A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

The NeuARt II system: a viewing tool for neuroanatomical data based on published neuroanatomical atlases

BACKGROUND: Anatomical studies of neural circuitry describing the basic wiring diagram of the brain produce intrinsically spatial, highly complex data of great value to the neuroscience community. Published neuroanatomical atlases provide a spatial framework for these studies. We have built an informatics framework based on these atlases for the representation of neuroanatomical knowledge. This framework not only captures current methods of anatomical data acquisition and analysis, it allows these studies to be collated, compared and synthesized within a single system. RESULTS: We have developed an atlas-viewing application ('NeuARt II') in the Java language with unique functional properties. These include the ability to use copyrighted atlases as templates within which users may view, save and retrieve data-maps and annotate them with volumetric delineations. NeuARt II also permits users to view multiple levels on multiple atlases at once. Each data-map in this system is simply a stack of vector images with one image per atlas level, so any set of accurate drawings made onto a supported atlas (in vector graphics format) could be uploaded into NeuARt II. Presently the database is populated with a corpus of high-quality neuroanatomical data from the laboratory of Dr Larry Swanson (consisting 64 highly-detailed maps of PHAL tract-tracing experiments, made up of 1039 separate drawings that were published in 27 primary research publications over 17 years). Herein we take selective examples from these data to demonstrate the features of NeuArt II. Our informatics tool permits users to browse, query and compare these maps. The NeuARt II tool operates within a bioinformatics knowledge management platform (called 'NeuroScholar') either as a standalone or a plug-in application. CONCLUSION: Anatomical localization is fundamental to neuroscientific work and atlases provide an easily-understood framework that is widely used by neuroanatomists and non-neuroanatomists alike. NeuARt II, the neuroinformatics tool presented here, provides an accurate and powerful way of representing neuroanatomical data in the context of commonly-used brain atlases for visualization, comparison and analysis. Furthermore, it provides a framework that supports the delivery and manipulation of mapped data either as a standalone system or as a component in a larger knowledge management system

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Hypotheses, evidence and relationships: The HypER approach for representing scientific knowledge claims

Biological knowledge is increasingly represented as a collection of (entity-relationship-entity) triplets. These are queried, mined, appended to papers, and published. However, this representation ignores the argumentation contained within a paper and the relationships between hypotheses, claims and evidence put forth in the article. In this paper, we propose an alternate view of the research article as a network of 'hypotheses and evidence'. Our knowledge representation focuses on scientific discourse as a rhetorical activity, which leads to a different direction in the development of tools and processes for modeling this discourse. We propose to extract knowledge from the article to allow the construction of a system where a specific scientific claim is connected, through trails of meaningful relationships, to experimental evidence. We discuss some current efforts and future plans in this area

Group-wise 3D registration based templates to study the evolution of ant worker neuroanatomy

The evolutionary success of ants and other social insects is considered to be intrinsically linked to division of labor and emergent collective intelligence. The role of the brains of individual ants in generating these processes, however, is poorly understood. One genus of ant of special interest is Pheidole, which includes more than a thousand species, most of which are dimorphic, i.e. their colonies contain two subcastes of workers: minors and majors. Using confocal imaging and manual annotations, it has been demonstrated that minor and major workers of different ages of three species of Pheidole have distinct patterns of brain size and subregion scaling. However, these studies require laborious effort to quantify brain region volumes and are subject to potential bias. To address these issues, we propose a group-wise 3D registration approach to build for the first time bias-free brain atlases of intra- and inter-subcaste individuals and automatize the segmentation of new individuals.Comment: 10 pages, 5 figures, preprint for conference (not reviewed

Evolving structure-function mappings in cognitive neuroscience using genetic programming

A challenging goal of psychology and neuroscience is to map cognitive functions onto neuroanatomical structures. This paper shows how computational methods based upon evolutionary algorithms can facilitate the search for satisfactory mappings by efficiently combining constraints from neuroanatomy and physiology (the structures) with constraints from behavioural experiments (the functions). This methodology involves creation of a database coding for known neuroanatomical and physiological constraints, for mental programs made of primitive cognitive functions, and for typical experiments with their behavioural results. The evolutionary algorithms evolve theories mapping structures to functions in order to optimize the fit with the actual data. These theories lead to new, empirically testable predictions. The role of the prefrontal cortex in humans is discussed as an example. This methodology can be applied to the study of structures or functions alone, and can also be used to study other complex systems. (This article does not exactly replicate the final version published in the Journal of Swiss Psychology. It is not a copy of the original published article and is not suitable for citation.

Explicit processing of verbal and spatial features during letter-location binding modulates oscillatory activity of a fronto-parietal network.

The present study investigated the binding of verbal and spatial features in immediate memory. In a recent study, we demonstrated incidental and asymmetrical letter-location binding effects when participants attended to letter features (but not when they attended to location features) that were associated with greater oscillatory activity over prefrontal and posterior regions during the retention period. We were interested to investigate whether the patterns of brain activity associated with the incidental binding of letters and locations observed when only the verbal feature is attended differ from those reflecting the binding resulting from the controlled/explicit processing of both verbal and spatial features. To achieve this, neural activity was recorded using magnetoencephalography (MEG) while participants performed two working memory tasks. Both tasks were identical in terms of their perceptual characteristics and only differed with respect to the task instructions. One of the tasks required participants to process both letters and locations. In the other, participants were instructed to memorize only the letters, regardless of their location. Time–frequency representation of MEG data based on the wavelet transform of the signals was calculated on a single trial basis during the maintenance period of both tasks. Critically, despite equivalent behavioural binding effects in both tasks, single and dual feature encoding relied on different neuroanatomical and neural oscillatory correlates. We propose that enhanced activation of an anterior–posterior dorsal network observed in the task requiring the processing of both features reflects the necessity for allocating greater resources to intentionally process verbal and spatial features in this task