These findings offer a data-driven framework for identifying robust subtypes that signify specific, coherent, meaningful associations between symptoms, behavior, brain function, and observable real-world function, and that cut across DSM-IV-defined diagnoses of major depressive disorder, panic disorder, and posttraumatic stress disorder.

Series of horizontal saccadic eye movements (EMs) are known to improve episodic memory retrieval in healthy adults and to facilitate the processing of traumatic memories in eye movement desensitization and reprocessing (EMDR) therapy. Several authors have proposed that EMs achieve these effects by increasing the functional connectivity of the two brain hemispheres, but direct evidence for this proposal is lacking. The aim of this study was to investigate whether memory enhancement following bilateral EMs is associated with increased interhemispheric coherence in the electroencephalogram (EEG). Fourteen healthy young adults were asked to freely recall lists of studied neutral and emotional words after a series of bilateral EMs and a control procedure. Baseline EEG activity was recorded before and after the EM and control procedures. Phase and amplitude coherence between bilaterally homologous brain areas were calculated for six frequency bands and electrode pairs across the entire scalp. Behavioral analyses showed that participants recalled more emotional (but not neutral) words following the EM procedure than following the control procedure. However, the EEG analyses indicated no evidence that the EMs altered participants’ interhemispheric coherence or that improvements in recall were correlated with such changes in coherence. These findings cast doubt on the interhemispheric interaction hypothesis, and therefore may have important implications for future research on the neurobiological mechanism underlying EMDR.

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BackgroundUnderstanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression (“RAD”) project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time.Methods and designHere we present the protocol for the “RAD” project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who “walk through the door” of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain–based subgroups over time and to assess whether these subgroups predict real–world functional capacity over time. First enrollment was August 2013, and is ongoing.DiscussionThis project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward.Trial registrationClinicalTrials.gov Identifier: NCT02220309. Registered: August 13, 2014.

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The orbital and medial prefrontal cortex (OMPFC) has been implicated in decision-making, reward and emotion processing, and psychopathology, such as depression and obsessive–compulsive disorder. Human and monkey anatomical studies indicate the presence of various cortical subdivisions and suggest that these are organized in two extended networks, a medial and an orbital one. Attempts have been made to replicate these neuroanatomical findings in vivo using MRI techniques for imaging connectivity. These revealed several consistencies, but also many inconsistencies between reported results. Here, we use fMRI resting-state functional connectivity (FC) and data-driven modularity optimization to parcellate the OMPFC to investigate replicability of in vivo parcellation more systematically. By collecting two resting-state data sets per participant, we were able to quantify the reliability of the observed modules and their boundaries. Results show that there was significantly more than chance overlap in modules and their boundaries at the level of individual data sets. Moreover, some of these consistent boundaries significantly co-localized across participants. Hierarchical clustering showed that the whole-brain FC profiles of the OMPFC subregions separate them in two networks, a medial and orbital one, which overlap with the organization proposed by Barbas and Pandya (J Comp Neurol 286:353–375, 1989) and Ongür and Price (Cereb Cortex 10:206–219, 2000). We conclude that in vivo resting-state FC can delineate reliable and neuroanatomically plausible subdivisions that agree with established cytoarchitectonic trends and connectivity patterns, while other subdivisions do not show the same consistency across data sets and studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-017-1378-2) contains supplementary material, which is available to authorized users.

Background Pathophysiology models of major depression (MD) center on the dysfunction of various cortical areas within the orbital and medial prefrontal cortex (OMPFC). While independent structural and functional abnormalities in these areas are consistent findings in MD, the complex interactions among them and the rest of the cortex remain largely unexplored. Methods We used resting state functional magnetic resonance imaging (fMRI) connectivity to systematically map alterations in the communication between OMPFC fields and the rest of the brain in MD. Functional connectivity (FC) maps from participants with current MD (N=35), unaffected first-degree relatives (N=36) and healthy controls (N=38) were subjected to conjunction analyses to distinguish FC markers of MD vulnerability and FC markers of MD disease). Results FC abnormalities in MD vulnerability were found for dorsal medial wall regions and the anterior insula and concerned altered communication of these areas with the inferior parietal cortex and dorsal posterior cingulate, occipital areas and the brainstem. FC aberrations in current MD included the anterior insula, rostral and dorsal anterior cingulate and lateral orbitofrontal areas and concerned altered communication with the dorsal striatum, the cerebellum, the precuneus, the anterior PFC, somato-motor cortex, dorsolateral PFC, and visual areas in the occipital and inferior temporal lobes. Conclusions Functionally delineated parcellation maps can be used to identify putative connectivity markers in extended cortical regions such as the OMPFC. The anterior insula and the rostral anterior cingulate play a central role in the pathophysiology of MD, being consistently implicated both in the MD vulnerability and MD disease states.

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