A pull to be close: The differentiating effects of oxytocin and grief stimulus type on approach behavior in complicated grief.

Theoretical models of complicated grief (CG) suggest that maladaptive motivational tendencies (e.g., perseverative proximity-seeking of the deceased; excessive avoidance of reminders) interfere with a person's ability to recover from their loved one's death. Due in part to conflicting evidence, little mechanistic understanding of how these behaviors develop in grief exists. We sought to (1) identify behavioral differences between CG and non-CG groups based on approach/avoidance bias for grief-, deceased-, and social-related stimuli, and (2) test the role of the neuropeptide oxytocin in shaping approach/avoidance bias. Widowed older adults with (n = 17) and without (n = 22) CG completed an approach/avoidance task measuring implicit bias for both personalized and non-specific grief-related stimuli (among other stimuli). In a double-blinded, randomized, counterbalanced design, each participant attended both an intranasal oxytocin session and a placebo session. Aims were to (1) identify differential effects of CG and stimulus type on implicit approach/avoidance bias [placebo session], and (2) investigate interactive effects of CG, stimulus type, and oxytocin vs. placebo on approach/avoidance bias [both sessions]. In the placebo session, participants in the non-CG group demonstrated an approach bias across all stimuli. Intranasal oxytocin had an overall slowing effect on the CG group's response times. Further, oxytocin decreased avoidance bias in response to photos of the deceased spouse in the CG group only. Findings support the hypothesis that oxytocin has a differential effect on motivational tendency in CG compared to non-CG, strengthening evidence for its role in CG. Findings also emphasize the need to consider differences in personalized vs. generic stimuli when designing grief-relevant tasks.

Functional neuroimaging of resilience to trauma: convergent evidence and challenges for future research.

Resilience is broadly defined as the ability to adapt successfully following stressful life events. Here, we review functional MRI studies that investigated key psychological factors that have been consistently linked to resilience to severe adversity and trauma exposure. These domains include emotion regulation (including cognitive reappraisal), reward responsivity, and cognitive control. Further, we briefly review functional imaging evidence related to emerging areas of study that may potentially facilitate resilience: namely social cognition, active coping, and successful fear extinction. Finally, we also touch upon ongoing issues in neuroimaging study design that will need to be addressed to enable us to harness insight from such studies to improve treatments for - or, ideally, guard against the development of - debilitating post-traumatic stress syndromes.

Dwelling in prolonged grief: Resting state functional connectivity during oxytocin and placebo administration.

Clinical theories of adaptation in bereavement highlight a need for flexible shifting between mental states. However, prolonged motivational salience of the deceased partner may be a complicating factor, particularly when coupled with perseverative thinking about the loss. We investigated how prolonged grief symptoms might relate to resting state functional brain network connectivity in a sample of older adults (n = 38) who experienced the death of a partner 6-36 months prior, and whether intranasal oxytocin (as a neuropeptide involved in pair-bonding) had differential effects in participants with higher prolonged grief symptoms. Higher scores on the Inventory of Complicated Grief (ICG) were associated with lower anticorrelation (i.e., higher functional connectivity) between the defaultretrosplenial - cingulo-operculardACC network pair. Intranasal oxytocin increased functional connectivity in the same defaultretrosplenial - cingulo-operculardACC circuit but ICG scores did not moderate effects of oxytocin, contrary to our prediction. Higher ICG scores were associated with longer dwell time in a dynamic functional connectivity state featuring positive correlations among default, frontoparietal, and cingulo-opercular networks, across both placebo and oxytocin sessions. Dwell time was not significantly affected by oxytocin, and higher prolonged grief symptoms were not associated with more variability in dynamic functional connectivity states over the scan. Results offer preliminary evidence that prolonged grief symptoms in older adults are associated with patterns of static and time-varying functional network connectivity and may specifically involve a default network-salience-related circuit that is sensitive to oxytocin.

Quality control in functional MRI studies with MRIQC and fMRIPrep.

The implementation of adequate quality assessment (QA) and quality control (QC) protocols within the magnetic resonance imaging (MRI) research workflow is resource- and time-consuming and even more so is their execution. As a result, QA/QC practices highly vary across laboratories and "MRI schools", ranging from highly specialized knowledge spots to environments where QA/QC is considered overly onerous and costly despite evidence showing that below-standard data increase the false positive and false negative rates of the final results. Here, we demonstrate a protocol based on the visual assessment of images one-by-one with reports generated by MRIQC and fMRIPrep, for the QC of data in functional (blood-oxygen dependent-level; BOLD) MRI analyses. We particularize the proposed, open-ended scope of application to whole-brain voxel-wise analyses of BOLD to correspondingly enumerate and define the exclusion criteria applied at the QC checkpoints. We apply our protocol on a composite dataset (n = 181 subjects) drawn from open fMRI studies, resulting in the exclusion of 97% of the data (176 subjects). This high exclusion rate was expected because subjects were selected to showcase artifacts. We describe the artifacts and defects more commonly found in the dataset that justified exclusion. We moreover release all the materials we generated in this assessment and document all the QC decisions with the expectation of contributing to the standardization of these procedures and engaging in the discussion of QA/QC by the community.

Grieving as a form of learning: Insights from neuroscience applied to grief and loss.

Recent grief research suggests that the influential cognitive stress theory should be updated with evidence from cognitive neuroscience. Combining human and animal neuroscience with attachment theory, we propose that semantic knowledge of the everlasting nature of the attachment figure and episodic, autobiographical memories of the death are in conflict, perhaps explaining the duration of grieving and generating predictions about complications in prolonged grief disorder (PGD). Our gone-but-also-everlasting model emphasizes that grieving may be a form of learning, requiring time and experiential feedback. Difficulties before loss, such as spousal dependency or pre-existing hippocampal volume, can prolong learning and predict PGD. Complications such as avoidance, rumination, and stress-induced hippocampal atrophy may also develop after loss and create functional or structural mechanisms predicting PGD.

Changes in Functional Connectivity Following Treatment With Emotion Regulation Therapy.

Emotion regulation therapy (ERT) is an efficacious treatment for distress disorders (i.e., depression and anxiety), predicated on a conceptual model wherein difficult to treat distress arises from intense emotionality (e.g., neuroticism, dispositional negativity) and is prolonged by negative self-referentiality (e.g., worry, rumination). Individuals with distress disorders exhibit disruptions in two corresponding brain networks including the salience network (SN) reflecting emotion/motivation and the default mode network (DMN) reflecting self-referentiality. Using resting-state functional connectivity (rsFC) analyses, seeded with primary regions in each of these networks, we investigated whether ERT was associated with theoretically consistent changes across nodes of these networks and whether these changes related to improvements in clinical outcomes. This study examined 21 generalized anxiety disorder (GAD) patients [with and without major depressive disorder (MDD)] drawn from a larger intervention trial (Renna et al., 2018a), who completed resting state fMRI scans before and after receiving 16 sessions of ERT. We utilized seed-based connectivity analysis with seeds in the posterior cingulate cortex (PCC), right anterior insula, and right posterior insula, to investigate whether ERT was associated with changes in connectivity of nodes of the DMN and SN networks to regions across the brain. Findings revealed statistically significant treatment linked changes in both the DMN and SN network nodes, and these changes were associated with clinical improvement corresponding to medium effect sizes. The results are discussed in light of a nuanced understanding of the role of connectivity changes in GAD and MDD, and begin to provide neural network support for the hypothesized treatment model predicated by ERT.

Intranasal oxytocin and OXTR genotype effects on resting state functional connectivity: A systematic review.

OBJECTIVE: Evaluate effects of intranasal oxytocin (IN-OT) and OXTR genotype on resting state functional connectivity in the human brain. METHODS: We searched research databases for peer-reviewed empirical studies. Of 71 unique citations, 18 articles (13 IN-OT, five OXTR) met full inclusion criteria. RESULTS: Two studies examined effects on large-scale networks; most examined acute effects on amygdala connectivity with other social and affective regions. OXTR studies identified three polymorphisms (rs2254298, rs2268498, rs53576) having allele- and sex-dependent effects on prefrontal functional connectivity, and additive effects of OXTR risk alleles on reward circuitry. Age, sex, early life stress, and psychopathology emerged as potential moderators of both IN-OT and OXTR effects. DISCUSSION: IN-OT appears to modulate resting state functional connectivity in a manner similar to its effects on task fMRI, consistent with hypothesized models of IN-OT. However, conclusions are limited by the narrow range of neuroanatomical seed regions, and methodological and experimental design heterogeneity. Future studies should take into account individual differences. Findings may provide insight into mechanisms through which IN-OT impacts human behavior.

Distinct Functional Connectivities Predict Clinical Response with Emotion Regulation Therapy.

Despite the success of available medical and psychosocial treatments, a sizable subgroup of individuals with commonly co-occurring disorders, generalized anxiety disorder (GAD) and major depressive disorder (MDD), fail to make sufficient treatment gains thereby prolonging their deficits in life functioning and satisfaction. Clinically, these patients often display temperamental features reflecting heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss (e.g., somatic anxiety) as well as inordinate negative self-referential processing (e.g., worry, rumination). This profile may reflect disruption in two important neural networks associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network, DN). Emotion Regulation Therapy (ERT) was developed to target this hypothesized profile and its neurobehavioral markers. In the present study, 22 GAD patients (with and without MDD) completed resting state MRI scans before receiving 16 sessions of ERT. To test study these hypotheses, we examined the associations between baseline patterns of intrinsic functional connectivity (iFC) of the insula and of hubs within the DN (anterior and dorsal medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]) and treatment-related changes in worry, somatic anxiety symptoms and decentering. Results suggest that greater treatment linked reductions in worry were associated with iFC clusters in both the insular and parietal cortices. Greater treatment linked gains in decentering, a metacognitive process that involves the capacity to observe items that arise in the mind with healthy psychological distance that is targeted by ERT, was associated with iFC clusters in the anterior and posterior DN. The current study adds to the growing body of research implicating disruptions in the default and salience networks as promising targets of treatment for GAD with and without co-occurring MDD.

An emotional processing writing intervention and heart rate variability: the role of emotional approach.

Expressing and understanding one's own emotional responses to negative events, particularly those that challenge the attainment of important life goals, is thought to confer physiological benefit. Individual preferences and/or abilities in approaching emotions might condition the efficacy of interventions designed to encourage written emotional processing (EP). This study examines the physiological impact (as indexed by heart rate variability (HRV)) of an emotional processing writing (EPW) task as well as the moderating influence of a dispositional preference for coping through emotional approach (EP and emotional expression (EE)), in response to a laboratory stress task designed to challenge an important life goal. Participants (n = 98) were randomly assigned to either EPW or fact control writing (FCW) following the stress task. Regression analyses revealed a significant dispositional EP by condition interaction, such that high EP participants in the EPW condition demonstrated higher HRV after writing compared to low EP participants. No significant main effects of condition or EE coping were observed. These findings suggest that EPW interventions may be best suited for those with preference or ability to process emotions related to a stressor or might require adaptation for those who less often cope through emotional approach.

Impact of Comorbid Depressive Disorders on Subjective and Physiological Responses to Emotion in Generalized Anxiety Disorder.

Generalized anxiety disorder (GAD) and unipolar depressive disorders (UDD) have been shown to differ from each other in dimensions of affective functioning despite their high rates of comorbidity. We showed emotional film clips to a community sample (n = 170) with GAD, GAD with secondary UDD, or no diagnosis. Groups had comparable subjective responses to the clips, but the GAD group had significantly lower heart rate variability (HRV) during fear and after sadness, compared to controls. While HRV in the GAD and control groups rose in response to the sadness and happiness clips, it returned to baseline levels afterwards in the GAD group, potentially indicating lesser ability to sustain attention on emotional stimuli. HRV in the GAD + UDD group changed only in response to sadness, but was otherwise unvarying between timepoints. Though preliminary, these findings suggest comorbid UDD as a potential moderator of emotional responding in GAD.

Recent Advances in Laboratory Assessment of Emotion Regulation.

Over the past 15 years, the emotion regulation perspective has been widely integrated into theoretical and applied contexts in clinical psychology and beyond. Recent refinements to behavioral, subjective, psychophysiological and neuroimaging methods allow emotion regulation to be captured and assessed in the laboratory with greater precision. Technological advances enabling investigators to leverage information from multiple modalities are increasingly accessible, and as such, will further efforts to generate testable hypotheses about specific mechanisms implicated in emotion regulation and difficulties therein. In combination with theory-driven design, progressively sophisticated methods for laboratory assessment have potential to further emotion regulation as both a valid scientific construct and a useful paradigm for human emotion and behavior that has applicability to both clinical and non-clinical contexts.