Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study

Background

Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict.

Methods

Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach.

Results

Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network.

Conclusions

Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.     

Neural chaos and schizophrenia

Recent data indicate that random-like processes are related to the defects in the organization of semantic memory in schizophrenia which is more disorganized and less definable than those of controls with more semantic links and more bizarre and atypical associations. These aspects of schizophrenic cognition are similar to characteristics of chaotic nonlinear dynamical systems. In this context, the hypothesis tested in this study is that dynamic changes of electrodermal activity (EDA) as a measure of brain and autonomic activity may serve as a characteristic which can be used as an indicator of possible neural chaotic process in schizophrenia. In the present study, bilateral EDA in rest conditions were measured in 40 schizophrenic patients and 40 healthy subjects. Results of nonlinear and statistical analysis indicate left-side significant differences of positive largest Lyapunov exponents in schizophrenia patients compared to the control group. This might be interpreted that the neural activity during rest in schizophrenic patients is significantly more chaotic than in the control group. The relationship was confirmed by surrogate data testing. These data suggest that increased neural chaos in patients with schizophrenia may influence brain processes that can cause random-like disorganization of mental processes.     

Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity

Objective:

An important endeavor involves increasing our understanding of biobehavioral processes underlying different types of obesity. The current study investigated the neural correlates of cognitive control (involving conflict monitoring and response inhibition) in obese individuals with binge eating disorder (BED) as compared to BMI‐matched non‐BED obese (OB) individuals and lean comparison (LC) participants. Alterations in cognitive control may contribute to differences in behavioral control over eating behaviors in BED and obesity.

Design and Methods:

Participants underwent functional magnetic resonance imaging while completing the Stroop color‐word interference task.

Results and Conclusions:

Relative to the OB and LC groups, activity in the BED group was differentiated by relative hypoactivity in brain areas involved in self‐regulation and impulse control. Specifically, the BED group showed diminished activity in the ventromedial prefrontal cortex (vmPFC), inferior frontal gyrus (IFG), and insula during Stroop performance. In addition, dietary restraint scores were negatively correlated with right IFG and vmPFC activation in the BED group, but not in the OB or HC groups. Thus, BED individuals' diminished ability to recruit impulse‐control‐related brain regions appears associated with impaired dietary restraint. The observed differences in neural correlates of inhibitory processing in BED relative to OB and LC groups suggest distinct eurobiological contributions to binge eating as a subgroup of obese individuals.     

Unstable Prefrontal Response to Emotional Conflict and Activation of Lower Limbic Structures and Brainstem in Remitted Panic Disorder

Background

The neural mechanisms of panic disorder (PD) are only incompletely understood. Higher sensitivity of patients to unspecific fear cues and similarities to conditioned fear suggest involvement of lower limbic and brainstem structures. We investigated if emotion perception is altered in remitted PD as a trait feature.

Methodology/Principal Findings

We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study neural and behavioural responses of 18 remitted PD patients and 18 healthy subjects to the emotional conflict paradigm that is based on the presentation of emotionally congruent and incongruent face/word pairs. We observed that patients showed stronger behavioural interference and lower adaptation to interference conflict. Overall performance in patients was slower but not less accurate. In the context of preceding congruence, stronger dorsal anterior cingulate cortex (dACC) activation during conflict detection was found in patients. In the context of preceding incongruence, controls expanded dACC activity and succeeded in reducing behavioural interference. In contrast, patients demonstrated a dropout of dACC and dorsomedial prefrontal cortex (dmPFC) recruitment but activation of the lower limbic areas (including right amygdala) and brainstem.

Conclusions/Significance

This study provides evidence that stimulus order in the presentation of emotional stimuli has a markedly larger influence on the brain''s response in remitted PD than in controls, leading to abnormal responses of the dACC/dmPFC and lower limbic structures (including the amygdala) and brainstem. Processing of non-panic related emotional stimuli is disturbed in PD patients despite clinical remission.     

Epileptiform activity in alcohol dependent patients and possibilities of its indirect measurement

Background

Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms.

Methods and Findings

We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p<0.01).

Conclusions

The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients.     

Trial history effects in stroop task performance are independent of top-down control

In this study we sought to elucidate what mechanisms underlie the effects of trial history on information processing. We explicitly focused on the contribution of conflict control and S-R binding to sequential trial effects. Performance and brain activity were measured during two hours of continuous Stroop task performance. Mental fatigue, known to influence top-down processing, was used to elucidate separate effects via top-down and bottom-up mechanisms. Here we confirm that performance in the Stroop task is indeed strongly modulated by stimulus history. Performance was affected by the kind of advance information available; dependent on this information adjustments were made, resulting in differential effects of cognitive conflict, and S-R binding on subsequent performance. The influence of mental fatigue on information processing was mainly related to general effects on attention.     

Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala

Effective mental functioning requires that cognition be protected from emotional conflict due to interference by task-irrelevant emotionally salient stimuli. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Drawing on the classic Stroop conflict task, we developed a protocol that allowed us to dissociate the generation and monitoring of emotional conflict from its resolution. Using functional magnetic resonance imaging (fMRI), we find that activity in the amygdala and dorsomedial and dorsolateral prefrontal cortices reflects the amount of emotional conflict. By contrast, the resolution of emotional conflict is associated with activation of the rostral anterior cingulate cortex. Activation of the rostral cingulate is predicted by the amount of previous-trial conflict-related neural activity and is accompanied by a simultaneous and correlated reduction of amygdalar activity. These data suggest that emotional conflict is resolved through top-down inhibition of amygdalar activity by the rostral cingulate cortex.     

Spontaneous eyeblinks are correlated with responses during the Stroop task

The timing and frequency of spontaneous eyeblinking is thought to be influenced by ongoing internal cognitive or neurophysiological processes, but how precisely these processes influence the dynamics of eyeblinking is still unclear. This study aimed to better understand the functional role of eyeblinking during cognitive processes by investigating the temporal pattern of eyeblinks during the performance of attentional tasks. The timing of spontaneous eyeblinks was recorded from 28 healthy subjects during the performance of both visual and auditory versions of the Stroop task, and the temporal distributions of eyeblinks were estimated in relation to the timing of stimulus presentation and vocal response during the tasks. We found that the spontaneous eyeblink rate increased during Stroop task performance compared with the resting rate. Importantly, the subjects (17/28 during the visual Stroop, 20/28 during the auditory Stroop) were more likely to blink before a vocal response in both tasks (150-250 msec) and the remaining subjects were more likely to blink soon after the vocal response (200-300 msec), regardless of the stimulus type (congruent or incongruent) or task difficulty. These findings show that spontaneous eyeblinks are closely associated with responses during the performance of the Stroop task on a short time scale and suggest that spontaneous eyeblinks likely signal a shift in the internal cognitive or attentional state of the subjects.     

Change in Body Fat Mass Is Independently Associated with Executive Functions in Older Women: A Secondary Analysis of a 12-Month Randomized Controlled Trial

Objectives

To investigate the independent contribution of change in sub-total body fat and lean mass to cognitive performance, specifically the executive processes of selective attention and conflict resolution, in community-dwelling older women.

Methods

This secondary analysis included 114 women aged 65 to 75 years old. Participants were randomly allocated to once-weekly resistance training, twice-weekly resistance training, or twice-weekly balance and tone training. The primary outcome measure was the executive processes of selective attention and conflict resolution as assessed by the Stroop Test. Sub-total body fat and lean mass were measured by dual-energy x-ray absorptiometry (DXA) to determine the independent association of change in both sub-total body fat and sub-total body lean mass with Stroop Test performance at trial completion.

Results

A multiple linear regression model showed reductions in sub-total body fat mass to be independently associated with better performance on the Stroop Test at trial completion after accounting for baseline Stroop performance, age, baseline global cognitive state, baseline number of comorbidities, baseline depression, and experimental group. The total variance explained was 39.5%; change in sub-total body fat mass explained 3.9% of the variance. Change in sub-total body lean mass was not independently associated with Stroop Test performance (P>0.05).

Conclusion

Our findings suggest that reductions in sub-total body fat mass – not sub-total lean mass – is associated with better performance of selective attention and conflict resolution.     

The effect of tryptophan depletion on brain activation measured by functional magnetic resonance imaging during the Stroop test in healthy subjects

We investigated the role of serotonin in cognitive activation of the frontal cortex. The serotonergic system was affected by the administration of an amino acids mixture without tryptophan (tryptophan depletion). In a placebo-controlled double-blind cross-over study with 20 healthy volunteers, we tested the hypothesis that a tryptophan (serotonin) decrease affects the activation of prefrontal cortex by the Stroop test. Cognitive brain activation was evaluated by functional magnetic resonance imaging (fMRI). Tryptophan depletion decreased the plasma tryptophan level up to 90 % for five hours after the tryptophan-free drink had been consumed when compared with the same mixture with tryptophan (p?0.0001). Tryptophan depletion did not affect the Stroop test performance. We compared fMRI activation in both conditions (tryptophan depletion and placebo) with plasma tryptophan levels as the covariates. The tryptophan depletion increased the activation (fMRI signal) in the bilateral mediofrontal cortex, anterior cingulate and left dorsolateral prefrontal cortex. The present findings allow the postulate that serotonergic medial forebrain and cingulum bundle pathways play a role in the activity of cortical structures involved in Stroop test processing.     

Emotion Self-Regulation,Psychophysiological Coherence,and Test Anxiety: Results from an Experiment Using Electrophysiological Measures

This study investigated the effects of a novel, classroom-based emotion self-regulation program (TestEdge) on measures of test anxiety, socioemotional function, test performance, and heart rate variability (HRV) in high school students. The program teaches students how to self-generate a specific psychophysiological state—psychophysiological coherence—which has been shown to improve nervous system function, emotional stability, and cognitive performance. Implemented as part of a larger study investigating the population of tenth grade students in two California high schools (N = 980), the research reported here was conducted as a controlled pre- and post-intervention laboratory experiment, using electrophysiological measures, on a random stratified sample of students from the intervention and control schools (N = 136). The Stroop color-word conflict test was used as the experiment’s stimulus to simulate the stress of taking a high-stakes test, while continuous HRV recordings were gathered. The post-intervention electrophysiological results showed a pattern of improvement across all HRV measures, indicating that students who received the intervention program had learned how to better manage their emotions and to self-activate the psychophysiological coherence state under stressful conditions. Moreover, students with high test anxiety exhibited increased HRV and heart rhythm coherence even during a resting baseline condition (without conscious use of the program’s techniques), suggesting that they had internalized the benefits of the intervention. Consistent with these results, students exhibited reduced test anxiety and reduced negative affect after the intervention. Finally, there is suggestive evidence from a matched-pairs analysis that reduced test anxiety and increased psychophysiological coherence appear to be directly associated with improved test performance—a finding consistent with evidence from the larger study.     

Schizophrenia--a parameters' game?

Schizophrenia is a severe, currently incurable, relatively common mental condition. Its symptoms are complex and widespread. It structurally and functionally affects cortical and subcortical regions involved in cognitive, emotional and motivational aspects of behavior. Its diagnosis is based on statistical behavior rather than on its actual cause and its treatment is elusive.We elaborate a theoretical paradigm that accounts for some of the most important features of this illness. Our nonlinear mathematical model, built upon recent hypotheses of neural vulnerability and limbic dysregulation, addresses the amygdala—hippocampus—prefrontal interactions and their evolution under perturbation. The dependence of the dynamics on the system's parameters offers an analytical context for the “normality/disease” dichotomy. The concept of bifurcation could be the key to understanding the threshold between these two states.The nonlinearity parameter (Lyapunov number) is responsible in our setup for tuning the limbic vulnerability characteristic to schizophrenia. Studying its effect on the dynamics helps us understand how stressful events and medication can switch the system from a regime of safety to one of instability, and conversely. The approach has potential for pre-symptomatic risk assessments and for long-term predictions.     

Human preferences for symmetry: subjective experience, cognitive conflict and cortical brain activity

This study examines the links between human perceptions, cognitive biases and neural processing of symmetrical stimuli. While preferences for symmetry have largely been examined in the context of disorders such as obsessive-compulsive disorder and autism spectrum disorders, we examine various these phenomena in non-clinical subjects and suggest that such preferences are distributed throughout the typical population as part of our cognitive and neural architecture. In Experiment 1, 82 young adults reported on the frequency of their obsessive-compulsive spectrum behaviors. Subjects also performed an emotional Stroop or variant of an Implicit Association Task (the OC-CIT) developed to assess cognitive biases for symmetry. Data not only reveal that subjects evidence a cognitive conflict when asked to match images of positive affect with asymmetrical stimuli, and disgust with symmetry, but also that their slowed reaction times when asked to do so were predicted by reports of OC behavior, particularly checking behavior. In Experiment 2, 26 participants were administered an oddball Event-Related Potential task specifically designed to assess sensitivity to symmetry as well as the OC-CIT. These data revealed that reaction times on the OC-CIT were strongly predicted by frontal electrode sites indicating faster processing of an asymmetrical stimulus (unparallel lines) relative to a symmetrical stimulus (parallel lines). The results point to an overall cognitive bias linking disgust with asymmetry and suggest that such cognitive biases are reflected in neural responses to symmetrical/asymmetrical stimuli.     

Predictability of human EEG: a dynamical approach

The electroencephalogram recordings from human scalp are analysed in the framework of recent methods of nonlinear dynamics. Three stages of brain activity are considered: the alpha waves (eyes closed), the deep sleep (stage four) and the Creutzfeld-Jakob coma. Two dynamical parameters of the attractors are evaluated. These are the Lyapunov exponents, which measure the divergence or convergence of trajectories in phase space and the Kolmogorov or metric entropy, whose inverse gives the mean predicting time of a given EEG signal. In all the stages considered, the results reveal the presence of at least two positive Lyapunov exponents, which are the footprints of chaos. This number increases to three positive exponents in the case of alpha waves, indicating that although for very short episodes the alpha waves seem extremely coherent, the variability of the brain increases markedly over larger periods of activity. The degree of entropy/chaos increases from coma to deep sleep and then to alpha waves. The large predicting time observed for deep sleep suggests that these waves are related to a slow rate of information processing. The predicting time of the alpha waves is much smaller, indicating a rapid loss of information. Finally, with the help of the Lyapunov exponents, the attractor's dimensions are evaluated using two different conjectures and compared to values obtained previously by the Grassberger-Procaccia algorithm.     

When language breaks into pieces. A conflict between communication through isolated signals and language

Here, we study a communication model where signals associate to stimuli. The model assumes that signals follow Zipf's law and the exponent of the law depends on a balance between maximizing the information transfer and saving the cost of signal use. We study the effect of tuning that balance on the structure of signal-stimulus associations. The model starts from two recent results. First, the exponent grows as the weight of information transfer increases. Second, a rudimentary form of language is obtained when the network of signal-stimulus associations is almost connected. Here, we show the existence of a sudden destruction of language once a critical balance is crossed. The model shows that maximizing the information transfer through isolated signals and language are in conflict. The model proposes a strong reason for not finding large exponents in complex communication systems: language is in danger. Besides, the findings suggest that human words may need to be ambiguous to keep language alive. Interestingly, the model predicts that large exponents should be associated to decreased synaptic density. It is not surprising that the largest exponents correspond to schizophrenic patients since, according to the spirit of Feinberg's hypothesis, i.e. decreased synaptic density may lead to schizophrenia. Our findings suggest that the exponent of Zipf's law is intimately related to language and that it could be used to detect anomalous structure and organization of the brain.     

Unconsciously Triggered Conflict Adaptation

In conflict tasks such as the Stroop, the Eriksen flanker or the Simon task, it is generally observed that the detection of conflict in the current trial reduces the impact of conflicting information in the subsequent trial; a phenomenon termed conflict adaptation. This higher-order cognitive control function has been assumed to be restricted to cases where conflict is experienced consciously. In the present experiment we manipulated the awareness of conflict-inducing stimuli in a metacontrast masking paradigm to directly test this assumption. Conflicting response tendencies were elicited either consciously (through primes that were weakly masked) or unconsciously (strongly masked primes). We demonstrate trial-by-trial conflict adaptation effects after conscious as well as unconscious conflict, which could not be explained by direct stimulus/response repetitions. These findings show that unconscious information can have a longer-lasting influence on our behavior than previously thought and further stretch the functional boundaries of unconscious cognition.     

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks.     

Positive Affect and Cognitive Restoration: Investigating the Role of Valence and Arousal

Positive moods are thought to restore self-control resources following depletion. However, it is not well understood whether this effect is due to affective valence (pleasantness), arousal (activation), or a combination of both. Across four studies, we set out to investigate the role of positive moods on cognitive and behavioral measures of self-regulation in an ego-depletion paradigm. In studies 1 and 2, we independently manipulated affective valence and arousal and assessed self-regulation with a Stroop task. Results did not suggest a restorative effect of either on cognitive resources. In study 3, we employed both behavioral (the ‘handgrip task’) and cognitive (Stroop) assessments of self-regulation. Again, no significant effect of mood was observed on the Stroop task. Additionally, participants did not persist significantly longer on the handgrip task following a positive mood induction. Finally, in study 4, high vs. low states of arousal were manipulated and self-regulation was assessed via pre- and post-manipulation Stroop performance. In study 4, Stroop performance improved slightly more across time points for those in the high arousal condition than for those in the low arousal condition. Therefore, across four studies, we failed to find a consistent pattern of results suggesting that positive moods restore cognitive resources.     

The Relationship between Stroop and Stop-Signal Measures of Inhibition in Adolescents: Influences from Variations in Context and Measure Estimation

The Stroop and stop-signal tasks are commonly used to index prepotent response inhibition in studies of cognitive development and individual differences. Inhibitory measures from the two tasks have been derived using a variety of methods. Findings of low inter-correlations amongst these measures have been interpreted as evidence for different kinds of inhibitory functions. Our previous study found Stroop and stop-signal accuracy measures to be uncorrelated and they loaded on different inhibitory components in a principal component analysis. The present study examined whether this finding is replicated across different task contexts, derived measures, and methods of derivation. Adolescents (N = 247) were administered a number-quantity Stroop and word and number stop-signal tasks. For each stop-signal task, inhibitory efficiency was estimated using a stop-signal reaction time measure estimated with the central versus the integration methods. For the Stroop interference task, inhibitory efficiency was indexed by reaction time measures (including inverse efficiency scores) generated from difference scores and regression residuals, and delta-plot slopes. The reaction time measures from the two tasks were generally not correlated. The only exception was that Stroop inhibitory ability, indexed by Stroop errors, was related to stop-signal inhibitory efficiency, indexed by stop-signal reaction time. These findings are consistent with previous findings suggesting that measures from the Stroop and stop-signal tasks are influenced by different underlying processes. The impact of variations in dependent measure derivation on the resulting reliabilities of Stroop and stop-signal measures and on observed correlations between them were examined. Variables that may have contributed to the null findings are discussed.