Publications by authors named "Birgit Abler"

58 Publications

Neural signature of error processing in major depression.

Eur Arch Psychiatry Clin Neurosci 2021 Feb 17. Epub 2021 Feb 17.

Department of Psychiatry and Psychotherapy III, Ulm University Hospital, Leimgrubenweg 12-14, Ulm, Germany.

The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.
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http://dx.doi.org/10.1007/s00406-021-01238-yDOI Listing
February 2021

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

Differential neural processing of unpleasant sensory stimulation in patients with major depression.

Eur Arch Psychiatry Clin Neurosci 2020 Apr 11. Epub 2020 Apr 11.

Department of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany.

An altered processing of negative salient stimuli has been suggested to play a central role in the pathophysiology of major depression (MD). Besides negative affective and social stimuli, physical pain as a subtype of negative sensory stimulation has been investigated in this context. However, the few neuroimaging studies on unpleasant sensory stimulation or pain processing in MD report heterogeneous findings. Here, we investigated 47 young females, 22 with MD and 25 healthy controls (HC) using fMRI (3.0 T). Four levels of increasingly unpleasant electrical stimulation were applied. Ratings of stimulus intensity were assessed by a visual analogue scale. fMRI-data were analyzed using a 2 × 4 ANOVA. Behavioral results revealed no group differences regarding accuracy of unpleasant stimulation level ratings and sensitivity to stimulation. Regarding neural activation related to increasing levels of unpleasant stimulation, we observed increasing activation of brain regions related to the pain and salient stimulus processing corresponding to increasingly unpleasant stimulation in controls. This modulation was significantly smaller in MD compared to controls, particularly in the dorsal anterior cingulate cortex, the somatosensory cortex, and the posterior insula. Overall, brain regions associated with the processing of unpleasant sensory stimulation, but also associated with the salience network, were highly reactive but less modulated in female patients with MD. These results support and extent findings on altered processing of salience and of negative sensory stimuli even of a non-painful quality in female patients with MD.
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http://dx.doi.org/10.1007/s00406-020-01123-0DOI Listing
April 2020

Differential neural processing of unpleasant sensory stimulation in patients with major depression.

Eur Arch Psychiatry Clin Neurosci 2020 Apr 11. Epub 2020 Apr 11.

Department of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany.

An altered processing of negative salient stimuli has been suggested to play a central role in the pathophysiology of major depression (MD). Besides negative affective and social stimuli, physical pain as a subtype of negative sensory stimulation has been investigated in this context. However, the few neuroimaging studies on unpleasant sensory stimulation or pain processing in MD report heterogeneous findings. Here, we investigated 47 young females, 22 with MD and 25 healthy controls (HC) using fMRI (3.0 T). Four levels of increasingly unpleasant electrical stimulation were applied. Ratings of stimulus intensity were assessed by a visual analogue scale. fMRI-data were analyzed using a 2 × 4 ANOVA. Behavioral results revealed no group differences regarding accuracy of unpleasant stimulation level ratings and sensitivity to stimulation. Regarding neural activation related to increasing levels of unpleasant stimulation, we observed increasing activation of brain regions related to the pain and salient stimulus processing corresponding to increasingly unpleasant stimulation in controls. This modulation was significantly smaller in MD compared to controls, particularly in the dorsal anterior cingulate cortex, the somatosensory cortex, and the posterior insula. Overall, brain regions associated with the processing of unpleasant sensory stimulation, but also associated with the salience network, were highly reactive but less modulated in female patients with MD. These results support and extent findings on altered processing of salience and of negative sensory stimuli even of a non-painful quality in female patients with MD.
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http://dx.doi.org/10.1007/s00406-020-01123-0DOI Listing
April 2020

Serotonergic, Dopaminergic, and Noradrenergic Modulation of Erotic Stimulus Processing in the Male Human Brain.

J Clin Med 2019 Mar 14;8(3). Epub 2019 Mar 14.

Department of Psychiatry and Psychotherapy III, Ulm University, 89075 Ulm, Germany.

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades. Pharmacological functional magnetic resonance imaging (fMRI) provides a valuable tool to examine the interaction between neuromodulator systems and functional network anatomy relevant for human sexual behavior. In addition, this approach enables the examination of potential neural mechanisms regarding treatment-related sexual dysfunction under psychopharmacological agents. In this article, we introduce common neurobiological concepts regarding cerebral sexual responses based on neuroimaging findings and we discuss challenges and findings regarding investigating the neuromodulation of neural sexual stimulus processing. In particular, we summarize findings from our research program investigating how neural correlates of sexual stimulus processing are modulated by serotonergic, dopaminergic, and noradrenergic antidepressant medication in healthy males.
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http://dx.doi.org/10.3390/jcm8030363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463265PMC
March 2019

Adolescent depression and brain development: evidence from voxel-based morphometry

J Psychiatry Neurosci 2019 Jul;44(4):237-245

From the Department of Child and Adolescent Psychiatry and Psychotherapy, Ulm University Hospital, Ulm, Germany (Straub, Brown, Bonenberger, Plener); the Department of Psychiatry and Psychotherapy III, Ulm University Hospital, Ulm, Germany (Malejko, Grön, Abler); and the Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Plener).

Background: Investigating adolescents and young adults may provide a unique opportunity to understand developmental aspects of the neurobiology of depression. During adolescence, a considerable physiologic reorganization of both grey and white matter of the brain takes place, and it has been suggested that differences in grey-matter volumes during adolescence may reflect different maturational processes.

Methods: We investigated grey-matter volumes in a comparatively large sample (n = 103) of adolescents and young adults (aged 12 to 27 years), 60 of them with a diagnosis of current depression.

Results: Replicating previous studies, we found a clear wholebrain effect of age: the older the participants, the lower their global grey-matter volumes, particularly in the paracingulate and prefrontal cortices. Contrasting depressed and healthy youth in a whole-brain approach, we found greater grey-matter volumes in the dorsolateral prefrontal cortex of those with depression. Furthermore, a region-of-interest analysis indicated lower grey-matter volumes in the hippocampus in participants with depression compared with healthy controls.

Limitations: The present study was limited because of a skewed sex distribution, its cross-sectional design and the fact that some participants were taking an antidepressant.

Conclusion: During adolescence, restructuring of the brain is characterized by marked decreases in prefrontal grey-matter volumes, interpreted as a correlate of brain maturation. Findings of greater volumes in the prefrontal cortex, particularly in younger adolescents with depression, may suggest that these participants were more prone to delayed brain maturation or increased neuroplasticity. This finding may represent a risk factor for depression or constitute an effect of developing depression.
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http://dx.doi.org/10.1503/jpn.170233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606428PMC
July 2019

Neural Correlates of Social Inclusion in Borderline Personality Disorder.

Front Psychiatry 2018 3;9:653. Epub 2018 Dec 3.

Department of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, Germany.

Humans engage in social interactions and have a fundamental need and motivation to establish and maintain social connections. Neuroimaging studies particularly focused on the neural substrates of social exclusion in healthy subjects (HC), borderline personality disorder (BPD), and major depression (MD). However, there is evidence regarding neural alterations also during social inclusion in BPD that we intended to elucidate in our study. Considering that patients with BPD often have comorbid MD, we investigated patients with BPD, and comorbid MD, patients with MD without BPD, and a sample of HC. By investigating these two clinical samples within one study design, we attempted to disentangle potential confounds arising by psychiatric disorder or medication and to relate neural alterations under social inclusion specifically to BPD. We investigated 48 females (15 BPD and MD, 16 MD, and 17 HC) aged between 18 and 40 years by fMRI (3T), using the established cyberball paradigm with social exclusion, inclusion, and passive watching conditions. Significant group-by-condition interaction effects ( < 0.05, FWE-corrected on cluster level) were observed within the dorsolateral (dlPFC) and dorsomedial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus. Comparisons of estimated neural activations revealed that significant interaction effects were related to a relative increase in neural activations during social inclusion in BPD. In detail, we observed a significant increase in differential (social inclusion vs. passive watching) neural activation within the dmPFC and the PCC in BPD compared to both, MD and HC. However, significant interaction effects within the dlPFC and the TPJ could not specifically be linked to BPD considering that they did not differ significantly between the two clinical groups in comparisons. Our study supports previous results on effects of social and inclusion in BPD, and provides further evidence regarding disorder specific neural alterations in BPD for brain regions associated with self-referential and mentalizing processes during social inclusion.
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http://dx.doi.org/10.3389/fpsyt.2018.00653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287007PMC
December 2018

Neural Correlates of Social Inclusion in Borderline Personality Disorder.

Front Psychiatry 2018 3;9:653. Epub 2018 Dec 3.

Department of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, Germany.

Humans engage in social interactions and have a fundamental need and motivation to establish and maintain social connections. Neuroimaging studies particularly focused on the neural substrates of social exclusion in healthy subjects (HC), borderline personality disorder (BPD), and major depression (MD). However, there is evidence regarding neural alterations also during social inclusion in BPD that we intended to elucidate in our study. Considering that patients with BPD often have comorbid MD, we investigated patients with BPD, and comorbid MD, patients with MD without BPD, and a sample of HC. By investigating these two clinical samples within one study design, we attempted to disentangle potential confounds arising by psychiatric disorder or medication and to relate neural alterations under social inclusion specifically to BPD. We investigated 48 females (15 BPD and MD, 16 MD, and 17 HC) aged between 18 and 40 years by fMRI (3T), using the established cyberball paradigm with social exclusion, inclusion, and passive watching conditions. Significant group-by-condition interaction effects ( < 0.05, FWE-corrected on cluster level) were observed within the dorsolateral (dlPFC) and dorsomedial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus. Comparisons of estimated neural activations revealed that significant interaction effects were related to a relative increase in neural activations during social inclusion in BPD. In detail, we observed a significant increase in differential (social inclusion vs. passive watching) neural activation within the dmPFC and the PCC in BPD compared to both, MD and HC. However, significant interaction effects within the dlPFC and the TPJ could not specifically be linked to BPD considering that they did not differ significantly between the two clinical groups in comparisons. Our study supports previous results on effects of social and inclusion in BPD, and provides further evidence regarding disorder specific neural alterations in BPD for brain regions associated with self-referential and mentalizing processes during social inclusion.
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http://dx.doi.org/10.3389/fpsyt.2018.00653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287007PMC
December 2018

Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing.

Front Psychiatry 2018 31;9:346. Epub 2018 Jul 31.

Department of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany.

We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing. We therefore investigated the sample of 17 healthy males in a mean age of 23.8 years again by functional magnetic resonance imaging (fMRI), to explore the noradrenergic effects on neural reward prediction error signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and placebo each for 7 days within a randomized, double-blind, within-subject cross-over design. During fMRI, we used an established monetary incentive task to assess neural reward expectation and prediction error signals within the bilateral Nacc using an independent anatomical mask for a region of interest (ROI) analysis. Activations within the same ROI were also assessed for the erotic picture paradigm. We confirmed our previous results from the whole brain analysis for the selected ROI by significant ( < 0.05 FWE-corrected) attenuated activations within the Nacc during visual sexual stimulation under reboxetine compared to placebo. However, activations in the Nacc concerning prediction error processing and monetary reward expectation were unimpaired under reboxetine compared to placebo, along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioral processing were not altered by amisulpride compared to placebo. The observed attenuated neural activations within the Nacc during visual erotic stimulation along with unimpaired neural prediction error and monetary reward expectation processing provide evidence for a differential modulation of the neural reward system by the noradrenergic agent reboxetine depending on the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.
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http://dx.doi.org/10.3389/fpsyt.2018.00346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079271PMC
July 2018

Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing.

Front Psychiatry 2018 31;9:346. Epub 2018 Jul 31.

Department of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany.

We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing. We therefore investigated the sample of 17 healthy males in a mean age of 23.8 years again by functional magnetic resonance imaging (fMRI), to explore the noradrenergic effects on neural reward prediction error signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and placebo each for 7 days within a randomized, double-blind, within-subject cross-over design. During fMRI, we used an established monetary incentive task to assess neural reward expectation and prediction error signals within the bilateral Nacc using an independent anatomical mask for a region of interest (ROI) analysis. Activations within the same ROI were also assessed for the erotic picture paradigm. We confirmed our previous results from the whole brain analysis for the selected ROI by significant ( < 0.05 FWE-corrected) attenuated activations within the Nacc during visual sexual stimulation under reboxetine compared to placebo. However, activations in the Nacc concerning prediction error processing and monetary reward expectation were unimpaired under reboxetine compared to placebo, along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioral processing were not altered by amisulpride compared to placebo. The observed attenuated neural activations within the Nacc during visual erotic stimulation along with unimpaired neural prediction error and monetary reward expectation processing provide evidence for a differential modulation of the neural reward system by the noradrenergic agent reboxetine depending on the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.
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http://dx.doi.org/10.3389/fpsyt.2018.00346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079271PMC
July 2018

Noradrenergic modulation of neural erotic stimulus perception.

Eur Neuropsychopharmacol 2017 09 3;27(9):845-853. Epub 2017 Jul 3.

Department of Psychiatry, Ulm University, Ulm, Germany.

We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components. We now investigated the same sample under these two agents with static erotic picture stimulation as alternative stimulus presentation mode to potentially observe further neural treatment effects of reboxetine. 19 healthy males were investigated under reboxetine, amisulpride and placebo for 7 days each within a double-blind cross-over design. During fMRI static erotic picture were presented with preceding anticipation periods. Subjective sexual functions were assessed by a self-reported questionnaire. Neural activations were attenuated within the caudate nucleus, putamen, ventral striatum, the pregenual and anterior midcingulate cortex and in the orbitofrontal cortex under reboxetine. Subjective diminished sexual arousal under reboxetine was correlated with attenuated neural reactivity within the posterior insula. Again, amisulpride left neural activations along with subjective sexual functioning unimpaired. Neither reboxetine nor amisulpride altered differential neural activations during anticipation of erotic stimuli. Our results verified detrimental effects of noradrenergic agents on neural motivational but also emotional and autonomic components of sexual behavior. Considering the overlap of neural network alterations with those evoked by serotonergic agents, our results suggest similar neuromodulatory effects of serotonergic and noradrenergic agents on common neural pathways relevant for sexual behavior.
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http://dx.doi.org/10.1016/j.euroneuro.2017.06.015DOI Listing
September 2017

Neural Correlates of Psychotherapeutic Treatment of Post-traumatic Stress Disorder: A Systematic Literature Review.

Front Psychiatry 2017 19;8:85. Epub 2017 May 19.

Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Ulm, Ulm, Germany.

Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disease with changes in neural circuitries. Neurobiological models conceptualize the symptoms of PTSD as correlates of a dysfunctional stress reaction to traumatic events. Functional imaging studies showed an increased amygdala and a decreased prefrontal cortex response in PTSD patients. As psychotherapeutic approaches represent the gold standard for PTSD treatment, it is important to examine its underlying neurobiological correlates.

Methods: Studies published until August 2016 were selected through systematic literature research in the databases PubMed, PsychInfo, and Cochrane Library's Central Register of Controlled Trials or were identified manually by searching reference lists of selected articles. Search terms were "neural correlates" OR "fMRI" OR "SPECT," AND "therapy" AND "PTSD." A total of 19 articles were included in the present review whereof 15 studies compared pre-to-post-therapy signal changes, six studies related pre-treatment activity to pre-to-post-symptom improvement, and four studies compared neural correlates of responders versus non-responders. The disposed therapy forms were cognitive behavioral therapy (CBT), eye movement desensitization and reprocessing, cognitive therapy, exposure therapy, mindfulness-based intervention, brief eclectic psychotherapy, and unspecified therapy.

Results: Successful psychotherapy of PTSD was repeatedly shown to be accompanied by decreased activity in the amygdala and the insula as well as increased activity in the dorsal anterior cingulate cortex (dACC) and hippocampus. Elevated dACC activity prior to treatment was related to subsequent treatment success and a positive predictor for treatment response. Elevated amygdala and insula pre-treatment activities were related to treatment failure.

Discussion: Decreased activity in limbic brain regions and increased activity in frontal brain areas in PTSD patients after successful psychotherapeutic treatment might reflect regained top-down control over previously impaired bottom-up processes.
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http://dx.doi.org/10.3389/fpsyt.2017.00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437215PMC
May 2017

Effects of a brief cognitive behavioural therapy group intervention on baseline brain perfusion in adolescents with major depressive disorder.

Neuroreport 2017 Apr;28(6):348-353

Departments of aPsychiatry and Psychotherapy III bChild and Adolescent Psychiatry and Psychotherapy, University Clinic of Ulm, Ulm, Germany.

A number of neuroimaging studies have identified altered regional cerebral blood flow (rCBF) related to major depressive disorder (MDD) in adult samples, particularly in the lateral prefrontal, cingular and temporal regions. In contrast, neuroimaging investigations in adolescents with MDD are rare, although investigating young patients during a significant period of brain maturation might offer valuable insights into the neural mechanisms of MDD. We acquired perfusion images obtained with continuous arterial spin labelling in 21 medication-naive adolescents with MDD before and after a five-session cognitive behavioural group therapy (group CBT). A control group included medication-naive patients under treatment as usual while waiting for the psychotherapy. We found relatively increased rCBF in the right dorsolateral prefrontal cortex (DLPFC; BA 46), the right caudate nucleus and the left inferior parietal lobe (BA 40) after CBT compared with before CBT. Relatively increased rCBF in the right DLPFC postgroup CBT was confirmed by time (post vs. pre)×group (intervention/waiting list) interaction analyses. In the waiting group, relatively increased rCBF was found in the thalamus and the anterior cingulate cortex (BA 24). The relatively small number of patients included in this pilot study has to be considered. Our findings indicate that noninvasive resting perfusion scanning is suitable to identify CBT-related changes in adolescents with MDD. rCBF increase in the DLPFC following a significant reduction in MDD symptoms in adolescents might represent the core neural correlate of changes in 'top-down' cognitive processing, a possible correlate of improved self-regulation and cognitive control.
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http://dx.doi.org/10.1097/WNR.0000000000000770DOI Listing
April 2017

Effects of a brief cognitive behavioural therapy group intervention on baseline brain perfusion in adolescents with major depressive disorder.

Neuroreport 2017 Apr;28(6):348-353

Departments of aPsychiatry and Psychotherapy III bChild and Adolescent Psychiatry and Psychotherapy, University Clinic of Ulm, Ulm, Germany.

A number of neuroimaging studies have identified altered regional cerebral blood flow (rCBF) related to major depressive disorder (MDD) in adult samples, particularly in the lateral prefrontal, cingular and temporal regions. In contrast, neuroimaging investigations in adolescents with MDD are rare, although investigating young patients during a significant period of brain maturation might offer valuable insights into the neural mechanisms of MDD. We acquired perfusion images obtained with continuous arterial spin labelling in 21 medication-naive adolescents with MDD before and after a five-session cognitive behavioural group therapy (group CBT). A control group included medication-naive patients under treatment as usual while waiting for the psychotherapy. We found relatively increased rCBF in the right dorsolateral prefrontal cortex (DLPFC; BA 46), the right caudate nucleus and the left inferior parietal lobe (BA 40) after CBT compared with before CBT. Relatively increased rCBF in the right DLPFC postgroup CBT was confirmed by time (post vs. pre)×group (intervention/waiting list) interaction analyses. In the waiting group, relatively increased rCBF was found in the thalamus and the anterior cingulate cortex (BA 24). The relatively small number of patients included in this pilot study has to be considered. Our findings indicate that noninvasive resting perfusion scanning is suitable to identify CBT-related changes in adolescents with MDD. rCBF increase in the DLPFC following a significant reduction in MDD symptoms in adolescents might represent the core neural correlate of changes in 'top-down' cognitive processing, a possible correlate of improved self-regulation and cognitive control.
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http://dx.doi.org/10.1097/WNR.0000000000000770DOI Listing
April 2017

Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

Neuroreport 2016 Jan;27(1):18-22

aDepartment of Psychiatry and Psychotherapy III, Ulm University, Ulm bDepartment of Psychiatry, Otto von Guericke University Magdeburg cGerman Center for Neurodegenerative Diseases (DZNE) dLeibniz Institute for Neurobiology, Magdeburg, Germany.

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.
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http://dx.doi.org/10.1097/WNR.0000000000000487DOI Listing
January 2016

Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

Neuroreport 2016 Jan;27(1):18-22

aDepartment of Psychiatry and Psychotherapy III, Ulm University, Ulm bDepartment of Psychiatry, Otto von Guericke University Magdeburg cGerman Center for Neurodegenerative Diseases (DZNE) dLeibniz Institute for Neurobiology, Magdeburg, Germany.

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.
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http://dx.doi.org/10.1097/WNR.0000000000000487DOI Listing
January 2016

Local and Global Resting State Activity in the Noradrenergic and Dopaminergic Pathway Modulated by Reboxetine and Amisulpride in Healthy Subjects.

Int J Neuropsychopharmacol 2015 Jul 25;19(2). Epub 2015 Jul 25.

Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany (Drs Metzger and Walter); Department of Psychiatry, University of Ulm, Germany (Drs Wiegers, Abler, and Graf); Leibniz Institute for Neurobiology, Magdeburg, Germany (Drs Metzger and Walter); Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany (Dr Metzger); German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany (Dr Metzger).

Background: Various psychiatric populations are currently investigated with resting state fMRI, with the aim of individualizing diagnostics and treatment options and improving treatment outcomes. Many of these studies are conducted in large naturalistic samples, providing rich insights regarding disease-related neural alterations, but with the common psychopharmacological medication limiting interpretations of the results. We therefore investigated the effects of common noradrenergic and anti-dopaminergic medications on local and global resting state activity (rs-activity) in healthy volunteers to further the understanding of the respective effects independent from disease-related alterations.

Methods: Within a randomized, double-blind, placebo-controlled crossover design, we investigated 19 healthy male subjects by resting state fMRI after the intake of reboxetine (4 mg/d), amisulpride (200mg/d), and placebo for 7 days each. Treatment-related differences in local and global rs-activity were measured by the fractional amplitude of low frequency fluctuations (fALFF) and resting state functional connectivity (rs-FC).

Results: fALFF revealed alterations of local rs-activity within regions of the core noradrenergic pathway, including the locus coeruleus under reboxetine, correlated with its plasma levels. Moreover, reboxetine led to increased rs-FC between regions within this pathway, i.e. the locus coeruleus, tectum, thalamus, and amygdala. Amisulpride modulated local rs-activity of regions within the dopaminergic pathway, with the altered signal in the putamen correlating with amisulpride plasma levels. Correspondingly, amisulpride increased rs-FC between regions of the dopaminergic pathway comprising the substantia nigra and putamen.

Conclusion: Our data provide evidence of how psychopharmacological agents alter local and global rs-activity within the respective neuroanatomical pathways in healthy subjects, which may help with interpreting data in psychiatric populations.
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http://dx.doi.org/10.1093/ijnp/pyv080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772816PMC
July 2015

The neural correlates of movement intentions: A pilot study comparing hypnotic and simulated paralysis.

Conscious Cogn 2015 Sep 1;35:158-70. Epub 2015 Jun 1.

Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany. Electronic address:

The distinct feeling of wanting to act and thereby causing our own actions is crucial to our self-perception as free human agents. Disturbances of the link between intention and action occur in several disorders. Little is known, however, about the neural correlates of wanting or intending to act. To investigate these for simple voluntary movements, we used a paradigm involving hypnotic paralysis and functional magnetic resonance imaging. Eight healthy women were instructed to sequentially perform left and right hand movements during a normal condition, as well as during simulated weakness, simulated paralysis and hypnotic paralysis of the right hand. Right frontopolar cortex was selectively hypoactivated for attempted right hand movement during simulated paralysis while it was active in all other conditions. Since simulated paralysis was the only condition lacking an intention to move, the activation in frontopolar cortex might be related to the intention or volition to move.
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http://dx.doi.org/10.1016/j.concog.2015.05.010DOI Listing
September 2015

Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

Int J Neuropsychopharmacol 2014 Oct 31;18(2). Epub 2014 Oct 31.

Department of Psychiatry III, Ulm University, Ulm, Germany (Drs Graf, Wiegers, Grön, and Abler); Department of Psychiatry, Otto von Guericke University, Magdeburg, Germany (Drs Metzger and Walter); Leibniz Institute for Neurobiology, Magdeburg, Germany (Drs Metzger and Walter).

Background: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects.

Methods: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire.

Results: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged.

Conclusions: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents.
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http://dx.doi.org/10.1093/ijnp/pyu004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368880PMC
October 2014

Prodromal Huntington disease as a model for functional compensation of early neurodegeneration.

PLoS One 2014 26;9(12):e114569. Epub 2014 Dec 26.

Department of Psychiatry, Ulm University, Leimgrubenweg 12-14, 89522, Ulm, Germany.

Functional compensation demonstrated as mechanism to offset neuronal loss in early Alzheimer disease may also occur in other adult-onset neurodegenerative diseases, particularly Huntington disease (HD) with its genetic determination and gradual changes in structural integrity. In HD, neurodegeneration typically initiates in the dorsal striatum, successively affecting ventral striatal areas. Investigating carriers of the HD mutation with evident dorsal, but only minimal or no ventral striatal atrophy, we expected to find evidence for compensation of ventral striatal functioning. We investigated 14 pre- or early symptomatic carriers of the mutation leading to HD and 18 matched healthy controls. Participants underwent structural T1 magnetic resonance imaging (MRI) and functional MRI during a reward task that probes ventral striatal functioning. Motor functioning and attention were assessed with reaction time (RT) tasks. Structural images confirmed a specific decrease of dorsal striatal but only marginal ventral striatal volume in HD relative to control subjects, paralleling prolonged RT in the motor response tasks. While behavioral performance in the reward task during fMRI scanning was unimpaired, reward-related fMRI signaling in the HD group was differentially enhanced in the bilateral ventral striatum and in bilateral orbitofrontal cortex/anterior insula, as another region sensitive to reward processing. We provide evidence for the concept of functional compensation in premanifest HD which may suggest a defense mechanism in neurodegeneration. Given the so far inevitable course of HD with its genetically determined endpoint, this disease may provide another model to study the different aspects of the concept of functional compensation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114569PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277279PMC
August 2015

Facilitating access to emotions: neural signature of EMDR stimulation.

PLoS One 2014 28;9(8):e106350. Epub 2014 Aug 28.

Department of Psychiatry, Ulm University, Ulm, Germany.

Background: Eye Movement Desensitisation and Reprocessing (EMDR) is a method in psychotherapy effective in treating symptoms of posttraumatic stress disorder. The client attends to alternating bilateral visual, auditory or sensory stimulation while confronted with emotionally disturbing material. It is thought that the bilateral stimulation as a specific element of EMDR facilitates accessing and processing of negative material while presumably creating new associative links. We hypothesized that the putatively facilitated access should be reflected in increased activation of the amygdala upon bilateral EMDR stimulation even in healthy subjects.

Methods: We investigated 22 healthy female university students (mean 23.5 years) with fMRI. Subjects were scanned while confronted with blocks of disgusting and neutral picture stimuli. One third of the blocks was presented without any additional stimulation, one third with bilateral simultaneous auditory stimulation, and one third with bilateral alternating auditory stimulation as used in EMDR.

Results: Contrasting disgusting vs. neutral picture stimuli confirmed the expected robust effect of amygdala activation for all auditory stimulation conditions. The interaction analysis with the type of auditory stimulation revealed a specific increase in activation of the right amygdala for the bilateral alternating auditory stimulation. Activation of the left dorsolateral prefrontal cortex showed the opposite effect with decreased activation.

Conclusions: We demonstrate first time evidence for a putative neurobiological basis of the bilateral alternating stimulation as used in the EMDR method. The increase in limbic processing along with decreased frontal activation is in line with theoretical models of how bilateral alternating stimulation could help with therapeutic reintegration of information, and present findings may pave the way for future research on EMDR in the context of posttraumatic stress disorder.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106350PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148424PMC
November 2015

Development, implementation, and evaluation of a movie-based curriculum to teach psychopathology.

Teach Learn Med 2014 ;26(1):86-9

a Department of Psychiatry and Psychotherapy III , University of Ulm , Ulm , Germany.

Background: Because medical students' attitudes toward psychiatry are often fostered by media, we provided an elective movie-based seminar to teach psychopathology.

Description: We assessed attitudes toward psychiatry by using the Attitudes towards Psychiatry (ATP 35) scale in a pre-post design. Furthermore we evaluated the knowledge of diagnostic criteria in a pre-post design within one sample.

Evaluation: Of the 75 students who attended the seminar during 3 consecutive semesters, 54 (60.8% female) participated in the pre-post assessment. We observed a significant positive change in attitudes toward psychiatry and a significant gain of knowledge.

Conclusions: Using movies is a feasible and effective method to teach psychiatry.
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http://dx.doi.org/10.1080/10401334.2013.857340DOI Listing
October 2014

Antidepressant-related sexual dysfunction - perspectives from neuroimaging.

Pharmacol Biochem Behav 2014 Jun 11;121:138-45. Epub 2013 Dec 11.

Department of Psychiatry, Ulm University, Leimgrubenweg 12-14, 89075 Ulm, Germany. Electronic address:

Sexual dysfunction is not only a common symptom in major depression but also a frequent side-effect of antidepressant medication, mainly of the selective serotonin reuptake-inhibitors (SSRI) that are often prescribed as a first line treatment option. Despite of the increasing incidence and prescription rates, neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly understood and investigations on this topic are scarce. Neuroimaging techniques, mainly functional magnetic resonance imaging (fMRI), provide a feasible approach to investigate these mechanisms since SSRI-related sexual dysfunction is most likely related to central nervous processes. This review summarizes the recent literature regarding the basic clinical findings and imaging correlates of antidepressant-related sexual dysfunction linking brain regions and networks potentially involved to phases and subcomponents of sexual processing and antidepressant action. In particular, fMRI studies on SSRI antidepressants including paroxetine and SNRIs including bupropion are highlighted.
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http://dx.doi.org/10.1016/j.pbb.2013.12.003DOI Listing
June 2014

It's all about money: oral contraception alters neural reward processing.

Neuroreport 2013 Dec;24(17):951-5

Departments of aChild and Adolescent Psychiatry and Psychotherapy bPsychiatry and Psychotherapy, University of Ulm, Ulm, Germany.

Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.
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http://dx.doi.org/10.1097/WNR.0000000000000024DOI Listing
December 2013

SSRI-related modulation of sexual functioning is predicted by pre-treatment resting state functional connectivity in healthy men.

Arch Sex Behav 2013 Aug 15;42(6):935-47. Epub 2013 Jun 15.

Department of Psychiatry and Psychotherapy, Centre for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.

Sexual dysfunction related to treatment with selective serotonin reuptake inhibitors (SSRIs) is a common reason for discontinuation of otherwise effective antidepressant treatment regimens. Thus, identification of subjects at risk for this side effect remains a crucial challenge. After demonstrating task-related neural correlates of impaired sexual functioning under treatment with the SSRI paroxetine (Abler et al., 2011), we studied (1) if resting state brain function before treatment predicts subsequent development of treatment-related modulation of sexual function, and (2) which neural circuits relate to different aspects of the impairment. Effects of paroxetine and bupropion administration over 1 week on subjective sexual functioning were investigated in 17 healthy male volunteers in a placebo-controlled, randomized cross-over design using the Massachusetts General Hospital Sexual Function Questionnaire. Data from a 10 min eyes-closed resting state scan were used to analyze functional connectivity under placebo in previously identified brain regions, focussing on the sublenticular extended amygdala (SLEA), dopaminergic midbrain, and anterior cingulate cortex. Resting state functional connectivities of the pregenual anterior cingulate cortex (pgACC), midbrain, and insula to the SLEA sufficiently predicted the development of subjective SSRI-related decreased sexual functioning and distinguished vulnerable from resilient subjects. Furthermore, connectivity with the midbrain particularly predicted orgasm-related deficits, while connectivity with pgACC predicted sexual satisfaction. Linking SSRI-related subjective sexual functioning to pre-treatment resting state connectivities in cortico-subcortical network of sexual processing, we demonstrated the potential of novel, non-invasive and passive brain imaging techniques to guide therapeutic decisions and adjust treatment protocols in psychiatric disorders and sexual medicine.
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http://dx.doi.org/10.1007/s10508-013-0103-3DOI Listing
August 2013

Effects of amisulpride on human resting cerebral perfusion.

Psychopharmacology (Berl) 2013 Sep 13;229(1):95-103. Epub 2013 Apr 13.

Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany.

Rationale: Quantitative neuroimaging studies show that different neuroleptics have similar effects on resting metabolism/perfusion in the basal ganglia, but vary in their effect on the cortex, especially in the prefrontal and temporal lobes. These differences may represent signatures of the action of medication on distinctive receptor combinations.

Objectives: This study seeks to determine the effect on cerebral perfusion at rest of low-dose amisulpride, a neuroleptic with a receptor profile relatively selective to dopaminergic D2-receptors and both antidepressant and antipsychotic efficacy.

Methods: Continuous arterial spin labelling in a placebo-controlled, double blind, crossover study at steady state of N = 20 healthy male adults.

Results: Relative to placebo, amisulpride was associated with extensive and significant cortical decrements in resting perfusion levels, particularly in the prefrontal lobes (p = 0.01, corrected). Decrements spared the basal ganglia, where perfusion was slightly increased.

Conclusions: In contrast to earlier reports on other neuroleptics, amisulpride was associated with intense cortical perfusion decrements at rest. These results are consistent with an existing model in which dopaminergic blockade is associated not only with metabolism/perfusion increases in the basal ganglia, but also with decreases in the cerebral cortex that in most neuroleptics are compensated by action on other receptor systems. The selective receptor profile of amisulpride may explain the extensive cortical decrements.
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http://dx.doi.org/10.1007/s00213-013-3091-zDOI Listing
September 2013

Neural correlates of erotic stimulation under different levels of female sexual hormones.

PLoS One 2013 13;8(2):e54447. Epub 2013 Feb 13.

Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany.

Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results may provide a basis for future imaging studies on sexual processing in females, especially in the context of less explicit erotic stimulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572100PMC
August 2013

Modulation of attention network activation under antidepressant agents in healthy subjects.

Int J Neuropsychopharmacol 2013 Jul 3;16(6):1219-30. Epub 2012 Dec 3.

Department of Psychiatry, Ulm University, Ulm, Germany.

While antidepressants are supposed to exert similar effects on mood and drive via various mechanisms of action, diverging effects are observed regarding side-effects and accordingly on neural correlates of motivation, emotion, reward and salient stimuli processing as a function of the drugs impact on neurotransmission. In the context of erotic stimulation, a unidirectional modulation of attentional functioning despite opposite effects on sexual arousal has been suggested for the selective serotonin reuptake-inhibitor (SSRI) paroxetine and the selective dopamine and noradrenaline reuptake-inhibitor (SDNRI) bupropion. To further elucidate the effects of antidepressant-related alterations of neural attention networks, we investigated 18 healthy males under subchronic administration (7 d) of paroxetine (20 mg), bupropion (150 mg) and placebo within a randomized placebo-controlled cross-over double-blind functional magnetic resonance imaging (fMRI) design during an established preceding attention task. Neuropsychological effects beyond the fMRI-paradigm were assessed by measuring alertness and divided attention. Comparing preceding attention periods of salient vs. neutral pictures, we revealed congruent effects of both drugs vs. placebo within the anterior midcingulate cortex, dorsolateral prefrontal cortex, anterior prefrontal cortex, superior temporal gyrus, anterior insula and the thalamus. Relatively decreased activation in this network was paralleled by slower reaction times in the divided attention task in both verum conditions compared to placebo. Our results suggest similar effects of antidepressant treatments on behavioural and neural attentional functioning by diverging neurochemical pathways. Concurrent alterations of brain regions within a fronto-parietal and cingulo-opercular attention network for top-down control could point to basic neural mechanisms of antidepressant action irrespective of receptor profiles.
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http://dx.doi.org/10.1017/S1461145712001368DOI Listing
July 2013