Micro-CT of rodents: State-of-the-art and future perspectives

Micron-scale computed tomography (micro-CT) is an essential tool for phenotyping and for elucidating diseases and their therapies. This work is focused on preclinical micro-CT imaging, reviewing relevant principles, technologies, and applications. Commonly, micro-CT provides high-resolution anatomic information, either on its own or in conjunction with lower-resolution functional imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). More recently, however, advanced applications of micro-CT produce functional information by translating clinical applications to model systems (e.g. measuring cardiac functional metrics) and by pioneering new ones (e.g. measuring tumor vascular permeability with nanoparticle contrast agents). The primary limitations of micro-CT imaging are the associated radiation dose and relatively poor soft tissue contrast. We review several image reconstruction strategies based on iterative, statistical, and gradient sparsity regularization, demonstrating that high image quality is achievable with low radiation dose given ever more powerful computational resources. We also review two contrast mechanisms under intense development. The first is spectral contrast for quantitative material discrimination in combination with passive or actively targeted nanoparticle contrast agents. The second is phase contrast which measures refraction in biological tissues for improved contrast and potentially reduced radiation dose relative to standard absorption imaging. These technological advancements promise to develop micro-CT into a commonplace, functional and even molecular imaging modality.     

Concurrent word generation and motor performance: further evidence for language-motor interaction

Embodied/modality-specific theories of semantic memory propose that sensorimotor representations play an important role in perception and action. A large body of evidence supports the notion that concepts involving human motor action (i.e., semantic-motor representations) are processed in both language and motor regions of the brain. However, most studies have focused on perceptual tasks, leaving unanswered questions about language-motor interaction during production tasks. Thus, we investigated the effects of shared semantic-motor representations on concurrent language and motor production tasks in healthy young adults, manipulating the semantic task (motor-related vs. nonmotor-related words) and the motor task (i.e., standing still and finger-tapping). In Experiment 1 (n = 20), we demonstrated that motor-related word generation was sufficient to affect postural control. In Experiment 2 (n = 40), we demonstrated that motor-related word generation was sufficient to facilitate word generation and finger tapping. We conclude that engaging semantic-motor representations can have a reciprocal influence on motor and language production. Our study provides additional support for functional language-motor interaction, as well as embodied/modality-specific theories.     

When Music and Long-Term Memory Interact: Effects of Musical Expertise on Functional and Structural Plasticity in the Hippocampus

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.     

Can we use diffusion MRI as a bio-marker of neurodegenerative processes?

Magnetic resonance imaging (MRI) is an imaging technique with a rapidly expanding application range. This methodology, which relies on quantum physics and substance magnetic properties, is now being routinely used in the clinics and medical research. With the advent of measuring functional brain activity with MRI (functional MRI), this methodology has reached a larger section of the neuroscience community (e.g. psychologists, neurobiologists). In the past, the use of MRI as a biomarker or as an assay to probe tissue pathophysiological condition was limited. However, with the new applications of MRI: molecular imaging, contrast-enhanced imaging and diffusion imaging, MRI is turning into a powerful tool for in vivo characterization of tissue pathophysiology. This review focuses on the diffusion MRI. Although it only measures the averaged Brownian translational motion of water molecules, using different analysis schemes, one can extract a wide range of quantitative indices that represent tissue morphology and compartmentalization. Statistical and visualization routines help to relate these indices to biologically relevant measures such as cell density, water content and size distribution. The aim of this review is to shed light on the potential of this methodology to be used in biological research. To that end, this review is intended for the non-MRI specialists who wish to pursue biological research with this methodology. We will overview the current applications of diffusion MRI and its relation to cellular biology of brain tissue.     

Behavioral correlates of cortical semantic representations modeled by word vectors

The quantitative modeling of semantic representations in the brain plays a key role in understanding the neural basis of semantic processing. Previous studies have demonstrated that word vectors, which were originally developed for use in the field of natural language processing, provide a powerful tool for such quantitative modeling. However, whether semantic representations in the brain revealed by the word vector-based models actually capture our perception of semantic information remains unclear, as there has been no study explicitly examining the behavioral correlates of the modeled brain semantic representations. To address this issue, we compared the semantic structure of nouns and adjectives in the brain estimated from word vector-based brain models with that evaluated from human behavior. The brain models were constructed using voxelwise modeling to predict the functional magnetic resonance imaging (fMRI) response to natural movies from semantic contents in each movie scene through a word vector space. The semantic dissimilarity of brain word representations was then evaluated using the brain models. Meanwhile, data on human behavior reflecting the perception of semantic dissimilarity between words were collected in psychological experiments. We found a significant correlation between brain model- and behavior-derived semantic dissimilarities of words. This finding suggests that semantic representations in the brain modeled via word vectors appropriately capture our perception of word meanings.     

The counting Stroop: a cognitive interference task

The counting Stroop is a validated Stroop task variant. Initially designed as a functional magnetic resonance imaging (fMRI) task for identifying brain regions subserving cognition and attention (dorsal anterior midcingulate cortex (daMCC) and dorsolateral prefrontal cortex (DLPFC)), it has been used to study cognition in healthy volunteers and to identify functional brain abnormalities in neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD). During the counting Stroop, subjects report by button-press the number of words (one to four) appearing on the screen, regardless of word meaning. Neutral-word control trials contain single semantic category common animals (e.g., 'dog' written three times), while interference trials contain number words that are incongruent with the correct response (e.g., 'two' written four times). The counting Stroop can be completed in approximately 20 min per subject and can be used offline (behavioral performance) or with fMRI, positron emission tomography, event-related potentials, magnetoencephalography or intracranial recordings.     

Women’s Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex

Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman’s perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift’s social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift’s social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant’s attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods—preference for the member is a powerful modulator of social reward processing.     

Peptoids as tools and sensors

A review of molecular tools and sensors assembled on N-substituted glycine, or α-peptoid, oligomers between 2013 and November 2018 with the following sections: (a) Peptoids as crystal growth modifiers, (b) Peptoids as catalysts, (c) Ion and molecule sequestration and transport, (d) Peptoid sensors, (e) Macromolecule recognition, (f) Cellular transporters, (g) Medical imaging, (h) Future direction and (i) Summary and outlook. Peptoids are a promising class of peptide mimic making them an excellent platform for functional molecule preparation. Attributes of peptoid oligomers include: (a) the ease of precise sequence definition and mono-dispersity; (b) access to a vast chemical space within simple and repeating chemical preparative steps and (c) thermal, chemical and biological stability all lending support for their application in a number of areas, with some that have been realised to date. The peptoid tool and sensor examples selected have realised practical utility. They serve to illustrate the rapidity of new insight that can generate in many disparate areas of science and technology, enabling the quick assembly of design criteria for efficient peptoid molecular tools and sensors.     

Simultaneous topography and recognition imaging on endothelial cells

Determining the landscape of specific binding sites on biological samples with high spatial accuracy (in the order of several nanometres) is an important task in many fields of biological science. During the past five years, dynamic recognition imaging (e.g. simultaneous topography and recognition (TREC) imaging) has proven to be a powerful technique in biophysical research. This technique becomes an indispensable tool for high-resolution receptor mapping as it has been successfully demonstrated on different biomolecular model systems. In these studies, the topographical imaging of receptor molecules is combined with molecular recognition by their cognate ligands bound to the atomic force microscope (AFM) tip via a flexible and distensible tether. In this review, we describe the principles of TREC imaging and provide a flavour of its recent application on endothelial cells.     

Knowledge Retrieval from PubMed Abstracts and Electronic Medical Records with the Multiple Sclerosis Ontology

BackgroundIn order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS).MethodsThe MS Ontology was created using scientific literature and expert review under the Protégé OWL environment. We developed a dictionary with semantic synonyms and translations to different languages for mining EMR. The MS Ontology was integrated with other ontologies and dictionaries (diseases/comorbidities, gene/protein, pathways, drug) into the text-mining tool SCAIView. We analyzed the EMRs from 624 patients with MS using the MS ontology dictionary in order to identify drug usage and comorbidities in MS. Testing competency questions and functional evaluation using F statistics further validated the usefulness of MS ontology.ResultsValidation of the lexicalized ontology by means of named entity recognition-based methods showed an adequate performance (F score = 0.73). The MS Ontology retrieved 80% of the genes associated with MS from scientific abstracts and identified additional pathways targeted by approved disease-modifying drugs (e.g. apoptosis pathways associated with mitoxantrone, rituximab and fingolimod). The analysis of the EMR from patients with MS identified current usage of disease modifying drugs and symptomatic therapy as well as comorbidities, which are in agreement with recent reports.ConclusionThe MS Ontology provides a semantic framework that is able to automatically extract information from both scientific literature and EMR from patients with MS, revealing new pathogenesis insights as well as new clinical information.     

Biological trait composition of European stream invertebrate communities: assessing the effects of various trait filter types

Understanding the action of filters on the biological trait composition of communities is constrained by the multitude of filter types (e.g. abiotic vs biotic, actual vs historical) that may cause changes of a multitude of traits (e.g. small vs large body size, short vs long life cycle) at a multitude of spatial scales (e.g. continent vs landscape vs local site). Using published data on the as natural as possible abundances and 11 biological traits (described through 63 categories) of 254 European stream invertebrate genera, we assessed how already available knowledge can serve to identify the importance of the action of different types of trait filters at two spatial scales. Therefore, we analysed observed and simulated abundance‐weighted trait compositions at the local scale of 384 running water sites (RWS) and at the landscape scale of 14 large biogeographical regions (LER). Actual abiotic filters acted significantly and independently of the taxonomic richness on the invertebrate traits at the RWS‐ and LER‐scale, whereas biotic filters had no significant effect. Evidence for the action of historical trait filters across Europe was only weak at both scales. Size, reproductive cycle, respiration and locomotion technique, feeding habits and vulnerability to disturbance responded to altitude and stream width of the RWS according to existing views about the effects of riparian, physiological, interstitial or disturbance controls of these traits. These controls acted independently on trait categories that did not co‐occur within the genera, because correlations of size categories with other trait categories were higher in the abundance‐weighted trait array (across communities) than in the original trait array (across genera). Overall, many of the 63 trait categories were scarcely affected by the trait filters considered in this study. Therefore, we briefly discuss potential effects of continental filters and of stream system‐specific, local physical filters, as the latter should produce similar trait patterns on a global scale. Our study suggests that analyses of the currently available knowledge can simplify the complicated hypothetical framework on trait filter actions, which sharpens the focus on future research needs.     

Same modulation but different starting points: performance modulates age differences in inferior frontal cortex activity during word-retrieval

The neural basis of word-retrieval deficits in normal aging has rarely been assessed and the few previous functional imaging studies found enhanced activity in right prefrontal areas in healthy older compared to younger adults. However, more pronounced right prefrontal recruitment has primarily been observed during challenging task conditions. Moreover, increased task difficulty may result in enhanced activity in the ventral inferior frontal gyrus (vIFG) bilaterally in younger participants as well. Thus, the question arises whether increased activity in older participants represents an age-related phenomenon or reflects task difficulty effects. In the present study, we manipulated task difficulty during overt semantic and phonemic word-generation and used functional magnetic resonance imaging to assess activity patterns in the vIFG in healthy younger and older adults (N = 16/group; mean age: 24 vs. 69 years). Both groups produced fewer correct responses during the more difficult task conditions. Overall, older participants produced fewer correct responses and showed more pronounced task-related activity in the right vIFG. However, increased activity during the more difficult conditions was found in both groups. Absolute degree of activity was correlated with performance across groups, tasks and difficulty levels. Activity modulation (difficult vs. easy conditions) was correlated with the respective drop in performance across groups and tasks. In conclusion, vIFG activity levels and modulation of activity were mediated by performance accuracy in a similar way in both groups. Group differences in the right vIFG activity were explained by performance accuracy which needs to be considered in future functional imaging studies of healthy and pathological aging.     

A neuropsychological perspective on the link between language and praxis in modern humans

Hypotheses about the emergence of human cognitive abilities postulate strong evolutionary links between language and praxis, including the possibility that language was originally gestural. The present review considers functional and neuroanatomical links between language and praxis in brain-damaged patients with aphasia and/or apraxia. The neural systems supporting these functions are predominantly located in the left hemisphere. There are many parallels between action and language for recognition, imitation and gestural communication suggesting that they rely partially on large, common networks, differentially recruited depending on the nature of the task. However, this relationship is not unequivocal and the production and understanding of gestural communication are dependent on the context in apraxic patients and remains to be clarified in aphasic patients. The phonological, semantic and syntactic levels of language seem to share some common cognitive resources with the praxic system. In conclusion, neuropsychological observations do not allow support or rejection of the hypothesis that gestural communication may have constituted an evolutionary link between tool use and language. Rather they suggest that the complexity of human behaviour is based on large interconnected networks and on the evolution of specific properties within strategic areas of the left cerebral hemisphere.     

The medial temporal lobe supports conceptual implicit memory

The medial temporal lobe (MTL) is generally thought to be critical for explicit, but not implicit, memory. Here, we demonstrate that the perirhinal cortex (PRc), within the MTL, plays a role in conceptually-driven implicit memory. Amnesic patients with MTL lesions that converged on the left PRc exhibited deficits on two conceptual implicit tasks (i.e., exemplar generation and semantic decision). A separate functional magnetic resonance imaging (fMRI) study in healthy subjects indicated that PRc activation during encoding of words was predictive of subsequent exemplar generation. Moreover, across subjects, the magnitude of the fMRI and behavioral conceptual priming effects were directly related. Additionally, the PRc region implicated in the fMRI study was the same region of maximal lesion overlap in the patients with impaired conceptual priming. These patient and imaging results converge to suggest that the PRc plays a critical role in conceptual implicit memory, and possibly conceptual processing in general.     

Reproducibility and discriminability of brain patterns of semantic categories enhanced by congruent audiovisual stimuli

One of the central questions in cognitive neuroscience is the precise neural representation, or brain pattern, associated with a semantic category. In this study, we explored the influence of audiovisual stimuli on the brain patterns of concepts or semantic categories through a functional magnetic resonance imaging (fMRI) experiment. We used a pattern search method to extract brain patterns corresponding to two semantic categories: "old people" and "young people." These brain patterns were elicited by semantically congruent audiovisual, semantically incongruent audiovisual, unimodal visual, and unimodal auditory stimuli belonging to the two semantic categories. We calculated the reproducibility index, which measures the similarity of the patterns within the same category. We also decoded the semantic categories from these brain patterns. The decoding accuracy reflects the discriminability of the brain patterns between two categories. The results showed that both the reproducibility index of brain patterns and the decoding accuracy were significantly higher for semantically congruent audiovisual stimuli than for unimodal visual and unimodal auditory stimuli, while the semantically incongruent stimuli did not elicit brain patterns with significantly higher reproducibility index or decoding accuracy. Thus, the semantically congruent audiovisual stimuli enhanced the within-class reproducibility of brain patterns and the between-class discriminability of brain patterns, and facilitate neural representations of semantic categories or concepts. Furthermore, we analyzed the brain activity in superior temporal sulcus and middle temporal gyrus (STS/MTG). The strength of the fMRI signal and the reproducibility index were enhanced by the semantically congruent audiovisual stimuli. Our results support the use of the reproducibility index as a potential tool to supplement the fMRI signal amplitude for evaluating multimodal integration.     

In vivo flow cytometry: a horizon of opportunities

Flow cytometry (FCM) has been a fundamental tool of biological discovery for many years. Invasive extraction of cells from a living organism, however, may lead to changes in cell properties and prevents studying cells in their native environment. These problems can be overcome by use of in vivo FCM, which provides detection and imaging of circulating normal and abnormal cells directly in blood or lymph flow. The goal of this review is to provide a brief history, features, and challenges of this new generation of FCM methods and instruments. Spectrum of possibilities of in vivo FCM in biological science (e.g., cell metabolism, immune function, or apoptosis) and medical fields (e.g., cancer, infection, and cardiovascular disorder) including integrated photoacoustic-photothermal theranostics of circulating abnormal cells are discussed with focus on recent advances of this new platform.     

A global meta‐analysis of the relative extent of intraspecific trait variation in plant communities

Recent studies have shown that accounting for intraspecific trait variation (ITV) may better address major questions in community ecology. However, a general picture of the relative extent of ITV compared to interspecific trait variation in plant communities is still missing. Here, we conducted a meta‐analysis of the relative extent of ITV within and among plant communities worldwide, using a data set encompassing 629 communities (plots) and 36 functional traits. Overall, ITV accounted for 25% of the total trait variation within communities and 32% of the total trait variation among communities on average. The relative extent of ITV tended to be greater for whole‐plant (e.g. plant height) vs. organ‐level traits and for leaf chemical (e.g. leaf N and P concentration) vs. leaf morphological (e.g. leaf area and thickness) traits. The relative amount of ITV decreased with increasing species richness and spatial extent, but did not vary with plant growth form or climate. These results highlight global patterns in the relative importance of ITV in plant communities, providing practical guidelines for when researchers should include ITV in trait‐based community and ecosystem studies.     

Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy

Cellular biomolecules contain unique molecular vibrations that can be visualized by coherent anti-Stokes Raman scattering (CARS) microscopy without the need for labels. Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. The CARS imaging modality provides a unique tool for biological chemists to elucidate the state of a cellular environment without perturbing it and to perceive the functional effects of added molecules.     

Reading and reading disturbance

Recent functional neuroimaging studies are generating novel insights into our knowledge of skilled and disturbed reading. In neurologically normal subjects, a double dissociation in neural activation in response to reading words and pseudowords has been revealed that corresponds to that observed in the comparison of semantic and phonological tasks. In patients with acquired dyslexia, functional imaging is demonstrating re-organisation within the reading system; in developmental dyslexia, functional imaging is being used to identify the impact of rehabilitation. Together, these findings have implications for cognitive models of reading that have previously relied on input from behavioural data.