Publications

{Introduction: Task-based fMRI data collected from Human Connectome Project were analyzed using the general linear model. The acquired Z values were plotted as a histogram. Theoretically, the null distribution of Z values should resemble a standard Gaussian distribution. However, we found that the histogram of Z values is often not centered around zero [mean shifted]. In fact, 12 percent of over 3000 Z maps showed a systematic shift bigger than 0.2 standard deviation.This is problematic because statistical inference based on mean shifted Z values can lead to incorrect results. Conclusions: Head motion parameters showed small but significant correlation with the mode of the Z value distribution. Furthermore, shift of the Z value distribution was not dependent on subject based on comparison between motor tfMRI and language tfMRI. Lastly, voxels within white matter region also showed systematically shifted Z values which implies that neuronal alone is not causing the shift. Further investigation is required to pinpoint the cause of the Z score distribution shift. Methods: Material Task-evoked fMRI and motion parameters were acquired from Human Connectome Project WU-Minn HCP 1200 Subjects Data (HCP S1200)[4]. Motor tfMRI and language tfMRI were used in this study. In motor tfMRI (N\textequals1049), the design consisted of five motor tasks including left finger tapping, right finger tapping, left toe squeezing, right toe squeezing and tongue moving blocks. In language tfMRI (N\textequals1048), the design included story block where subjects were presented auditory stories and math block where subjects were presented math task aurally. Acquired images were preprocessed by minimal HCP preprocessing pipeline[2]. Head motion data included estimated rotation in three coordinates, estimated translation in three coordinates and derivative of each parameter for each acquired slices. Method Acquired HCP fMRI images were further processed with high-pass filter discarding temporal frequency below 1/100Hz[3]. Then analysis was performed using general linear model (GLM)[1]. With results from GLM analysis, statistical inference was performed. With motor tfMRI, two Z maps were produced for each subjects contrasting left finger tapping blocks to right finger tapping blocks and contrasting left toe squeezing blocks to right toe squeezing blocks. With language tfMRI, story block and math block was contrasted to create another Z map for each subjects. Shift of the Z score distributions were represented as three values; mean, median and mode. Mode of the distribution was estimated; (mode) \textequals 3\textasteriskcentered(median) - 2\textasteriskcentered(mean) Head motion was represented as four variables; maximum head rotation, maximum head translation, summed root mean square (RMS) of head rotation and summed root mean square (RMS) of head translation Results: Among 3146 Z maps, about 12 were shifted more than 0.2 standard deviation. An example of shifted Z value distribution is shown in figure 1. Analysis 1: Correlation between mode of the Z value distribution and head motion variables were very small (Table 1). Biggest correlation was shown between language tfMRI Z map and maximum head translation (Pearson\textquotesingles r \textequals 0.217, p\textless 0.01). Analysis 2: Z map shift in finger tapping contrast and toe tapping contrast were highly correlated (Pearson\textquotesingles r \textequals 0.696, p \textless 0.01). However, Z map shift in language tfMRI was not correlated with neither that of finger tapping contrast (Pearson\textquotesingles r \textequals -0.012, p \textequals 0.70) nor toe squeezing contrast (Pearson\textquotesingles r \textequals -0.073, p \textequals 0.02). Analysis 3: Z score distribution for voxels within the white matter was shifted as well. Range of the Z distribution shift within white matter was similar to range of the Z distribution shift within the whole brain.}

{Pseudo-continuous-arterial-spin-labeling (PCASL) has been successfully applied in the liver and kidney providing high signal-to-noise-ratio. The goal of this work is to assess the potential of PCASL technique to measure the pulmonary perfusion at 1.5 T. Effective labeling of pulmonary blood flow was achieved by ECG triggering and an orientation of the labeling plane perpendicular to the pulmonary trunk. Fast True-FISP imaging with short TE of 0.9 ms was used to obtain high signal from lung parenchyma. The PCASL-True-FISP technique provides high quality perfusion images of the lung and allows quantitative measurements of pulmonary perfusion both in multiple breath-holds and under free breathing condition.}

{In this work, we measured eddy currents for a very high order B0 shim system. The eddy currents were measured using two methods: a low-resolution B0 mapping sequence and a NMR field camera. The high temporal resolution of the field camera allowed the eddy currents to be corrected using a digital pre-emphasis setup.}

{Purpose Metabolite cycling (MC) is an MRS technique for the simultaneous acquisition of water and metabolite spectra that avoids chemical exchange saturation transfer effects and for which water may serve as a reference signal or contain additional information in functional or diffusion studies. Here, MC was developed for human investigations at ultrahigh field. Methods MC-STEAM and MC-semi-LASER are introduced at 9.4T with an optimized inversion pulse and elaborate coil setup. Experimental and simulation results are given for the implementation of adiabatic inversion pulses for MC. The two techniques are compared, and the effect of frequency and phase correction based on the MC water spectra is evaluated. Finally, absolute quantification of metabolites is performed. Results The proposed coil configuration results in a maximum math formula of 48 $\mu$$\Tau$ in a voxel within the occipital lobe. Frequency and phase correction of single acquisitions improve signal-to-noise ratio (SNR) and linewidth, leading to high-resolution spectra. The improvement of SNR of N-acetylaspartate (SNRNAA) for frequency aligned data, acquired with MC-STEAM and MC-semi-LASER, are 37 and 30, respectively (P \textless 0.05). Moreover, a doubling of the SNRNAA for MC-semi-LASER in comparison with MC-STEAM is observed (P \textless 0.05). Concentration levels for 18 metabolites from the human occipital lobe are reported, as acquired with both MC-STEAM and MC-semi-LASER. Conclusion This work introduces a novel methodology for single-voxel MRS on a 9.4T whole-body scanner and highlights the advantages of semi-LASER compared to STEAM in terms of excitation profile. In comparison with MC-STEAM, MC-semi-LASER yields spectra with higher SNR.}

{The anterior insular cortex (AIC) is often regarded as a key \textquotedblleftnode\textquotedblright of the salience network that mediates the central representation and goal-directed control of homeostatic bodily states by coordinating brain networks. Given the possible role of the AIC in brain network dynamics, we combined electrophysiology and electrical microstimulation in the left and right AIC with functional magnetic resonance imaging (fMRI) to examine blood-oxygen-level-dependent (BOLD) signal changes in cortical and subcortical areas in 4 anesthetized macaque monkeys in a 7T scanner. 10-channel laminar electrodes were introduced in the \textquoteleftvon Economo neuron area\textquoteright of the AIC to record ongoing spontaneous neuronal activity during two-shot echo-planar imaging with a temporal resolution of 2 seconds. Focusing on the local field potential gamma band (56-79 Hz) unilateral events were detected and used to trigger the BOLD signal, a method called \textquoteleftneural-event-triggered fMRI\textquoteright (NET-fMRI) (Logothetis et al. Nature 2012 491:547-53). The results showed markedly different patterns of whole-brain activation and deactivation for the left and right AIC. Subsequently, the laminar electrodes were replaced with single channel iridium electrodes to alternately deliver electrical microstimulation pulses (200$\mu$s biphasic charge-balanced pulses with a 100 Hz frequency) to the left and right AIC. Although the stimulations activated the same brain areas (e.g. amygdala, thalamus) the whole-brain activity following left stimulation tended to be stronger and more prevalent. These results, combined with our tract-tracing data begin to unravel the functional organization underlying the role of the AIC in functional brain networks and brainstem autonomic control regulation.}

{Purpose To describe the process of calibrating a B0 shim system using high-degree (or high order) spherical harmonic models of the measured shim fields, to provide a method that considers amplitude dependency of these models, and to show the advantage of very high-degree B0 shimming for whole-brain and single-slice applications at 9.4 Tesla (T). Methods An insert shim with up to fourth and partial fifth/sixth degree (order) spherical harmonics was used with a Siemens 9.4T scanner. Each shim field was measured and modeled as input for the shimming algorithm. Optimal shim currents can therefore be calculated in a single iteration. A range of shim currents was used in the modeling to account for possible amplitude nonlinearities. The modeled shim fields were used to compare different degrees of whole-brain B0 shimming on healthy subjects. Results The ideal shim fields did not correctly shim the subject brains. However, using the modeled shim fields improved the B0 homogeneity from 55.1 (second degree) to 44.68 Hz (partial fifth/sixth degree) on the whole brains of 9 healthy volunteers, with a total applied current of 0.77 and 6.8 A, respectively. Conclusions The necessity of calibrating the shim system was shown. Better B0 homogeneity drastically reduces signal dropout and distortions for echo-planar imaging, and significantly improves the linewidths of MR spectroscopy imaging.}

{The temporal difference (TD) learning framework is a major paradigm for understanding value-based decision making and related neural activities (e.g., dopamine activity). The representation of time in neural processes modeled by a TD framework, however, is poorly understood. To address this issue, we propose a TD formulation that separates the time of the operator (neural valuation processes), which we refer to as internal time, from the time of the observer (experiment), which we refer to as conventional time. We provide the formulation and theoretical characteristics of this TD model based on internal time, called internal-time TD, and explore the possible consequences of the use of this model in neural value-based decision making. Due to the separation of the two times, internal-time TD computations, such as TD error, are expressed differently, depending on both the time frame and time unit. We examine this operator-observer problem in relation to the time representation used in previous TD models. An internal time TD value function exhibits the co-appearance of exponential and hyperbolic discounting at different delays in intertemporal choice tasks. We further examine the effects of internal time noise on TD error, the dynamic construction of internal time, and the modulation of internal time with the internal time hypothesis of serotonin function. We also relate the internal TD formulation to research on interval timing and subjective time.}

{In binocular rivalry, our perception alternates spontaneously between mutually exclusive or mixed interpretations, although the physical stimulus remains constant. This enables us to study visual consciousness, as it allows a dissociation of sensory processing and conscious perception. Previous BOLD fMRI imaging studies in humans have implicated the role of the fronto-parietal network in mediating perceptual alternations. However, the extent of and the nature of these modulations has been argued to reflect consequences of conscious perception, like introspection, monitoring and decision making. To resolve this issue we used a no-report binocular rivalry paradigm of vertically moving gratings, based on an Optokinetic Nystagmus (OKN) read-out of the content of consciousness. We show that slow cortical states in the delta-theta (1-9 Hz), and beta (20-40 Hz) regimes coupled via their up and down states, in the prefrontal cortex, are predictive of an upcoming change only when the percept switches spontaneously, but not physically. Physical transitions in the animal\textquoterights percept manifest themselves strongly post-switch in the same oscillatory range. Moreover, we also show a clear dissociation between the change in the polarity of the OKN and this slow-state activity preceding a spontaneous transition. Furthermore, we found robust modulation in visually selective spiking activity recorded from the prefrontal cortex contingent on the animal\textquoterights perception. The magnitude of these modulations was comparable to the activity elicited in response to presentation of monocular visual input. Taken together, these results strongly suggest that oscillatory activity in the prefrontal cortex plays a central role in refreshing the content of visual consciousness and spiking activity is modulated in accordance with conscious perception in a no report binocular rivalry paradigm.}

{Current neuroscientific models of bodily self-consciousness (BSC) argue that inaccurate integration of sensory signals leads to altered states of BSC. Indeed, using virtual reality technology, observers viewing a fake or virtual body while being exposed to tactile stimulation of the real body, can experience illusory ownership over\textendashand mislocalization towards\textemdashthe virtual body (Full-Body Illusion, FBI). Among the sensory inputs contributing to BSC, the vestibular system is believed to play a central role due to its importance in estimating self-motion and orientation. This theory is supported by clinical evidence that vestibular loss patients are more prone to altered BSC states, and by recent experimental evidence that visuo-vestibular conflicts can disrupt BSC in healthy individuals. Nevertheless, the contribution of vestibular information and self-motion perception to BSC remains largely unexplored. Here, we investigate the relationship between alterations of BSC and self-motion sensitivity in healthy individuals. Fifteen participants were exposed to visuo-vibrotactile conflicts designed to induce an FBI, and subsequently to visual rotations that evoked illusory self-motion (vection). We found that synchronous visuo-vibrotactile stimulation successfully induced the FBI, and further observed a relationship between the strength of the FBI and the time necessary for complete vection to arise. Specifically, higher self-reported FBI scores across synchronous and asynchronous conditions were associated to shorter vection latencies. Our findings are in agreement with clinical observations that vestibular loss patients have higher FBI susceptibility and lower vection latencies, and argue for increased visual over vestibular dependency during altered states of BSC.}

{Real-time monitoring of biological processes under physiological and pathological conditions is still a great challenge for magnetic resonance imaging (MRI), despite its extensive clinical applications. Calcium(II) is an ideal target for functional MRI purposes, as it is involved in immense number of signaling events in the brain as a secondary messenger. For instance, its extracellular concentration substantially fluctuates during the ischemic stroke [1, 2]. Thus, possibility to track calcium(II) signaling noninvasively would deepen the understanding of numerous physiological processes and allow direct monitoring of neuronal activity. With that objective, two MR contrast agents bearing same calcium chelating part were employed. They were designed in such a manner that one agent (compound 1) triggers MRI signal changes at variable calcium(II) concentrations, while the other (compound 2) remains calcium-insensitive and does not alter MRI signal at different calcium(II) concentrations. In vitro experiments demonstrated that compound 1 exhibits \textgreater90 \textpercent increase in longitudinal relaxivity (r1) upon saturation with calcium(II), while r1 of compound 2 remained constant at same conditions, making them ideal candidates for studying the calcium(II) fluctuations as a calcium-responsive and a control MRI agent, respectively. To monitor calcium(II) changes in vivo, a model of ischemic stroke and the remote middle cerebral artery occlusion (MCAo) approach was used. For these experiments, contrast agents were intracranially injected in Wistar rats (300-340 g), using osmotic pumps for continuous agent delivery (1 $\mu$L/h). Thereafter, silicone coated threat (occluder) was introduced through support tubing, and connected with intra-arterial tubing placed inside the common carotid artery. Preparation was completed when occluder was advanced until 2 mm after bifurcation with pterygopalatine artery. First set of MRI acquisitions (7T Bruker BioSpec 70/30 USR) was divided in three parts: pre-ischemia, ischemia, and reperfusion periods, and consisted of acquiring T1-weighted imaging protocol every two minutes. Ischemia was caused and held for 50-60 min by advancing the occluder for 6-8 mm until resistance was felt; later the reperfusion was performed, with reverse occluder actions. Following T1-weighted imaging part, diffusion-weighted and T2-weighted (after more than 4 hours from the onset of ischemia) imaging protocols were acquired to confirm occurrence of stroke. MRI data analysis of acquired T1-weighted signals was based on Kmeans clustering, and obtained results were compared for various numbers of clusters (2-6). The reported MRI signals were normalized to the first acquired signal (at t\textequals0 min). The in vivo experiments confirmed in vitro responses of employed MR contrast agents. Specifically, T1-weighted images and corresponding masks with 2 clusters show that clusters 1 (cluster with the larger mean value) clearly correspond to center of injections (Figure 1a). Furthermore, the T1-weighted MRI signal of compound 1 varied noticeably because of MCAo stimulation. The MRI signal declined upon MCAo induction, which can be explained through drop of [Ca2+] and accordingly r1 reduction of compound 1. Consequently, r1 recovered upon reperfusion and restoration of [Ca2+], hence also the initial MRI signal trend. On the other hand, the MRI signal of compound 2 changed solely due to continuous injection of the contrast agent, and did not show any alterations to MCAo induction or tissue reperfusion (Figure 1b). In conclusion, calcium-responsive MRI probes were employed here to demonstrate calcium(II) monitoring in vivo upon the ischemic stroke induction. Considering that neuronal activity is always accompanied with calcium(II) flux, this method yet allows visualization and mapping of neural activity using calcium(II) as its direct indicator. To this end, the introduction of this methodology may circumvent the use of conventional fMRI based on BOLD signal and enable assessment of neuronal activity in direct fashion.}

{Full-field visual rotation around the vertical axis induces a sense of self-motion (vection), optokinetic nystagmus (OKN), and, eventually, also motion sickness (MS). If the lights are then suddenly switched off, optokinetic afternystagmus (OKAN) occurs. This is due to the discharge of the velocity storage mechanism (VSM), a central integrative network that has been suggested to be involved in motion sickness. We previously showed that visually induced motion sickness (VIMS) following optokinetic stimulation is dependent on vection intensity. To shed light on this relationship, the current study investigated whether vection intensity is related to VSM activity, and thus, to the OKAN. In repetitive trials (eight per condition), 15 stationary participants were exposed to 120 s of visual yaw rotation (60\mbox{$^\circ$}/s), followed by 90 s in darkness. The visual stimulus either induced strong vection (i.e., scene rotating normally) or weak vection (central and peripheral part moving in opposite directions). Eye movements and subjective vection intensity were continuously measured. Results showed that OKAN occurred less frequently and with lower initial magnitude in the weak-vection condition compared to the strong-vection condition. OKAN decay time constants were not significantly different. The results suggest that the stimuli that produced strong vection also enhanced the charging of the VSM. As VSM activity presumably is a factor in motion sickness, the enhanced VSM activity in our strong-vection condition hints at an involvement of the VSM in VIMS, and could explain why visual stimuli producing a strong sense of vection also elicit high levels of VIMS.}

{Teleoperation of Unmanned Aerial Vehicles (UAVs) is a valuable tool in scenarios where the operator needs to be protected from hazardous environments or where on-board operation is impossible. Technical limitations, e.g., sensor performance, noise and latencies introduced in the transmission, and ineffective display of the information to the operator can lead to reduced performance and in the worst case a loss of the remote vehicle. The spatial decoupling between the operator and the vehicle is one of the main challenges in teleoperation. This dissertation provides an analysis of providing two types of additional feedback, i.e., vehicle-state and task-related motion feedback, by physically moving the operator using the CyberMotion Simulator. The additional information included in the motion feedback can be used by the operator to improve performance and control behavior of remote UAVs.}

{In this work, a novel acceleration method (MultiNet PyGrappa) is introduced which enables high in-plane acceleration factors for non-lipid suppressed 1H MRSI data. By using a variable density undersampling scheme and reconstructing the missing data points with multiple neural networks, this method enables a more robust reconstruction of highly undersampled data. High resolution metabolite maps acquired at 9.4T in the human brain using the proposed method are presented.}

{Magnetic resonance spectroscopic imaging (MRSI) is a powerful tool for mapping metabolite levels across the brain, however, it generally suffers from long scan times. This severely hinders its application in clinical settings. Additionally, the presence of nuisance signals (e.g. the subcutaneous lipid signals close to the skull region in brain metabolite mapping) makes it challenging to apply conventional acceleration techniques to shorten the scan times. The goal of this work is, therefore, to increase the overall applicability of high resolution metabolite mapping using 1H MRSI by introducing a novel GRAPPA acceleration acquisition/reconstruction technique. An improved reconstruction method (MultiNet) is introduced that uses machine learning, specifically neural networks, to reconstruct accelerated data. The method is further modified to use more neural networks with nonlinear hidden layers and is then combined with a variable density undersampling scheme (MultiNet PyGRAPPA) to enable higher in-plane acceleration factors of R \textequals 5.6 and R \textequals 7 for a non-lipid suppressed ultra-short TR and TE 1H FID MRSI sequence. The proposed method is evaluated for high resolution metabolite mapping of the human brain at 9.4T. The results show that the proposed method is superior to conventional GRAPPA: there is no significant residual lipid aliasing artifact in the images when the proposed MultiNet method is used. Furthermore, the MultiNet PyGRAPPA acquisition/reconstruction method with R \textequals 5.6 results in reproducible high resolution metabolite maps (with an in-plane matrix size of 64 $\times$ 64) that can be acquired in 2.8 min on 9.4T. In conclusion, using multiple neural networks to predict the missing points in GRAPPA reconstruction results in a more reliable data recovery while keeping the noise levels under control. Combining this high fidelity reconstruction with variable density undersampling (MultiNet PyGRAPPA) enables higher in-plane acceleration factors even for non-lipid suppressed 1H FID MRSI, without introducing any structured aliasing artifact in the image.}

{The relatively low spatial resolution (ca. 250 mm3) of 1H-MRS hinders its application towards probing heterogeneous diseased tissue, e.g. tumor tissue. Therefore, we present mmqCEST, a metabolic imaging technique based on the saturation transfer from RF-tagged metabolites to the bulk water [1]. mmqCEST decodes a frequency-dependent metabolite-weighted contrast in the Z-spectra into (multicolor) quantitative metabolic maps with a high spatial resolution (ca. 3.4 mm3).}

{Purpose The goal of this study is to develop and evaluate a multiline balanced steady-state free-precession (bSSFP) sequence for passband functional MRI at ultrahigh field. Methods Passband bSSFP functional MRI experiments using a visual task were performed on a 9.4 T system with echo trains ranging from one up to seven echoes. We analyze the acquisition efficiency, temporal and thermal signal-to-noise ratio, as well as the observed blood oxygen\textendashlevel-dependent (BOLD) signal changes. Results With increasing repetition time and echo train length, the BOLD-related signal change as well as the thermal and temporal noise were improved. Activation patterns and signal changes were stable and reproducible across subjects. Conclusions We propose a multiline bSSFP for functional BOLD imaging that approaches the speed of echo-planar imaging and that shows an increased BOLD sensitivity compared with single-line bSSFP.}

{We examined the dynamic functional connectivity of the von Economo neuron (VEN) area of the anterior insula cortex (AIC) using two-shot echo-planar functional magnetic resonance imaging with direct electrical stimulation (DES-fMRI), seed-based connectivity analysis (SBCA), and local field potential recordings (NET-fMRI) in the anesthetized macaque monkey. The electrical stimulation (n\textequals3) of the left or right VEN area activated several distinct subcortical limbic nuclei (e.g. amygdala, midline thalamic nucleus [MTN]) and high-order cortical areas (e.g. superior temporal sulcus, extrastriate visual areas). Both the left and the right stimulation produced a rather lateralized activation pattern, with the activation elicited from one side roughly mirroring the activation obtained from the other side. Nevertheless, stimulation of the left VEN area elicited a consistently more intense and broader bilateral activation. The correlation patterns obtained with a SBCA of the same data set, using the left and right VEN area as seeds, confirmed the activation patterns elicited by the electrical stimulation. Conversely, SBCA using spontaneous data sets, collected in the same animals without electrical stimulation, revealed not only a correlation between both VEN areas but also a broader bilateral correlation pattern that remained identical regardless of the seeded side. Whereas many limbic and cortical activations produced by the electrical stimulations were matched by a correlation with the spontaneous activity of the VEN areas, the MTN was neither correlated nor anticorrelated with the spontaneous activity. Finally, in the NET-fMRI with the same spontaneous functional scans, the occurrence of oscillatory events (e.g. alpha, theta, gamma) in the left or right VEN area triggered varying patterns of activity that differed from the electrical stimulation patterns while being nonetheless markedly asymmetric. Events from the left or right VEN area often correlated with respectively massive activation or deactivation patterns. The present study reveals that small individual regions of the brain can simultaneously display a broad diversity of functional connectivity patterns. The asymmetric activity patterns associated with the left and right VEN areas corroborate prior evidence for a left-right functional asymmetry in the AIC (Craig, 2005, Trends Cogn Sci). The spatially restricted or broad activation of limbic and high-order regions from the right and left VEN areas, respectively, might underlie the asymmetric role of the AIC in monitoring internal bodily states during cognitive processes, including subjective perceptual awareness.}

{Due to high sensitivity to B1+-inhomogeneities, Chemical Exchange Saturation Transfer MRI requires a correction or mitigation of the B1+-inhomogeneity at ultra-high magnetic field strengths (B0 $\geq$ 7 Tesla). A novel approach for mitigation of B1+-inhomogeneity effects that affects the saturation process is presented. The method employs two interleaved excitation modes during the saturation pulse train. Simulations show a decrease of the relative difference of the MTRRex metric caused by B1+ inhomogeneity. This \textquotedblleftMultiple Interleaved Mode Saturation\textquotedblright scheme leads to improved homogeneity in both, phantom and in vivo measurements at 7 Tesla.}

{We analyzed the areal distribution of von Economo (VEN) and fork (FN) neurons in the human anterior insular cortex (AIC). The AIC, including the frontoinsula (FI), from eight freshly-fixed human brains (3 pairs of left and right insulae, and 5 single left or right insulae) were cut in the coronal plane at a 50-micron thickness. The sections were stained with cresyl violet to reveal all neuronal cell bodies and the proximal portion of their dendrites (Nissl stain), with silver nitrate to reveal myelinated fibers (Gallyas stain), or with an anti-parvalbumin antibody to reveal local interneurons. All stained sections were digitized with a 0.5-micron in plane resolution and 1-micron vertical stack using a scanning microscope. The distribution of the VEN and FN was charted using high-magnification examination of the Nissl slides. The AIC was parcellated using low-magnification examination of all three sets of slides with pre-established multi-architectonic criteria (Evrard et al., J Comp Neurol 2014 522:64-97). The VEN and FN were co-mingled within a rather vast region (or \textquoteleftVEN domain\textquoteright) inside the ventral agranular region of AIC, with no apparent extension in the dorsal AIC or the dysgranular and granular insula. The VEN domain was delimited by a rather abrupt reduction of the numbers of both neurons. A comparison of the localization of the VEN domain with the architectonic parcellation of the AIC revealed (1) that its overall outer limit optimally overlapped with sharp architectonic boundaries, and (2) that it was further subdivided into at least three distinct architectonic areas (or \textquoteleftVEN areas\textquoteright), rather than being homogeneous. While these three areas consistently occurred, their exact topology differed between the left and right hemispheres. Our prior examination of the macaque AIC revealed a complete overlap of the delimitation of a VEN/FN cluster with architectonic boundaries; however, this cluster formed one unique architectonic area, rather than being divided into several areas (Horn FM and Evrard HC, in preparation). The highly consistent overlap of the VEN distribution and architectonic boundaries (or \textquotedblleftelemental localization\textquotedblright) in humans and monkeys indicates the existence of a robust selective pressure on the development of the AIC throughout evolution. The multiplication of the number of VEN areas likely correlates with the disproportionately faster growth of the AIC, including in particular FI, in humans compared to other primate species (Bauernfeind et al., J Hum Evol 2013 64:263-79). This multiplication might underlie the possible evolutionary emergence of the subjective awareness of feelings in the human AIC (Craig, Nat Rev Neurosci 2009 10:59-70).}

{In contrast to spatial memory acquired in enclosed spaces (i.e., rooms), memory for navigable spaces (e.g., buildings) is less well understood. We had subjects learn eight target objects spread across a virtual environment, consisting of two apparent regions. Separation of regions was triggered by visual and semantic similarity (wall colour, object categories), walking distance and turning angle complexity (longest and most complex path at transition point), and spatio-temporal contingency (regions learned subsequently). A subsequent pointing task revealed increased pointing latency with increasing corridor distance to the target, and a facilitative effect of being bodily aligned with the local corridor. Moreover, pointing to targets located within one\textquoterights current region was faster compared to pointing to targets in the other region, and alignment with region specific orientations enhanced pointing latency. In sum, our results indicate the formation of local and regional memory units that manifest in the form of spatial reference frames. Our local and regional effects give way to the interpretation that, when confronted with a complex navigable space, multiple levels of spatial integration are stored, potentially in a hierarchical fashion. Importantly, our results cannot be explained by concepts of exclusive local corridor units or exclusive global, all-embracing memory units.}

{Ultralow-field (ULF) nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are promising spectroscopy and imaging methods allowing for, e.g., the simultaneous detection of multiple nuclei or imaging in the vicinity of metals. To overcome the inherently low signal-to-noise ratio that usually hampers a wider application, we present an alternative approach to prepolarized ULF MRS employing hyperpolarization techniques like signal amplification by reversible exchange (SABRE) or Overhauser dynamic nuclear polarization (ODNP). Both techniques allow continuous hyperpolarization of 1H as well as other MR-active nuclei. For the implementation, a superconducting quantum interference device (SQUID)-based ULF MRS/MRI detection scheme was constructed. Due to the very low intrinsic noise level, SQUIDs are superior to conventional Faraday detection coils at ULFs. Additionally, the broadband characteristics of SQUIDs enable them to simultaneously detect the MR signal of different nuclei such as 13C, 19F, or 1H. Since SQUIDs detect the MR signal directly, they are an ideal tool for a quantitative investigation of hyperpolarization techniques such as SABRE or ODNP.}

{Holistic processing is the tendency to perceive an object as an indecomposable whole rather than by its parts. Psychological research has shown that faces are processed holistically. However, recent studies have shown that non-expertise objects with salient Gestalt information are also processed holistically, questioning whether this phenomena is unique to faces. Neuroimaging studies have linked holistic processing of faces to brain activity in face-responsive regions of the occipital-temporal cortex. However, these studies specifically localized face-responsive brain regions, but not object, scene or perceptual grouping related brain regions. In this study, we aimed to explore the neural correlates of holistic face processing in a larger range of brain regions, in order to investigate how specific the activation is to face regions. We used fMRI to record the brain activity of subjects performing a composite face task. Participants viewed pairs of faces and determined whether the top halves of the faces were the same or different. Additionally, we localized specific regions of interest defined by their responses to faces, objects, scenes and perceptual grouping, allowing us to investigate how activity in these regions changed during the composite face task. Surprisingly, we found that activity in the occipital face area, fusiform face area and anterior temporal face area did not show a clear pattern of activity relating to the behavioural composite effect. However, activity in the parahippocampal place area, superior parietal lobule and early visual cortex all showed a pattern of activity consistent with the behavioural composite effect. These results suggest that holistic processing occurs in brain regions involved in spatial processing, perceptual grouping and early vision, rather than being limited to face-responsive brain regions. We hypothesize that holistic perception may be driven by these factors rather than identity discrimination, in line with the behavioural finding of the composite effect in non-expertise objects.}

{Highly synchronized oscillations, or ripples (\textasciitilde200Hz), are generated in the hippocampus (HPC) during awake immobility or non-REM (NREM) sleep and has long been suggested to mediate the hippocampal-cortical communication underlying memory consolidation. The medial prefrontal cortex (mPFC) receives direct input from the HPC and many mnemonic processes depend on these two brain regions. The HPC-mPFC pathway is considered critical for consolidation of declarative memory and is currently one of the most studied memory-related pathways. A memory-supporting network is, however, not limited by the HPC and the mPFC. The thalamic mediodorsal (MD) nucleus is likely a part of an extended memory network. The MD is reciprocally connected with the mPFC and has long been implicated in different mnemonic functions. Our fMRI-based mapping of the whole brain activity associated with ripples occurrence suggested that silencing of a subset of subcortical regions, including thalamus, may reduce interference for hippocampal-cortical communication (Logothetis et al., 2012). We characterized neural activity in the MD around times of the hippocampal ripples in spontaneously behaving rats. Generally, the MD population activity was strongly suppressed around ripples. A substantial reduction of the MD firing occurred 0.4 - 2.4 sec (mean: 1.1 $\pm$ 0.1 sec) before the ripple peak and lasted for 2.1 $\pm$ 0.2 sec. Moreover, the degree of MD activity suppression correlated with the ripple amplitude. The ripple-associated decrease of the MD firing rate was the strongest and the most consistent during awake immobility. In contrast, during NREM sleep bidirectional modulation of the MD activity was observed: the MD firing was actually enhanced around ripples that were temporally coupled with sleep spindles, while it was decreased around spindle-uncoupled ripples. Our results suggest possible competitive interaction between the hippocampal-cortical and thalamo-cortical networks supporting \textquoteleftoff-line\textquoteright and \textquotelefton-line\textquoteright information processing, respectively.}

{Forming a persistentmemory trace requires hippocampal-cortical interaction. Population bursts in the hippocampal network occurring during awake immobility or NREMsleep propagate throughout the entire hippocampal formation and generate transient dynamic interactions locally, but also between the hippocampus (HPC) and cortex. This synchronized population activity is revealed in the local field potentials as brief, high-frequency (about 200 Hz) oscillations, or ripples, which are thought to mediate the hippocampal-cortical communication underlying memory consolidation [1]. The medial prefrontal cortex (mPFC) receives direct input from the HPC andmanymnemonic processes depend on these two brain regions [2]. The HPC-mPFC pathway is considered critical for consolidation of declarative memory and is currently one of the most studied memory-related pathways. A memory-supporting network is, however, not limited by the HPC and the mPFC. The thalamic mediodorsal (MD) nucleus is likely a part of an extended memory network. The MD is reciprocally connected with the mPFC and has long been implicated in different mnemonic functions [3]. Our fMRI-based mapping of the whole brain activity associated with ripples occurrence suggested that silencing of a subset of subcortical regions, including thalamus, may reduce interference for hippocampal-cortical communication [4]. We characterized neural activity in the MD around times of the hippocampal ripples in spontaneously behaving rats. Generally, the MD population activity was strongly suppressed around ripples. A substantial reduction of MD firing occurred 0.4\textendash2.4 sec (mean: 1.1$\pm$0.1 sec) before the ripple peak and lasted for 2.1$\pm$0.2 sec. Moreover, the degree of MD activity suppression correlated with the ripple amplitude. The ripple-associated decrease of the MD firing rate was the strongest and the most consistent during awake immobility. In contrast, during NREM sleep bidirectional modulation of the MD activity was observed: the MD firing was actually enhanced around ripples that were temporally coupled with sleep spindles, while it was decreased around spindle-uncoupled ripples. Our results suggest possible competitive interaction between the hippocampal-cortical and thalamo-cortical networks supporting \textquoteleftoff-line\textquoteright and \textquotelefton-line\textquoteright information processing, respectively.}

{Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five-point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence-specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.}

{Rhythmic drumming has long been used to alter consciousness and induce states of trance. Rhythm-induced trance is common in shamanism, humanity\textquoterights most ancient healing tradition. Despite similar techniques across cultures and powerful phenomenology, little is known about the mechanisms underlying trance. We examined the neural correlates of rhythm-induced trance in experienced shamanic practitioners. In the first study, we used fMRI to examine the neural patterns associated with trance. Shamanic practitioners (n\textequals15) underwent 8 minute brain scans while they listened to rhythmic drumming and entered a trance state (or remained in non-trance in a control condition). In trance, brain networks displayed notable reconfigurations, including increased connectivity in regions associated with internal thought (the default mode\textquoterights posterior cingulate cortex) and cognitive control (dorsal anterior cingulate cortex and insula), as well as decreased connectivity within the brainstem and auditory pathway. This network configuration suggests perceptual decoupling and that the repetitive drumming was gated out to maintain an internally oriented stream of consciousness. In a follow-up EEG study, we used a similar design to examine auditory gating and network activity while shamanic practitioners (n\textequals18) experienced rhythm-induced trance and a control state. In response to clicks embedded in the drumming, the N100 and P200 ERP components were decreased during Trance. This indicates decreased sensory encoding and elaborative processing during trance. Together this work suggests that repetitive drumming promotes an internally directed state via perceptual decoupling, and explicates why trance is a common way to promote insight across cultures.}

{Previous behavioral and neurophysiological research has shown better memory for horizontal than for vertical locations. In these studies, participants navigated toward these locations. In the present study we investigated whether the orientation of the spatial plane per se was responsible for this difference. We thus had participants learn locations visually from a single perspective and retrieve them from multiple viewpoints. In three experiments, participants studied colored tags on a horizontally or vertically oriented board within a virtual room and recalled these locations with different layout orientations (Exp. 1) or from different room-based perspectives (Exps. 2 and 3). All experiments revealed evidence for equal recall performance in horizontal and vertical memory. In addition, the patterns for recall from different test orientations were rather similar. Consequently, our results suggest that memory is qualitatively similar for both vertical and horizontal two-dimensional locations, given that these locations are learned from a single viewpoint. Thus, prior differences in spatial memory may have originated from the structure of the space or the fact that participants navigated through it. Additionally, the strong performance advantages for perspective shifts (Exps. 2 and 3) relative to layout rotations (Exp. 1) suggest that configurational judgments are not only based on memory of the relations between target objects, but also encompass the relations between target objects and the surrounding room-for example, in the form of a memorized view.}

{Purpose This study investigates metabolite concentrations using metabolite-cycled 1H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. Methods A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. Results The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, $\sim$0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. Conclusion We showed the first implementation of non-water-suppressed metabolite-cycled 1H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed.}

{Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.}

{Using volumetric snapshot-GRE CEST MRI at 9.4T with high frequency sampling, we were able to separate novel CEST peaks at +2.7 ppm, +1.2 ppm and -1.7 ppm reliably in the CEST-spectrum and showed creation of maps of these CEST MRI contrasts in the healthy human brain to be feasible in vivo.}

{Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: \textquotedblleftfalse-positive\textquotedblright feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.}

{Timecourses that exhibit identical behaviour at distinct measurement occasions are reliable. Voodoo connectivity occurs when connectivity among brain regions exceeds within subject timecourse reliability. Thus, timecourse reliability limits the true detectable connectivity. We reproduced a working memory related connectome consisting of 561 paths obtained from 67 individuals. We tested \textgreater100000 fc-MRI pipelines and show that Savitzky Golay (SG) filters maximize true connectivity while conserving cognitively relevant changes of signals. This is noteworthy for approaches that focus on rapidly changing aspects of connectomes. Furthermore, SG filters detect zombie activity. These resting state oscillations are not under human control and contaminate working state signals. SPM filters exhibit more voodoo connectivity than SG filters. With the SPM filter based pipeline, we observed a connectivity of r\textequals0.44 and a poor true connectivity of r\textequals0.23, but with the SG pipeline we observed a connectivity of r\textequals0.59 and a fair true connectivity of r\textequals0.43. The number of paths detected with fair true connectivity (r \textgreater0.4) was 4 for the pipeline that was based on the SPM filter but 352 for the SG based pipeline. However, superior statistical properties of SG pipelines may not reflect neural reality. Hence, causal external validation of fc-MRI pipelines is crucial. Without such studies, different pipelines produce at best alternative maps.}

{Introduction: We require spatial problem solving skills regularly not only for common tasks, but also in dangerous circumstances such as emergency procedures, as the fire department encounters on a regular basis. Despite its importance, the topic has not been sufficiently investigated. Understanding the underlying cognitive processes that are involved in solving these problems will help provide supportive software and training methods to make collaborative spatial search more efficient and ideally less dangerous. Methods: The presented study aims to continue previous research conducted using two-dimensional means. We try to replicate previous findings in two experiments using an immersive virtual environment and investigate the extent of how a common reference frame can influence collaborative spatial search. Additionally, this study allows to examine how seeing your own orientation can influence spatial problem solving individually. Results: Results of two experiment suggest differences in performance between individual and collaborative search concerning complexity, showing a clear advantage of collaborative search when it comes to time, while the efficiency of each participant suffers greatly in these cases. A second experiment using common reference frames by introducing a compass-like arrow for collaborative search does not give a general advantage. The use of a compass may give a slight advantage for individuals in less complex environments. Discussion: It becomes clear that shared mental models do not automatically give an advantage in a realistic three-dimensional setting without training. Common reference frames should therefore not be generalized and need to be further investigated and differentiated to be integrated into supportive software or training methods.}

{A 3D snapshot CEST sequence is optimized for contrast originating from hydroxyl groups of glucose molecules. Multi-B1-multi-pH measurements allow fitting of exchange rates of four glucose hydroxyl groups, which are then used to optimize pre-saturation parameters in simulation. The optimal protocol gave highly reproducible signals in 6 healthy volunteers, and showed no contrast when tested in a brain tumor patient. This protocol provides a robust baseline for glucose injection studies.}

{Recently we demonstrated that a selective detection of endogenous bulk mobile proteins in living tissue can be realized by the novel approach of dual-frequency irradiation CEST (dualCEST)-MRI1 without contamination of saturation transfer effects of metabolites, lipids and semi-solids. For this approach, specificity is achieved by measuring the intramolecular magnetization transfer (i.e. saturation crosstalk T) between CEST signals resonating at two different frequency offsets $\Delta$$\omega$ and $\Delta$$\omega$c (Fig. 1a). Such a non-invasive imaging technique may be of particular interest for the detection of pathological alterations of protein expression, such as in neurodegenerative diseases or cancer. Until now, application in clinical trials was prevented by the inherently small signal-to-noise ratio (SNR) in comparison to conventional CEST approaches. Here, we present further developments in signal preparation, image acquisition and post-processing techniques enabling dualCEST examinations in a reasonable and clinicallyrelevant time frame.}

{In this study the acquisition of high resolution (64x64) metabolite maps at 9.4T using a non-lipid suppressed ultra-short TR and TE 1H FID MRSI sequence is accelerated using an improved over-discretized SENSE reconstruction and B0 correction method. The improved reconstruction is compared to conventional SENSE and GRAPPA reconstruction, and reproducible metabolite maps are acquired using this technique.}

{The aim of this work was to use post-processing methods to improve the data quality of metabolite maps acquired on the human brain at 9.4 T with accelerated acquisition schemes. This was accomplished by combining an improved sensitivity encoding (SENSE) reconstruction with a B0 correction of spatially over-discretized magnetic resonance spectroscopic imaging (MRSI) data. Since MRSI scans suffer from long scan duration, investigating different acceleration techniques has recently been the focus of several studies. Due to strong B0 inhomogeneity and strict specific absorption rate (SAR) limitations at ultra-high fields, the use of a low-SAR sequence combined with an acceleration technique that is compatible with dynamic B0 shim updating is preferable. Hence, in this study, a non-lipid-suppressed ultra-short TE and TR 1H free induction decay MRSI sequence is combined with an in-plane SENSE acceleration technique to obtain high-resolution metabolite maps in a clinically feasible scan time. One of the major issues in applying parallel imaging techniques to non-lipid-suppressed MRSI is the presence of strong lipid aliasing artifacts, which if not thoroughly resolved will hinder the accurate quantification of the metabolites of interest. To achieve a more robust reconstruction, an over-discretized SENSE reconstruction (with direct control over the shape of the spatial response function) was combined with an over-discretized B0 correction. This method is compared with conventional SENSE reconstruction for seven acceleration schemes on four healthy volunteers. The over-discretized method consistently outperformed conventional SENSE, resulting in an average of 23 $\pm$ 1.2\textpercent higher signal-to-noise ratio and 8 $\pm$ 2.9\textpercent less error in the fitting of the N-acetylaspartate signal over a whole brain slice. The highest achievable acceleration factor with the proposed technique was determined to be 4. Finally, using the over-discretized method, high-resolution (97 $\mu$L nominal voxel size) metabolite maps can be acquired in 3.75 min at 9.4 T. This enables the acquisition of high-resolution metabolite maps with more spatial coverage at ultra-high fields.}

{Purpose To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. Methods A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. Results A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T1 of water and B1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer\textendashweighted imaging. Conclusion Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.}

{NMR is one of the most versatile and useful physical effects used for human imaging, chemical analysis and the elucidation of molecular structures. Yet, the full potential of NMR is hardly ever used, because only a small fraction of the nuclear spin ensemble is polarized - i.e. aligned with the applied static magnetic field. This fraction is termed nuclear spin polarization P. As a result, no more than a few parts per million of all nuclear spins effectively contribute to the signal in all magnetic fields (B0) available for NMR or MRI today. Because P is approximately linear with B0, a stronger field offers some but limited improvements. Hyperpolarization methods seek other means to increase P and thus the MR signal. A unique source of pure spin order is the spin singlet state of dihydrogen, parahydrogen (pH2), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows enhancing the NMR signal by several orders of magnitude. In contrast to other methods, this process is very fast (seconds) and can take place in the liquid state. Nuclear spin polarization of the order of unity was demonstrated, manifesting as significant NMR and MRI signal enhancement by several orders of magnitude. Considerable progress was made in the past decade in the area of pH2-based hyperpolarization techniques for biomedical applications. It is the goal of this minireview to provide a comprehensive, selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, contrast agents\textquotesingle preparation and application.}

{The role of lateral prefrontal cortex (LPFC) in mediating conscious perception has been recently questioned due to potential confounds resulting from the parallel operation of task related processes. We have previously demonstrated encoding of contents of visual consciousness in LPFC neurons during a no-report task involving perceptual suppression. Here, we report a separate LPFC population that exhibits task-phase related activity during the same task. The activity profile of these neurons could be captured as canonical response patterns (CRPs), with their peak amplitudes sequentially distributed across different task phases. Perceptually suppressed visual input had a negligible impact on sequential firing and functional connectivity structure. Importantly, task-phase related neurons were functionally segregated from the neuronal population, which encoded conscious perception. These results suggest that neurons exhibiting task-phase related activity operate in the LPFC concurrently with, but segregated from neurons representing conscious content during a no-report task involving perceptual suppression.}

{When a stimulus has two competing interpretations, perception tends to alternate over time: bistable perception. A special case hereof occurs when the two eyes receive differing information in the same retinal space, perception also alternates: binocular rivalry (BR). Functional magnetic resonance imaging (fMRI) studies have shown the right anterior intraparietal sulcus (IPS) as well as posterior superior parietal lobule (SPL) activated during perceptual transitions. However, the causal role of these regions remains unclear, as distinct transcranial magnetic stimulation (TMS) studies have reported either shortening or lengthening TMS effects on perceptual dominance durations. Reasons for these divergent results may lie in the use of different stimuli or of distinct TMS protocols. Here we tested effects of a single, inhibitory TMS protocol, continuous theta burst stimulation (cTBS), applied to the IPS, SPL, and vertex control on distinct classes of bistable perception in three separate samples of participants (total N \textequals 52). In sample one we used structure from motion (SFM) bistable perception, in sample two BR between random dots that was either reported, unreported or unreportable, and in sample three both of the above stimuli as well as BR between flickering checkerboards. Contrary to our expectation, cTBS neither consistently affected dominance durations across the stimuli, test sites, nor samples. This null effect was supported by Bayes factors. In a last experiment we correlated participants\textquoteright cTBS induced change in BR dominance with the change in motor-evoked potentials (MEP) following cTBS to primary motor cortex. While MEP amplitude was reduced, corroborating the inhibitory effect of cTBS, we observed no correlation with the cTBS effect on BR. Given the comparably large N used in the present study, the replication of our null-finding across several classes of bi-stable stimuli, and the lack of correlation of cTBS effects between motor and parietal cortex, the present findings cast doubt on the efficacy of the cTBS protocol over parietal cortex and the generalisation of cTBS effects from motor to parietal cortex.}

{Introduction: Magnetic resonance spectroscopy (MRS) measurements of excitatory and inhibitory neurotransmission may provide valuable insights into the underlying neurobiology of altered functional connectivity in psychiatric disorders. Consequently, local measures of glutamate (Glu) and GABA are often reported to moderate resting-state functional connectivity measures (Duncan et al., 2013; Horn et al., 2010; Kapogiannis et al., 2013). However, the inherently low signal-to-noise ratio of conventional MRS measurements necessitates voxel sizes far exceeding those of fMRI measurements, leading to crude measures of local neurometabolism. Here, we tested the hypothesis that decomposing the pregenual anterior cingulate\textquotesingles (pgACC) functional connectome into a more fine-grained fMRI-based resolution provides incremental information on the neurotransmitters governing its function. To this end, we employed a novel, data-driven approach that aims to predict (pgACC) glutamatergic and GABAergic signatures by assigning weights to seed-voxel connections according to their predictive power. Methods: 77 healthy participants underwent an MRI protocol consisting of structural, functional, and MRS measurements at 7 Tesla. The MRS voxel (20 x 15 x 10 mm3) was placed in the pgACC according to a previously established protocol (Dou et al., 2013). GABA and Glu levels were fitted using the LCModel software (Provencher, 2001) and expressed relative to total creatine. GABA measures were log transformed. We used the default CONN pipeline (Whitfield-Gabrieli et al., 2012) for fMRI preprocessing without smoothing. Data were then z-scored, despiked, and detrended, after which six motion parameters were regressed out. We created a composite mask of each subject\textquotesingles MRS mask for subsequent analyses. As seed voxels, we selected only those fMRI voxels in the composite MRS mask. The time series of the seed voxels were correlated with mean time series of the 132 CONN atlas nodes. To account for the statistical redundancy of the voxel-based predictor matrix, we employed PLS regression, which projects the predictor variables into a latent space (similar to principal component analysis) while optimizing the prediction of the outcome. We entered the resulting connectivity matrices into two PLS regression models (McIntosh et al., 2004) using 1 component to predict pgACC Glu or GABA. To statistically assess the obtained model fit (residual sum of squares), we performed a permutation test with 1000 permutations of the outcome measure. Conclusions: A novel, data-driven approach employing PLS regression allowed us to predict Glu, but not GABA from the functional connectivity profiles of pgACC seed voxels. For Glu, the resulting weight matrix showed that a widespread pattern of functional connectivity contributes to the successful prediction of local glutamate suggesting that glutamate levels might have a diffuse global effect on functional connectivity. Further analyses will be performed to cross-validate the prediction models and explore whether specific seed voxels in the pgACC have higher predictive power than others.}

{A pedophilic disorder is characterised by abnormal sexual urges towards prepubescent children. Child abusive behavior is frequently a result of lack of behavioral inhibition and current treatment options entail, next to suppressing unchangeable sexual orientation, measures to increase cognitive and attentional control. We tested, if in brain regions subserving attentional control of behavior and perception of salient stimuli, such inhibition deficit can be observed also on the level of inhibitory neurotransmitters. We measured GABA concentration in the dorsal anterior cingulate cortex (dACC) and in a control region, the pregenual anterior cingulate cortex (pgACC) in pedophilic sex offenders (N \textequals 13) and matched controls (N \textequals 13) using a 7 Tesla STEAM magnetic resonance spectroscopy (MRS). In dACC but not in the control region pedophilic sex offenders showed reduced GABA/Cr concentrations compared to healthy controls. The reduction was robust after controlling for potential influence of age and gray matter proportion within the MRS voxel (p \textless 0.04). Importantly, reduced GABA/Cr in patients was correlated with lower self-control measured with the Barratt Impulsiveness Scale (p \textequals 0.028, r \textequals \textminus0.689). In a region related to cognitive control and salience mapping, pedophilic sex offenders showed reduction of the inhibitory neurotransmitter GABA which may be seen as a neuronal correlate of inhibition and behavioral control.}

{According to a long-standing hypothesis in motor control, complex body motion is organized in terms of movement primitives, reducing massively the dimensionality of the underlying control problems. For body movements, this low-dimensional organization has been convincingly demonstrated by the learning of low-dimensional representations from kinematic and EMG data. In contrast, the effective dimensionality of dynamic facial expressions is unknown, and dominant analysis approaches have been based on heuristically defined facial \textquotedblleftaction units,\textquotedblright which reflect contributions of individual face muscles. We determined the effective dimensionality of dynamic facial expressions by learning of a low-dimensional model from 11 facial expressions. We found an amazingly low dimensionality with only two movement primitives being sufficient to simulate these dynamic expressions with high accuracy. This low dimensionality is confirmed statistically, by Bayesian model comparison of models with different numbers of primitives, and by a psychophysical experiment that demonstrates that expressions, simulated with only two primitives, are indistinguishable from natural ones. In addition, we find statistically optimal integration of the emotion information specified by these primitives in visual perception. Taken together, our results indicate that facial expressions might be controlled by a very small number of independent control units, permitting very low-dimensional parametrization of the associated facial expression.}