Georg Grön

Non-suicidal self-injury (NSSI), as a highly prevalent psychiatric symptom in adolescents and young adults, is defined as the deliberate destruction of body tissue without suicidal intent. Impulsivity and dysfunctional response inhibition have been suggested to play a central role in adolescents’ vulnerability to self-harm. To investigate the potentially distinct neurobiology of NSSI, we used a well-established Go/No Go task in which activation of the inferior frontal gyrus (IFG) and dorsal anterior cingulate cortex (dACC) is interpreted as a neural correlate of processing failed response inhibition. Task-based functional magnetic resonance imaging data were obtained from 14 adolescents with a diagnosis of major depression and a history of NSSI (MD-NSSI), 13 depressed adolescents without NSSI (MD-only), and 14 healthy controls (HC). In line with hypotheses of dysfunctional response inhibition, we observed increased rates of commission errors in MD-NSSI along with significantly reduced error-related activations of the dACC and IFG. Intact response inhibition, as reflected by low commission error rates not different from HC, was observed in MD-only, along with increased activation of the error-processing network. Our findings support the hypothesis of a distinct neurobiological signature of NSSI. Further research on biomarkers of NSSI could focus on behavioral and neural correlates of failed response inhibition.

Positron emission tomography (PET) studies have shown involvement of the striatum when treating adult attention-deficit/hyperactivity disorder (ADHD) with methylphenidate (MPH). Results from resting-state functional magnetic resonance imaging (rs-fMRI) for the same issue were less unequivocal. Here, a new analytical framework was set up to investigate medication effects using seed-based rs-fMRI analysis to infer brain regions with alterations in intrinsic functional connectivity (IFC) corresponding with ADHD symptom reduction. In a within-subjects study design, 53 stimulant-naïve adult ADHD patients were investigated before and after 6 weeks of MPH treatment, using two major clinical symptom scales and rs-fMRI. The same data were acquired in a sample of 50 age- and sex-matched healthy controls at baseline. A consensual atlas provided seeds for five predefined major resting-state networks. In order to avoid biasing of medication effects due to putative treatment failure, the entire ADHD sample was first categorized into treatment Responders (N = 36) and Non-Responders (N = 17) using machine learning-based classification with the clinical scales as primary data. Imaging data revealed medication effects only in Responders. In that group, IFC of bilateral putamen changed significantly with medication and approached almost normal levels of IFC. Present results align well with results from previous PET studies, with seed-based rs-fMRI as an entirely different neuroimaging method.

Background: Intraindividual intertrial variability has been suggested as an endophenotype of attention-deficit/hyperactivity disorder (ADHD). It is usually evaluated as response time variability (RTV) in reaction time tasks, and RTV has emerged as a robust and stable feature of ADHD. Among attempts to elucidate the neurobiological underpinnings of RTV, it has been suggested that alterations in white matter microstructure may explain RTV. Methods: We used diffusion tensor imaging (DTI) in a group of 53 adults with ADHD and 50 healthy controls. We obtained RTV parameters from a simple reaction-time task, in which participants were asked to respond to the appearance of white crosses on a screen using button presses. Results: We observed significant between-group differences for the ex-Gaussian parameter τ, indicating that the mean of extremely slow responses was greater for adults with ADHD than controls. Fractional anisotropy (FA) derived from DTI was significantly different between groups in 2 clusters of the corticothalamic tract. In the ADHD group, relatively decreased FA values were significantly associated with the parameter τ, such that lower FA values in the corticothalamic tract predicted greater τ as an index of RTV. We did not observe this association in healthy controls. Limitations: For comparison with previous studies, we used FA as a dependent variable of interest. However, although this metric is sensitive to white matter structural properties, there are ambiguities in its interpretation. Conclusion: Even in a simple reaction-time task, RTV proved again to be a stable feature of ADHD. It was associated with altered white matter structural properties of the corticothalamic tract in adults with ADHD.

Anxiety- and trauma-related disorders are severe illnesses with high prevalence. Current treatment options leave room for improvement and the endocannabinoid system (ECS) has become a key target in psychopharmacological research. Rodent models suggest an anxiolytic effect of endocannabinoids and demonstrated that the ECS is involved in the modulation of fear learning and aversive memory consolidation. So far, one prominent target was inhibition of fatty acid amino hydrolase (FAAH), the degrading enzyme of the endocannabinoid anandamide (AEA). Research in humans remains scarce, but genetic studies have found that the single-nucleotide polymorphism (SNP) FAAH C385A (rs324420) is associated with lower catabolic performance of FAAH and increased levels of AEA. Translational research on the ECS in fear learning processes is rare, yet crucial to understand the mechanisms involved. To address this lack of research, we designed a fear conditioning, extinction learning paradigm with 51 healthy, male humans who underwent functional magnetic resonance imaging (fMRI) before analysing baseline and task-related changes of AEA, as well as the FAAH polymorphism (rs324420). The results indicate higher AEA levels in AC-heterozygotes than in CC-individuals (SNP rs324420), but no difference between the groups during extinction learning. However, neural activation of the anterior cingulate cortex and anterior insular cortex during extinction learning correlated positively with AEA baseline levels, and task-related changes in AEA were found particularly during fear extinction, with a modulatory effect on neural activation related to extinction learning. Results indicate a putative role for AEA in fear extinction learning. Pre-treatment with AEA-enhancing drugs could promote extinction learning during psychotherapeutic interventions.

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.

Borderline Personality Disorder (BPD) is clinically characterized by emotional instability, interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). During NSSI, patients with BPD typically report analgesic or hypoalgesic phenomena, and pain perception and pain processing in BPD have been repeatedly investigated. Most of the studies so far focused on affective-motivational and cognitive-evaluative neural components of pain within categorial study designs. By contrast, rather basic somatosensory aspects such as neural intensity-encoding of somatosensory stimuli were not examined in further details. Thus, we investigated patients with BPD and healthy controls (HC) by functional magnetic resonance imaging (fMRI) during an unpleasant sensory stimulation task with parametrically increasing stimulus intensities. 15 females diagnosed with BPD and 15 HCs were investigated with fMRI during four individually adjusted levels of electrical stimulus intensities. Ratings of stimulus intensity were assessed by button presses during fMRI. fMRI-data were analyzed by analyses of variances (ANOVA) at a statistical threshold of p < 0.05 FWE-corrected on cluster level. Subjective ratings of stimulus intensities were alike between BPD and HC, and intensity levels identified with equal accuracy. Significant intensity-encoding neural activations were observed within the primary and secondary somtasensory cortex, the posterior insula, the posterior midcingulate cortex (pMCC) and the supplementary motor area (SMA) in both, HC and BPD. Notably, there were no significant between-groups differences in intensity-encoding neural activations, even at lowered significance thresholds. Present results suggest a similar neural somatosensory stimulus intensity encoding in BPD as previously observed on a behavioral level. The alterations in neural affective-motivational or cognitive-evaluative components reported so far may be restricted to pain rather than unpleasant stimulus processing and were absent in our study.

The experience of flow ensues when humans engage in a demanding task while task demands are balanced with the individual’s level of skill or ability. Here, we further tested the hypothesis that the medial prefrontal cortex (MPFC) plays a causal role in mediating flow experience using transcranial direct current stimulation (tDCS) to interfere with MPFC’s deactivation evoked by a flow paradigm and measured by magnetic resonance (MR)-based perfusion imaging. In a balanced, within-subjects repeated measure design, three treatments of tDCS (sham, anodal, cathodal) were applied in a sample of 22 healthy male participants. tDCS-modulatory effects on flow-specific regional cerebral blood flow (rCBF) and subjective flow experience significantly depended on participants’ baseline level of flow experience during sham tDCS. Those participants with lower-flow experience during sham tDCS (LF) benefitted from tDCS, particularly from the anodal polarity, whereas both active treatments did not substantially affect subjects with relatively higher baseline flow experience (HF). Functionally, in LF subjects, relative deactivation of the right amygdala got more pronounced under anodal and cathodal tDCS, and changed inconsistently in HF subjects. Inter-individual regression analyses of rCBF data suggested that involvement of the subgenual anterior cingulate cortex appears crucial for affecting the response pattern in the right amygdala and can be modulated by tDCS. Present data support the notion that valuable insights into the neural mechanism of flow can be obtained using tDCS. However, a clearer understanding of tDCS’ baseline dependency in terms of individual variations in brain connectivity states appears a necessary prerequisite to exploit this technique further.

Background Corrupted gradient directions (GD) in diffusion weighted images may seriously affect reliability of diffusion tensor imaging (DTI)-based comparisons at the group level. In the present study a quality control (QC) algorithm¹was employed to eliminate corrupted GD from DTI data. Effects of this procedure on comparisons between Huntington disease (HD) subjects and controls were assessed at the group level. Methods Sixty-one HD patients in early stages and forty matched healthy controls were studied in a longitudinal design (baseline and two follow-ups at three time points over 15 months), in a multicenter setting with standardised acquisition protocols on four different MR scanners at four European study sites². QC was used to identify corrupted GD in DTI data sets. Differences in fractional anisotropy (FA) maps at the group level with and without elimination of corrupted GD were analysed. Results The elimination of corrupted GD had an impact on individual FA maps as well as on cross-sectional group comparisons between HD subjects and controls. Following application of the QC algorithm, a lower number of small clusters of FA changes were observed, compared with the analysis without QC-based elimination. However, the grosso modo pattern of regional reductions and increases in FA values was unchanged. Conclusion An impact on the result patterns of the comparison of FA maps between HD subjects and controls was observed depending on whether QC-based elimination of corrupted GD was performed. QC-based elimination of corrupted GD in DTI scans reduces the risk of type I and type II errors in cross-sectional group comparison of FA maps contributing to an increase in reliability and stability of group comparisons. Acknowledgment This work was supported by the European Union under the Seventh Framework programme – PADDINGTON Project, Grant Agreement No. 261358, and the European Huntington’s Disease Network (EHDN), project 070 – PADDINGTON. References Müller HP, et al. PLoS Curr2011, RRN1232 Müller HP, et al. Neuroimage Clinical2013,2:161–167