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Creativity is a sine qua non ability for almost all aspects of everyday life. Although very profound behavioural models were provided by 21st century psychologists, the neural correlates of these personality features associated with creativity are largely unknown. Recent models suggest strong relationships between dopamine release and various creative skills. Herein, we employed functional connectivity analyses of resting-state functional magnetic imaging data in order to shed light on these neural underpinnings of creative aspects. For improved sensitivity, we performed the study at ultra-high magnetic field (7 T). Seed regions were defined based on subcortical (ventral tegmental area/substantia nigra, nucleus caudatus) activation foci of a remote associates task (RAT). In addition, bilateral PCC was used as seed region to examine the default-mode network. Network strength across subjects was regressed against a battery of psychological variables related to creativity. Dopaminergic network variations turned out to be indicative for individual differences in creative traits. In this regard, the caudate network showed stronger connectivity in individuals with higher extraversion measures, while connectivity with the midbrain network was found increased with higher ideational behaviour and emotional stability.

Here, we briefly describe the real-time fMRI data that is provided for testing the functionality of the open-source Python/Matlab framework for neurofeedback, termed Open NeuroFeedback Training (OpenNFT, Koush et al. [1]). The data set contains real-time fMRI runs from three anonymized participants (i.e., one neurofeedback run per participant), their structural scans and pre-selected ROIs/masks/weights. The data allows for simulating the neurofeedback experiment without an MR scanner, exploring the software functionality, and measuring data processing times on the local hardware. In accordance with the descriptions in our main article, we provide data of (1) periodically displayed (intermittent) activation-based feedback; (2) intermittent effective connectivity feedback, based on dynamic causal modeling (DCM) estimations; and (3) continuous classification-based feedback based on support-vector-machine (SVM) estimations. The data is available on our public GitHub repository: https://github.com/OpenNFT/OpenNFT_Demo/releases. ISSN:2352-3409

Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration. While MtFs received estradiol and anti-androgens, FtM subjects underwent high-dose testosterone treatment. The longitudinal processing stream of the FreeSurfer software suite was used for the automated assessment and delineation of brain volumes to assess the structural changes over the treatment period of cross-sex hormone administration. Most prominent results were found for MtFs receiving estradiol and anti-androgens in the form of significant decreases in the hippocampal region. Further analysis revealed that these decreases were reflected by increases in the ventricles. Additionally, changes in progesterone levels correlated with changes in gray matter structures in MtF subjects. In line with prior studies, our results indicate hormonal influences on subcortical structures related to memory and emotional processing. Additionally, this study adds valuable knowledge that progesterone may play an important role in this process.

Sex-steroid hormones have repeatedly been shown to influence empathy, which is in turn reflected in resting state functional connectivity (rsFC). Cross-sex hormone treatment in transgender individuals provides the opportunity to examine changes to rsFC over gender transition. We aimed to investigate whether sex-steroid hormones influence rsFC patterns related to unique aspects of empathy, namely emotion recognition and description as well as emotional contagion. RsFC data was acquired with 7Tesla magnetic resonance imaging in 24 male-to-female (MtF) and 33 female-to-male (FtM) transgender individuals before treatment, in addition to 33 male- and 44 female controls. Of the transgender participants, 15 MtF and 20 FtM were additionally assessed after 4 weeks and 4 months of treatment. Empathy scores were acquired at the same time-points. MtF differed at baseline from all other groups and assimilated over the course of gender transition in a rsFC network around the supramarginal gyrus, a region central to interpersonal emotion processing. While changes to sex-steroid hormones did not correlate with rsFC in this network, a sex hormone independent association between empathy scores and rsFC was found. Our results underline that 1) MtF transgender persons demonstrate unique rsFC patterns in a network related to empathy and 2) changes within this network over gender transition are likely related to changes in emotion recognition, -description, and -contagion, and are sex-steroid hormone independent.

Recent technological progress enables MRI recordings at ultra-high fields of 7 T and above leading to brain images of higher resolution and increased signal-to-noise ratio. Despite these benefits, imaging at 7 T exhibits distinct challenges due to B1 field inhomogeneities, causing decreased image quality and problems in data analysis. Although several strategies have been proposed, a systematic investigation of bias-corrected 7 T data for voxel-based morphometry (VBM) is still missing and it is an ongoing matter of debate if VBM at 7 T can be carried out properly. Here, an optimized VBM study was conducted, evaluating the impact of field strength (3T vs. 7 T) and pulse sequence (MPRAGE vs. MP2RAGE) on gray matter volume (GMV) estimates. More specifically, twenty-two participants were measured under the conditions 3T MPRAGE, 7 T MPRAGE and 7 T MP2RAGE. Due to the fact that 7 T MPRAGE data exhibited strong intensity inhomogeneities, an alternative preprocessing pipeline was proposed and applied for that data. VBM analysis revealed higher GMV estimates for 7 T predominantly in superior cortical areas, caudate nucleus, cingulate cortex and the hippocampus. On the other hand, 3T yielded higher estimates especially in inferior cortical areas of the brain, cerebellum, thalamus and putamen compared to 7 T. Besides minor exceptions, these results were observed for 7 T MPRAGE as well for the 7 T MP2RAGE measurements. Results gained in the inferior parts of the brain should be taken with caution, as native GM segmentations displayed misclassifications in these regions for both 7 T sequences. This was supported by the test-retest measurements showing highest variability in these inferior regions of the brain for 7 T and also for the advanced MP2RAGE sequence. Hence, our data support the use of 7 T MRI for VBM analysis in cortical areas, but direct comparison between field strengths and sequences requires careful assessment. Similarly, analysis of the inferior cortical regions, cerebellum and subcortical regions still remains challenging at 7 T even if the advanced MP2RAGE sequence is used.

Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex.

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation., Highlights • Monetary incentive delay task was assessed in separate EEG and fMRI sessions. • Both gain and loss anticipation activated well known reward-related areas. • P300 amplitude differentiated reward cue from non-reward cues. • P300 amplitudes positively correlated with BOLD response in the ventral striatum. • Ventral striatum activation associated with general motivational processes.

Progressing from 3T to 7 T functional MRI enables marked improvements of human brain imaging in vivo. Although direct comparisons demonstrated advantages concerning blood oxygen level dependent (BOLD) signal response and spatial specificity, these mostly focused on single brain regions with rather simple tasks. Considering that physiological noise also increases with higher field strength, it is not entirely clear whether the advantages of 7T translate equally to the entire brain during tasks which elicit more complex neuronal processing. Therefore, we investigated the difference between 3T and 7 T in response to transcutaneous electrical painful and non-painful stimulation in 22 healthy subjects. For painful stimuli vs. baseline, stronger activations were observed at 7 T in several brain regions including the insula and supplementary motor area, but not the secondary somatosensory cortex (p

Functional magnetic resonance imaging (fMRI) has become the primary non-invasive method for investigating the human brain function. With an increasing number of ultra-high field MR systems worldwide possibilities of higher spatial and temporal resolution in combination with increased sensitivity and specificity are expected to advance detailed imaging of distinct cortical brain areas and subcortical structures. One target region of particular importance to applications in psychiatry and psychology is the amygdala. However, ultra-high field magnetic resonance imaging of these ventral brain regions is a challenging endeavor that requires particular methodological considerations. Ventral brain areas are particularly prone to signal losses arising from strong magnetic field inhomogeneities along susceptibility borders. In addition, physiological artifacts from respiration and cardiac action cause considerable fluctuations in the MR signal. Here we show that, despite these challenges, fMRI data from the amygdala may be obtained with high temporal and spatial resolution combined with increased signal-to-noise ratio. Maps of neural activation during a facial emotion discrimination paradigm at 7T are presented and clearly show the gain in percental signal change compared to 3T results, demonstrating the potential benefits of ultra-high field functional MR imaging also in ventral brain areas.

Question Transcranial magnetic stimulation (TMS) has become a promising therapeutic treatment and neuroscientific research tool, yet how it works is not fully understood. We developed a dedicated MR coil array positioned beneath the TMS coil that allows for concurrent stimulation and imaging and flexible positioning while ensuring TMS efficiency, high MR sensitivity and the use of parallel/multiband imaging sequences. Here we aimed to explain acute effects of TMS over left DLPFC using a new online TMS/fMRI setup in combination with advanced imaging and neuronavigation methods. Resting State functional connectivity and DTI Tractography shall further explain resulting activation patterns at a network level. Methods The study was performed on a 3T Tim Trio scanner (Siemens, Erlangen, Germany). The TMS system used included a MagProX100 stimulator and MRi-B91 MR-compatible TMS coil (Magventure, Farum, Denmark). Five right-handed female subjects (age: 28.6 ± 4.3 years) were examined. Functional images were acquired using EPI (echo-planar imaging) sequence with TR/TE = 1000/33 ms, 28 slices, 1.5 × 1.5 × 3mm3. The experimental procedure is depicted in Fig. 1. FMRI data analyses were performed using SPM12. The design matrix comprised four regressors representing different stimulation amplitudes. DTI tractography was performed using DSI Studio. Figure options Download full-size image Download high-quality image (729 K) Download as PowerPoint slide Results TMS led to intensity-dependent activation increase in the left DLPFC and the contralateral DLPFC ( Figure options Download full-size image Download high-quality image (874 K) Download as PowerPoint slide Fig. 2): Higher stimulation intensities evoked higher bilateral activation. ACC showed a more complex response pattern. Resting-state functional connectivity maps using the stimulation target as seed-voxel showed a network very similar to the TMS-derived activation pattern (Fig. 2). DTI tractography provided additional information about the axonal connection between the left DLPFC stimulation site and the right DLPFC activation cluster. Conclusion This is the first study to assess the acute influence of TMS over DLPFC at an individual level, made possible by a dedicated concurrent TMS/fMRI coil array. Here we show a dose-dependent increase in activity not only underneath the stimulation site but also on the contralateral homologous area and apparent mediating responses in the ACC. This network is confirmed by additional resting-state and tractography data.

Question While the precise mechanism of action is still unclear, rTMS is an effective FDA-approved treatment in depression and shows beneficial behavioral effects in a range of pathologies. A better understanding could improve treatment success and reduce the number of non-treatment responders. This study is the first to investigate effectiveness and specificity of rTMS over left DLPFC using a large-scale (n = 60) sham-controlled cross-over design and an unbiased resting-state (RS) approach. Methods 60 healthy subjects (age: 25.01 ± 4.6 years, f/m: 31/29) underwent rTMS DLPFC and sham stimulation (see Fig. 1) Download : Download high-res image (493KB) Download : Download full-size image . Resting state (rs) fMRI scans were acquired before and twice after stimulation. We investigated BOLD signal changes in functional connectivity (fc) following 10 Hz rTMS (24 × 5 s trains, ITI 20s, 1200 pulses @ 90%MT) during a classic resting state paradigm. We examined rsfc changes using an unbiased approach based on a set of 20 well-established resting state networks derived from multicenter-data independent component analysis by Biswal et al. (2010a, http://fcon_1000.projects.nitrc.org ). Results Comparisons between pre and post stimulation revealed that 19 out of a total of 20 IC networks remained unchanged, i.e. showed no statistically significant differences before and after rTMS irrespective of real/sham stimulation (Fig. 2 A, blue) Download : Download high-res image (1MB) Download : Download full-size image . Only one network (IC17, red dashed) which includes the ACC and PFC showed DLPFC rTMS-related connectivity changes (while staying stable throughout the whole procedure in sham session, Fig. 2 B): The ACC had increased connection strength in the post-rTMS scan within this network, particularly with the DLPFC (stimulation site), bilateral insula and striatum. Conclusion For the first time this study shows in a model-free approach that rTMS over left DLPFC modulates functional connectivity within a specific network while other networks stay stable. This network is typically associated with attention, mood, reward processing and psychiatric conditions that are linked to maladaptive changes in these domains. This could have further implications on treatment, screening and treatment response monitoring of psychiatric conditions.

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