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The regulation of emotions is an ongoing internal process and often a challenge. Current related neural models concern the intended control of reactions towards external events, mediated by prefrontal cortex regions upon basal emotion processing as in the amygdala. Cognitive strategies to regulate emotions in the context of affective disorders or stress reduction, increasingly applied in clinical practice, are also related to mindfulness techniques. We questioned their effects on neural emotion processing and investigated brain activity during purely internal mental self-referential processes of making current emotions and self-related cognitions aware. Thirty healthy subjects performed a task comprising periods of cognitive self-reflection, of introspection for actual own emotions and feelings, and of a neutral condition, while they were scanned with functional magnetic resonance imaging. Brain activations of twenty-seven subjects during emotion-introspection and self-reflection, and also a conjunction of both, were compared with the neutral condition. The conditions of self-reflection and emotion-introspection showed distinguishable activations in medial and ventrolateral prefrontal areas, in parietal regions and in the amygdala. Notably, amygdala activity decreased during emotion-introspection and increased compared to 'neutral' during self-reflection. The results indicate that already the self-referential mental state of making the actual emotional state aware is capable of attenuating emotional arousal. This extends current theories of emotion regulation and has implications for the application of mindfulness techniques as a component of psychotherapeutic strategies in affective disorders and also for possible everyday emotion regulation. AbstractThe regulation of emotions is an ongoing internal process and often a challenge. Current related neural models concern the intended control of reactions towards external events, mediated by prefrontal cortex regions upon basal emotion processing as in the amygdala. Cognitive strategies to regulate emotions in the context of affective disorders or stress reduction, increasingly applied in clinical practice, are also related to mindfulness techniques. We questioned their effects on neural emotion processing and investigated brain activity during purely internal mental selfreferential processes of making current emotions and self-related cognitions aware. Thirty healthy subjects performed a task comprising periods of cognitive self-reflection, of introspection for actual own emotions and feelings, and of a neutral condition, while they were scanned with functional magnetic resonance imaging. Brain activations of twenty-seven subjects during emotion-introspection and self-reflection, and also a conjunction of both, were compared with the neutral condition. The conditions of self-reflection and emotion-introspection showed distinguishable activations in medial and ventrolateral prefrontal areas, in parietal regions and in the amygdala. Notably, amygdala activ...

Since we do not know what future holds for us, we prepare for expected emotional events in order to deal with a pleasant or threatening environment. From an evolutionary perspective, it makes sense to be particularly prepared for the worst-case scenario. We were interested to evaluate whether this assumption is reflected in the central nervous information processing associated with expecting visual stimuli of unknown emotional valence. While being scanned with functional magnetic resonance imaging, healthy subjects were cued to expect and then perceive visual stimuli with a known emotional valence as pleasant, unpleasant, and neutral, as well as stimuli of unknown valence that could have been either pleasant or unpleasant. While anticipating pictures of unknown valence, the activity of emotion processing brain areas was similar to activity associated with expecting unpleasant pictures, but there were no areas in which the activity was similar to the activity when expecting pleasant pictures. The activity of the revealed regions, including bilateral insula, right inferior frontal gyrus, medial thalamus, and red nucleus, further correlated with the individual ratings of mood: the worse the mood, the higher the activity. These areas are supposedly involved in a network for internal adaptation and preparation processes in order to act according to potential or certain unpleasant events. Their activity appears to reflect a 'pessimistic' bias by anticipating the events of unknown valence to be unpleasant.

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Serotonergic and noradrenergic pathways are the main targets of antidepressants. Their differential effects on emotion processing-related brain activation are, however, to be further characterized. We aimed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task, which was earlier shown to be associated with depressiveness. In a single-blind pseudo-randomized crossover study, 21 healthy subjects (16 subjects finally included in the analysis) participated to ingest a single dose at three time points of either 40 mg citalopram, a selective serotonin-reuptake inhibitor, 8 mg reboxetine, a selective noradrenaline-reuptake inhibitor, or placebo 2-3 h before functional magnetic resonance imaging (fMRI). During fMRI, subjects performed a task comprising the anticipation and perception of pictures of either 'known' (positive, negative, neutral) or 'unknown' valence (randomly 50% positive or negative). In direct comparison with citalopram and with placebo, reboxetine increased brain activity in the medial thalamus. Citalopram modulated certain prefrontal and insular areas more prominently. Other frontal and parieto-occipital areas were modulated by both drugs. In conclusion, the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas, and a prefrontal and insular focus of serotonergic modulation. These findings could have implications for future selection criteria concerning personalized antidepressant medication 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 depression.

Background: Self-referential emotions such as shame/guilt and pride provide evaluative information about persons themselves. In addition to emotional aspects, social and self-referential processes play a role in self-referential emotions. Prior studies have rather focused on comparing self-referential and other-referential processes of one valence, triggered mostly by external stimuli. In the current study, we aimed at investigating the valence-specific neural correlates of shame/guilt and pride, evoked by the remembrance of a corresponding autobiographical event during functional magnetic resonance imaging. Method: A total of 25 healthy volunteers were studied. The task comprised a negative (shame/guilt), a positive (pride) and a neutral condition (expecting the distractor). Each condition was initiated by a simple cue, followed by the remembrance and finished by a distracting picture. Results: Pride and shame/guilt conditions both activated typical emotion-processing circuits including the amygdala, insula and ventral striatum, as well as self-referential brain regions such as the bilateral dorsomedial prefrontal cortex. Comparing the two emotional conditions, emotion-processing circuits were more activated by pride than by shame, possibly due to either hedonic experiences or stronger involvement of the participants in positive self-referential emotions due to a self-positivity bias. However, the ventral striatum was similarly activated by pride and shame/guilt. In the whole-brain analysis, both self-referential emotion conditions activated medial prefrontal and posterior cingulate regions, corresponding to the self-referential aspect and the autobiographical evocation of the respective emotions. Conclusion: Autobiographically evoked self-referential emotions activated basic emotional as well as self-referential circuits. Except for the ventral striatum, emotional circuits were more active with pride than with shame.

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22–66) and study sample size remains small (median n=30, IQR 20–48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1–7 days), 176 early subacute (8–90 days), 34 late subacute (91–180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600–1430) min/session, 1 (IQR, 1–1) session/d, 5 (IQR, 5–5) d/wk for 4 (IQR, 3–5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.