Neural correlates of ‘pessimistic' attitude in depression

Background Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that ‘pessimism'-related emotion processing would characterize brain activity in major depression. Method During functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences - pleasant, unpleasant and neutral - and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the ‘unknown' expectation was compared with the ‘known' expectation conditions. Results While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. Conclusions Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a ‘pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depressio

Anticipatory feelings: Neural correlates and linguistic markers

This review introduces anticipatory feelings (AF) as a new construct related to the process of anticipation and prediction of future events. AF, defined as the state of awareness of physiological and neurocognitive changes that occur within an oganism in the form of a process of adapting to future events, are an important component of anticipation and expectancy. They encompass bodily-related interoceptive and affective components and are influenced by intrapersonal and dispositional factors, such as optimism, hope, pessimism, or worry. In the present review, we consider evidence from animal and human research, including neuroimaging studies, to characterize the brain structures and brain networks involved in AF. The majority of studies reviewed revealed three brain regions involved in future oriented feelings: 1) the insula; 2) the ventromedial prefrontal cortex (vmPFC); and 3) the amygdala. Moreover, these brain regions were confirmed by a meta-analysis, using a platform for large-scale, automated synthesis of fMRI data. Finally, by adopting a neurolinguistic and a big data approach, we illustrate how AF are expressed in language

Neural correlates of personality dimensions and affective measures during the anticipation of emotional stimuli

Neuroticism and extraversion are proposed personality dimensions for individual emotion processing. Neuroticism is correlated with depression and anxiety disorders, implicating a common neurobiological basis. Extraversion is rather inversely correlated with anxiety and depression. We examined neural correlates of personality in relation to depressiveness and anxiety in healthy adult subjects with functional magnetic resonance imaging during the cued anticipation of emotional stimuli. Distributed particularly prefrontal but also other cortical regions and the thalamus were associated with extraversion. Parieto-occipital and temporal regions and subcortically the caudate were correlated with neuroticism and affective measures. Neuroticism-related regions were partially cross-correlated with anxiety and depression and vice versa. Extraversion-related activity was not correlated with the other measures. The neural correlates of extraversion compared with those of neuroticism and affective measures fit with concepts of different neurobiological bases of the personality dimensions and point at predispositions for affective disorder

Altered emotion processing circuits during the anticipation of emotional stimuli in women with borderline personality disorder

Borderline personality disorder (BPD) is associated with disturbed emotion processing, typically encompassing intense and fast emotional reactions toward affective stimuli. In this study, we were interested in whether emotional dysregulation in BPD occurs not only during the perception of emotional stimuli, but also during the anticipation of upcoming emotional pictures in the absence of concrete stimuli. Eighteen female patients with a diagnosis of BPD and 18 healthy control subjects anticipated cued visual stimuli with prior known emotional valence or prior unknown emotional content during functional magnetic resonance imaging. Brain activity during the anticipation of emotional stimuli was compared between both groups. When anticipating negative pictures, BPD patients demonstrated less signal change in the left dorsal anterior cingulate cortex (dACC) and left middle cingulate cortex (MCC), and enhanced activations in the left pregenual ACC, left posterior cingulate cortex (PCC) as well as in left visual cortical areas including the lingual gyrus. During the anticipation of ambiguously announced stimuli, brain activity in BPD was also reduced in the left MCC extending into the medial and bilateral dorsolateral prefrontal cortex. Results point out that deficient recruitment of brain areas related to cognitive-emotional interaction already during the anticipation phase may add to emotional dysregulation in BPD. Stronger activation of the PCC could correspond to an increased autobiographical reference in BPD. Moreover, increased preparatory visual activity during negative anticipation may contribute to hypersensitivity toward emotional cues in this disorder

Differential modulation of emotion processing brain regions by noradrenergic and serotonergic antidepressants

Rationale: Most widely used antidepressant drugs affect the serotonergic and noradrenergic pathways. However, there are currently no neurobiological criteria for selecting between these targets and predicting the treatment response in individual depressed patients. Objectives: The current study is aimed at differentiating brain regions known to be pathophysiologically and functionally involved in depression-related emotion processing with respect to their susceptibility to serotonergic and noradrenergic modulation. Methods: In a single-blind pseudo-randomized crossover study, 16 healthy subjects (out of 21 enrolled) were included in analysis after ingesting a single dose of citalopram (a selective serotonin-reuptake inhibitor, 40mg), reboxetine (a selective noradrenaline-reuptake inhibitor, 8mg), or placebo at three time points prior to functional magnetic resonance imaging (fMRI). During fMRI, subjects anticipated and subsequently viewed emotional pictures. Effects of serotonergic and noradrenergic modulation versus placebo on brain activity during the perception of negative pictures were analyzed with a repeated measures ANOVA in the whole brain and in specific regions of interest relevant to depression. Results: Noradrenergic modulation by reboxetine increased brain activity in the thalamus, right dorsolateral prefrontal cortex and occipital regions during the perception of negative emotional stimuli. Citalopram primarily affected the ventrolateral prefrontal cortical regions. Conclusion: The brain regions involved in the processing of negative emotional stimuli were differentially modulated by selective noradrenergic and serotonergic drugs: thalamic activity was increased by reboxetine, whereas citalopram primarily affected ventrolateral prefrontal regions. Thus, dysfunction in these regions, which could be identified in depressed patients, may predict treatment responses to either noradrenergic or serotonergic antidepressant

SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli

Introduction: The prediction of antidepressant treatment response may improve outcome. Functional magnetic resonance imaging (fMRI) of emotion processing in major depressive disorder (MDD) may reveal regional brain function serving as predictors of response to treatment with selective serotonin reuptake inhibitor (SSRI). Methods: We examined the association between pre-treatment neural activity by means of fMRI during the perception of emotional stimuli in 22 patients with MDD and the treatment outcome after 6 weeks' medication with an SSRI. A whole brain correlation analysis with Beck Depression Inventory (BDI) change between pre- to post-treatment was conducted to identify neural regions associated with treatment response. Results: During the perception of positive stimuli, responders were characterized by more activation in posterior cingulate cortex (PCC), medial prefrontal cortex, and thalamus as well as middle temporal gyrus. During perception of negative stimuli, PCC, and pregenual anterior cingulate cortex showed the highest correlation with treatment response. Furthermore, responders exhibited higher activation to emotional stimuli than to neutral stimuli in all the above-mentioned regions, while non-responders demonstrated an attenuated neural response to emotional compared to neutral stimuli. Conclusion: Our data suggest that the activity of distinct brain regions is correlated with SSRI treatment outcome and may serve as treatment response predictor. While some regions, in which activity was correlated with treatment response, can be assigned to networks that have been implied in the pathophysiology of depression, most of our regions of interest could also be matched to the default mode network (DMN). Higher DMN activity has been associated with increased rumination as well as negative self-referential processing in previous studies. This may suggest our responders to SSRI to be characterized by such dysregulations and that SSRIs might modify the function associated with this network

Major depressive disorder and alterations in insular cortical activity: A review of current functional magnetic imaging (fMRI) research

Major depressive disorder (MDD) is characterized by a dysregulated fronto-limbic network. The hyperactivation of limbic regions leads to increased attention and processing of emotional information, with a bias toward negative stimuli. Pathological ruminative behavior is a common symptom of depressive disorder whereby the individual is unable to disengage from internal mental processing of emotionally-salient events. In fact, lower deactivations of the neural baseline resting state may account for the increased internal self-focus. The insular cortex, with its extensive connections to fronto-limbic and association areas has recently also been implicated to be a part of this network. Given its wide-reaching connectivity, it has been putatively implicated as an integration center of autonomic, visceromotor, emotional and interoceptive information. The following paper will review recent imaging findings of altered insular function and connectivity in depressive pathology

The Human Likeness Dimension of the “Uncanny Valley Hypothesis”: Behavioral and Functional MRI Findings

The uncanny valley hypothesis (Mori, 1970) predicts differential experience of negative and positive affect as a function of human likeness. Affective experience of humanlike robots and computer-generated characters (avatars) dominates “uncanny” research, but findings are inconsistent. Importantly, it is unknown how objects are actually perceived along the hypothesis’ dimension of human likeness (DOH), defined in terms of human physical similarity. To examine whether the DOH can also be defined in terms of effects of categorical perception (CP), stimuli from morph continua with controlled differences in physical human likeness between avatar and human faces as endpoints were presented. Two behavioral studies found a sharp category boundary along the DOH and enhanced visual discrimination (i.e., CP) of fine-grained differences between pairs of faces at the category boundary. Discrimination was better for face pairs presenting category change in the human-to-avatar than avatar-to-human direction along the DOH. To investigate brain representation of physical change and category change along the DOH, an event-related functional magnetic resonance imaging study used the same stimuli in a pair-repetition priming paradigm. Bilateral mid-fusiform areas and a different right mid-fusiform area were sensitive to physical change within the human and avatar categories, respectively, whereas entirely different regions were sensitive to the human-to-avatar (caudate head, putamen, thalamus, red nucleus) and avatar-to-human (hippocampus, amygdala, mid-insula) direction of category change. These findings show that Mori’s DOH definition does not reflect subjective perception of human likeness and suggest that future “uncanny” studies consider CP and the DOH’s category structure in guiding experience of non-human objects

THE ROLE OF PROBABILISTIC INFORMATION ON AFFECTIVE PREDICTIONS: NEURAL AND SUBJECTIVE CORRELATES AS MODULATED BY INTOLERANCE OF UNCERTAINTY

Emotions have been recently reconsidered as interoceptive predictive models, “constructed” by the brain on the basis of contextual information and prior experience, with the aim to predict relevant stimuli or events, and to provide the organism with optimal resources for survival. Nevertheless, the specific mechanisms underlying the construction of affective predictions both at the neural and subjective experience level remain unclear. More specifically, both the role played by contextual information and prior experience on the one hand, and the potential interactions with dispositional characteristics such as Intolerance of Uncertainty (IU), which is considered a trans-diagnostic risk factor for affective disorders, on the other hand, have yet to be unraveled. The present thesis aimed to answer these open questions. As a first aim, we investigated how contextual information of different predictive value modulates the neural correlates of affective predictions construction. Second, we explored how prior probabilistic experience affects the construction of affective predictions at the subjective experience level. Third and last, we studied how individual differences in IU impact on the construction of affective predictions as a function of contextual information and prior experience. Taken together, this thesis contributes to untangling the dynamics of affective prediction construction at the neural and subjective experience level. Contextual information and prior experience were found to differently influence (depending on their predictive value), and to interact with IU, in shaping the neural correlates and the subjective experience of emotion along the construction of affective predictions. Thus, this work offers both a theoretical contribution to predictive models of emotion, by better clarifying the mechanisms subtending prediction construction at the neural and subjective experience levels, and potential clinical implications for the prevention and treatment of anxiety disorders, given the trans-diagnostic nature of IU as a risk factor for the development of affective psychopathology.Emotions have been recently reconsidered as interoceptive predictive models, “constructed” by the brain on the basis of contextual information and prior experience, with the aim to predict relevant stimuli or events, and to provide the organism with optimal resources for survival. Nevertheless, the specific mechanisms underlying the construction of affective predictions both at the neural and subjective experience level remain unclear. More specifically, both the role played by contextual information and prior experience on the one hand, and the potential interactions with dispositional characteristics such as Intolerance of Uncertainty (IU), which is considered a trans-diagnostic risk factor for affective disorders, on the other hand, have yet to be unraveled. The present thesis aimed to answer these open questions. As a first aim, we investigated how contextual information of different predictive value modulates the neural correlates of affective predictions construction. Second, we explored how prior probabilistic experience affects the construction of affective predictions at the subjective experience level. Third and last, we studied how individual differences in IU impact on the construction of affective predictions as a function of contextual information and prior experience. Taken together, this thesis contributes to untangling the dynamics of affective prediction construction at the neural and subjective experience level. Contextual information and prior experience were found to differently influence (depending on their predictive value), and to interact with IU, in shaping the neural correlates and the subjective experience of emotion along the construction of affective predictions. Thus, this work offers both a theoretical contribution to predictive models of emotion, by better clarifying the mechanisms subtending prediction construction at the neural and subjective experience levels, and potential clinical implications for the prevention and treatment of anxiety disorders, given the trans-diagnostic nature of IU as a risk factor for the development of affective psychopathology