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      Neuroimaging-based biomarkers for treatment selection in major depressive disorder Translated title: Biomarcadores en base a neuroimágenes para la selección del tratamiento del trastorno depresivo mayor Translated title: Biomarqueurs de neuro-imagerie pour la sélection du traitement lors de trouble dépressif majeur

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          Abstract

          The use of neuroimaging approaches to identify likely treatment outcomes in patients with major depressive disorder is developing rapidly. Emerging work suggests that resting state pretreatment metabolic activity in the fronto-insular cortex may distinguish between patients likely to respond to psychotherapy or medication and may function as a treatment-selection biomarker. In contrast, high metabolic activity in the subgenual anterior cingulate cortex may be predictive of poor outcomes to both medication and psychotherapy, suggesting that nonstandard treatments may be pursued earlier in the treatment course. Although these findings will require replication before clinical adoption, they provide preliminary support for the concept that brain states can be measured and applied to the selection of a specific treatment most likely to be beneficial for an individual patient.

          Translated abstract

          Está en pleno desarrollo el empleo de técnicas de neuroimágenes para identificar las probabilidades del resultado del tratamiento en pacientes con trastorno depresivo mayor, Hay trabajos recientes que sugieren que la actividad metabólica en estado de reposo en la corteza fronto-insular pretratamiento puede distinguir entre pacientes con probabilidad de responder a psicoterapia o a medicación, y puede funcionar como un biomarcador para la selección del tratamiento. A la inversa, la alta actividad metabólica en la corteza angulada anterior subgenual puede predecir un pobre resultado tanto para los fármacos como para la psicoterapia, lo que sugiere que los tratamientos no habituales se podrían emplear más precozmente, Aunque estos hallazgos requieren ser replicados antes de incorporarse en la clínica, ellos aportan un soporte preliminar para el concepto que se refiere a que los estados cerebrales pueden ser medidos y empleados en la selección de un tratamiento específico que tenga la mayor probabilidad de beneficiar a un paciente individual.

          Translated abstract

          L'utilisation des techniques de neuro-imagerie pour identifier les résultats thérapeutiques chez des patients atteints de trouble dépressif majeur, se développe rapidement. D'après des travaux récents, l'activité métabolique de repos avant traitement dans le cortex fronto-insulaire pourrait différencier les patients susceptibles de répondre à une psychothérapie ou un médicament et pourrait représenter un biomarqueur du choix thérapeutique. Au contraire, une activité métabolique élevée dans le cortex angulaire antérieur ventral pourrait prédire de mauvais résultats, à la fois pour un traitement psychothérapeutique ou médicamenteux, indiquant de prévoir plus tôt dans le traitement la mise en place de mesures thérapeutiques non usuelles. Ces résultats demandent à être répétés et validés avant d'être adoptés en clinique, mais ils suggèrent le concept que des états cérébraux sont mesurables et peuvent être appliqués à la sélection d'un traitement spécifique plus à même de bénéficier à un patient donné.

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          Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate.

          Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression. However, the antidepressant mechanism remains unknown and its therapeutic efficacy remains limited. Recent data suggest that some left DLPFC targets are more effective than others; however, the reasons for this heterogeneity and how to capitalize on this information remain unclear. Intrinsic (resting state) functional magnetic resonance imaging data from 98 normal subjects were used to compute functional connectivity with various left DLPFC TMS targets employed in the literature. Differences in functional connectivity related to differences in previously reported clinical efficacy were identified. This information was translated into a connectivity-based targeting strategy to identify optimized left DLPFC TMS coordinates. Results in normal subjects were tested for reproducibility in an independent cohort of 13 patients with depression. Differences in functional connectivity were related to previously reported differences in clinical efficacy across a distributed set of cortical and limbic regions. Dorsolateral prefrontal cortex TMS sites with better clinical efficacy were more negatively correlated (anticorrelated) with the subgenual cingulate. Optimum connectivity-based stimulation coordinates were identified in Brodmann area 46. Results were reproducible in patients with depression. Reported antidepressant efficacy of different left DLPFC TMS sites is related to the anticorrelation of each site with the subgenual cingulate, potentially lending insight into the antidepressant mechanism of TMS and suggesting a role for intrinsically anticorrelated networks in depression. These results can be translated into a connectivity-based targeting strategy for focal brain stimulation that might be used to optimize clinical response. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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            Functional connectivity of the insula in the resting brain.

            The human insula is hidden in the depth of the cerebral hemisphere by the overlying frontal and temporal opercula, and consists of three cytoarchitectonically distinct regions: the anterior agranular area, posterior granular area, and the transitional dysgranular zone; each has distinct histochemical staining patterns and specific connectivity. Even though there are several studies reporting the functional connectivity of the insula with the cingulated cortex, its relationships with other brain areas remain elusive in humans. Therefore, we decided to use resting state functional connectivity to elucidate in details its connectivity, in terms of cortical and subcortical areas, and also of lateralization. We investigated correlations in BOLD fluctuations between specific regions of interest of the insula and other brain areas of right-handed healthy volunteers, on both sides of the brain. Our findings document two major complementary networks involving the ventral-anterior and dorsal-posterior insula: one network links the anterior insula to the middle and inferior temporal cortex and anterior cingulate cortex, and is primarily related to limbic regions which play a role in emotional aspects; the second links the middle-posterior insula to premotor, sensorimotor, supplementary motor and middle-posterior cingulate cortices, indicating a role for the insula in sensorimotor integration. The clear bipartition of the insula was confirmed by negative correlation analysis. Correlation maps are partially lateralized: the salience network, related to the ventral anterior insula, displays stronger connections with the anterior cingulate cortex on the right side, and with the frontal cortex on the left side; the posterior network has stronger connections with the superior temporal cortex and the occipital cortex on the right side. These results are in agreement with connectivity studies in primates, and support the use of resting state functional analysis to investigate connectivity in the living human brain. Copyright © 2010 Elsevier Inc. All rights reserved.
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              Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic.

              Recent decades have witnessed tremendous advances in the neuroscience of emotion, learning and memory, and in animal models for understanding depression and anxiety. This review focuses on new rationally designed psychiatric treatments derived from preclinical human and animal studies. Nonpharmacological treatments that affect disrupted emotion circuits include vagal nerve stimulation, rapid transcranial magnetic stimulation and deep brain stimulation, all borrowed from neurological interventions that attempt to target known pathological foci. Other approaches include drugs that are given in relation to specific learning events to enhance or disrupt endogenous emotional learning processes. Imaging data suggest that common regions of brain activation are targeted with pharmacological and somatic treatments as well as with the emotional learning in psychotherapy. Although many of these approaches are experimental, the rapidly developing understanding of emotional circuit regulation is likely to provide exciting and powerful future treatments for debilitating mood and anxiety disorders.
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                Author and article information

                Contributors
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                December 2014
                December 2014
                : 16
                : 4
                : 479-490
                Affiliations
                Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA
                Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA
                Author notes
                Article
                10.31887/DCNS.2014.16.4/bdunlop
                4336918
                25733953
                b69c62be-4b08-47a5-b0be-1bdbee177598
                Copyright: © 2014 Institut la Conférence Hippocrate - Servier Research Group

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Translational Research

                Neurosciences
                antidepressive agent,biological marker,depression,effect modifier,individualized medicine,magnetic resonance imaging,patient outcome assessment,positron-emission tomography,psychotherapy

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