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ISSN / EISSN : 1053-8119 / 1095-9572
Current Publisher: Elsevier BV (10.1016)
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Total articles ≅ 24,397
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Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117839

Using advanced diffusion MRI, we aimed to assess the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) using 3-tissue diffusion signal compositions in ischemic stroke. Data were obtained from the Cognition and Neocortical Volume After Stroke (CANVAS) study. Diffusion-weighted MR and high-resolution structural brain images were acquired 3- (baseline) and 12-months (follow-up) post-stroke. WMHs were automatically segmented and longitudinal assessment at 12-months was used to retrospectively delineate NAWM voxels at baseline converting to WMHs. NAWM voxels converting to WMHs were further dichotomized into either: “growing” WMHs if NAWM adhered to existing WMH voxels, or “isolated de-novo" WMHs if NAWM was unconnected to WMH voxels identified at baseline. Microstructural properties were assessed using 3-tissue diffusion signal compositions consisting of white matter-like (WM-like: TW), gray matter-like (GM-like: TG), and cerebrospinal fluid-like (CSF-like: TC) signal fractions. Our findings showed that NAWM converting to WMHs already exhibited similar changes in tissue compositions at baseline to WMHs with lower TW and increased TC (fluid-like, i.e. free-water) and TG compared to persistent NAWM. We also found that microstructural properties of persistent NAWM were related to overall WMH burden with greater free-water content in patients with high WMH load. These findings suggest that NAWM preceding conversion to WMHs are accompanied by greater fluid-like properties indicating increased tissue water content. Increased GM-like properties may indicate a more isotropic microstructure of tissue reflecting a degree of hindered diffusion in NAWM regions vulnerable to WMH development. These results support the usefulness of microstructural compositions as a sensitive marker of NAWM vulnerability to WMH pathogenesis.
, Bj Roach, Cb Holroyd, Mp Paulus, , A Boos, Jm Ford,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117874

Slot machines are a popular form of gambling, offering a tractable way to experimentally model reward processes. This study used a 3-reel slot paradigm to assess psychologically distinct phases of reward processing, reflecting anticipation, and early- and late-stage outcome processing. EEG measures of winning, nearly missing (a losing outcome revealed at the final, third reel), and “totally” missing (a losing outcome revealed earlier, at the second reel) were collected from healthy adults (n=54). Condition effects were evaluated in: i) event-related potential (ERP) components reflecting anticipatory attention (stimulus preceding negativity, SPN) and outcome processing (reward positivity, RewP and late-positive potential, LPP) and ii) total power and phase synchrony of theta and delta band oscillations. Behaviorally, trial initiation was fastest after a near miss outcome and slowest after a winning outcome. As expected, a significant SPN was observed for possible wins (AA) vs. total misses (AB), consistent with reward anticipation. Larger win (AAA) vs. near miss (AAB) amplitudes were observed for the RewP; LPP amplitudes were largest for wins (AAA), intermediate for near misses (AAB), and smallest for total misses (ABC), reflecting significant early (RewP) and late-stage (LPP) outcome processing effects. There was an effect of reel position on the RewP, with larger amplitude in the final reel (AAA-AAB) relative to the 2nd-reel locked difference waves (AA-AB). Across all outcomes, near misses elicited the largest and most phase-synchronized theta responses, while wins elicited larger and more phase-synchronized delta responses than total misses, with delta band measures not distinguishing between near misses and wins. . Phase locking measures contrasting win vs. near miss delta and theta synchronization, within time windows corresponding to ERP measurements, covaried with RewP, but not SPN or LPP, amplitude. Lastly, EEG measures showed differential relationships with age and self-reported consummatory pleasure. In the context of slot machine play, where reward anticipation and attainment place minimal demands on effort and skill, ERP and time-frequency methods capture distinct neurophysiological signatures of reward anticipation and outcome processing.
, Valerio Rubino, Antonio Di Soccio, ,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117876

Relational information about items in memory is thought to be represented in our brain thanks to an internal comprehensive model, also referred to as a “cognitive map”. In the human neuroimaging literature, two signatures of bi-dimensional cognitive maps have been reported: the grid-like code and the distance-dependent code. While these kinds of representation were previously observed during spatial navigation and, more recently, during processing of perceptual stimuli, it is still an open question whether they also underlie the representation of the most basic items of language: words. Here we taught human participants the meaning of novel words as arbitrary labels for a set of audiovisual objects varying orthogonally in size and sound. The novel words were therefore conceivable as points in a navigable 2D map of meaning. While subjects performed a word comparison task, we recorded their brain activity using functional magnetic resonance imaging (fMRI). By applying a combination of representational similarity and fMRI-adaptation analyses, we found evidence of (i) a grid-like code, in the right postero-medial entorhinal cortex, representing the relative angular positions of words in the word space, and (ii) a distance-dependent code, in medial prefrontal, orbitofrontal, and mid-cingulate cortices, representing the Euclidean distance between words. Additionally, we found evidence that the brain also separately represents the single dimensions of word meaning: their implied size, encoded in visual areas, and their implied sound, in Heschl's gyrus/Insula. These results support the idea that the meaning of words, when they are organized along two dimensions, is represented in the human brain across multiple maps of different dimensionality. How do we represent the meaning of words and perform comparative judgements on them in our brain? According to influential theories, concepts are conceivable as points of an internal map (where distance represents similarity) that, as the physical space, can be mentally navigated. Here we use fMRI to show that when humans compare newly learnt words, they recruit a grid-like and a distance code, the same types of neural codes that, in mammals, represent relations between locations in the environment and support physical navigation between them.
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117875

The concept of cognitive reserve proposes that specific life experiences result in more flexible or resilient cognitive processing allowing some people to cope better with age- or disease-related brain changes than others. Imaging studies seeking to understand the neural implementation of cognitive reserve have most often used task-related fMRI studies. Using that approach, we recently described a task-invariant cognitive-reserve network whose expression correlated with IQ and that moderated between cortical thickness and cognitive performance. Here we sought to identify a pattern of resting BOLD connectivity related to cognitive reserve. We identified a connectome pattern whose connectivity correlated with IQ in both the derivation sample and a separate replication sample. The majority of the edges showing positive relationships with IQ implicate frontal regions. In the derivation sample, connectivity either moderated the relationship between mean cortical thickness and a set of cognitive outcomes or accounted for unique variance in cognitive performance after accounting for cortical thickness. In a replication sample we found that expression of this connectome correlated significantly with the primary endpoint of IQ, and also accounted for unique variance in cognitive performance beyond cortical thickness. Our findings represent an intermediate level of replication and are unlikely to have arisen purely by type-I error. This connectivity pattern therefore meets some of our theoretical criteria for a cognitive reserve-related network and provides insight into the neural implementation of cognitive reserve. Further, expression of this connectome could potentially be used as a direct measure of cognitive reserve, and as an outcome measure for intervention studies that seek to influence cognitive reserve. Future validation of and re-derivation of the pattern in expanded data sets by our and other groups will lead to further improved estimates of cognitive reserve in resting functional connectivity.
, Oliver Kraff, Steffen Goerke, Frederik B. Laun, Jannis Hanspach, , Philipp Ehses, Moritz Zaiss, , Sina Straub, et al.
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117910

This study evaluates inter-site and intra-site reproducibility at ten different 7 T sites for quantitative brain imaging. Two subjects – termed the “traveling heads” – were imaged at ten different 7 T sites with a harmonized quantitative brain MR imaging protocol. In conjunction with the system calibration, MP2RAGE, QSM, CEST and multi-parametric mapping/relaxometry were examined. Quantitative measurements with MP2RAGE showed very high reproducibility across sites and subjects, and errors were in concordance with previous results and other field strengths. QSM had high inter-site reproducibility for relevant subcortical volumes. CEST imaging revealed systematic differences between the sites, but reproducibility was comparable to results in the literature. Relaxometry had also very high agreement between sites, but due to the high sensitivity, differences caused by different applications of the B1 calibration of the two RF coil types used were observed. Our results show that quantitative brain imaging can be performed with high reproducibility at 7 T and with similar reliability as found at 3 T for multicenter studies of the supratentorial brain.
Annie Cheng, Dirk B. Walther, ,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117920

Despite over two decades of research on the neural mechanisms underlying human visual scene, or place, processing, it remains unknown what exactly a “scene” is. Intuitively, we are always inside a scene, while interacting with the outside of objects. Hence, we hypothesize that one diagnostic feature of a scene may be concavity, portraying “inside”, and predict that if concavity is a scene-diagnostic feature, then: 1) images that depict concavity, even non-scene images (e.g., the “inside” of an object – or concave object), will be behaviorally categorized as scenes more often than those that depict convexity, and 2) the cortical scene-processing system will respond more to concave images than to convex images. As predicted, participants categorized concave objects as scenes more often than convex objects, and, using functional magnetic resonance imaging (fMRI), two scene-selective cortical regions (the parahippocampal place area, PPA, and the occipital place area, OPA) responded significantly more to concave than convex objects. Surprisingly, we found no behavioral or neural differences between images of concave versus convex buildings. However, in a follow-up experiment, using tightly-controlled images, we unmasked a selective sensitivity to concavity over convexity of scene boundaries (i.e., walls) in PPA and OPA. Furthermore, we found that even highly impoverished line drawings of concave shapes are behaviorally categorized as scenes more often than convex shapes. Together, these results provide converging behavioral and neural evidence that concavity is a diagnostic feature of visual scenes.
J. Härtner, S. Strauss, J. Pfannmöller,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117912

Intracortical mapping in monkeys revealed a full body map in all four cytoarchitectonic subdivisions of the contralateral primary somatosensory cortex (S1), as well as positive associations between spatio-tactile acuity performance of the fingers and their representation field size especially within cytoarchitectonic Area 3b and Area 1. Previous non-invasive investigations on these associations in humans assumed a monotonous decrease of representation field size from index finger to little finger although the field sizes are known to change in response to training or in disease. Recent developments improved noninvasive functional mapping of S1 by a) adding a cognitive task during repetitive stimulation to decrease habituation to the stimuli, b) smaller voxel size of fMRI-sequences, c) surface-based analysis accounting for cortical curvature, and d) increase of spatial specificity for fMRI data analysis by avoidance of smoothing, partial volume effects, and pial vein signals. We here applied repetitive pneumatic stimulation of digit 1 (D1; thumb) and digit 5 (D5; little finger) on both hands to investigate finger/hand representation maps in the complete S1, but also in cytoarchitectonic Areas 1, 2, 3a, and 3b separately, in 21 healthy volunteers using 3T fMRI. The distances between activation maxima of D1 and D5 were evaluated by two independent raters, blinded for performance parameters. The fingertip representations showed a somatotopy and were localized in the transition region between the crown and the anterior wall of the post central gyrus agreeing with Area 1 and 3b. Participants were comprehensively tested for tactile performance using von Freyhair filaments to determine cutaneous sensory thresholds (CST) as well as grating orientation thresholds (GOT) and two-point resolution (TPD) for spatio-tactile acuity testing. Motor performance was evaluated with pinch grip performance (Roeder test). We found bilateral associations of D1-D5 distance for GOT thresholds and partially also for TPD in Area 3b and in Area 1, but not if using the complete S1 mask. In conclusion, we here demonstrate that 3T fMRI is capable to map associations between spatio-tactile acuity and the fingertip representation in Area 3b and Area 1 in healthy participants.
Wei Gao, Bharat Biswal, Shengdong Chen, Xinran Wu,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117918

Emotional regulation is known to be associated with activity in the amygdala. The amygdala is an emotion-generative region that comprises of structurally and functionally distinct nuclei. However, little is known about the contributions of different frontal-amygdala sub-region pathways to emotion regulation. Here, we investigated how functional couplings between frontal regions and amygdala sub-regions are involved in different spontaneous emotion regulation processes by using an individual-difference approach and a generalized psycho-physiological interaction (gPPI) approach. Specifically, 50 healthy participants reported their dispositional use of spontaneous cognitive reappraisal and expressive suppression in daily life and their actual use of these two strategies during the performance of an emotional-picture watching task. Results showed that functional coupling between the orbitofrontal cortex (OFC) and the basolateral amygdala (BLA) was associated with higher scores of both dispositional and actual uses of reappraisal. Similarly, functional coupling between the dorsolateral prefrontal cortex (dlPFC) and the centromedial amygdala (CMA) was associated with higher scores of both dispositional and actual uses of suppression. Mediation analyses indicated that functional coupling of the right OFC-BLA partially mediated the association between reappraisal and emotional response, irrespective of whether reappraisal was measured by dispositional use (indirect effect(SE)=-0.2021 (0.0811), 95%CI(BC)= [-0.3851, -0.0655]) or actual use (indirect effect(SE)=-0.1951 (0.0796), 95%CI(BC)= [-0.3654, -0.0518])). These findings suggest that spontaneous reappraisal and suppression involve distinct frontal- amygdala functional couplings, and the modulation of BLA activity from OFC may be necessary for changing emotional response during spontaneous reappraisal.
, Brunno M. de Campos, , , Andrew P. Bagshaw
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117840

Functional connectivity (FC) of the motor network (MN) is often used to investigate how intrinsic properties of the brain are associated with motor abilities and performance. In addition, the MN is a key feature in clinical work to map the recovery after stroke and aid the understanding of neurodegenerative disorders. Time of day variation and individual differences in circadian timing, however, have not yet been considered collectively when looking at FC. A total of 33 healthy, right handed individuals (13 male, 23.1 ± 4.2 years) took part in the study. Actigraphy, sleep diaries and circadian phase markers (dim light melatonin onset and cortisol awakening response) were used to determine early (ECP, n = 13) and late (LCP, n = 20) circadian phenotype groups. Resting state functional MRI testing sessions were conducted at 14:00 h, 20:00 h and 08:00 h and preceded by a maximum voluntary contraction test for isometric grip strength to measure motor performance. Significant differences in FC of the MN between ECPs and LCPs were found, as well as significant variations between different times of day. A higher amplitude in diurnal variation of FC and performance was observed in LCPs compared to ECPs, with the morning being most significantly affected. Overall, lower FC was significantly associated with poorer motor performance. Our findings uncover intrinsic differences between times of day and circadian phenotype groups. This suggests that central mechanisms contribute to diurnal variation in motor performance and the functional integrity of the MN at rest influences the ability to perform in a motor task.
, , , , Lars H Pinborg, Sune H Keller, Peter S Jensen, ,
Published: 15 May 2021
NeuroImage, Volume 232; doi:10.1016/j.neuroimage.2021.117878

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABAA receptors (GABAARs), generated on the basis of in vivo [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.
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