Integrated cross-network connectivity of amygdala, insula, and subgenual cingulate associated with facial emotion perception in healthy controls and remitted major depressive disorder.

Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.

Multivariate pattern analysis strategies in detection of remitted major depressive disorder using resting state functional connectivity.

Understanding abnormal resting-state functional connectivity of distributed brain networks may aid in probing and targeting mechanisms involved in major depressive disorder (MDD). To date, few studies have used resting state functional magnetic resonance imaging (rs-fMRI) to attempt to discriminate individuals with MDD from individuals without MDD, and to our knowledge no investigations have examined a remitted (r) population. In this study, we examined the efficiency of support vector machine (SVM) classifier to successfully discriminate rMDD individuals from healthy controls (HCs) in a narrow early-adult age range. We empirically evaluated four feature selection methods including multivariate Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net feature selection algorithms. Our results showed that SVM classification with Elastic Net feature selection achieved the highest classification accuracy of 76.1% (sensitivity of 81.5% and specificity of 68.9%) by leave-one-out cross-validation across subjects from a dataset consisting of 38 rMDD individuals and 29 healthy controls. The highest discriminating functional connections were between the left amygdala, left posterior cingulate cortex, bilateral dorso-lateral prefrontal cortex, and right ventral striatum. These appear to be key nodes in the etiopathophysiology of MDD, within and between default mode, salience and cognitive control networks. This technique demonstrates early promise for using rs-fMRI connectivity as a putative neurobiological marker capable of distinguishing between individuals with and without rMDD. These methods may be extended to periods of risk prior to illness onset, thereby allowing for earlier diagnosis, prevention, and intervention.

Shared white matter alterations across emotional disorders: A voxel-based meta-analysis of fractional anisotropy.

BACKGROUND: White matter (WM) integrity may represent a shared biomarker for emotional disorders (ED). Aims: To identify transdiagnostic biomarkers of reduced WM by meta-analysis of findings across multiple EDs. METHOD: Web of Science was searched systematically for studies of whole brain analysis of fractional anisotropy (FA) in adults with major depressive disorder, bipolar disorder, social anxiety disorder, obsessive-compulsive disorder or posttraumatic stress disorder compared with a healthy control (HC) group. Peak MNI coordinates were extracted from 37 studies of voxel-based analysis (892 HC and 962 with ED) and meta-analyzed using seed-based d Mapping (SDM) Version 4.31. Separate meta-analyses were also conducted for each disorder. RESULTS: In the transdiagnostic meta-analysis, reduced FA was identified in ED studies compared to HCs in the left inferior fronto-occipital fasciculus, forceps minor, uncinate fasciculus, anterior thalamic radiation, superior corona radiata, bilateral superior longitudinal fasciculi, and cerebellum. Disorder-specific meta-analyses revealed the OCD group had the most similarities in reduced FA to other EDs, with every cluster of reduced FA overlapping with at least one other diagnosis. The PTSD group was the most distinct, with no clusters of reduced FA overlapping with any other diagnosis. The BD group were the only disorder to show increased FA in any region, and showed a more bilateral pattern of WM changes, compared to the other groups which tended to demonstrate a left lateralized pattern of FA reductions. CONCLUSIONS: Distinct diagnostic categories of ED show commonalities in WM tracts with reduced FA when compared to HC, which links brain networks involved in cognitive and affective processing. This meta-analysis facilitates an increased understanding of the biological markers that are shared by these ED.

Targeting Ruminative Thinking in Adolescents at Risk for Depressive Relapse: Rumination-Focused Cognitive Behavior Therapy in a Pilot Randomized Controlled Trial with Resting State fMRI.

This pilot randomized control trial was designed to examine whether Rumination-Focused Cognitive Behavior Therapy (RFCBT) reduces rumination and residual depressive symptoms among adolescents with a history of Major Depressive Disorder (MDD) who are at risk for relapse. We also examined whether these changes in symptoms were associated with changes in functional connectivity of the posterior cingulate cortex (PCC), a key node in the default mode network (DMN). Thirty-three adolescents (ages 12-18) were randomized to eight weeks of RFCBT or an assessment only (AO) control. Twenty two adolescents successfully completed fMRI scans pre- and post-intervention. Adolescents were recruited from the clinic and community and met criteria for at least one previous episode of MDD and were currently in full or partial remission. An Independent Evaluator interviewed parent and child before and after the eight-week intervention. The left PCC (-5, -50, 36) seed was used to probe resting state functional connectivity of the DMN. Adolescents who received RFCBT demonstrated reduced rumination (F = -2.76, df = 112, p < .01, 95% CI [-4.72,-0.80]) and self-report depression across eight weeks (F = -2.58, df = 113, p < .01, 95% CI [-4.21, -0.94]). Youth who received RFCBT also demonstrated significant decreases in connectivity between the left PCC and the right inferior frontal gyrus (IFG) and bilateral inferior temporal gyri (ITG). Degree of change in connectivity was correlated with changes in self-report depression and rumination. These data suggest that rumination can be reduced over eight weeks and that this reduction is associated with parallel decreases in residual depressive symptoms and decreased functional connectivity of the left PCC with cognitive control nodes. These changes may enhance the ability of vulnerable youth to stay well during the transition to adulthood. TRIAL REGISTRATION: ClinicalTrials.gov NCT01905267.

Increased coupling of intrinsic networks in remitted depressed youth predicts rumination and cognitive control.

OBJECTIVE: Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD. METHOD: fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18-23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain. RESULTS: Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely. CONCLUSIONS: Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.