Drevets WC. Orbitofrontal cortex function and structure in depression. Ann NY Acad Sci 1121: 499-527
Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-2670, USA. Annals of the New York Academy of Sciences
(Impact Factor: 4.38).
01/2008; 1121(1):499-527. DOI: 10.1196/annals.1401.029
The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.
Available from: Markus Junghöfer
- "In the present study, we aimed to investigate baseline as well as post-treatment neural correlates of passive emotional picture processing without additional tasks in patients with MDD by means of whole-head MEG. The measure of event-related magnetic fields in combination with inverse source modeling allows for detecting even rapid, transient, and preconscious cortical activations which may not necessarily result in measurable A c c e p t e d M a n u s c r i p t 6 hemodynamic changes and may become object to hemodynamic masking due to compensatory attempts of attenuating the expression or experience of aversive emotions (Drevets, 2007). Our predictions were that medication-free patients with depression as compared to healthy controls would show an overall decreased sensitivity towards arousing pictures in correlation with a particularly right-sided temporo-parietal hypoactivation and a dysfunctional affective modulation at prefrontal cortex regions. "
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ABSTRACT: In major depressive disorder (MDD), electrophysiological (EEG) and imaging studies suggest reduced neural activity in parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were for the first time analyzed in a pre-/post-treatment design by means of magnetoencephalography (MEG) allowing for detecting temporal dynamics of brain activation.
Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant unpleasant and neutral pictures. Fifteen patients were followed-up with a second MEG session after four-week antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. Clinical course of depression was assessed using the Hamilton Depression scale (HAMD-21).
Prior to treatment, an overall neocortical hypoactivation during emotional processing particularly at parietal regions and areas at the right temporoparietal junction (TPJ) as well as abnormal valence-specific reactions at right parietal and bilateral dorsolateral PFC (dlPFC) regions were observed in patients compared to controls. These effects occurred < 150 ms suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy.
The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.
© The Author 2015. Published by Oxford University Press on behalf of CINP.
Available from: Aron K Barbey
- ", 2011 ) . For example , severity of depression correlates positively with activity in ventromedial polar cortex and amygdala , possibly representing an increased vigilance for potential threats to self - esteem ( Drevets , 2007 ; Murray et al . , 2011 ; Price and Drevets , 2012 ) . "
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ABSTRACT: Counterfactual reasoning is a hallmark of human thought, enabling the capacity to shift from perceiving the immediate environment to an alternative, imagined perspective. Mental representations of counterfactual possibilities (e.g., imagined past events or future outcomes not yet at hand) provide the basis for learning from past experience, enable planning and prediction, support creativity and insight, and give rise to emotions and social attributions (e.g., regret and blame). Yet remarkably little is known about the psychological and neural foundations of counterfactual reasoning. In this review, we survey recent findings from psychology and neuroscience indicating that counterfactual thought depends on an integrative network of systems for affective processing, mental simulation, and cognitive control. We review evidence to elucidate how these mechanisms are systematically altered through psychiatric illness and neurological disease. We propose that counterfactual thinking depends on the coordination of multiple information processing systems that together enable adaptive behavior and goal-directed decision making and make recommendations for the study of counterfactual inference in health, aging, and disease.
- "Diagnostic categories have been the basis for neuroimaging and genome-wide association studies (Garvey et al., 1986; Clayton, 1990; Moore and Williams, 2009; Savitz and Drevets, 2009), but disease-specific risk factors identified by extant investigations have been equivocal based on the current categorical system of mood disorder diagnoses (Dolan et al., 1993; Sheline et al., 1999; Ravnkilde et al., 2003; Lange et al., 2004; Drevets, 2007; Hamilton et al., 2008; Surguladze et al., 2008). This has led to the pursuit of intermediate phenotypes, sometimes called endophenotypes . "
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ABSTRACT: Major depressive disorder and bipolar disorder share symptoms that may reflect core mood disorder features. This has led to the pursuit of intermediate phenotypes and a dimensional approach to understand neurobiological disruptions in mood disorders. Executive dysfunction, including cognitive control, may represent a promising intermediate phenotype across major depressive disorder and bipolar disorder. This study examined dimensions of cognitive control in women with major depressive disorder or bipolar disorder in comparison to healthy control subjects using two separate, consecutive experiments. For Experiment 1, participants completed a behavioural cognitive control task (healthy controls = 150, major depressive disorder = 260, bipolar disorder = 202; age range 17-84 years). A sample of those participants (healthy controls = 17, major depressive disorder = 19, and bipolar disorder = 16) completed a similar cognitive control task in an event-related design functional magnetic resonance imaging protocol for Experiment 2. Results for Experiment 1 showed greater impairments on the cognitive control task in patients with mood disorders relative to healthy controls (P < 0.001), with more of those in the mood disorder group falling into the 'impaired' range when using clinical cut-offs (<5th percentile). Experiment 2 revealed only a few areas of shared activation differences in mood disorder greater than healthy controls. Activation analyses using performance as a regressor, irrespective of diagnosis, revealed within and extra-network areas that were more active in poor performers. In summary, performance and activation during cognitive control tasks may represent an intermediate phenotype for mood disorders. However, cognitive control dysfunction is not uniform across women with mood disorders, and activation is linked to performance more so than disease. These findings support subtype and dimensional approaches to understanding risk and expression of mood disorders and are a promising area of inquiry, in line with the Research Domain Criteria initiative of NIMH.
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