Simone Grimm - Academia.edu (original) (raw)

Papers by Simone Grimm

NeuroImage, 2016

Cognition-emotion interaction in the brain can be investigated by incorporating stimuli with emot... more Cognition-emotion interaction in the brain can be investigated by incorporating stimuli with emotional content into cognitive tasks. Emotional stimuli in the context of a working memory (WM) task yield increased activation in WM-related lateral prefrontal regions, whereas cognitive effort enhances deactivation in emotion-related cortical midline regions. N-methyl-d-aspartate glutamate receptors (NMDA-Rs) are critically involved in WM, and NMDA-R antagonists, such as ketamine, accordingly affect WM but also have a profound impact on emotional processing, as underscored by the rapid reduction of depressive symptoms after administration of a single dose of ketamine. The effect of ketamine on both cognitive and emotional processing therefore makes it a useful tool to further explore cognition-emotion interaction in the brain. Twenty-three healthy subjects were administered ketamine to investigate whether its effects on WM performance and brain reactivity depend on emotional content or emotional valence of stimuli. Furthermore, we aimed at investigating how ketamine affects the integration of emotion and WM processes in emotion-related cortical midline regions and WM-related lateral prefrontal regions. Results show that ketamine modulates cognition-emotion interaction in the brain by inducing lateralized and valence-specific effects in emotion-related cortical midline regions, WM-related lateral prefrontal regions and insula. In emotion-related cortical midline regions ketamine abolishes enhancement of deactivation normally observed during cognitive effort, while in the right DLPFC and the left insula the previously described pattern of increased activation due to emotional content is abrogated exclusively for negative stimuli. Our data therefore shows a specific effect of ketamine on cognition-emotion interaction in the brain and indicates that its effect on amelioration of negative biases in MDD patients might be related to less interference of cognitive processing by negative emotional content.

Neuropsychopharmacology, 2015

Previous evidence shows that acute stress changes both amygdala activity and its connectivity wit... more 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 (PPI) 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 emotional abuse (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 play a crucial role in the altered sensitivity to OXT effects in individuals who have experienced emotional abuse in their childhood.Neuropsychopharmacology accepted article preview online, 29 April 2015. doi:10.1038/npp.2015.123.

World journal of psychiatry, Jan 22, 2013

To investigate neural and behavioral correlates of emotional experiences as potential vulnerabili... more To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. Fourteen remitted participants with a history of major depression and fourteen closely matched healthy control participants took part in the study. We used two psychiatric interviews (Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and one self-report scale (Beck Depression Inventory) to assess remission. Healthy control participants were interviewed by an experienced psychiatrist to exclude those who showed any current or lifetime psychiatric or neurological disorders. To explore psychosocial and cognitive-interpersonal underpinnings of potential vulnerability markers of depression, early life stress, coping styles and alexithymia were also assessed. We induced pleasant and unpleasant emotional states using congruent combinations of music and human emotional faces to investigate neural and behavioral correlates of emotional...

Biological psychiatry, Jan 15, 2008

Although recent neuroimaging and therapeutic transcranial magnetic cortex stimulation (TMS) studi... more Although recent neuroimaging and therapeutic transcranial magnetic cortex stimulation (TMS) studies suggest imbalance between left and right dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD) the fundamental neuropsychological characterization of left DLPFC hypoactivity and right DLPFC hyperactivity in MDD remains poorly understood. We used event-related functional magnetic resonance imaging (fMRI) to investigate neural activity in left and right DLPFC related to unattended (unexpected) and attended (expected) judgment of emotions. Participating in the study were 20 medication-free patients with MDD and 30 healthy subjects. The MDD patients showed hypoactivity in the left DLPFC during both unattended and attended emotional judgment and hyperactivity in the right DLPFC during attended emotional judgment. In contrast to healthy subjects, left DLPFC activity during emotional judgment was not parametrically modulated by negative emotional valence and was inversely...

European Psychiatry, 2014

Background: Functional transcranial Doppler sonography (fTCD) of basal cerebral arteries is a non... more Background: Functional transcranial Doppler sonography (fTCD) of basal cerebral arteries is a non-invasive technique that allows monitoring of cerebral hemodynamics during cognitive performance with a high temporal resolution. There is ample evidence that age impacts on performance and cerebral hemodynamics. This study investigated those associations between a sample of young adult healthy subjects performing the Trail Making Test (TMT), a means of selective attention and complex cognitive functioning.

Journal of Visualized Experiments, 2014

The main goal of this study was to assess the usability of a tablet-computer-based application (E... more The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

Frontiers in human neuroscience, 2013

Previous studies suggest that there may be a distinct relationship between spontaneous neural act... more Previous studies suggest that there may be a distinct relationship between spontaneous neural activity and subsequent or concurrent self-specific stimulus-induced activity. This study aims to test the impact of spontaneous activity as recorded in an eyes-open (EO) resting state as opposed to eyes-closed (EC) on self-specific versus non-self-specific auditory stimulus-induced activity in fMRI. In our first experiment we used self-specific stimuli comprised of the subject's own name and non-self-specific stimuli comprised of a friend's name and an unknown name, presented during EO versus EC baselines in a 3 name condition × 2 baseline design. In Experiment 2 we directly measured spontaneous activity in the absence of stimuli during EO versus EC to confirm a modulatory effect of the two baseline conditions in the regions found to show an interaction effect in Experiment 1. Spontaneous activity during EO was significantly higher than during EC in bilateral auditory cortex and no...

ABSTRACT Background / Purpose: Ketamine is a potent glutamatergic NMDA receptor antagonist with r... more ABSTRACT Background / Purpose: Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses, thus providing a valuable research tool for the investigation of the neurobiology of mood disorders. Increasing evidence under-scores the role of glutamate dependent neuroplasticity and glutamatergic neurotransmission and metabolism in the patho-physiology of major depressive disorder.Hence, the effects of ketamine on functional brain activity during emotional and cognitive processing have to be further investigated in order to understand its rapid antidepressant properties.This imaging study in 14 healthy subjects aims at probing the neuropharmacological effects of a single intravenous subanaesthetic ketamine infusion on fMRI-BOLD responses during a working memory task using affective stimuli compared to baseline conditions. Main conclusion: Ketamine administration had no effect on working memory performance, accordingly neural activity in the DLPFC did not differ between the baseline and the ketamine session. However, there was a significant ketamine effect on negative BOLD- responses in anterior (pregenual anterior cingulate), but not posterior (posterior cingulate) regions of the default- mode network and thus seems to induce a decoupling of neural activity in anterior and posterior regions of the network

Scientific American Mind, 2013

Psychoneuroendocrinology, 2015

The ability to predict the behavior of others based on their mental states is crucial for social ... more 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.

World Journal of Biological Psychiatry, 2011

Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resti... more Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed signifi cantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed signifi cantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our fi ndings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus.

Social Cognitive and Affective Neuroscience, 2014

Early life stress (ELS) is associated with altered stress responsivity, structural and functional... more 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.

Social Cognitive and Affective Neuroscience, 2012

Extraversion is considered one of the core traits of personality. Low extraversion has been assoc... more Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

Schizophrenia Research, 2005

Background: Based on animal data, NMDA receptor hypofunction has been suggested as a model for po... more Background: Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. Methods: We investigated 16 healthy subjects which were assigned to either placebo (n=7; saline) or ketamine (n=9; 0.6 mg/kg/ h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. Results: The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. 0920-9964/$ -see front matter D (G. Northoff). Schizophrenia Research 72 (2005) 235 -248 www.elsevier.com/locate/schres Conclusion: The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia. D

Psychopharmacology, 2013

Rationale The neuropeptide oxytocin (OXT) has been shown to modulate a variety of human social be... more Rationale The neuropeptide oxytocin (OXT) has been shown to modulate a variety of human social behaviors. However, little is known about its impact on emotional memory processing. Previous research demonstrated both memory-enhancing and memory-impairing oxytocinergic effects. Methods We investigated the influence of a single (prior to encoding) and a repeated (prior to encoding and retrieval) intranasal administration of OXT on recognition memory for stimuli taken from the International Affective Picture System. In addition, we assessed the interaction of emotion regulation during encoding and OXT-induced memory effects. In a double-blind, placebo-controlled design, 80 healthy young males performed an emotion regulation task followed by a surprising recognition memory task after 60 min. Results Results show that repeated OXT administration significantly improved memory certainty for negative social stimuli. Regarding the influence of emotion regulation, the promnestic effect of OXT was more pronounced when participants had been instructed to increase their negative emotions during encoding. Conclusions Our findings indicate that OXT facilitates the processing of negative social stimuli during memory encoding and retrieval, possibly by enhancing the perception of aversive aspects in social situations.

Psychoneuroendocrinology, 2014

Working me mory-re lat e d front al t he t a act ivit y is de cre ase d unde r acut e st re ss Ma... more Working me mory-re lat e d front al t he t a act ivit y is de cre ase d unde r acut e st re ss Mat t i Ga r t n e r

PLoS ONE, 2012

Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant prop... more Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamatemodulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the ''dorsal nexus ''(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.