Effects of stress

Complex cognitive tasks such as mental arithmetic heavily rely on intact, well-coordinated prefrontal cortex (PFC) function. Converging evidence suggests that frontal midline theta (FMT) oscillations play an important role during the execution of such PFC-dependent tasks. Additionally, it is well- established that acute stress impairs PFC function, and recent evidence suggests that FMT is decreased under stress. In this EEG study, we investigated FMT oscillations during a mental arithmetic task that was carried out in a stressful and a neutral control condition. Our results show late- onset, sustained FMT increases during mental arithmetic. In the neutral condition FMT started to increase earlier than in the stress condition. Direct comparison of the conditions quantified this difference by showing stronger FMT increases in the neutral condition in an early time window. Between- subject correlation analysis showed that attenuated FMT under stress was related to slowed reaction times. Our results suggest that FMT is associated with stimulus independent mental processes during the natural and complex PFC- dependent task of mental arithmetic, and is a possible marker for intact PFC function that is disrupted under stress

Interaction of HPA axis genetics and early life stress shapes emotion recognition in healthy adults

Background: Early life stress (ELS) affects facial emotion recognition (FER), as well as the underlying brain network. However, there is considerable inter-individual variability in these ELS-caused alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is assumed to mediate neural and behavioural sequelae of ELS, the genetic disposition towards HPA axis reactivity might explain differential vulnerabilities. Methods: An additive genetic profile score (GPS) of HPA axis reactivity was built from 6 SNPs in 3 HPA axisrelated genes (FKBP5, CRHR1, NR3C1). We studied two independent samples. As a proof of concept, GPS was tested as a predictor of cortisol increase to a psychosocial challenge (MIST) in a healthy community sample of n=40. For the main study, a sample of n=170 completed a video-based FER task and retrospectively reported ELS experiences in the Childhood Trauma Questionnaire (CTQ). Results: GPS positively predicted cortisol increase in the stress challenge over and above covariates. CTQ and genetic profile scores interacted to predict facial emotion recognition, such that ELS had a detrimental effect on emotion processing only in individuals with higher GPS. Post-hoc moderation analyses revealed that, while a less stress-responsive genetic profile was protective against ELS effects, individuals carrying a moderate to high GPS were affected by ELS in their ability to infer emotion from facial expressions. Discussion: These results suggest that a biologically informed genetic profile score can capture the genetic disposition to HPA axis reactivity and moderates the influence of early environmental factors on facial emotion recognition. Further research should investigate the neural mechanisms underlying this moderation. The GPS used here might prove a powerful tool for studying inter-individual differences in vulnerability to early life stress

A symptom-based approach in predicting ECT outcome in depressed patients employing MADRS single items

Establishing symptom-based predictors of electroconvulsive therapy (ECT) outcome seems promising, however, findings concerning the predictive value of distinct depressive symptoms or subtypes are limited; previous factor-analytic approaches based on the Montgomery-Åsberg Depression Rating Scale (MADRS) remained inconclusive, as proposed factors varied across samples. In this naturalistic study, we refrained from these previous factor-analytic approaches and examined the predictive value of MADRS single items and their change during the course of ECT concerning ECT outcome. We used logistic and linear regression models to analyze MADRS data routinely assessed at three time points in 96 depressed psychiatric inpatients over the course of ECT. Mean age was 53 years (SD 14.79), gender ratio was 58:38 (F:M), baseline MADRS score was M = 30.20 (SD 5.42). MADRS single items were strong predictors of ECT response, remission and overall symptom reduction, especially items 1 (apparent sadness), 2 (reported sadness) and 8 (inability to feel), assessing affective symptoms. Strongest effects were found for regression models including item 2 (reported sadness) with up to 80% correct prediction of ECT outcome. ROC analyses were performed to estimate the optimal cut-point for treatment response. MADRS single items during the course of ECT might pose simple, reliable, time- and cost-effective predictors of ECT outcome. More severe affective symptoms of depression at baseline and a stronger reduction of these affective symptoms during the course of ECT seem to be positively associated with ECT outcome. Precise cut-off values for clinical use were proposed. Generally, these findings underline the benefits of a symptom-based approach in depression research and treatment in addition to depression sum-scores and generalized diagnoses

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker

Background: Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy. Methods: We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan. Results: Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome. Conclusions: Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine. Keywords: antidepressant effects; ketamine; multimodal neuroimaging biomarker; pgACC; pregenual anterior cingulate cortex

Aberrant Long-Range Temporal Correlations in Depression Are Attenuated after Psychological Treatment

The spontaneous oscillatory activity in the human brain shows long-range temporal correlations (LRTC) that extend over time scales of seconds to minutes. Previous research has demonstrated aberrant LRTC in depressed patients; however, it is unknown whether the neuronal dynamics normalize after psychological treatment. In this study, we recorded EEG during eyes-closed rest in depressed patients (N = 71) and healthy controls (N = 25), and investigated the temporal dynamics in depressed patients at baseline, and after attending either a brief mindfulness training or a stress reduction training. Compared to the healthy controls, depressed patients showed stronger LRTC in theta oscillations (4–7 Hz) at baseline. Following the psychological interventions both groups of patients demonstrated reduced LRTC in the theta band. The reduction of theta LRTC differed marginally between the groups, and explorative analyses of separate groups revealed noteworthy topographic differences. A positive relationship between the changes in LRTC, and changes in depressive symptoms was observed in the mindfulness group. In summary, our data show that aberrant temporal dynamics of ongoing oscillations in depressive patients are attenuated after treatment, and thus may help uncover the mechanisms with which psychotherapeutic interventions affect the brain

Eine Untersuchung zugrundeliegender neuronaler Oszillationen

The overall goal of this dissertation project was to investigate the role of neural oscillations in emotion-cognition interaction. The project focused on memory-related information processing, since memory processes are profoundly modulated by emotion and a strong link between memory and neural oscillations has been established. In three studies, emotional states were induced in healthy subjects using emotional film clips. Subjects had to carry out specific memory-related cognitive tasks under the influence of the respective induced emotional state. Emotional state induction procedures were chosen to achieve a relatively high level of ecological validity, and to take steps towards a translational research approach that holds the possibility to translate the findings into the context of affective disorders that are often accompanied by cognitive deficits. In the first study, an episodic memory task was carried out in different mood states, and in the second and third study, a working memory and a mental arithmetic task were carried in a stressful emotional state, compared to neutral control condition. All three studies showed that memory-related neural oscillations were modulated by the emotional state. Correlations between emotional state-dependent modulations of neural oscillations and behavioral performance suggest that oscillatory neural activity plays a meaningful role in the interaction between emotion and memory-related processes. In the outlook section, clinical implications and the possibility to externally modulate oscillations by different stimulation techniques are discussed. In summary, this work suggests that studying the role of neural oscillations in emotion-cognition interaction is an area of research that holds promising possibilities for both, basic and clinical research.Das übergeordnete Ziel dieser Dissertation bestand darin, die Rolle neuronaler Oszillationen in Prozessen der Emotions-Kognitions-Interaktion zu untersuchen. Der Fokus lag hierbei auf Gedächtnisprozessen, da zahlreiche Studien belegen, dass diese stark durch Emotionen beeinflussbar sind und ein bedeutsamer Zusammenhang zwischen Gedächtnis und neuronalen Oszillationen nachgewiesen wurde. In drei Studien wurden emotionale Zustände bei gesunden Probanden durch emotionale Filmausschnitte induziert. Die Aufgabe der Probanden bestand darin, die gedächtnisbezogenen Aufgaben unter dem Einfluss des induzierten emotionalen Zustands durchzuführen. Das Verfahren der emotionalen Zustandsinduktion wurde gewählt, um eine möglichst hohe ökologische Validität zu erreichen und um erste Schritte in Richtung eines translationalen Forschungsansatzes zu unternehmen, der die Möglichkeit bietet, die gewonnenen Erkenntnisse in den Kontext von affektiven Störungen zu übersetzen, welche oft mit kognitiven Defiziten einhergehen. In der ersten Studie wurde der Einfluss von verschiedenen Stimmungszuständen auf das episodische Gedächtnis untersucht. In Studie zwei und drei wurde der Einfluss von emotionalem Stress auf Arbeitsgedächtnis und mentale Arithmetik untersucht. Alle drei Studien zeigten, dass gedächtnisbezogene neuronale Oszillationen durch den emotionalen Zustand moduliert werden. Korrelative Zusammenhänge zwischen der emotionsabhängigen Modulation neuronaler Oszillationen und der Verhaltensleistung legen nahe, dass oszillatorische neuronale Aktivität eine bedeutende Rolle in der Interaktion zwischen Emotionen und gedächtnisbezogenen Prozessen spielt. Im Ausblick dieser Arbeit werden klinische Implikationen diskutiert, sowie die Möglichkeit, oszillatorische Aktivität durch elektrische Stimulation extern zu modulieren. Zusammenfassend legt diese Arbeit nahe, dass die Untersuchung der Rolle neuronaler Oszillationen in der Emotions- Kognitions-Interaktion einen vielversprechenden Forschungsbereich darstellt, der sowohl in der Grundlagen-, als auch in der klinischen Forschung zu neuen Erkenntnissen und Behandlungsmöglichkeiten führen kann

Commercial Brain Training: Efficacy, Transfer Effects, and the Influence of Personality Traits: A Study Conducted on Healthy Young Adults

In the present study, we investigated the effects of a four-week working memory (WM) and attention training program using commercial brain training (Synaptikon GmbH, Berlin). Sixty young healthy adults were assigned to the experimental and active control training programs. The training was conducted in a naturalistic home-based setting, while the pre- and post-examinations were conducted in a controlled laboratory setting. Transfer effects to an untrained WM task and to an untrained episodic memory task were examined. Furthermore, possible influences of personality, i.e., the five-factor model (FFM) traits and need for cognition (NFC), on training outcomes were examined. Additionally, the direct relationship between improvement in single trained tasks and improvement in the transfer tasks was investigated. Our results showed that both training groups significantly increased performance in the WM task, but only the WM training group increased their performance in the episodic memory transfer task. One of the training tasks, a visuospatial WM task, was particularly associated with improvement in the episodic memory task. Neuroticism and conscientiousness showed differential effects on the improvement in training and transfer tasks. It needs to be further examined whether these effects represent training effects or, for example, retest/practice or motivation effects

Do Empathic Individuals Behave More Prosocially? Neural Correlates for Altruistic Behavior in the Dictator Game and the Dark Side of Empathy

Do empathic individuals behave more prosocially? When we think of highly empathic individuals, we tend to assume that it is likely that those people will also help others. Most theories on empathy reflect this common understanding and claim that the personality trait empathy includes the willingness to help others, but it remains a matter of debate whether empathic individuals really help more. In economics, a prominent demonstration that our behavior is not always based on pure self-interest is the Dictator Game, which measures prosocial decisions in an allocation task. This economic game shows that we are willing to give money to strangers we do not know anything about. The present study aimed to test the relationship between dispositional empathy and prosocial acting by examining the neural underpinnings of prosocial behavior in the Dictator Game. Forty-one participants played different rounds of the Dictator Game while being scanned with functional magnetic resonance imaging (fMRI). Brain activation in the right temporoparietal junction area was associated with prosocial acting (number of prosocial decisions) and associated with empathic concern. Behavioral results demonstrated that empathic concern and personal distress predicted the number of prosocial decisions, but in a negative way. Correlations with the amount of money spent did not show any significant relationships. We discuss the results in terms of group-specific effects of affective empathy. Our results shed further light on the complex behavioral and neural mechanisms driving altruistic choices