Distinct Functional Connectivities Predict Clinical Response with Emotion Regulation Therapy

Abstract

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.

Changes in Functional Connectivity following Treatment with Emotion Regulation Therapy

“…To investigate changes in connectivity of nodes within the DMN and SN, particular seeds within the DMN (PCC) and SN (Insula) were chosen. Specifically, ROIs were defined based on Fresco et al (2017). For the PCC, a 2 mm sphere was created around the coordinates (−8, −56, 26).…”

“…This trial, which is the parent study for the current study, reported impressive and durable efficacy in reducing worry, rumination, self-reported and clinician rated GAD and MDD severity, and social disability, while increasing quality of life, attentional flexibility, decentering/distancing, reappraisal, and trait mindfulness. In an initial secondary analysis of these trial data, we reported that baseline patterns of resting state functional connectivity (rsFC) within the DMN and SN predicted clinical response to ERT (Fresco et al, 2017). Specifically, higher baseline insula connectivity with parietal cortex, and aMPFC connectivity with precuneus and occipital cortex were associated with decreases in worry.…”

“…The present study is drawn from a larger intervention trial (Renna et al, 2018a) and the baseline rsFC prediction study from the subset of the sample (Fresco et al, 2017). Findings from aforementioned trials with mindfulness interventions demonstrated changes in intrinsic functional connectivity in the DMN.…”

Emotion regulation therapy for cancer caregivers—an open trial of a mechanism-targeted approach to addressing caregiver distress

“…ERT has demonstrated considerable preliminary efficacy as well as initial support for the role of regulatory mechanisms using both behavioral and neural indices associated with ERT clinical outcomes (e.g., 34,35). In an open and randomized controlled trial of adults diagnosed with generalized anxiety, with or without co-occurring depression, patients evidenced gains on measures of PNT (e.g., worry, rumination) and reductions in trait anxiety, depressive symptoms, and quality of life.…”

Perseverate or decenter? Differential effects of metacognition on the relationship between parasympathetic inflexibility and symptoms of depression in a multi-wave study

“…Similarly, Fresco et al (2017) examined the associations between pretreatment neural patterns of intrinsic functional connectivity in hubs within the DMN to treatment-related changes in worry and decentering in generalized anxiety disorder patients (with and without MDD) receiving emotion regulation therapy (e.g., Fresco, Mennin, Heimberg, & Ritter, 2013; Mennin, Fresco, Ritter, & Heimberg, 2015). Findings revealed that treatment linked gains in decentering, as well as reductions in worry were predicted by reduced functional connectivity between the anterior mPFC and a cluster in occipital lobe, as well as by greater connectivity between DMN hubs and regions of the salience network.…”