No abstract

Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!‐moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!‐moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra‐high‐field 7 T fMRI during a German Version of the RAT. During this task, subjects were exposed to word triplets and instructed to find a solution word being associated with all the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!‐moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus, and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc), and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving.

No abstract

Self-other distinction is crucial for empathy, since it prevents the confusion of self-experienced emotions with those of others. We aimed to extend our understanding of the neurocognitive mechanisms of self-other distinction. Thirty-one female participants underwent continuous theta burst transcranial magnetic stimulation (cTBS) targeting the right supramarginal gyrus (rSMG), a sub-region of the temporoparietal junction previously shown to be involved in self-other distinction, and the vertex, a cortical control site. Right after stimulation they completed a visuotactile empathy task in an MRI scanner. Self-other distinction was assessed by differences in emotion judgments, and brain activity between conditions differing in the requirement for selfother distinction. Effects of brain stimulation on self-other distinction depended on individual differences in dispositional empathic understanding: cTBS of rSMG, compared to vertex, enhanced self-other distinction in participants with lower dispositional empathic understanding, but diminished it in participants with higher empathic understanding. On the neural level, this inverse relationship between empathic disposition and self-other distinction performance was linked to a reduction of cTBS-induced rSMG activity in persons with lower dispositional empathy, and an increase in those with lower dispositional empathy. These opposite impacts of cTBS were associated with two anatomically and functionally distinct networks. These findings open up novel perspectives on the causal role of rSMG in self-other distinction and empathy. They also suggest that considering individual differences may yield novel insights into how brain stimulation affects higher-level affect and cognition, and its neural correlates. SELF-OTHER DISTINCTION RTMS/FMRI 4 1. Introduction: Our emotional states can interfere with our empathic appreciation of how another person feels, and conversely, others' emotions can sometimes intrude and confuse the way we feel ourselves. These barriers to empathic understanding are referred to as the egocentric and altercentric biases, respectively, and can be overcome via self-other distinction, a mechanism enabling the regulation and resolution of discrepancies as well as confusions between selfexperienced feelings and those experienced by another person (Lamm, Bukowski, & Silani, 2016). Social neuroscience has recently set out to investigate the neural underpinnings of self-other distinction in empathy (Lamm et al., 2016; von Mohr, Finotti, Ambroziak, & Tsakiris, 2019), by means of tailored experimental paradigms. In one study (Silani, Lamm, Ruff, & Singer, 2013) combining behavioral, neuroimaging and brain stimulation experiments, we had shown that the right supramarginal gyrus (rSMG) plays a specific and causal role in empathy-related self-other distinction. The present study builds up on this prior evidence. Here, we investigated the neural network underpinning empathy-related self-other distinction, by combining theta burst transcranial magnetic stimulation (c...

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6–8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.

No abstract

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

No abstract