Altered frontoparietal connectivity in patients with obsessive-compulsive disorder during an fMRI cognitive reappraisal task

Patients with obsessive-compulsive disorder (OCD) present increased brain activity in orbitofrontal and limbic regions when experiencing negative emotions, which could be related to deficits in emotion regulation abilities. 30 OCD patients and 29 healthy controls (HC) performed a cognitive reappraisal functional magnetic resonance imaging (fMRI) task and completed emotion regulation and OCD symptomatology questionnaires. Besides task activation, connectivity was also compared between groups through psychophysiological interaction analysis (PPI), using regions previously reported to be hyperactive in OCD as seeds. Finally, brain-behavior correlations were performed between activation/connectivity strength in group differential regions and the questionnaires’ scores, as well as the emotional ratings reported during the task. Behaviorally, patients with OCD were less successful than controls at lowering the emotional impact of negative images. At the brain level, there were no significant between-group differences in brain activation. Contrarily, PPI analyses showed that HC had increased frontoparietal connectivity when experiencing negative emotions in comparison to OCD patients, while this pattern was reversed when regulating emotions (increased connectivity in patients). Finally, frontoparietal connectivity was correlated with measures of emotion regulation success and OCD symptomatology. Our findings point towards frontoparietal altered connectivity as a potential compensatory mechanism during emotion regulation in OCD patients

An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder

Background: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. Methods: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. Results: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. Conclusions: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders

Neural basis of positive and negative emotion regulation in remitted depression

The recurrent nature of Major Depressive Disorder (MDD) necessitates a better understanding of mechanisms facilitating relapse. MDD has often been associated with abnormal emotion regulation, underpinned by aberrant interactions between the prefrontal cortex and subcortical areas. We assessed whether neural regulation abnormalities remain after remission and relate to emotion regulation problems in daily life. At the baseline measurement of a randomized controlled trial, an emotion regulation task was performed during fMRI scanning by 46 remitted recurrent (rrMDD) patients and 24 healthy controls. We assessed both fMRI peak activity and the temporal dynamics of the neural response during passive attendance and explicit regulation of positive and negative emotions. Furthermore, we assessed regulation strategy use in daily life using questionnaires, and attentional biases using a modified attentional dot-probe task. RrMDD patients showed lower activation and different temporal dynamics in occipital, parietal, and prefrontal brain regions during passive attendance of emotional material compared to healthy controls. During explicit downregulation of negative emotions, no group differences were found. However, during explicit upregulation of positive emotions, rrMDD patients showed a different neural response over time in the insula. Behaviourally, rrMDD patients were characterized by dysfunctional regulation strategies in daily life. Within rrMDD patients, rumination was associated with activation within a limbic- prefrontal network. After remission, immediate emotional processing seems unaffected, but regulatory abnormalities remain, especially uninstructed and in daily life. Abnormal insula activation during positive upregulation suggests decreased monitoring of positive emotions. The relation between inadequate rumination and brain activity during emotion regulation suggests that regulation of both positive and negative affect is important in understanding neurocognitive underpinnings of resilience

Neurocognitive working mechanisms of the prevention of relapse in remitted recurrent depression (NEWPRIDE):protocol of a randomized controlled neuroimaging trial of preventive cognitive therapy

Background: Major Depressive Disorder (MDD) is a psychiatric disorder with a highly recurrent character, making prevention of relapse an important clinical goal. Preventive Cognitive Therapy (PCT) has been proven effective in preventing relapse, though not for every patient. A better understanding of relapse vulnerability and working mechanisms of preventive treatment may inform effective personalized intervention strategies. Neurocognitive models of MDD suggest that abnormalities in prefrontal control over limbic emotion-processing areas during emotional processing and regulation are important in understanding relapse vulnerability. Whether changes in these neurocognitive abnormalities are induced by PCT and thus play an important role in mediating the risk for recurrent depression, is currently unclear. In the Neurocognitive Working Mechanisms of the Prevention of Relapse In Depression (NEWPRIDE) study, we aim to 1) study neurocognitive factors underpinning the vulnerability for relapse, 2) understand the neurocognitive working mechanisms of PCT, 3) predict longitudinal treatment effects based on pre-treatment neurocognitive characteristics, and 4) validate the pupil dilation response as a marker for prefrontal activity, reflecting emotion regulation capacity and therapy success. Methods: In this randomized controlled trial, 75 remitted recurrent MDD (rrMDD) patients will be included. Detailed clinical and cognitive measurements, fMRI scanning and pupillometry will be performed at baseline and three-month follow-up. In the interval, 50 rrMDD patients will be randomized to eight sessions of PCT and 25 rrMDD patients to a waiting list. At baseline, 25 healthy control participants will be additionally included to objectify cross-sectional residual neurocognitive abnormalities in rrMDD. After 18 months, clinical assessments of relapse status are performed to investigate which therapy induced changes predict relapse in the 50 patients allocated to PCT. Discussion: The present trial is the first to study the neurocognitive vulnerability factors underlying relapse and mediating relapse prevention, their value for predicting PCT success and whether pupil dilation acts as a valuable marker in this regard. Ultimately, a deeper understanding of relapse prevention could contribute to the development of better targeted preventive interventions. Trial registration: Trial registration: Netherlands Trial Register, August 18, 2015, trial number NL5219

Emotion Dysregulation and Functional Connectivity in Children With and Without a History of Major Depressive Disorder

Recent interest has emerged in understanding the neural mechanisms by which deficits in emotion regulation (ER) may relate to the development of depression. Cortico-limbic alterations reported in emotion dysregulation and depression may be one possible link. We examined the relationships between emotion dysregulation in school age, corticolimbic resting state functional connectivity (rs-FC) in preadolescence, and depressive symptoms in adolescence. Participants were 143 children from a longitudinal preschool onset depression study who completed the Children Sadness Management Scale (CSMS), Child Depression Inventory (CDI), and two resting state MRI scans. We examined rs-FC between four primary regions of interest (ROIs; bilateral dorsolateral prefrontal cortex (dlPFC) and amygdalae) and six target ROIs thought to contribute to ER. Findings showed that greater school-age emotion dysregulation (higher CSMS) predicted: 1) increased bilateral dlPFC connectivity with bilateral insula and vmPFC in children with and without a history of depression; 2) greater right dlPFC- dACC rs-FC in children with a history of depression; and 3) greater positive rs-FC change from childhood to preadolescence between the bilateral dlPFC and right insula in all children. rs-FC during preadolescence, but not school age emotion dysregulation, predicted later CDI scores. These results suggest that childhood emotion dysregulation predicts rs-FC in preadolescence, which in turn, predicts depressive symptoms in adolescence. These findings elucidate one possible neurobehavioral trajectory for the developmental psychopathology of depression

Exploring the Effects of Brief Mindfulness and Reappraisal Training on Executive Control and Affect

Despite the efficacy of mindfulness-based interventions for a wide range of psychological problems, their mechanisms remain unknown. Analogue studies of key treatment components can help distinguish these approaches. One such component, focused-breathing meditation, has rarely been studied in direct comparison to another active and theoretically distinct technique, cognitive reappraisal. The present study examined the effects of mindful breathing and cognitive reappraisal instructions on negative affect and executive control, two potential mechanisms of mindfulness, in a laboratory setting. Non-clinical college undergraduates (N = 136) were randomly assigned to a 10-minute mindfulness, reappraisal, or mind-wandering control condition. Contrary to hypotheses, no between-group differences were found in sadness ratings, state mindfulness, or the inhibitory control dimension of executive control following the intervention. The mindfulness condition showed lower inattention compared to the mind-wandering condition. Implications of these results are discussed in terms of specific theoretical mechanisms of mindfulness- and cognitive-reappraisal-based interventions

Offline rTMS inhibition of the right dorsolateral prefrontal cortex impairs reappraisal efficacy

In this study we verified the causal role of the bilateral dorsolateral prefrontal cortex (DLPFC) in emotional regulation using a strategy of reappraisal, which involves intentionally changing the meaning of an affective event to reduce its emotional impact. Healthy participants (n = 26; mean age = 25.4) underwent three sessions of inhibitory continuous theta burst stimulation (cTBS) applied on three different days over the left or right DLPFC, or the vertex. After applying the stimulation protocol participants were presented with neutral and negative pictorial stimuli that had to be either passively watched or reappraised. The efficacy of emotional control was quantified using the Late Positive Potential (LPP), the neural marker of motivated attention and elaborated stimulus processing. The results showed that reappraisal was compromised after inhibitory stimulation of the right DLPFC compared to the vertex. This impairment of affective modulation was reflected in both early (350–750 ms) and late (750–1500 ms) time windows. As no session differences during the passive watching conditions were found, the decrease in reappraisal efficacy due to non-specific changes in basic perceptual processing was considered unlikely. Instead, we suggest that inhibition of the right DLPFC primarily affects the top-down mechanism of attentional deployment. This results in disturbances of attentional processes that are necessary to thoroughly elaborate the content of affective stimuli to enable their new, less negative interpretation

Contributions of Human Prefrontal Cortex to the Recogitation of Thought

Human beings have a unique ability to not only verbally articulate past and present experiences, as well as potential future ones, but also evaluate the mental representations of such things. Some evaluations do little good, in that they poorly reflect facts, create needless emotional distress, and contribute to the obstruction of personal goals, whereas some evaluations are the converse: They are grounded in logic, empiricism, and pragmatism and, therefore, are functional rather than dysfunctional. The aim of non-pharmacological mental health interventions is to revise dysfunctional thoughts into more adaptive, healthier ones; however, the neurocognitive mechanisms driving cognitive change have hitherto remained unclear. Therefore, this thesis examines the role of the prefrontal cortex (PFC) in this aspect of human higher cognition using the relatively new method of functional near-infrared spectroscopy (fNIRS). Chapter 1 advances recogitation as the mental ability on which cognitive restructuring largely depends, concluding that, as a cognitive task, it is a form of open-ended human problem-solving that uses metacognitive and reasoning faculties. Because these faculties share similar executive resources, Chapter 2 discusses the systems in the brain involved in controlled information processing, specifically the nature of executive functions and their neural bases. Chapter 3 builds on these ideas to propose an information-processing model of recogitation, which predicts the roles of different subsystems localized within the PFC and elsewhere in the context of emotion regulation. This chapter also highlights several theoretical and empirical challenges to investigating this neurocognitive theory and proposes some solutions, such as to use experimental designs that are more ecologically valid. Chapter 4 focuses on a neuroimaging method that is best suited to investigating questions of spatial localization in ecological experiments, namely functional near-infrared spectroscopy (fNIRS). Chapter 5 then demonstrates a novel approach to investigating the neural bases of interpersonal interactions in clinical settings using fNIRS. Chapter 6 explores physical activity as a ‘bottom-up’ approach to upregulating the PFC, in that it might help clinical populations with executive deficits to regulate their mental health from the ‘top-down’. Chapter 7 addresses some of the methodological issues of investigating clinical interactions and physical activity in more naturalistic settings by assessing an approach to recovering functional events from observed brain data. Chapter 8 draws several conclusions about the role of the PFC in improving psychological as well as physiological well-being, particularly that rostral PFC is inextricably involved in the cognitive effort to modulate dysfunctional thoughts, and proposes some important future directions for ecological research in cognitive neuroscience; for example, psychotherapy is perhaps too physically stagnant, so integrating exercise into treatment environments might boost the effectiveness of intervention strategies