Altered Emotional Processing Research Articles

EN

In healthy individuals, voluntary modification of self-relevance has proven effective in regulating subjective emotional experience as well as physiologic responses evoked by emotive stimuli. As social anxiety disorder (SAD) is characterized by both altered emotional and self-related processing, we tested if emotion regulation through self-focused reappraisal is effective in individuals with SAD. While undergoing 3 T functional magnetic resonance imaging, individuals with SAD and matched healthy controls either passively viewed neutral and aversive pictures or actively increased or decreased their negative emotional experience through the modification of self-relevance or personal distance to aversive pictures. Participants rated all pictures with regard to the intensity of elicited emotions and self-relatedness. We included 21 individuals with SAD and 23 controls in our study. Individuals with SAD reported significantly stronger emotional intensity across conditions and showed a nonsignificant tendency to judge pictures as more self-related than controls. Compared with controls, individuals with SAD showed an overactivation in bilateral temporoparietal regions and in the posterior midcingulate cortex during the passive viewing of aversive compared with neutral pictures. During instructed emotion regulation, activation patterns normalized and no significant group differences were detected. As no positive pictures were presented, results might be limited to the regulation of negative emotion. During passive viewing of aversive images, individuals with SAD showed evidence of neural hyperreactivity that may be interpreted as increased bodily self-consciousness and heightened perspective-taking. During voluntary increase and decrease of negative emotional intensity, group differences disappeared, suggesting self-focused reappraisal as a successful emotion regulation strategy for individuals with SAD.

Aberrant resting‐state functional connectivity in limbic and salience networks in treatment‐naïve clinically depressed adolescents

Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network. Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network). Compared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures. The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.

Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression

Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n=12) both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

Altered emotion processing circuits during the anticipation of emotional stimuli in women with borderline personality disorder

Borderline personality disorder (BPD) is associated with disturbed emotion processing, typically encompassing intense and fast emotional reactions toward affective stimuli. In this study, we were interested in whether emotional dysregulation in BPD occurs not only during the perception of emotional stimuli, but also during the anticipation of upcoming emotional pictures in the absence of concrete stimuli. Eighteen female patients with a diagnosis of BPD and 18 healthy control subjects anticipated cued visual stimuli with prior known emotional valence or prior unknown emotional content during functional magnetic resonance imaging. Brain activity during the anticipation of emotional stimuli was compared between both groups. When anticipating negative pictures, BPD patients demonstrated less signal change in the left dorsal anterior cingulate cortex (dACC) and left middle cingulate cortex (MCC), and enhanced activations in the left pregenual ACC, left posterior cingulate cortex (PCC) as well as in left visual cortical areas including the lingual gyrus. During the anticipation of ambiguously announced stimuli, brain activity in BPD was also reduced in the left MCC extending into the medial and bilateral dorsolateral prefrontal cortex. Results point out that deficient recruitment of brain areas related to cognitive-emotional interaction already during the anticipation phase may add to emotional dysregulation in BPD. Stronger activation of the PCC could correspond to an increased autobiographical reference in BPD. Moreover, increased preparatory visual activity during negative anticipation may contribute to hypersensitivity toward emotional cues in this disorder.

Altered affective processing in bipolar disorder: An fMRI study

BackgroundPrevious studies have reported that patients with bipolar disorder (BPD) exhibit altered emotional processing and regulation. However, results remain largely inconsistent across studies. The aim of the current study was to further examine affective processing in patients with bipolar disorder. MethodsTwenty-three patients diagnosed with BPD (Type I) and 18 healthy matched controls completed a backward-masked affect paradigm while undergoing functional magnetic resonance imaging. Participants also completed a computerized, overt task of facial emotional discrimination after scanning. ResultsResults demonstrated altered affective processing of happy and fearful stimuli in bipolar participants in the amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) relative to controls. BPD participants also displayed significant deficits in identifying fearful facial affect. LimitationsThis study has a moderate sample size, and the patients with BPD were significantly older than the healthy control participants; this did not appear to impact results, and although statistically significant, it is not likely biologically significant. ConclusionsThese findings may have implications for patients with BPD, as altered affective processing could result in deficits in reading social cues.

Negative Emotion Interference During a Synonym Matching Task in Pediatric Bipolar Disorder with and without Attention Deficit Hyperactivity Disorder

This study examined whether processing of emotional words impairs cognitive performance in acutely ill patients with pediatric bipolar disorder (PBD), with or without comorbid attention-deficit hyperactivity disorder (ADHD), relative to healthy controls (HC). Forty youths with PBD without ADHD, 20 youths with PBD and ADHD, and 29 HC (mean age = 12.97 ± 3.13) performed a Synonym Matching task, where they decided which of two probe words was the synonym of a target word. The three words presented on each trial all had the same emotional valence, which could be negative, positive, or neutral. Relative to HC both PBD groups exhibited worse accuracy for emotional words relative to neutral ones. This effect was greater with negative words and observed regardless of whether PBD patients had comorbid ADHD. In the PBD group without ADHD, manic symptoms correlated negatively with accuracy for negative words, and positively with reaction time (RT) for all word types. Our findings suggest a greater disruptive effect of emotional valence in both PBD groups relative to HC, reflecting the adverse effect of altered emotion processing on cognitive function in PBD. Future studies including an ADHD group will help clarify how ADHD symptoms may affect emotional interference independently of PBD.

Detecting emotion in others: increased insula and decreased medial prefrontal cortex activation during emotion processing in elite adventure racers

Understanding the neural processes that characterize elite performers is a first step to develop a neuroscience model that can be used to improve performance in stressful circumstances. Adventure racers are elite athletes that operate in small teams in the context of environmental and physical extremes. In particular, awareness of team member's emotional status is critical to the team's ability to navigate high-magnitude stressors. Thus, this functional magnetic resonance imaging (fMRI) study examined the hypothesis that adventure racers would show altered emotion processing in brain areas that are important for resilience and social awareness. Elite adventure racers (n = 10) were compared with healthy volunteers (n = 12) while performing a simple emotion face-processing (modified Hariri) task during fMRI. Across three types of emotional faces, adventure racers showed greater activation in right insula, left amygdala and dorsal anterior cingulate. Additionally, compared with healthy controls adventure racers showed attenuated right medial prefrontal cortex activation. These results are consistent with previous studies showing elite performers differentially activate neural substrates underlying interoception. Thus, adventure racers differentially deploy brain resources in an effort to recognize and process the internal sensations associated with emotions in others, which could be advantageous for team-based performance under stress.

Associations between serotonin transporter polymorphisms and cognitive processing applying the Emo 1-back task

Down regulation of serotonin transporter (5-HTT) expression has been associated with brain function and major depression. The aim of this study was to explore the allelic variation (short and long) of the 5-HTTLPR polymorphism in attention bias associated with top-down processing of emotion. One hundred sixty-two healthy participants underwent genotyping (5-HTTLPR), background interviews, psychological screening, and a computerised test session (The Emo 1-back task). Carriers of the short 5-HTTLPR alleles in the serotonin transporter gene (SLC6A4) demonstrated less accuracy in The Emo 1-back task when presented with successive images of sad or fearful faces, but not for happy or neutral emotional faces. The study suggests an association between 5-HTTLPR variation in the serotonin transporter gene and altered emotion processing.

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD.

Reduced deactivation in reward circuitry and midline structures during emotion processing in borderline personality disorder

Objectives. Borderline personality disorder (BPD) is characterized by a pervasive affective dysregulation. While recent imaging studies demonstrated the neural correlates of abnormal emotion processing in BPD and recently one study reported alterations of the reward circuit in this patient group, the exact neural mechanisms underlying the impact of abnormal emotion on reward behavior remain unclear. Methods. We therefore conducted an fMRI study in healthy controls and BPD patients to investigate the modulation of the anticipation of reward by simultaneously presented emotional pictures. Results. BPD patients revealed a disturbed differentiation between reward and non-reward anticipation in the bilateral pregenual anterior cingulate cortex if a positive or negative emotional picture is presented simultaneously. In the ventral striatum and the bilateral ventral tegmental area, BPD patients and healthy controls are able to differentiate between reward and non-reward even under emotional stimulation, but BPD patients show a reduced deactivation in the above mentioned regions compared to healthy controls. Conclusions. Altered emotion processing in BPD patients is likely to affect the reward system. More basic deficits in reward circuitry and other midline regions’ level of resting state activity may contribute to this effect.

Neural correlates of altered general emotion processing in social anxiety disorder

Specific anxiety disorders are characterized by altered emotion processing of phobia-specific stimuli at the neurobiological level. Recent work has concentrated on specific anxiety-provoking stimuli; focusing on arousal- or fear-related brain areas such as the amygdala. We analyzed brain activation during the cued anticipation of unpleasant or uncertain emotional stimuli as a means of modeling an unspecific anxiety-laden situation. Sixteen patients with social anxiety disorder (SAD) and eighteen healthy control subjects completed a task during functional magnetic resonance imaging involving the anticipation of cued visual stimuli with prior known emotional valence (positive, negative, and neutral) or prior unknown/ambiguous emotional content. The anticipated stimuli had no social phobia specific content. During the anticipation of emotional stimuli of prior known negative and prior ambiguous emotional valence, brain activity in patients with SAD was increased in the upper midbrain/dorsal thalamus, the amygdala, and in temporo-occipital and parietal regions as compared to control subjects. Activity was decreased in SAD in left orbitofrontal cortex. Activations in the amygdala and in occipital regions correlated with trait anxiety and social anxiety measures. In conclusion, SAD was associated with enhanced activation in brain regions involved in emotional arousal as well as in attention and perception processing during the anticipation of non-specific, general emotional stimuli. Hence, our results suggest that patients with SAD not only have an altered processing of specific feared stimuli, but also a more generally disturbed emotion processing in basic neural pathways. These findings have implications for diagnostic models and the treatment of SAD.

Emotional processing and executive functions in major depressive disorder: dorsal prefrontal activity correlates with performance in the intra-extra dimensional set shift.

Heinzel A, Northoff G, Boeker H, Boesiger P, Grimm S. Emotional processing and executive functions in major depressive disorder: dorsal prefrontal activity correlates with performance in the intra-extra dimensional set shift. Major depressive disorder (MDD) is characterised by predominately negatively valenced emotional symptoms that are often accompanied by cognitive impairments. We posited that cognitive impairments in MDD are related to altered emotional processing in prefrontal cortex. We compared 20 medication-free patients with MDD and 29 matched healthy controls. Both groups performed an emotional task during functional magnetic resonance imaging (fMRI). Furthermore, they completed the intra-extra dimensional set shift (IED) test probing for cognitive impairments. Then we correlated the results of the IED with the changes in fMRI BOLD signal in MDD patients and healthy subjects. The subcategory of the IED applying extradimensional shift (EDS) showed a divergent performance of the MDD group committing significantly more errors than the control group. Correlating the EDS errors with fMRI signal changes, the healthy subjects showed a positive correlation with the right ventrolateral prefrontal cortex and the right orbitofrontal cortex. MDD subjects, in contrast, showed a positive correlation in right dorsolateral prefrontal cortex (DLPFC) and a negative correlation in the left dorsomedial prefrontal cortex (DMPFC). We hypothesise that the differential correlation in healthy controls and MDD patients may reflect the use of different strategies in their performance. The impaired executive functions, as reflected by altered processing in right DLPFC and left DMPFC, may implicitly influence emotional processing in patients suffering from MDD.

Regional Brain Volume in Depression and Anxiety Disorders

Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may have, at least in part, a common etiology. To identify the unique and shared neuroanatomical profile of depression and anxiety, controlling for illness severity, medication use, sex, age of onset, and recurrence. Cross-sectional study. Netherlands Study of Depression and Anxiety. Outpatients with MDD (n = 68), comorbid MDD and anxiety (n = 88), panic disorder, and/or social anxiety disorder without comorbid MDD (n = 68) and healthy controls (n = 65). Volumetric magnetic resonance imaging was conducted for voxel-based morphometry analyses. We tested voxelwise for the effects of diagnosis, age at onset, and recurrence on gray matter density. Post hoc, we studied the effects of use of medication, illness severity, and sex. We demonstrated lower gray matter volumes of the rostral anterior cingulate gyrus extending into the dorsal anterior cingulate gyrus in MDD, comorbid MDD and anxiety, and anxiety disorders without comorbid MDD, independent of illness severity, sex, and medication use. Furthermore, we demonstrated reduced right lateral inferior frontal volumes in MDD and reduced left middle/superior temporal volume in anxiety disorders without comorbid MDD. Also, patients with onset of depression before 18 years of age showed lower volumes of the subgenual prefrontal cortex. Our findings indicate that reduced volume of the rostral-dorsal anterior cingulate gyrus is a generic effect in depression and anxiety disorders, independent of illness severity, medication use, and sex. This generic effect supports the notion of a shared etiology and may reflect a common symptom dimension related to altered emotion processing. Specific involvement of the inferior frontal cortex in MDD and lateral temporal cortex in anxiety disorders without comorbid MDD, on the other hand, may reflect disorder-specific symptom clusters. Early onset of depression is associated with a distinct neuroanatomical profile that may represent a vulnerability marker of depressive disorder.

Effects of Transcranial Direct Current Stimulation on Episodic Memory Related to Emotional Visual Stimuli

The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action.

Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?

The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A 'self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3-6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable?

Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response in anxious depression

Neuropeptide Y (NPY) has been found to play a role in the pathomechanism of both anxiety and depression. Thus, NPY is a promising candidate in the investigation of the clinical phenotype of "anxious depression". Five NPY gene variants were investigated for an influence on antidepressant treatment response in a sample of 256 patients with depression. Additionally, NPY gene impact on amygdala activation during facial emotion processing was analyzed in a subsample of 35 depressed patients. Particularly in anxious depression, the less active NPY rs16147 -399C allele conferred slow response after 2weeks and failure to achieve remission after four weeks of treatment. The rs16147 C allele was further associated with stronger bilateral amygdala activation in response to threatening faces in an allele-dose fashion. The present results point towards a possible influence of functional NPY gene variation on antidepressant treatment response in anxious depression, potentially conveyed by altered emotional processing.

Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression

BackgroundMajor depression (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive amygdala activity and under-recruitment of dorsolateral prefrontal cortex (DLPFC). The purpose of this study was to examine the effects of antidepressant treatment on anomalous neural activity in cognitive-control and emotion-processing circuitry. MethodsFunctional magnetic resonance imaging was conducted on depressed patients (n=23) (both before and after antidepressant treatment) compared with matched controls (n=18) while they performed a cognitive task involving attended and unattended fear-related stimuli. ResultsAfter eight weeks of SSRI antidepressant treatment, patients with depression showed significantly increased DLPFC activity to unattended fear-related stimuli and no longer differed from controls in either DLPFC or amygdala activity. ConclusionsThese results suggest that antidepressant treatment increases DLPFC under-activity during cognitive tasks that include emotional interference. LimitationsThe sample was fairly homogeneous and this may limit generalizability.

Evidence that baroreflex feedback influences long-term incidental visual memory in men

Sympathetic nervous system (SNS) activity at the time of acquisition is associated with human memory. However, rather than SNS activity per se, it may be afferent baroreflex feedback that is responsible for this effect. A pharmacological design was employed to unload (SNP, sodium nitro-prusside) and load (norepinephrine) baroreceptors. In addition to two placebo periods, epinephrine and esmolol (a peripherally acting β1-blocker) served as control conditions for altered cardiac perception. During drug infusion blood pressure, heart rate, and perception of heartbeat were tested. Twenty-four healthy men were participated. The participants viewed emotional slides while their electromyographic eye blink responses to random noise bursts were measured (affective startle modulation paradigm) to determine potential drug impact on emotional processing. Subjects were not informed that memory testing would take place after 4 weeks. Drugs did not impact startle, thus indicating unbiased emotional processing at the time of acquisition. Norepinephrine had no effect on heartbeat perception, but improved ( p = .002) recognition memory. SNP ( p = .0001) increased heartbeat perception but impaired ( p = .038) recognition memory. Epinephrine, on the other hand, increased heartbeat perception ( p = .0001) yet did not impair but partially improve memory (effect on high arousing pictures only: p = .05). Heartbeat perception in the placebo condition did not correlate with recognition memory ( p’s > .5). We suggest that baroreflex unloading, with subsequent feedback activation of the SNS, impairs long-term incidental visual recognition memory in humans while baroreflex loading enhances it. Further, we propose that these memory effects are neither secondary to cardiac sensations that accompany SNS activation nor to altered emotional picture processing at the time of acquisition.

Long-term effects on brain opioid and opioid receptor like-1 receptors after short periods of maternal separation in rats

Short periods of maternal separation of neonatal rats are known to induce attenuated behavioural and neuroendocrine responses to stress in adult life. The present study was carried out to evaluate whether 15 min separation from the dam during postnatal days 1–21 (MS15) can induce long-term changes in brain opioid (κ- and δ-receptors) and opioid receptor-like 1 (ORL1) densities in male Sprague–Dawley rats. Receptor autoradiography indicated that MS15 rats had increased δ-receptor density in the basomedial amygdala compared to animal facility reared rats 2 months after MS15. No differences in brain κ- or ORL1-receptor density were found. The results indicate that a manipulation early in life can induce persistent neurochemical changes in the δ-opioid receptor system, which suggests involvement of δ-opioid receptors in the altered emotional processing in these rats.