Melanie Feeser

Transcranial Direct Current Stimulation Enhances Cognitive Control During Emotion Regulation

BACKGROUND The ability to cognitively control emotions is critical for mental health. Previous studies have identified the dorsolateral prefrontal cortex (dlPFC) as a core region in cognitive reappraisal. However, there is only scarce evidence whether directly modulating dlPFC activity results in improved capacities for cognitive reappraisal. OBJECTIVE In this study, we used anodal transcranial direct current stimulation (tDCS) over the right dlPFC to investigate the effects of increased dlPFC excitability on cognitive reappraisal as indexed by subjective emotional arousal ratings and skin conductance responses. METHODS The study was designed as a double-blind, between-subjects, sham-controlled trial. Half of the healthy participants were randomly assigned to receive either active tDCS (n = 21, 1.5 mA for 20 min over the right dlPFC) or sham stimulation (n = 21). Participants viewed negative and neutral pictures from the International Affective Picture System while they were instructed to either downregulate, upregulate or maintain their emotions. After each picture presentation, participants rated the intensity of emotional arousal. Skin conductance responses and gaze fixation were assessed. RESULTS Our results revealed that anodal prefrontal tDCS during downregulation resulted in decreased skin conductance responses and decreased emotional arousal ratings. The opposite pattern was observed for the upregulation condition in which anodal tDCS resulted in higher arousal ratings accompanied by marginally enhanced skin conductance responses. CONCLUSION Our data indicates that tDCS facilitates cognitive reappraisal in both directions by either increasing or decreasing emotional responsiveness depending on the regulatory goal. This provides further evidence for the potential use of tDCS as a tool to modulate cognitive reappraisal. However, given the limitations of the present study, our findings need to be replicated and complimented by further studies.

Early life stress modulates amygdala-prefrontal functional connectivity: implications for oxytocin effects.

Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs‐FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala‐prefrontal rs‐FC, and examine whether ELS‐associated changes of rs‐FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala‐prefrontal circuit. Eighteen healthy young males participated in a resting‐state fMRI study of OXT effects using a double‐blind, randomized, placebo‐controlled, within‐subject crossover design. We measured the rs‐FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs‐FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC‐amygdala rs‐FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest‐task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest‐task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC‐amygdala rs‐FC and alters how rs‐FC of this circuit predicts its stress responsiveness. Such changes in pgACC‐amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS. Hum Brain Mapp 35:5328–5339, 2014.

Early life stress modulates oxytocin effects on limbic system during acute psychosocial stress

Early life stress (ELS) is associated with altered stress responsivity, structural and functional brain changes and an increased risk for the development of psychopathological conditions in later life. Due to its behavioral and physiological effects, the neuropeptide oxytocin (OXT) is a useful tool to investigate stress responsivity, even though the neurobiological underpinnings of its effects are still unknown. Here we investigate the effects of OXT on cortisol stress response and neural activity during psychosocial stress. Using functional magnetic resonance imaging in healthy subjects with and without a history of ELS, we found attenuated hormonal reactivity and significantly reduced limbic deactivation after OXT administration in subjects without a history of ELS. Subjects who experienced ELS showed both blunted stress reactivity and limbic deactivation during stress. Furthermore, in these subjects OXT had opposite effects with increased hormonal reactivity and increased limbic deactivation. Our results might implicate that reduced limbic deactivation and hypothalamic-pituitary-adrenal axis responsivity during psychosocial stress are markers for biological resilience after ELS. Effects of OXT in subjects with a history of maltreatment could therefore be considered detrimental and suggest careful consideration of OXT administration in such individuals.

Oxytocin improves mentalizing – Pronounced effects for individuals with attenuated ability to empathize

The ability to predict the behavior of others based on their mental states is crucial for social functioning. Previous studies have provided evidence for the role of Oxytocin (OXT) in enhancing the ability to mentalize. It has also been demonstrated that the effect of OXT seems to strongly depend on socio-cognitive skills with more pronounced effects in individuals with lower socio-cognitive skills. Although recent studies indicate that mentalizing is related to empathy, no study has yet examined whether the effects of OXT on mentalizing depend on the ability to empathize. 71 male participants participated in a double-blind, between-subjects, placebo-controlled experiment. The Reading the Mind in the Eye Test (RMET) was used to investigate mentalizing abilities. We analyzed the effect of OXT on easy and difficult items of the RMET depending on differential empathy scores of the participants as assessed with the Empathy Quotient (EQ). Our results showed that OXT improves mentalizing for difficult but not for easy items. We generally observed increased mentalizing accuracy in participants with higher empathy scores. Importantly, however, whereas the performance in participants with higher empathy scores was comparable in both OXT and placebo condition, OXT specifically enhanced mentalizing accuracy in participants with lower empathy scores. Our findings suggest that OXT enhances mentalizing abilities. However, we also demonstrate that not all participants benefited from OXT application. It seems that the effects of OXT strongly depend on baseline social-cognitive skills such as empathy.

Transcranial direct current stimulation of the prefrontal cortex: a means to modulate fear memories.

Targeting memory processes by noninvasive interventions is a potential gateway to modulate fear memories as shown by animal and human studies in recent years. Modulation of fear memories by noninvasive brain stimulation techniques might be an attractive approach, which, however, has not been examined so far. We investigated the effect of transcranial direct current stimulation (tDCS) applied to the right dorsolateral prefrontal cortex and left supraorbital region on fear memories in humans. Seventy-four young, healthy individuals were assigned randomly to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal – anodal, left supraorbital – cathodal) for 20 min at 1 mA current intensity or sham stimulation. A day later, fear responses of both groups were compared by monitoring skin conductance. On day 3, during fear response assessment, the tDCS group had a significantly (P<0.05) higher mean skin conductance in comparison with the sham group. These results suggest that tDCS (right prefrontal – anodal, left supraorbital – cathodal) enhanced fear memories, possibly by influencing the prefrontal cortex–amygdala circuit underlying the memory for fear.

Amygdala–Hippocampal Connectivity Changes During Acute Psychosocial Stress: Joint Effect of Early Life Stress and Oxytocin

Previous evidence shows that acute stress changes both amygdala activity and its connectivity with a distributed brain network. Early life stress (ELS), especially emotional abuse (EA), is associated with altered reactivity to psychosocial stress in adulthood and moderates or even reverses the stress-attenuating effect of oxytocin (OXT). The neural underpinnings of the interaction between ELS and OXT remain unclear, though. Therefore, we here investigate the joint effect of ELS and OXT on transient changes in amygdala-centered functional connectivity induced by acute psychosocial stress, using a double-blind, randomized, placebo-controlled, within-subject crossover design. Psychophysiological interaction analysis in the placebo session revealed stress-induced increases in functional connectivity between amygdala and medial prefrontal cortex, posterior cingulate cortex, putamen, caudate and thalamus. Regression analysis showed that EA was positively associated with stress-induced changes in connectivity between amygdala and hippocampus. Moreover, hierarchical linear regression showed that this positive association between EA and stress-induced amygdala–hippocampal connectivity was moderated after the administration of intranasal OXT. Amygdala–hippocampal connectivity in the OXT session correlated negatively with cortisol stress responses. Our findings suggest that altered amygdala-hippocampal functional connectivity during psychosocial stress may have a crucial role in the altered sensitivity to OXT effects in individuals who have experienced EA in their childhood.

Interaction of Early Life Stress and Corticotropin-Releasing Hormone Receptor Gene: Effects on Working Memory

BACKGROUND Early life stress (ELS) experience is associated with persisting working memory (WM) deficits; changes to the corticotropin-releasing hormone (CRH) system; and structural, functional, and epigenetic changes in the hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS experience to predict depression as well as neuroendocrine and neuronal reactivity. Although these findings indicate that vulnerable genotypes might also show impaired WM performance after ELS experience, no previous study investigated whether there is an interaction effect of CRHR1 polymorphisms and ELS experience on WM performance. METHODS Subjects (N = 451) were genotyped for rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to investigate the hypothesis that WM performance in healthy subjects may be subtly influenced by functional differences in CRHR1 and represents an early marker of increased vulnerability after exposure to ELS. RESULTS Exposure to ELS had a particularly strong impact on WM performance in subjects with the common homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM accuracy in AT carriers. CONCLUSIONS Our data indicate that specific CRHR1 polymorphisms moderate the effect of ELS experience on WM performance. Exposure to ELS in combination with a vulnerable genotype results in subtle memory deficits in adulthood, which might develop before psychopathological symptoms.

The beneficial effect of oxytocin on avoidance-related facial emotion recognition depends on early life stress experience

RationalePrevious studies have shown that oxytocin (OXT) enhances social cognitive processes. It has also been demonstrated that OXT does not uniformly facilitate social cognition. The effects of OXT administration strongly depend on the exposure to stressful experiences in early life. Emotional facial recognition is crucial for social cognition. However, no study has yet examined how the effects of OXT on the ability to identify emotional faces are altered by early life stress (ELS) experiences. Given the role of OXT in modulating social motivational processes, we specifically aimed to investigate its effects on the recognition of approach- and avoidance-related facial emotions.MethodsIn a double-blind, between-subjects, placebo-controlled design, 82 male participants performed an emotion recognition task with faces taken from the “Karolinska Directed Emotional Faces” set. We clustered the six basic emotions along the dimensions approach (happy, surprise, anger) and avoidance (fear, sadness, disgust). ELS was assessed with the Childhood Trauma Questionnaire (CTQ).ResultsOur results showed that OXT improved the ability to recognize avoidance-related emotional faces as compared to approach-related emotional faces. Whereas the performance for avoidance-related emotions in participants with higher ELS scores was comparable in both OXT and placebo condition, OXT enhanced emotion recognition in participants with lower ELS scores. Independent of OXT administration, we observed increased emotion recognition for avoidance-related faces in participants with high ELS scores.ConclusionsOur findings suggest that the investigation of OXT on social recognition requires a broad approach that takes ELS experiences as well as motivational processes into account.

Context insensitivity during positive and negative emotional expectancy in depression assessed with functional magnetic resonance imaging.

Patients with depression show an enhanced preoccupation with negative expectations and are often unable to look forward to positive events. Here we studied anticipatory emotional processes in unmedicated depressed patients using functional magnetic resonance imaging. Consistent with a negative processing bias, we hypothesized enhanced responses to negative and attenuated responses to positive expectancy cues in brain areas associated with emotional expectancy. Participants comprised 19 drug-free depressed patients and 19 matched healthy control subjects who viewed affective photographs. Pictures were preceded by an expectancy cue which signaled the emotional valence of the upcoming picture in half of the trials. Depressed patients showed attenuated blood-oxygen-level-dependent responses in the left lateral prefrontal cortex (inferior frontal gyrus, Brodmann area 44) during positive expectancy and-contrary to our hypothesis-in the right lateral orbitofrontal cortex (middle frontal gyrus, Brodmann area 47) during negative expectancy. This attenuation was specific for the anticipation (as opposed to the perception) of emotional pictures and correlated with a clinical measure of depressive symptoms. The observed attenuation suggests emotion-context insensitivity rather than a negative processing bias during anticipatory emotional processes in depression. This hyporeactivity may contribute to clinical features like anergia, apathy, and loss of motivation in the context of both positive and negative incentives.

State-Dependent Effects of Prefrontal Repetitive Transcranial Magnetic Stimulation on Emotional Working Memory

BACKGROUND A growing body of findings illustrates the importance of state-dependency in studies using brain stimulation. OBJECTIVE We aimed to investigate the effects of tDCS priming followed by rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) on emotional working memory. METHODS In a randomized single-blind within-subjects design, participants performed an emotional 3-back task at baseline and after tDCS priming (anodal, cathodal) and subsequent low-frequency rTMS (active, sham) of the right DLPFC. Stimuli consisted of words related to the distinct emotion categories fear and anger as well as neutral words. RESULTS Task accuracy increased for fear-related words and decreased for neutral words across stimulation conditions. No general state-dependent effects of prefrontal rTMS on working memory were found. We further showed a detrimental effect of negative emotional content on working memory performance. CONCLUSIONS Our findings support a hemispheric lateralization of emotion processing by demonstrating that the withdrawal-related emotion fear is associated with the right DLPFC and contribute to clarifying the interaction between working memory and emotion.