Publications

{Purpose: CEST allows for indirect detection of diluted molecules via their saturation transfer to the abundant water pool 1\textendash3. At 3T, the frequency separation of different CEST effects is difficult and many applications of CEST use MTRasym evaluation. In this study, we use low-power saturation to separate the two major contributors the MTRasym signal, namely APT (at +3.5 ppm) and NOE effects (at \textendash3.5 ppm), and investigate correlations with 18F-FET PET enhancement in brain tumors. Methods: 9 patients scanned on a 3T PET/MR system for suspected glioma or recurrent glioma were evaluated (1 radio-necrosis, 1 gliosis, 3 high grade, 4 low grade). Selective protein CEST Z-spectra were acquired with 4s saturation (100 Gaussian pulses, B1 \textequals 0.6 $\mu$T, pulse duration 20ms, duty cycle 50\textpercent) at 53 frequency offsets ranging from \textendash100 ppm to +100 ppm. CEST Z-spectra were de-noised using principle component analysis, retaining 15 principle components. Two-stage Lorentzian analysis was applied to estimate contributions from direct water saturation, magnetization transfer effects from macromolecules4, and selective CEST effects. Results: Selective NOE effects were stronger than APT CEST effects in both healthy and diseased tissues. Compared to contralateral tissues, tumor regions exhibit reduced NOE signals and mixed APT signals, consistent with results from previous studies 4,5. There was no correlation between PET uptake and CEST signals within the tumor. Conclusion: NOE and amide CEST separation is possible at 3T and provide additional information compared to 18F-FET PET.}

{Purpose Clinical use of magnetic resonance electrical impedance tomography (MREIT) still requires significant sensitivity improvements. Here, the measurement of the current-induced magnetic field ($\Delta$Bz,c) is improved using systematic efficiency analyses and optimization of multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. Theory and Methods Considering T1, T2, and math formula relaxation in the signal-to-noise ratios (SNRs) of the MR magnitude images, the efficiency of MESE and SSFP-FID MREIT experiments, and its dependence on the sequence parameters, are analytically analyzed and simulated. The theoretical results are experimentally validated in a saline-filled homogenous spherical phantom with relaxation parameters similar to brain tissue. Measurement of $\Delta$Bz,c is also performed in a cylindrical phantom with saline and chicken meat. Results The efficiency simulations and experimental results are in good agreement. When using optimal parameters, $\Delta$Bz,c can be reliably measured in the phantom even at injected current strengths of 1 mA or lower for both sequence types. The importance of using proper crusher gradient selection on the phase evolution in a MESE experiment is also demonstrated. Conclusion The efficiencies observed with the optimized sequence parameters will likely render in-vivo human brain MREIT feasible.}

{Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate in 1H MR spectra without 13C channels. The advantage of this technique is that some challenges of 13C MRS like non-standard hardware modifications etc. are avoided and the simultaneous observation of 12C- and 13 C-coupled protons is possible. On the other hand the latter also complicates the spectra. In this work, different sequences will be compared to optimize spectral resolution for glutamate and glutamine at 9.4 T.}

{Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate in pure 1H MRS spectra without a 13C channel. In this work, simulated 1H MRS spectra with FID, semi-Laser, and two PRESS sequences have been compared to optimize spectral resolution for glutamate and glutamine measurements at 9.4 T. Furthermore, spectral changes according to a two-compartment model were analyzed. As a result, this work indicates the fastest possible acquisition can be obtained with an FID sequence, while the best resolution possible can be obtained with a PRESS sequence.}

{Rapid variable-flip-angle T1 mapping techniques are frequently applied in clinical settings, but their accuracy is often impaired by incomplete spoiling or flip angle miscalibrations. To eliminate these two error sources simultaneously, a combined B1 and T1 mapping method is proposed based on spiral 2D multislice spoiled gradient echo imaging with high spoiling efficiency. The transition to steady state is minimized by an optimized single preparation pulse. A single-shot spiral readout during the preparation module enables ultrafast B1 mapping and as a result reproducible bias-free T1 mapping with whole-brain coverage at clinically relevant resolution in less than one minute.}

Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method allowing the detection as well as the quantification of several metabolites in the human brain. The introduction of ultra-high field (UHF) scanners ($\geq$7 T) led to an increase of the signal-to-noise ratio and a higher frequency dispersion, hence better spectral resolution. These advantages promote the potential of MRS. Despite the significant advantages of UHF for MRS, several technical challenges (such as B1+efficiency and inhomogeneity, increased power deposition, chemical shift displacement etc.) must be addressed for the efficient utilization of these prospective benefits. The methods and techniques developed during this Ph.D. demonstrated the feasibility of metabolite cycling (MC) at 9.4 T, and the advantages of non-water suppressed MRS regarding frequency and phase fluctuations. The newly developed sequences (MC-STEAM and MC-semi-LASER) enabled the acquisition of reliable spectra with enhanced frequency resolution, both upfield and downfield of water in 1H spectra. Furthermore, the designed RF coils, hardware setup (power splitters, phase cables, etc.), as well as, the gained knowledge regarding the achievement of efficient transmit fields and can be utilized in future MRS studies and applications. As a result, the human brain macromolecular baseline was investigated revealing additional macromolecular peaks and information regarding their concentration levels. Moreover, the chemical exchange rates of the downfield metabolites, as well as, their correlation with the upfield peaks were examined contributing further to the assignment of the downfield peaks. Finally, the performed functional MRS studies in which the MC-semi-LASER sequences were used, demonstrated the potentials of UHF and MC regarding the simultaneous investigation of water and metabolites alterations during visual stimulation.

{We present a 3D CEST sequence that allows 2mm isotropic whole-brain acquisition within 6s per frequency offset. The 4.5s CEST preparation is followed by a 1.5s centric-reordered 3D-EPI readout with water excitation. The single-shot readout improves robustness against physiological noise and provides complete freedom in the design of the saturation block. We acquired whole-brain CEST data at 7T and show metabolite maps obtained from a Lorentzian fit to the Z-spectra.}

{Gradient echo (GRE)-based acquisition provides a robust readout method for chemical exchange saturation transfer (CEST) at ultrahigh field (UHF). To develop a snapshot-CEST approach, the transient GRE signal and point spread function were investigated in detail, leading to optimized measurement parameters and reordering schemes for fast and robust volumetric CEST imaging. Simulation of the transient GRE signal was used to determine the optimal sequence parameters and the maximum feasible number of k-space lines. Point spread function analysis provided an insight into the induced k-space filtering and the performance of different rectangular reordering schemes in terms of blurring, signal-to-noise ratio (SNR) and relaxation dependence. Simulation results were confirmed in magnetic resonance imaging (MRI) measurements of healthy subjects. Minimal repetition time (TR) is beneficial for snapshot-GRE readout. At 9.4 T, for TR \textequals 4 ms and optimal flip angle close to the Ernst angle, a maximum of 562 k-space lines can be acquired after a single presaturation, providing decent SNR with high image quality. For spiral-centric reordered k-space acquisition, the image quality can be further improved using a rectangular spiral reordering scheme adjusted to the field of view. Application of the derived snapshot-CEST sequence for fast imaging acquisition in the human brain at 9.4 T shows excellent image quality in amide and nuclear Overhauser enhancement (NOE), and enables guanidyl CEST detection. The proposed snapshot-CEST establishes a fast and robust volumetric CEST approach ready for the imaging of known and novel exchange-weighted contrasts at UHF.}

{This study examined how navigators of large-scale environmental spaces come up with survey estimates of distant targets. Participants learned a route through a virtual city by walking it multiple times in one direction on an omnidirectional treadmill. After learning, they were teleported to intersections along the route and pointed to multiple other locations. Locations were always queried in chunks of related trials relative to a participant\textquoterights current position, either to all locations route forwards or all locations route backwards. For their first pointing, participants took twice as long as for the later pointings and latency correlated with the number of intersections to the target, which was not the case for later pointings. These findings are inconsistent with reading out coordinates from a cognitive map but fit well with constructive theories which suggest that participants integrated locations between their current location and the target along the learned path. Later pointings to adjacent intersections within a chunk of trials continued this process using the previous estimation. Additionally, in first pointings participants\textquoteright estimates were quicker and more accurate when targets were located route forwards than route backwards. This route direction effect shows that the long-term memory employed in generating survey estimates must be directed \textendash either in form of a directed graph or a combination of a directed route layer and an undirected survey layer.}

{Recent findings in spatial cognition suggest that people store information about unfamiliar environments with a preferred orientation, based on factors such as the intrinsic structure of layout, the environmental structure, one\textquotesingles learning viewpoint, the experimental instructions and the conversational partner\textquotesingles viewpoint. However, what is still unknown is the preferred orientation of familiar environments. This study employed the University Halls\textquotesingle rooms, to investigate the spatial reasoning about familiar and unfamiliar environments. Specifically, we asked participants to make a pointing task for objects located in their own rooms; and participants who didn\textquotesinglet own a room, to study one in VR and make the same task. We attempted to predict if participants in the familiar environment would demonstrate an orientation-free memory and if participants in the unfamiliar environment would demonstrate an orientation-dependent memory. Findings revealed reasoning about both familiar and unfamiliar environments is orientation-dependent. Reasoning for unfamiliar environments determines the preferred orientation by the starting orientation while for familiar environments by environmental cues, which can override the performance advantage of the preferred orientation.}

{When presented with disparate visual stimuli to corresponding retinal locations, the perceptual experience of a subject vacillates across time between the two sensory signals. This phenomenon, called binocular rivalry allows disentangling sensory stimulation from conscious awareness and has therefore been instrumental to unravelling the neural correlates of conscious perception. Probing various regions of the macaque brain while they are presented with incongruent visual input has revealed that the proportion of feature selective neurons whose activity correlates with conscious perception increases as one progresses in the visual cortical hierarchy, peaking in temporal and prefrontal cortices. Given the role of prefrontal cortex in mediating task related behavior, recent theoretical and experimental approaches propose utilizing no-report paradigms so as to distill the true correlates of perception from those related to manual reports and task monitoring. To this end, we conducted an electrophysiological investigation of the ventrolateral prefrontal cortex in monkeys trained to passively fixate, while they experienced binocular rivalry, instigated with oppositely drifting, sinusoidal gratings presented to the two eyes. Optokinetic nystagmus elicited at any given time served as an objective indicator of the ongoing percept. We found robust modulation in visually selective spiking activity recorded from the prefrontal cortex contingent on the animal\textquoterights perception. Moreover, the magnitude of these modulations was comparable to the activity elicited in response to presentation of monocular visual input. These results suggest that the spiking activity in the prefrontal cortex is modulated in accordance with conscious perception in a no report binocular rivalry paradigm.}

{Remote neurodegenerative changes above the level of injury are present following traumatic spinal cord injury (SCI), resulting in atrophy of the cervical cord of up to 30. This study investigates the underlying biochemical changes at the cellular and molecular level which may subtend the development of atrophy using latest magnetic resonance spectroscopy in the spinal cord in healthy controls and SCI patients. Furthermore, we screen for potential MRS biomarkers investigating the association of biochemical changes and clinical outcome.}

{The growing importance of Virtual Reality (VR) in recent years has put emphasis on the topic of avatars: Especially for shared VR experiences, it is important to provide a visual representation of the user. An important question is: What will these avatars look like? Even though VR offers great artistic freedom in the design of virtual avatars, serious applications of social VR will most likely prefer a design close to the real appearance of humans. For this, a natural choice is the derivation of an avatar from the true appearance of a human person, using photographs or 3D scans, for example. While this will result in a close resemblance to the real person, achieving ultimate photo-realism is challenging, especially considering the typically uncontrolled recording conditions present in normal situ- ations. Human avatars produced from such digital body captures are likely to be clearly distinguishable from photographs, which might result in negative reactions from observers due to conflicting cues. Instead of fighting the uphill battle to achieve ultimate photo-realism, we propose a deliberate deviation from realism by means of automatic stylization of such body captures. Here we recap previous research on this topic by us and others, summarize experimental results from an automatic stylization system, and discuss potential applications and future work.}

{Bioresponsive or smart contrast agents (SCAs) sensitive to Ca2+ are of extreme interest in the development of functional magnetic resonance imaging (MRI) techniques as they can aid in tracking neural activity in vivo. To this end, the design of macromolecular systems based on nanoscaffolds such as dendrimers functionalised with multiple MRI contrast agents have been used to conveniently increase the local concentration of paramagnetic MR reporters and slow the diffusion time of the probe, which are favourable in vivo characteristics. Moreover, previous studies with Ca-sensitive dendrimeric MRI probes revealed favourable properties crucial in the development of a ratiometric T2/T1-imaging method that provided a higher contrast-to-noise ratio compared to conventional T1- or T2-weighted imaging protocols. We therefore developed a series of novel dendrimeric MRI probes (DCAs) with differing structural properties and charge distributions. We thoroughly studied their features such as the relaxometric behaviour, size change and examined their electrostatic behaviours prior to and after the addition of Ca2+. The most active DCA displayed a common increase in r1 (3.11 mM-1 s-1 to 5.72 mM-1 s-1) and a remarkable increase in r2 (7.44 mM-1 s-1 to 34.57 mM-1 s-1), resulting in a r2/r1 ratio increase of the factor 2.52, which is greater than what was previously achieved. These changes in r1 and r2 were followed with a hydrodynamic diameter increase from 7.1 $\pm$ 1.2 to 8.5 $\pm$ 0.7 nm upon the addition of Ca2+, along with a decrease in the negative surface charge of the nanoparticle. Overall our findings indicate that highly responsive DCAs can be developed only through a combination of properties such as a change in hydration and size of the molecule, which come as a consequence of intramolecular structural and electrostatic changes in the particle. In turn, they provide a model for future preparations of responsive DCAs that can be utilized for both T1-weighted and ratiometric T2/T1-weighted imaging to visualize essential biological processes in a dynamic fashion.}

{Neuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [www.syphad.org]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug\textendashtarget interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug\textendashtarget interactions.}

{Ultra-high field has the potential to improve the quality of 31P spectroscopic applications due to the increased SNR and spectral dispersion. In addition, previous studies have reported a decreasing T1 with increasing field strength, which would further contribute to an improved quantification quality. In this study, we have measured the longitudinal relaxation time T1 in the visual cortex of healthy human subjects at 9.4 T, using an inversion-recovery technique. The values obtained were consistently lower than published data at 7 T, confirming observations of a decreasing T1 with field strength.}

{BOLD fMRI is widely used to study taskinduced signal changes (tfMRI) in conjunction with taskfree, i.e., restingstate (rsfMRI). However, an understanding of how these two types of measurements when utilized together can robustly infer principles of human brain organization and behaviour is still lacking. Specifically, previous literature sought to understand connections between rsfMRI and tfMRI measurements by demonstrating that functional correlation properties during rsfMRI remain largely unchanged during cognitive tasks. Here, we reevaluate recent work building on this link. The core idea of those works examined models with the specific goal of regressing features derived from rsfMRI scans onto tfMRI general linear model (GLM) maps to predict interindividual differencesa vital target for increasing the usefulness of fMRI in clinical settings. First, we introduce a baseline model evaluation metric for empirical results previously reported in the literature and reproduce results next to this metric. This baseline evaluation provides an essential component under which we interpret quantitative results obtained with machine learning methods used in this context. Second, we show how observing a dependence between tfMRI and rsfMRI may arise under different encoding models. This demonstration emphasizes (a) the need for proper model evaluation and (b) the need to thoroughly examine the implications of observing higher withinsubject prediction scores than betweensubject scores. Third, we show how improvements in previously established regression methods can be made using a regularization technique. We demonstrate this with empirical results on the latest data from the Human Connectome Project (HCP) release. Although it is known that intrinsic differences in rsfMRI and tfMRI patterns can be characterized to a certain extent, our work stresses the need for proper model evaluation in reporting quantitative results. Taken together, our work provides a new lens for the evaluation of previously reported results and an important commentary to a topic that has generated a great deal of attention and interest.}

{What cortical mechanisms allow humans to easily discern the expression or identity of a face? Subjects detected changes in expression or identity of a stream of dynamic faces while we measured BOLD responses from topographically and functionally defined areas throughout the visual hierarchy. Responses in dorsal areas increased during the expression task, whereas responses in ventral areas increased during the identity task, consistent with previous studies. Similar to ventral areas, early visual areas showed increased activity during the identity task. If visual responses are weighted by perceptual mechanisms according to their magnitude, these increased responses would lead to improved attentional selection of the task-appropriate facial aspect. Alternatively, increased responses could be a signature of a sensitivity enhancement mechanism that improves representations of the attended facial aspect. Consistent with the latter sensitivity enhancement mechanism, attending to expression led to enhanced decoding of exemplars of expression both in early visual and dorsal areas relative to attending identity. Similarly, decoding identity exemplars when attending to identity was improved in dorsal and ventral areas. We conclude that attending to expression or identity of dynamic faces is associated with increased selectivity in representations consistent with sensitivity enhancement.}

{We have recently reported that inactivation of the midline thalamic nucleus reuniens (RE) dramatically impaired the rat performance of a previously learnt spatial task (Mei et al., 2018). Our findings supported an emerging view that the RE may contribute to spatial memory by coordinating interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The HPC-PFC interactions occurring at different frequency ranges (e.g. theta, beta, or gamma) are thought to support specific steps of information processing. However, the detailed mechanisms of task-specific cross-regional interactions within the RE-HPC-PFC network remain poorly understood. We recorded extracellular activity from the RE, dorsal HPC and medial PFC in the rats learning a complex spatial task on a cross-word maze over 5 training sessions. We aim at characterizing the learning-induced dynamics of cross regional interactions. During task performance, the strongest theta power was present in the HPC, while it was much weaker in the RE and PFC. In the beginning of each trial, we observed systematic surge of the theta-synchronization between the PFC and RE, which was followed by increases in the RE-HPC and HPC-PFC theta-coherence. This activity dynamics seemed to be associated with a retrieval of the correct trajectory at the beginning of the trial. Thus, a decision making (e.g. right or left turn) on the maze likely required retrieval of cortically-stored information and its integration into active network. A strong theta-coherence within the entire RE-HPC-PFC network accompanied errors (e.g. entries to the wrong maze alleys). Besides, we compared the coherence between the RE, HPC, and PFC across training days. Our preliminary results further support the idea that the RE may indeed gate the bidirectional information flow within the HPC-PFC pathway. The RE may contribute to spatial learning as a network element enabling retrieval and storing task-related information in working memory. It remains, however, unclear if the RE is required for consolidation of spatial memory.}

{Pseudo-continuous-arterial-spin-labeling (PCASL) has been successfully applied in abdominal organs to image organ perfusion. The aim of this work was to evaluate the pulmonary blood flow in dependence on the cardiac cycle using PCASL at 1.5T. Labeling of pulmonary blood flow was achieved by ECG triggering and an labeling plane perpendicular to the pulmonary trunk (tagging duration 300ms). In five volunteers, eight measurements were acquired with fast True-FISP imaging (in-plane-resolution, 2.5$\times$2.5mm2, coronal view) with post-labeling delays between 100 and 1500ms. The PCASL-True-FISP technique was able to precisely assess blood flow of pulmonary arteries, as well as perfusion of the lung parenchyma.}

{Similarly to how we look for telltale signs of both parents\textquoteright facial features in their children\textquoterights faces, we are able to recognize two identities from one photo that mixes two persons\textquoteright faces together. When more people\textquoterights faces are used to create mixed faces, the identities of individual faces (i.e., \textquotedblleftparent\textquotedblright faces) become less recognizable (i.e., identity information is degraded). In our study, we investigated the limit of identity recognition in such identity-degraded faces and whether familiarity with the \textquotedblleftparent\textquotedblright faces enhances identity recognition from such mixed faces. We first tested whether people can extract the identities from a mix of three faces. Participants who were familiar with the \textquotedblleftparent\textquotedblright faces performed better than those who were not. We then tested whether participants can extract the identities of mixed faces generated with more faces. We showed a mixed face of 2 to 10 \textquotedblleftparent\textquotedblright faces together with a test face. Participants had to decide whether the test face was a parent of the mixed face. Both familiar and unfamiliar participants performed better than chance for mixed faces generated with up to eight faces. Finally, we tested at what level mixed faces lose their identity so that we cannot discern between two mixed faces generated with completely different \textquotedblleftparent\textquotedblright faces. We presented two mixed faces in a trial and participants performed a same/different task. Both mixed faces had the same number of identities (2 to 32), but had no parents in common. Participants were better than chance even for the 32-face mixed faces. Together, these results indicate that our face processing system is extremely sensitive to facial identity information. Familiarity helps identity recognition, but this advantage becomes less evident when identity information degrades (i.e., with increased number of \textquotedblleftparent\textquotedblright faces in a mixed face).}

{Previous studies on mental rotation (i.e., the ability to imagine objects undergoing rotation; MR) have mainly focused on visual input, with comparatively less information about tactile input. In this study, we examined whether the processes subtending MR of 3D stimuli with both input modalities are perceptually equivalent (i.e., when learning within-modalities is equal to transfers-of-learning between modalities). We compared participants\textquoteright performances in two consecutive task sessions either in no-switch conditions (Visual$\rightarrow$Visual or Tactile$\rightarrow$Tactile) or in switch conditions (Visual$\rightarrow$Tactile or Tactile$\rightarrow$Visual). Across both task sessions, we observed MR response differences with visual and tactile inputs, as well as difficult transfer-of-learning. In no-switch conditions, participants showed significant improvements on all dependent measures. In switch conditions, however, we only observed significant improvements in response speeds with tactile input (RTs, intercepts, slopes: Visual$\rightarrow$Tactile) and close to significant improvement in response accuracy with visual input (Tactile$\rightarrow$Visual). Model fit analyses (of the rotation angle effect on RTs) also suggested different specification in learning with tactile and visual input. In \textquotedblleftSession 1\textquotedblright, the RTs fitted similarly well to the rotation angles, for both types of perceptual responses. However, in \textquotedblleftSession 2\textquotedblright, trend lines in the fitting analyses changed in a stark way, in the switch and tactile no-switch conditions. These results suggest that MR with 3D objects is not necessarily a perceptually equivalent process. Specialization (and priming) in the exploration strategies (i.e., speed-accuracy trade-offs) might, however, be the main factor at play in these results\textemdashand not MR differences in and of themselves.}

{Sounds in our environment can capture our interest even if they bear no relevance to our ongoing occupation. In the context of driving, this could be a crying child in the backseat. Even if we do not exhibit any behavioral responses, our brains generate a characteristic ERP waveform to such sounds; this has been termed the distraction potential (Escera Corral, 2003). We have found that general steering demands attenuate the amplitudes of the early and late novelty P3 components of this distraction potential (Scheer, B\"ulthoff, Chuang, 2016). In particular, varying the complexity of a steering task\textquoterights control dynamics selectively attenuates the late novelty P3 component of the distraction potential, whilst having no effect on the early novelty P3. Other manipulations of steering difficulty, such as control disturbances, do not have a similar impact. These findings mirror those found in dual-task paradigms whereby similar conflicts were found with the P300 potentials generated by infrequent task-relevant tones (e.g., Wickens et al., 1983). Thus, we propose that the late novelty P3 component generated by complex and task-irrelevant sounds is comparable to the better established P300 potentials. Both components might reflect the availability of cross-modal executive working memory resources.}

{In recent investigations, the angular dependence of the BOLD signal with respect to the main magnetic field has been shown by Monte Carlo simulations and experimental approaches. This orientation dependence is often attributed to the contribution of large vessels (cortical surface and penetrating arteries/veins). However, the ability to resolve cortical layers and columns depends ultimately on the contribution of the MR signal generated by the capillary bed. In this work, we studied the MR signal attenuation generated by a vascular network model that was acquired from the parietal cortex of mice using a two-photon laser imaging techniques. We separately investigated the impact of macrovessels (\textgreater5 $\micro$m in diameter) and microvessels (\textless 5 $\micro$m in diameter) on the BOLD effect.}

{The neuronal system is only in a few areas a \quotedblbasecolored\textquotedblleft system, such as the substantia nigra, which received its name by the dark color based on the neuromelanin of dopaminergic neurons. Melanin is a pigment of skin and hair, so the question arose, if there might be a correlation of the coat color and brain areas containing dopaminergic neurons such as the olfactory bulb. Therefore we investigated the olfactory bulbs of female American minks bred specifically for their coat color and measured the absolute layer volumes of the four color varieties: dark black \textquotedblleftstandard\textquotedblright (Neovison vison var. atratus, a), light black \textquotedblleftsilverblue\textquotedblright (Neovison vison var. glaucus, g), light brown \textquotedblleftpastel\textquotedblright (Neovison vison var. suffuscus, s), dark brown \textquotedblleftwild\textquotedblright (Neovison vison var. carinum, c) using a morphometric system. The volume of the glomerular layer, including the periglomerular dopaminergic neurons, revealed a significant difference between the pale brown variety (suffuscus: 20.68$\pm$4.73mm3) versus the black varieties (glaucus: 14.79$\pm$0.91mm3 and atratus: 15.35$\pm$1.21mm3). Significant differences were also observed in the mitral cell layer (including passing periglomerular cells) of suffuscus (5.30$\pm$1.55mm3) versus the black varieties glaucus (3.54$\pm$0.65mm3) and atratus (3.78$\pm$0.37mm3) and in the internal plexiform layer (s: 5.36$\pm$0.86mm3; significant different vs g: 3.54$\pm$0.65 mm3 and a: 2.90$\pm$0.33mm3). No differences were found among any of the color varieties in the volumes of the fila, external plexiform, granule cell and subependymal layer, which are all composed of much fewer or no dopaminergic neurons. Our results indicate that, based on gene expression, the coat color might reflect neuronal structures.}

{The cortex exhibits a strict vascular architecture and vessel orientation to the B0 field should impact the local susceptibility and hence the local BOLD signal. Cortical folding could thus lead to local variations in the signal. Here, we used high-resolution 7T EPI rs-fMRI data and found substantial variations of the signal amplitdude\textquotesingles coefficient of variation ($\sigma$/$\mu$) with the local cortical orientation to B0. This effect was measurable throughout cortical depths with a maximised effect of +70 at the surface. We compare this to orientation-dependent blurring effects along the phase-encode axis, which we found to be significant too.}

{Touchscreens are a common fixture in current vehicles. With autonomous driving, we can expect touch interaction with such in-vehicle media systems to exponentially increase. In spite of vehicle suspension systems, road perturbations will continue to exert forces that can render in-vehicle touch interaction challenging. Using a motion simulator, we investigate how different vehicle speeds interact with road features (i.e., speed bumps) to influence touch interaction. We determine their effect on pointing accuracy and task completion time. We show that road bumps have a significant effect on touch input and can decrease accuracy by 19\textpercent. In light of this, we developed a Random Forest (RF) model that improves touch accuracy by 32.0\textpercent on our test set and by 22.5\textpercent on our validation set. As the lightweight model uses only features that can easily be determined through inertial measurement units, this model could be easily deployed in current automobiles.}

{The body constantly processes information about the outside world and the world inside itself. The mouth serves as a vital sensing gate for the taste, temperature and texture of food. Oral receptors relay sensory information about ingested contents to the insular cortex, which harbors the primary cortical center for gustatory information processing (Small, 2010). The insula receives afferent inputs not only from the mouth but also from the entire body, including the digestive system. The processing of bodily (or interoceptive) information in the insular cortex gives rise to subjective bodily sensations (e.g., taste, hunger, thirst, fullness, warmth) and, in turn, regulates bodily functions (Craig, 2003). Given the importance of these bodily feelings in metabolic wellness and in psychosomatic integration, mapping where each bodily process is represented in the insula is clearly needed. In several 7T fMRI studies with the anesthetized macaque monkey (n\textequals12), we introduced taste and rectal distention paradigms while measuring the sensory information relay to key subcortical and cortical network processing hubs. The insula, in particular, was consistently activated. Analyses of low- and high-intensity sweet, sour and salty taste stimuli disclosed tastant-specific activations across the mid-anterior dorsal insular cortex where other oral sensory afferents are represented, thereby alluding to a potential gustotopic map embedded within a full mouth representation. Rectal distention, on the other hand, activated specifically the ventral anterior insula, suggesting that purely sensory (e.g. taste, temperature and texture of food) and sensory-motor (e.g., distention and contraction of the gut) processing may be represented in two distinct insular territories.}

{The object orientation effect describes shorter perceived distances to the front than to the back of oriented objects. The present work extends previous studies in showing that the object orientation effect occurs not only for egocentric distances between an observer and an object, but also for exocentric distances, that are between two oriented objects. Participants watched animated virtual humans (avatars) which were either facing each other or looking away, and afterward adjusted a bar to estimate the perceived length. In two experiments, participants judged avatars facing each other as closer than avatars facing away from each other. As the judged distance was between two objects and did not involve the observer, results rule out an explanation that observers perceive object fronts as closer to prepare for future interaction with them. The second experiment tested an explanation by predictive coding, this is the extrapolation of the current state of affairs to likely future states here that avatars move forward. We used avatars standing on bridges either connecting them or running orthogonal to the inter-avatar line thus preventing forward movement. This variation of walkability did not influence participants\textquoteright judgments. We conclude that if predictive coding was used by participants, they did not consider the whole scene layout for prediction, but concentrated on avatars. Another potential explanation of the effect assumes a general asymmetrical distribution of inter-person distances: people facing each other might typically be closer to each other than when facing away and that this asymmetry is reflected as a bias in perception.}

{Avatars are important for games and immersive social media applications. Although avatars are still not complete digital copies of the user, they often aim to represent a user in terms of appearance (color and shape) and motion. Previous studies have shown that humans can recognize their own motions in point-light displays. Here, we investigated whether recognition of self-motion is dependent on the avatar\textquotesingles fidelity and the congruency of the avatar\textquotesingles sex with that of the participants. Participants performed different actions that were captured and subsequently remapped onto three different body representations: a point-light figure, a male, and a female virtual avatar. In the experiment, participants viewed the motions displayed on the three body representations and responded to whether the motion was their own. Our results show that there was no influence of body representation on self-motion recognition performance, participants were equally sensitive to recognize their own motion on the point-light figure and the virtual characters. In line with previous research, recognition performance was dependent on the action. Sensitivity was highest for uncommon actions, such as dancing and playing ping-pong, and was around chance level for running, suggesting that the degree of individuality of performing certain actions affects self-motion recognition performance. Our results show that people were able to recognize their own motions even when individual body shape cues were completely eliminated and when the avatar\textquotesingles sex differed from own. This suggests that people might rely more on kinematic information rather than shape and sex cues for recognizing own motion. This finding has important implications for avatar design in game and immersive social media applications.}

{The conscious representation of our physical appearance is important for many aspects of everyday life. Here, we asked whether different visual experiences of our bodies influence body width estimates. In Experiment 1, width estimates of three body parts (foot, hips, and shoulders) without any visual access were compared to estimates with visual feedback available in a mirror or from a first-person perspective. In the no visual access and mirror condition, participants additionally estimated their head width. There was no influence of viewing condition on body part width estimates. Consistent with previous research, all body part widths were overestimated with greater overestimation of hip and head width. In Experiment 2, participants estimated the size of unfamiliar noncorporeal objects to test whether this overestimation was partially due to the metric body size estimation method or our experimental conditions. Object width was overestimated with visual feedback in a mirror available as compared to when directly looking at the object, but only for objects placed at shoulder and head height. We conclude that at least some of the overestimation of body part width seems to be body specific and occurs regardless of the visual information provided about the own body.}

{Synaptic plasticity, neuronal replay, and cross-regional communication are considered key physiological processes underlying memory consolidation. Both cellular and systems-level consolidation hypotheses are supported by extensive empirical evidence. However, presently, little is known about the temporal relations between local synaptic modifications and activity dynamics within extended neuronal networks supporting memory. The diffuse ascending neuromodulatory systems, with the locus coeruleus (LC) noradrenergic system being one of them, appear to be ideal candidates for bridging the cellular and systems mechanisms of memory consolidation. According to a canonical view, noradrenaline release from the terminal fields of LC neurons creates a window of heightened synaptic plasticity within a recently activated neuronal network. Importantly, this neuromodulatory input is critical at times of actual learning experience but also functions \textquotedblleftoff-line,\textquotedblright when experience-activated neuronal ensembles replay and protein-dependent synaptic modifications occur. Tracking the connectivity strength within learning-related large-scale networks combined with monitoring neuromodulatory activity and behavioral assessment of memory appear irreplaceable methodology for examining interactions between cellular and systems mechanisms of memory consolidation, which are both dependent on neuromodulation.}

{Spatial navigation depends on the hippocampal function, but also requires bidirectional interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The cross-regional communication is typically regulated by critical nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is reciprocally connected to both HPC and PFC and may coordinate the information flow within the HPC\textendashPFC pathway. Here we examined if RE activity contributes to the spatial memory consolidation. Rats were trained to find reward following a complex trajectory on a crossword-like maze. Immediately after each of the five daily learning sessions the RE was reversibly inactivated by local injection of muscimol. The post-training RE inactivation affected neither the spatial task acquisition nor the memory retention, which was tested after a 20-d \textquotedblleftforgetting\textquotedblright period. In contrast, the RE inactivation in well-trained rats prior to the maze exposure impaired the task performance without affecting locomotion or appetitive motivation. Our results support the role of the RE in memory retrieval and/or \textquotedblleftonline\textquotedblright processing of spatial information, but do not provide evidence for its engagement in \textquotedblleftoff-line\textquotedblright processing, at least within a time window immediately following learning experience.}

{Sound is a potent elicitor of emotions. Auditory core, belt and parabelt regions have anatomical connections to a large array of limbic and paralimbic structures which are involved in the generation of affective activity. However, little is known about the functional role of auditory cortical regions in emotion processing. Using functional magnetic resonance imaging and music stimuli that evoke joy or fear, our study reveals that anterior and posterior regions of auditory association cortex have emotion-characteristic functional connectivity with limbic/paralimbic (insula, cingulate cortex, and striatum), somatosensory, visual, motor-related, and attentional structures. We found that these regions have remarkably high emotion-characteristic eigenvector centrality, revealing that they have influential positions within emotion-processing brain networks with "small-world" properties. By contrast, primary auditory fields showed surprisingly strong emotion-characteristic functional connectivity with intra-auditory regions. Our findings demonstrate that the auditory cortex hosts regions that are influential within networks underlying the affective processing of auditory information. We anticipate our results to incite research specifying the role of the auditory cortex-and sensory systems in general-in emotion processing, beyond the traditional view that sensory cortices have merely perceptual functions.}

BOLD fMRI has been wildly used for mapping brain activity, but the cellular contribution of BOLD signals is still controversial. In this study, we investigated the correlation between neuronal/astrocytic calcium and the BOLD signal using simultaneous GCaMP-mediated calcium and BOLD signal recording, in the event-related state and in resting state, in anesthetized and in free-moving rats. To our knowledge, the results provide the first demonstration that evoked and intrinsic astrocytic calcium signals could occur concurrently accompanied by opposite BOLD signals which are associated with vasodilation and vasoconstriction. We show that the intrinsic astrocytic calcium is involved in brain state changes and is related to the activation of central thalamus. First, by simultaneous LFP and fiber optic calcium recording, the results show that the coupling between LFP and calcium indicates that neuronal activity is the basis of the calcium signal in both neurons and astrocytes. Second, we found that evoked neuronal and astrocytic calcium signals are always positively correlated with BOLD responses. However, intrinsic astrocytic calcium signals are accompanied by the activation of the central thalamus followed by a striking negative BOLD signal in cortex, which suggests that central thalamus may be involved in the initiation of the intrinsic astrocytic calcium signal. Third, we confirmed that the intrinsic astrocytic calcium signal is preserved in free moving rats. Moreover, the occurrences of intrinsic astrocytic calcium spikes are coincident with the transition between different sleep stages, which suggests intrinsic astrocytic calcium spikes reflect brain state transitions. These results demonstrate that the correlation between astrocytic calcium and fMRI signals is related to the thalamic regulation of cortical states. On the other hand, by studying the relationship between vessel{\textendash}specific BOLD signals and spontaneous calcium activity from adjacent neurons, we show that low frequency spontaneous neuronal activity is the cellular mechanism of the BOLD signal during resting state.

{The initial-dip is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, and is believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed and its neuronal correlates unknown. Here, we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in HbR, with an early decrease and later rebound. However, HbT decreases were always large enough to counter spiking-induced increases in HbR. Moreover, the HbT-dip and HbR-rebound were strongly coupled to highly localized spiking activity. Our results suggest that the HbT-dip helps prevent accumulation of spiking-induced HbR concentration in capillaries by flushing out HbT, probably by active venule dilation.}

{The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing. For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI. Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy. To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words.}

{Understanding the forebrain neuromodulation by the noradrenergic locus coeruleus (LC) is fundamental for cognitive and systems neuroscience. The diffuse projections of individual LC neurons and presumably their synchronous spiking have long been perceived as features of the global nature of noradrenergic neuromodulation. Yet, the commonly referenced "synchrony" underlying global neuromodulation, has never been assessed in a large population, nor has it been related to projection target specificity. Here, we recorded up to 52 single units simultaneously (3164 unit pairs in total) in rat LC and characterized projections by stimulating 15 forebrain sites. Spike count correlations were surprisingly low and only 13 of pairwise spike trains had synchronized spontaneous discharge. Notably, even noxious sensory stimulation did not activate the population, only evoking synchronized responses in 1.6 of units on each trial. We also identified novel infra-slow (0.01-1 Hz) fluctuations of LC unit spiking that were asynchronous across the population. A minority, synchronized possibly by gap junctions, has restricted (non-global) forebrain projection patterns. Finally, we characterized two types of LC single units differing by waveform shape, propensity for synchronization, and interactions with cortex. These cell types formed finely-structured ensembles. Our findings suggest that the LC may convey a highly complex, differentiated, and potentially target-specific neuromodulatory signal.}

{Motivation: In spite of technological advances, autonomous cars and driver assistance systems can occasionally fail (Levin, 2018). Therefore, it remains necessary for humans to be continuously vigilant for instances of automation failure (Parasuraman, Sheridan, \& Wickens, 2000). Auditory warnings could assist by alerting users when there is a high likelihood of danger. In this work, we investigate how auditory warning cues can hasten emergency braking responses. Objective: This study investigates the use of auditory warnings for potential rear-end collisions, in the case of a failure in the autonomous cruise control (ACC) which measures and keeps the correct distance to front cars. In particular, we investigate the benefit of using looming sounds (i.e., sounds that grow in intensity) over static intensity sounds. Unlike static sounds, looming sounds convey two pieces of information: First, they give information that something is approaching. Second, they provide an estimation of the time of the collision. Background: Gray (2011) compared different auditory warning cues for braking situations in a realistic driving simulation that required full manual handling. He showed that looming sounds resulted in faster braking responses to potential collisions than sounds with unchanging intensities. Yet, it remains unclear if this difference is due to attentional redirection from other aspects of manual driving (e.g., lane-keeping) to emergency braking or whether looming sounds are especially suited for signaling an emergency braking response. Neuroimaging studies have shown that the brain processes looming stimuli preferentially (e.g. Bach, Furl, Barnes, \& Dolan, 2015). Furthermore, looming sounds support the speedy detection of visual looming objects (e.g. Alink et al., 2012). It has been claimed that this preferential crossmodal benefit of looming sounds occurs because they signal approaching threat. Consistent with this claim, it has been shown that looming sounds induce selective activation of the amygdala (Bach et al., 2008). Method: For this study, we tested 20 volunteers (13 females, 7 males) aged between 20 and 32 (M\textequals25). Our study was conducted in a driving simulator that was programmed to drive with ACC (Fig. 1). The participants\textquoteright only task was to watch the scene and to step on the braking pedal when a rear-end collision with a lead vehicle could occur. Possible crash situations were occasionally cued (66.7\textpercent) by either a static-intensity sound or a looming sound. Sounds could also be presented, in absence of danger (false alarms, 20 \textpercent). We measured braking times as well as the event-related potential (ERP) evoked by the auditory cues. To this end, the electroencephalogram (EEG) was recorded via 63 active electrodes while participants performed the task. The electrodes were distributed according to the international 10-20-system with the reference electrode positioned at FCz and the ground electrode at AFz. The electro-oculogram activity was recorded by four electrodes around the eyes. EEG data was filtered, cleaned using the Artifact Subspace Reconstruction method and re-referenced to the average reference. Afterwards, we cleaned the EEG using an independent component analysis (ICA) to reduce artifacts without losing too much data. We hand-selected eight out of 30 clusters, which were likely to represent noise, for removal and back-projected the remaining EEG activity for analysis at the electrode level. Results: Braking to potential crashes was significantly faster when either the looming (M\textequals825 ms, SD\textequals112) or the constant (M\textequals845 ms, SD\textequals123) sound were played compared to when no sound was presented (M\textequals1100 ms, SD\textequals112), F(2,36)\textequals199.5, p\textless.001. Moreover, looming sounds generated faster braking than static sounds, t(18)\textequals-2.46, p\textequals.036 (Fig. 2). There was no significant difference in false alarms between the looming and the constant sound condition, t(18)\textequals.57, p\textequals.58. A mass-univariate analysis of the ERP data revealed differences in the ERP in the time-interval between 240 and 280 ms after sound onset (Fig. 3a, b): The static sound evoked a larger fronto-central N2 and a larger left parietal P2 amplitude compared to the looming sound (Fig. 3). We found no differences in early, perceptual components or in the readiness potential. Discussion: The behavioral data indicates that looming sounds speed up braking reactions, even if no redirection of attention from driving to emergency braking is required. In other words, looming sounds result in fast emergency braking during manual vehicle handling (Gray, 2011), as well as partially automated driving (i.e., ACC). The EEG data shows that this looming benefit emerges as early as 200 ms after sound onset, as indicated by the smaller N2 after the looming sound compared to the static sound. We attribute this amplitude difference to the audiovisual incongruity between the looming visual stimulus and the static sound (Lindstr\"om et al., 2012). Specifically, we suggest that a looming sound which is consistent with a looming visual stimulus leads to faster braking times because it is easier to process. This is reflected by a smaller fronto-central N2. Furthermore, we speculate that the amplitude difference observed for the left parietal P2 probably derives from the same underlying neural mechanisms because both effects occurred within the same time window. Further work is necessary to specify the underlying neural sources that could have given rise to this. In summary, our results show that looming sounds benefit performance also when driving with ACC. Specifically, we find that it generated faster braking reactions. We believe that the reaction is facilitated by the faster processing of congruent audiovisual stimuli. Limitations and outlook: The neural sources that give rise to the observed looming benefit remain unknown. A source estimation analysis or neuroimaging techniques with high spatial resolution (e.g., MEG, fMRI) will provide further insight. Furthermore, although driver inattention is the targeted real-world problem of our inquiry, our participants were instructed to attend the driving scene. Future extensions of this work could introduce a secondary, non-driving task to examine the looming benefit when drivers are no longer required to drive and thus do not pay attention to the driving. Finally, looming objects can approach one\textquoterights vehicle from more directions than only the front. Thus, it could be worthwhile to investigate whether looming sounds from the side could result in faster evasion maneuvers, or whether the looming benefit is exclusive to emergency braking only.}

{We purpose an integrated RF-shim coil array, where the shimming current path and the RF receiving coil are arranged on two orthogonal planes to minimize the mutual coupling. This design was implemented as an array consisting of seven shim coils and a 32-channel RF-shim array. The 39-channel RF-shim coil array has marginal SNR loss and improved the global shimming by 9, compared to the 32-channel RF-shim array.}

{Functional neuroimaging is a powerful non-invasive tool for studying brain function, using changes in blood oxygenation as a proxy for underlying neuronal activity. The neuroimaging signal correlates with both spiking, and various bands of the local field potential (LFP), making the inability to discriminate between them a serious limitation for interpreting hemodynamic changes. Here, we record activity from the striate cortex in two anesthetized monkeys (Macaca mulatta), using simultaneous functional near-infrared spectroscopy (fNIRS) and intra-cortical electrophysiology. We find that low-frequency LFPs correlate with hemodynamic signal\textquotesingles peak amplitude, whereas spiking correlates with its peak-time and initial-dip. We also find spiking to be more spatially localized than low-frequency LFPs. Our results suggest that differences in spread of spiking and low-frequency LFPs across cortical surface influence different parameters of the hemodynamic response. Together, these results demonstrate that the hemodynamic response-amplitude is a poor correlate of spiking activity. Instead, we demonstrate that the timing of the initial-dip and the hemodynamic response are much more reliable correlates of spiking, reflecting bursts in spike-rate and total spike-counts respectively.}

{Purpose The ultimate intrinsic signal-to-noise ratio (UISNR) represents an upper bound for the achievable SNR of any receive coil. To reach this threshold a complete basis set of equivalent surface currents is required. This study systematically investigated to what extent either loop- or dipole-like current patterns are able to reach the UISNR threshold in a realistic human head model between 1.5 T and 11.7 T. Based on this analysis, we derived guidelines for coil designers to choose the best array element at a given field strength. Moreover, we present ideal current patterns yielding the UISNR in a realistic body model. Methods We distributed generic current patterns on a cylindrical and helmet-shaped surface around a realistic human head model. We excited electromagnetic fields in the human head by using eigenfunctions of the spherical and cylindrical Helmholtz operator. The electromagnetic field problem was solved by a fast volume integral equation solver. Results At 7 T and above, adding curl-free current patterns to divergence-free current patterns substantially increased the SNR in the human head (locally \textgreater20). This was true for the helmet-shaped and the cylindrical surface. On the cylindrical surface, dipole-like current patterns had high SNR performance in central regions at ultra-high field strength. The UISNR increased superlinearly with B0 in most parts of the cerebrum but only sublinearly in the periphery of the human head. Conclusion The combination of loop and dipole elements could enhance the SNR performance in the human head at ultra-high field strength.}

{The S2-SSFP echo (the echo before the RF pulse in non-balanced SSFP sequences, or F-0, PSIF, CE-FAST, T2-FFE) is a refocused echo and has thus been proposed for BOLD imaging to suppress larger vessels, similar to the classical spin echo. Here we demonstrate in Monte Carlo simulations that the primary S1-SSFP gradient echo shows nearly identical properties as the S2-SSFP echo. Both echoes of this non-balanced SSFP sequence can be used for BOLD imaging exhibiting a pure spin echo behavior, i.e suppression of larger vessels.}