In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidalthalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. improvement in response to psychotherapy. For more information, please contact Kathy K Peng, (650) 725-9510. It was also ameliorated by a neurocognitive intervention and associated with a better treatment outcome. This study provides insight into a possible mechanism through which the vlPFC may contribute to emotion perception. populations. Participants were classified by subtype. The first study evaluated 181 trauma-exposed individuals one-, six-, and 14 months following trauma exposure. Across the subregions, GAD patients had increased connectivity with a previously characterized frontoparietal executive control network and decreased connectivity with an insula- and cingulate-based salience network.Our findings provide new insights into the functional neuroanatomy of the human amygdala and converge with connectivity studies in experimental animals. The results revealed 2 distinct circuits: a lateral prefrontal "cognitive control" system that resolved nonemotional conflict and was associated with enhanced processing of task-relevant stimuli in sensory cortices, and a rostral anterior cingulate "emotional control" system that resolved emotional conflict and was associated with decreased amygdalar responses to emotional distracters. It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Stanford is currently not accepting patients for this trial. Renna, M. E., Seeley, S. H., Heimberg, R. G., Etkin, A., Fresco, D. M., Mennin, D. S. Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol. Conclusion: Early web-based interventions targeting causative mechanisms of PTSD can be informed by the model presented in this paper. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. View details for DOI 10.1016/j.bandc.2015.06.002, View details for DOI 10.1080/00332747.2015.1069656, View details for Web of Science ID 000363596900010. A Stanford University-based research team led by BBRF 2012 Young Investigator Amit Etkin, M.D., Ph.D., has had the objective of translating fMRI-based insights on changes in brain connectivity in PTSD to a technology that would be easier to use in the clinic, where it might help combat vets and others with PTSD. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. For more information, please contact Lisa McTeague, PhD, 650-725-9510. Marusak, H. A., Martin, K. R., Etkin, A., Thomason, M. E. Neurobiological signatures of anxiety and depression in resting-state functional magnetic resonance imaging. Follow-up analyses on other healthy participant data sets tested connectivity related to regions arising from the meta-analysis and the relationship of gray matter volume to cognition.Based on the voxel-based morphometry meta-analysis of 193 studies comprising 15â892 individuals across 6 diverse diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety), we found that gray matter loss converged across diagnoses in 3 regions: the dorsal anterior cingulate, right insula, and left insula. time during assessment procedures. Only a small proportion of trainees and psychiatrists, however, reported a strong knowledge base in neuroscience. Oathes, D. J., Patenaude, B., Schatzberg, A. F., Etkin, A. A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Compensatory engagement of cognitive control circuitry in depression illustrates how the complex nature of psychopathology arises from the interaction of deficits and compensation, all of which can occur at an implicit level. McTeague, L. M., Rosenberg, B. M., Lopez, J. W., Carreon, D. M., Huemer, J., Jiang, Y., Chick, C. F., Eickhoff, S. B., Etkin, A. The authors examined emotional conflict processing using a salient stimulus associated with observable and interpretable behavioral outcomes and with activation in limbic and prefrontal regions implicated in anxiety and depression.Thirty-two healthy comparison subjects, 18 patients with generalized anxiety disorder only, 14 patients with major depression only, and 25 patients with comorbid generalized anxiety disorder and major depression were studied using functional MRI while they performed an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. These results allow for maintaining the theory that the rostral dmPFC is involved in conscious threat appraisal. In William Shakespeare’s Henry IV, Part 1, Hotspur returns from battle a changed man. The authors tested whether a statistical approach aimed at identifying individual-level neuroimaging abnormalities that are more prevalent in case subjects than in control subjects could reveal new clinically meaningful insights into the heterogeneity of PTSD.Resting-state functional MRI data were recorded from 87 unmedicated PTSD case subjects and 105 war zone-exposed healthy control subjects. Aim 1: To examine causal interactions between two major brain networks in depression. As a part of this study, participants will receive brain MRIs and office assessments before
Default mode network mechanisms of transcranial magnetic stimulation in depression. Medication-free outpatients with nonpsychotic major depressive disorder (N=1008; 665 completers) were assessed before treatment using 13 computerized tests of psychomotor, executive, memory-attention, processing speed, inhibitory, and emotional functions. Anger is a common and debilitating symptom of post-traumatic stress disorder (PTSD). Amit Etkin, MD, PhD, is a Professor of Psychiatry and Behavioral Sciences at Stanford University and a member of the Wu Tsai Neurosciences Institute. Identification of a Common Neurobiological Substrate for Mental Illness. Anger Expression in Patients With PTSD: Clinical, Cognitive, and Neural Correlates. Etkin, A., Phil, M., Pittenger, C., Polan, H. J., Kandel, E. R. Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms.Prediction of response to sertraline involved several within- and between-network connectivity patterns. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. This pattern of perceptual bias is consistent with effects observed in a wide range of affective disorders, in which vlPFC dysfunction has also been reported. Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., Schatzberg, A. F. Limbic Activity Modulation Guided by Functional Magnetic Resonance Imaging-Inspired Electroencephalography Improves Implicit Emotion Regulation. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. 2007;24(3):202-18. doi: 10.1002/da.20208. Brain Research, Vol. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Arnow, B. These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients.Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). In this review we survey the current knowledge about changes in brain function following psychotherapeutic intervention that are detectable with current neuroimaging techniques. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence.RESULTS: The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. Overall, 64 of 164 (39.0%) of the participants achieved remission.A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. The investigators are seeking people who have been exposed to a traumatic event in the past and have symptoms of posttraumatic stress disorder (PTSD) currently. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments. Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD. They also predict responsiveness to transcranial magnetic stimulation therapy (n = 154). Stanford is currently not accepting patients for this trial. Findings across neuropsychology and neuroimaging point to broad-based impairments that cross traditional diagnostic boundaries. View details for DOI 10.1176/appi.ajp.2012.11071105, View details for Web of Science ID 000305853400007, View details for Web of Science ID 000303440700001. 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. Symptoms included general distress, common to anxiety and depression, and anxiety-specific (anxious arousal) or depression-specific (anhedonia) symptoms. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. in two targeted and interacting networks, using concurrent transcranial magnetic stimulation
Seventy seven patients completed 8 weeks of antidepressant treatment. Chen, A. C., Oathes, D. J., Chang, C., Bradley, T., Zhou, Z., Williams, L. M., Glover, G. H., Deisseroth, K., Etkin, A. We found that patients with chronic pain had exaggerated and abnormal amygdala connectivity with central executive network, which was most exaggerated in patients with the greatest pain catastrophizing. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. Methods: Participants in both studies were adult survivors of traumatic events admitted to two general hospitals' emergency departments (EDs) in Israel. Frontoparietal Activation During Response Inhibition Predicts Remission to Antidepressants in Patients With Major Depression. However, current single-coil rTMS technology only allows for effects in surface cortical structures. As predicted, in healthy subjects resting-state connectivity dissociated between posterior hippocampal connectivity with the default-mode network, and anterior hippocampal connectivity to limbic-prefrontal circuitry. An electroencephalographic signature predicts antidepressant response in major depression. The research proposes to use an innovative solution to shape brain circuits that support
View details for Web of Science ID 000391646800011. Cooper, C. M., Fatt, C., Jha, M., Fonzo, G., Grannemann, B. D., Carmody, T., Ali, A., Aslan, S., Almeida, J. C., Deckersbach, T., Fava, M., Kurian, B. T., McGrath, P. J., McInnis, M., Parsey, R. V., Weissman, M., Phillips, M., Lu, H., Etkin, A., Trivedi, M. H. Classification of TMS evoked potentials using ERP time signatures and SVM versus deep learning. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Moreover, the algorithm was superior to the artifact rejection performance of relatively novice individuals, who would be the likely users of spTMS-EEG as the technique becomes more broadly disseminated. OBJECTIVE: Disrupted emotional processing is a common feature of many psychiatric disorders. Emotional processing in anterior cingulate and medial prefrontal cortex, Explicit and implicit emotion regulation: A dual-process framework, A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat. Conclusions: Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment. To identify subtypes, the researchers used electroencephalogram, EEG, to collect brainwave data from 201 participants -- 106 with PTSD and 95 healthy controls. Advances in cognitive neuroscience now allow us to ground an understanding of these cognitive regulatory deficits in the function and interaction of key brain networks. The consistency of these findings with those of the Sequenced Treatment Alternatives to Relieve Depression trial suggests that subtypes may be of minimal value in antidepressant selection. Low-frequency (.008-.1 Hz) signal amplitude and functional connectivity analyses of resting-state functional magnetic resonance imaging data focused on a priori cortical and subcortical regions of interest.Support was found for effects of diagnosis above and beyond effects related to symptom levels as well as for effects of symptom levels above and beyond effects of diagnostic categories. Brain functions governing treatment outcome are not well characterized. Overall, 2,016 depressed participants (18 to 65Â years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. A., Crossley, N., Hallmayer, J., Fossati, S., Rothbaum, B. O., Marmar, C. R., Bullmore, E. T., O'Hara, R. Brain regulation of emotional conflict predicts antidepressant treatment response for depression. After correction for multiple comparisons, connectome-wide analyses revealed moderation by connections within and between widespread cortical regions-most prominently parietal-for both the antidepressant and placebo groups. Addressing the Causality Gap in Human Psychiatric Neuroscience, PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation. Functional neuroanatomy of anxiety: a neural circuit perspective. Stanford is currently not accepting patients for this trial. For more information, please contact Kathy Peng, B.A., 650-725-9510. Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V., Greicius, M. D. Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia, Resolving emotional conflict: A role for the rostral anterior cingulate cortex in modulating activity in the amygdala. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. The studies used identical clinical and neurocognitive tools, which included assessment of PTSD symptoms and diagnosis, and a battery of neurocognitive tests. Our work is organized around the study of the neuroscience of emotion and cognitive regulation, as well as basic aspects of neural circuit functioning and control, in healthy subjects and individuals with a range of psychiatric disorders. View details for DOI 10.1038/nrdp.2016.65, View details for Web of Science ID 000384877200001. Connectivity features that moderate treatment response differentially by treatment group were distinct from connectivity features that change from baseline to 1 week into treatment. intervention in alleviating symptoms and improving emotion regulation in individuals with
Furthermore, we have observed that regions of the multiple demand network, which overlap with the salience network (dorsal anterior cingulate and bilateral anterior insula) are characterized by reduced gray matter transdiagnostically and predict weaker neurocognitive performance. This concordance provides an organizing model that emphasizes the importance of shared neural substrates across psychopathology, despite likely diverse etiologies, which is currently not an explicit component of psychiatric nosology. Unconscious processing modulated activity only in the basolateral subregion of the amygdala, while conscious processing modulated activity only in the dorsal amygdala (containing the central nucleus). Fine, N. B., Achituv, M., Etkin, A., Merin, O., Shalev, A. Y. Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional Studies. The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). The authors searched for common and disorder-specific functional neurobiological deficits in several anxiety disorders. Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment. Depress Anxiety. Reflecting the emphasis in DSM-5, we also include impairment and distress.Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). By contrast, deficits in activation and connectivity of the ventral anterior cingulate and amygdala, areas previously implicated in regulating emotional conflict, were found in all patient groups. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Dr. Etkin … In the current study, we acutely disrupted vlPFC function in twenty healthy adult participants by administering sham stimulation and transcranial magnetic stimulation (TMS), in randomized order, during performance of an emotional perception task. Therefore, these findings help refine our understanding of anxiety disorders and their interrelationships. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. The authors ex-amined brain systems relevant to emotional reactivity These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. View details for DOI 10.3389/fpsyt.2018.00477, View details for Web of Science ID 000446343200001. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Anxiety is a commonly experienced subjective state that can have both adaptive and maladaptive properties. Deficits in brain networks that support cognitive regulatory functions are prevalent in many psychiatric disorders. View details for DOI 10.1038/npp.2014.311, View details for Web of Science ID 000351022900021, View details for PubMedCentralID PMC4367470. Nat Biomed Eng. Some differences were found based on the level of interest in a future academic role.This web-based study demonstrates that psychiatry residents see neuroscience education as important in their training and worthy of greater attention. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.Neuropsychopharmacology advance online publication, 29 April 2015; doi:10.1038/npp.2015.89. feel significant distress when reminded of a traumatic event or feel depressed, anxious or
Accumulating findings have revealed that phenotypically diverse psychiatric disorders share a common factor or vulnerability to dysfunction that is in turn related to broad neurocognitive deficits. Jarcho, J. M., Fox, N. A., Pine, D. S., Etkin, A., Leibenluft, E., Shechner, T., Ernst, M. Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial. Human neuroimaging has been a core component of both research in psychiatry and conceptual models of the brain circuit-level mechanisms underlying psychopathology. View details for DOI 10.1016/j.jpsychires.2014.12.018. However, the test-retest reliability of TEPs, critical to their use in clinical biomarker and interventional studies, remains poorly understood.We quantified TEP reliability to: (i) determine the minimal TEP amplitude change which significantly exceeds that associated with simply re-testing, (ii) locate the most reliable scalp regions of interest (ROIs) and TEP peaks, and (iii) determine the minimal number of TEP pulses for achieving reliability.TEPs resulting from stimulation of the left dorsolateral prefrontal cortex were collected on two separate days in sixteen healthy participants. Understanding 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. 2021 Feb 1. doi: 10.1038/s41551-020-00666-w. Online ahead of print. Remission rates increased from 37% for all those who received sertraline to 53% for those who were lucky to have received it and sertraline was their perfusion-preferred treatment.This large study showed that perfusion patterns in brain regions involved with reward, salience, affective, and default mode processing moderate treatment response favouring sertraline over placebo. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). Administering targeted neurocognitive training shortly after trauma exposure is a daunting challenge. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Marusak, H. A., Etkin, A., Thomason, M. E. Selection of cognitive tests for trials of therapeutic agents - Authors' reply. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Summary: A neuroimaging and behavioral signature associated with connectivity in the ventral attention network has been identified in a subgroup of PTSD patients who fail to respond to treatment. View details for Web of Science ID 000187664700012, View details for Web of Science ID 000165509500037, Professor, Psychiatry and Behavioral Sciences, Chair, Steering Committee, Major Laboratories and Clinical Translational Neurosciences Incubator, Department of Psychiatry and Behavioral Sciences, Stanford University (2018 - Present), Associate Chair, Research Strategy and Oversight, Department of Psychiatry and Behavioral Sciences, Stanford University (2018 - Present), Joel Elkes Research Award, American College of Neuropsychopharmacology (2018), Young Scientist Awardee, World Economic Forum (2015), Chairman's Award for Advancing Science, Stanford University (2014), Dana Neuroscience Scholar award, Dana Foundation (2012), Fellow, Kavli-National Academy of Science "Frontiers of Science" (2011-2013), Biobehavioral Research Awards for Innovative New Scientists (BRAINS) R01 Award, NIMH (2010), PhD awarded with distinction, Columbia University (2005), Associate Editor, Neuropsychopharmacology (2012 - 2019), Editorial Board, Depression and Anxiety (2010 - Present), Chair, Scientific Program Committee, Society of Biological Psychiatry (2014 - Present), Fellow, American College of Neuropsychopharmacology (2011 - Present), Member, Society of Biological Psychiatry (2011 - Present), Scientific Advisory Board, Laureate Institute for Brain Research (Tulsa, OK) (2015 - Present), Scientific Advisory Board, Akili Interactive (2016 - Present), Scientific Advisory Board, Mindstrong Health (2017 - Present), Board Certification, American Board of Psychiatry and Neurology, Psychiatry (2011), MD, Columbia University, Medicine (2006), PhD, Columbia University, Neurobiology (2005), MPhil, Columbia University, Neurobiology (2003), BS, Massachusetts Institute of Technology, Biology (1997), Department: Psych/Major Laboratories and Clinical & Translational Neurosciences Incubator, Brain-Based Biomarkers in Response to TMS in MDD, A Novel Neurobehavioral Intervention for Emotion Regulation in Anxiety and Depression Across the Lifespan. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology.
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