures; most which form part of the limbic system and are altered in depression. Other studies have demonstrated changes in these structures during antidepressant treatment, mainly in the amygdala. Future research should attempt to explain, for example, the implications of changes in early emotional processing on mood and remission of depression, and the differences between acute and chronic treatment.

Effect of levodopa on healthy volunteers' facial emotion perception: an FMRI study.

OBJECTIVE: A link between the brain dopaminergic (DA) system and emotional processing seems to be supported by the DA nature of neural systems surrounding emotional recognition, the occurrence of emotional deficits in medical disorders involving a DA dysfunction, and the effect of DA agonists or antagonists on emotional processing. The authors tested the influence of levodopa administration on emotional processing in a functional MRI (fMRI) study of 10 elderly volunteers. METHODS: A placebo-controlled, cross-over experimental design was used. Subjects received either levodopa (100 mg) or placebo in 2 fMRI sessions. Performance was evaluated with a passive facial emotion perception test. RESULTS: During the placebo situation, the region-of-interest (ROI) analysis showed that emotional processing activated the bilateral amygdala. In levodopa volunteers, this activation was missing. The statistical comparison between the 2 situations (emotional vs control condition) revealed a highly significant reduction in activation of the bilateral amygdala for the levodopa fMRI session (P corrected <0.0001 in the left and P = 0.002 in the right amygdala). CONCLUSION: These results suggest that administration of levodopa to healthy volunteers directly or indirectly impairs the amygdalar activation during the emotional perception task. The authors hypothesized that amygdala activation may conform to an inverted U-shaped function in relation to changing dopamine levels.