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Introduction: Using tools effectively is a fundamental human ability. Besides the proper recall of semantic knowledge, the application of mechanical problem solving strategies allows one to execute tool-related tasks properly. Past fMRI studies have shown a mainly left-lateralized network, including ventral, ventro-dorsal, and dorso-dorsal streams while using familiar tools with access to semantic information. However, to what degree the network is recruited when applying mechanical problem solving strategies to handle novel tools remains unclear. Methods: An event-related fMRI study including 22 participants was conducted. During scanning, participants had to manipulate novel tools, the function of which they could infer by mechanical problem solving. Brain activity was measured during actual novel tool use and selection, both during the planning and execution phase. Results: Similar brain activation during tool use and tool selection could be observed, ranging from left-hemispheric inferior parietal to frontal regions in the ventro-dorsal stream with lack of ventral activation. Task-specific activations were more pronounced during the planning phases. Discussion: During mechanical problem solving brain activation is more pronounced in the ventro-dorsal stream, where mechanical understanding and motor control need to be integrated. Similar networks recruited during tool selection compared to tool use trials reflect mental simulation strategies used to determine the appropriate tool-recipient fit. The ventral stream, linked to the recall of semantic knowledge, plays a subordinate role during this task and a stronger involvement of anterior regions reflect the relevance of the frontal lobe contributing to mechanical problem solving.

Electroencephalography (EEG) data, acquired simultaneously with magnetic resonance imaging (MRI), must be corrected for artefacts related to MR gradient switches (GS) and the cardioballistic (CB) effect. Canonical approaches require additional signal acquisition for artefact detection (e.g., MR volume onsets, ECG), without which the EEG data would be rendered uncleanable from these artefacts. • We present two broadly applicable methods for artefact detection based on peak detection combined with temporal constraints with respect to periodicity directly from the EEG data itself; no additional signals are required.We validated the performance of our methods versus the two canonical approaches for detection of GS/CB artefact, respectively, on 26 healthy human EEG-functional MRI resting-state datasets. Utilising various performance metrics, we found our methods to perform as well as – and sometimes better than - the canonical standard approaches. With as little as one EEG channel recording, our methods can be applied to detect GS/CB artefacts in EEG data acquired simultaneously with MRI in the absence of MR volume onsets and/or an ECG recording. The detected artefact onsets can then be fed into the standard artefact correction software.

IntroductionHealthy aging affects several domains of cognitive and motor performance and is further associated with multiple structural and functional neural reorganization patterns. However, gap of knowledge exists, referring to the impact of these age-related alterations on the neural basis of tool use–an important, complex action involved in everyday life throughout the entire lifespan. The current fMRI study aims to investigate age-related changes of neural correlates involved in planning and executing a complex object manipulation task, further providing a better understanding of impaired tool use performance in apraxia patients.MethodsA balanced number of sixteen older and younger healthy adults repeatedly manipulated everyday tools in an event-related Go-No-Go fMRI paradigm.ResultsOur data indicates that the left-lateralized network, including widely distributed frontal, temporal, parietal and occipital regions, involved in tool use performance is not subjected to age-related functional reorganization processes. However, age-related changes regarding the applied strategical procedure can be detected, indicating stronger investment into the planning, preparatory phase of such an action in older participants.

In this contribution the frequency domain fluorescence lifetime imaging microscopy (FD-FLIM) technique is evaluated for post-consumer wood sorting. The fluorescence characteristics of several wood samples were determined, whereby two excitation wavelengths (405 and 488 nm) were used. The measured data were processed using algorithmic methods to identify the wood species and post-consumer wood category. With the excitation wavelength of 405 nm, 16 out of 19 samples could be correctly assigned to the corresponding post-consumer wood category by means of the fluorescence lifetimes. Thus, the experimental results revealed the high potential of the FD-FLIM technique for automated post-consumer wood sorting.

Abstract Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying ‘source-level’ activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from −0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms.

Plastic waste is one of the biggest growing factors contributing to environmental pollution. So far there has been no established method to detect and identify plastics in environmental matrices. Thus, a method based on their characteristic fluorescence behavior is used to investigate whether plastics can be detected and identified in tap water under laboratory conditions. The experiments show that the identification of plastics as a function of water depth is possible. As the identification becomes more difficult with higher water depths, investigations with a highly sensitive imaging method were carried out to obtain an areal integration of the fluorescent light and thus better results.

Very early Alzheimer's disease (AD) - i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia - is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC) patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n = 33) and patients with AD in the stages of MCI (AD-MCI, n = 38) and mild dementia (AD-D, n = 36). Outcome measures were voxel-based morphometry (VBM) values and region-of-interest-based iFC maps of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D). Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D), particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions, including that of amygdala.

Organized patterns of system-wide neural activity adapt fluently within the brain to adjust behavioral performance to environmental demands. In major depressive disorder (MD), markedly different co-activation patterns across the brain emerge from a rather similar structural substrate. Despite the application of advanced methods to describe the functional architecture, e.g., between intrinsic brain networks (IBNs), the underlying mechanisms mediating these differences remain elusive. Here we propose a novel complementary approach for quantifying the functional relations between IBNs based on the Kuramoto model. We directly estimate the Kuramoto coupling parameters (K) from IBN time courses derived from empirical fMRI data in 24 MD patients and 24 healthy controls. We find a large pattern with a significant number of Ks depending on the disease severity score Hamilton D, as assessed by permutation testing. We successfully reproduced the dependency in an independent test data set of 44 MD patients and 37 healthy controls. Comparing the results to functional connectivity from partial correlations (FC), to phase synchrony (PS) as well as to first order auto-regressive measures (AR) between the same IBNs did not show similar correlations. In subsequent validation experiments with artificial data we find that a ground truth of parametric dependencies on artificial regressors can be recovered. The results indicate that the calculation of Ks can be a useful addition to standard methods of quantifying the brain's functional architecture.

Detection and quantification of milk protein residues can be of utmost importance for validation of cleaning process efficiency in removing even traces of residues as well as quality assurance and product safety. However, currently available assays cannot provide a combination of high sensitivity and a simultaneous quantification of the individual milk proteins. Furthermore, a low protein-to-protein-variability and high compatibility with other reagents such as residual cleaning agents (e.g. surfactants) cannot be ensured. Therefore, a new method was developed comprised of a pre-concentration of proteins by solid-phase extraction and optimisation of the sensitivity of an existing reversed-phase high performance liquid chromatography method for the separate quantification of bovine milk proteins κ-Casein, αS2-Casein, αS1-Casein, β-Casein, α-Lactalbumin, and β-Lactoglobulin. Hereby, solid-phase extraction enables robust and reproducible purification and concentration of protein residues with a high protein recovery rate and flexible adjustment of concentration factors. The increased sensitivity of the reversed-phase high performance liquid chromatography method was achieved by changes in the measurement wavelength and guanidine buffer concentration. This new method enables reproducible concentration, purification and quantification of protein concentrations below 7 ng mL−1 and thus can be used to detect milk protein residues in highly diluted aqueous systems. • Concentration, purification and quantification of milk protein residues with a high recovery rate of proteins (> 94%) and high reproducibility (coefficient of variation (CV)

Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.

There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-β distributions. Here we compared spatial patterns of amyloid-β-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-β and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-β aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-β-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-β pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-β-plaque concentration. The local negative association between amyloid-β and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-β on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-β and intrinsic connectivity, with the distribution of amyloid-β pathology following functional connectivity gradients within and across intrinsic networks.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of uncontrolled immune activation with distinct clinical features including fever, cytopenia, splenomegaly, and sepsis-like symptoms. In a young adolescent patient a novel germline GATA2 variant (NM_032638.5 (GATA2): c.177C>G, p.Tyr59Ter) was discovered and had resulted in non-tuberculous mycobacterial (NTM) infection and aggressive HLH. Strikingly, impaired degranulation of cytotoxic T-lymphocytes (CTL) and natural killer (NK)-cells was detected in CD107a-analyses. The affected patient was treated with HLA-matched unrelated alloHSCT, and subsequently all hematologic and infectious abnormalities including HLH and NTM resolved. This case supports early alloHSCT in GATA2 deficiencies as curative approach regardless of active NTM infection. Future studies on GATA2 c.177C>G, p.Tyr59*Ter might unravel its potential role in cytotoxic effector cell function and its contribution to HLH pathogenesis.

Introduction. We aim to investigate the effect of vitamin D on metabolic parameters in a population with prediabetes and to detect possible sex differences. Methods. In 621 patients with diagnosed prediabetes, glucose, lipid, and anthropometric parameters were measured. Furthermore, the interaction of 25-OH-vitamin D (25-hydroxyvitamin D) with metabolic and glucose metabolism parameters was analysed in the total prediabetic population, as well as after stratification by sex (female vs. male prediabetic subgroup), by logistic regression. Results. 25-OH-vitamin D was negatively related to cholesterol, BMI, fatty liver index, insulin, and HOMA-IR. Especially in the male prediabetic cohort, 25-OH-vitamin D levels negatively correlated with total cholesterol levels (r = −0.17, p=0.001), with triglycerides (r = −0.17, p=0.001), and with HbA1c levels (r = −0.14, p=0.010). Only in the female cohort with prediabetes, we found a negative correlation of 25-OH-vitamin D levels with systolic (r = −0.18, p=0.005) and diastolic blood pressures (r = −0.23, p

Visual metacognition—the introspection and evaluation of one’s own visual perceptual processes—is measured through both decision confidence and “metacognitive efficiency.” Metacognitive efficiency refers to an individual’s ability to accurately judge incorrect and correct decisions through confidence ratings given their task performance. Previous imaging studies in humans and nonhuman primates reported widely distributed brain regions being involved in decision confidence and metacognition. However, the neural correlates of metacognition are remarkably inconsistent across studies concerning spatial outline. Therefore, this study investigates the neural correlates of visual metacognition by examining co-activation across regions that scale with visual decision confidence. We hypothesized that interacting processes of perceptual and metacognitive performance contribute to the arising decision confidence in distributed, but segregable co-activating brain regions. To test this hypothesis, we performed task-fMRI in healthy humans during a visual backward masking task with four-scale, post-decision confidence ratings. We measured blood oxygenation covariation patterns, which served as a physiological proxy for co-activation across brain regions. Decision confidence ratings and an individual’s metacognitive efficiency served as behavioral measures for metacognition. We found three distinct co-activation clusters involved in decision confidence: the first included right-centered fronto-temporal-parietal regions, the second included left temporal and parietal regions, and the left basal forebrain (BF), and the third included cerebellar regions. The right fronto-temporal-parietal cluster including the supplementary eye field and the right basal forebrain showed stronger co-activation in subjects with higher metacognitive efficiency. Our results provide novel evidence for co-activation of widely distributed fronto-parieto-temporal regions involved in visual confidence. The supplementary eye field was the only region that activated for both decision confidence and metacognitive efficiency, suggesting the supplementary eye field plays a key role in visual metacognition. Our results link findings in electrophysiology studies and human fMRI studies and provide evidence that confidence estimates arise from the integration of multiple information processing pathways.