Electrophysiological signatures of inequity-dependent reward encoding in the human OFC.

Social decision making requires the integration of reward valuation and social cognition systems, both dependent on the orbitofrontal cortex (OFC). How these two OFC functions interact is largely unknown. We recorded intracranial activity from the OFC of ten patients making choices in a social context where reward inequity with a social counterpart varied and could be either advantageous or disadvantageous. We find that OFC high-frequency activity (HFA; 70-150 Hz) encodes self-reward, consistent with previous reports. We also observe encoding of the social counterpart's reward, as well as the type of inequity being experienced. Additionally, we find evidence of inequity-dependent reward encoding: depending on the type of inequity, electrodes rapidly and reversibly switch between different reward-encoding profiles. These results provide direct evidence for encoding of self- and other rewards in the human OFC and highlight the dynamic nature of encoding in the OFC as a function of social context.

Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety.

BACKGROUND: Despite tremendous advances in characterizing human neural circuits that govern emotional and cognitive functions impaired in depression and anxiety, we lack a circuit-based taxonomy for depression and anxiety that captures transdiagnostic heterogeneity and informs clinical decision making. METHODS: We developed and tested a novel system for quantifying 6 brain circuits reproducibly and at the individual patient level. We implemented standardized circuit definitions relative to a healthy reference sample and algorithms to generate circuit clinical scores for the overall circuit and its constituent regions. RESULTS: In new data from primary and generalizability samples of depression and anxiety (N = 250), we demonstrated that overall disconnections within task-free salience and default mode circuits map onto symptoms of anxious avoidance, loss of pleasure, threat dysregulation, and negative emotional biases-core characteristics that transcend diagnoses-and poorer daily function. Regional dysfunctions within task-evoked cognitive control and affective circuits may implicate symptoms of cognitive and valence-congruent emotional functions. Circuit dysfunction scores also distinguished response to antidepressant and behavioral intervention treatments in an independent sample (n = 205). CONCLUSIONS: Our findings articulate circuit dimensions that relate to transdiagnostic symptoms across mood and anxiety disorders. Our novel system offers a foundation for deploying standardized circuit assessments across research groups, trials, and clinics to advance more precise classifications and treatment targets for psychiatry.

Correction: Paying attention to attention in depression.

In the original Article, Naoise Mac Giollabhui was incorrectly cited as "Giollabhui, N. M" instead of "Mac Giollabhui, N" in reference 163. This has been updated in the HTML and PDF versions of this Article.

Paying attention to attention in depression.

Attention is the gate through which sensory information enters our conscious experiences. Oftentimes, patients with major depressive disorder (MDD) complain of concentration difficulties that negatively impact their day-to-day function, and these attention problems are not alleviated by current first-line treatments. In spite of attention's influence on many aspects of cognitive and emotional functioning, and the inclusion of concentration difficulties in the diagnostic criteria for MDD, the focus of depression as a disease is typically on mood features, with attentional features considered less of an imperative for investigation. Here, we summarize the breadth and depth of findings from the cognitive neurosciences regarding the neural mechanisms supporting goal-directed attention in order to better understand how these might go awry in depression. First, we characterize behavioral impairments in selective, sustained, and divided attention in depressed individuals. We then discuss interactions between goal-directed attention and other aspects of cognition (cognitive control, perception, and decision-making) and emotional functioning (negative biases, internally-focused attention, and interactions of mood and attention). We then review evidence for neurobiological mechanisms supporting attention, including the organization of large-scale neural networks and electrophysiological synchrony. Finally, we discuss the failure of current first-line treatments to alleviate attention impairments in MDD and review evidence for more targeted pharmacological, brain stimulation, and behavioral interventions. By synthesizing findings across disciplines and delineating avenues for future research, we aim to provide a clearer outline of how attention impairments may arise in the context of MDD and how, mechanistically, they may negatively impact daily functioning across various domains.

Intrinsic functional connectivity predicts remission on antidepressants: a randomized controlled trial to identify clinically applicable imaging biomarkers.

Default mode network (DMN) dysfunction (particularly within the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC)) has been implicated in major depressive disorder (MDD); however, its contribution to treatment outcome has not been clearly established. Here we tested the role of DMN functional connectivity as a general and differential biomarker for predicting treatment outcomes in a large, unmedicated adult sample with MDD. Seventy-five MDD outpatients completed fMRI scans before and 8 weeks after randomization to escitalopram, sertraline, or venlafaxine-XR. A whole-brain voxel-wise t-test identified profiles of pretreatment intrinsic functional connectivity that distinguished patients who were subsequently classified as remitters or non-remitters at follow-up. Connectivity was seeded in the PCC, an important node of the DMN. We further characterized differences between remitters, non-remitters, and 31 healthy controls and characterized changes pretreatment to posttreatment. Remitters were distinguished from non-remitters by relatively intact connectivity between the PCC and ACC/mPFC, not distinguishable from healthy controls, while non-remitters showed relative hypo-connectivity. In validation analyses, we demonstrate that PCC-ACC/mPFC connectivity predicts remission status with >80% cross-validated accuracy. In analyses testing whether intrinsic connectivity differentially relates to outcomes for a specific type of antidepressant, interaction models did not survive the corrected threshold. Our findings demonstrate that the overall capacity to remit on commonly used antidepressants may depend on intact organization of intrinsic functional connectivity between PCC and ACC/mPFC prior to treatment. The findings highlight the potential utility of functional scans for advancing a more precise approach to tailoring antidepressant treatment choices.