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Behavioral and brain-related changes in word production have been claimed to predominantly occur after 70 years of age. Most studies investigating age-related changes in adulthood only compared young to older adults, failing to determine whether neural processes underlying word production change at an earlier age than observed in behavior. This study aims to fill this gap by investigating whether changes in neurophysiological processes underlying word production are aligned with behavioral changes. Behavior and the electrophysiological event-related potential patterns of word production were assessed during a picture naming task in 95 participants across five adult lifespan age groups (ranging from 16 to 80 years old). While behavioral performance decreased starting from 70 years of age, significant neurophysiological changes were present at the age of 40 years old, in a time window (between 150 and 220 ms) likely associated with lexical-semantic processes underlying referential word production. These results show that neurophysiological modifications precede the behavioral changes in language production; they can be interpreted in line with the suggestion that the lexical-semantic reorganization in mid-adulthood influences the maintenance of language skills longer than for other cognitive functions.

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Alcohol use is a leading risk factor for substantial health loss, disability, and death. Thus, there is a general interest in developing computational tools to classify electroencephalographic (EEG) signals in alcoholism, but there are a limited number of studies on convolutional neural network (CNN) classification of alcoholism using topographic EEG signals. We produced an original dataset recorded from Brazilian subjects performing a language recognition task. Then, we transformed the Event-Related Potentials (ERPs) into topographic maps by using the ERP's statistical parameters across time, and used a CNN network to classify the topographic dataset. We tested the effect of the size of the dataset in the accuracy of the CNNs and proposed a data augmentation approach to increase the size of the topographic dataset to improve the accuracies. Our results encourage the use of CNNs to classify abnormal topographic EEG patterns associated with alcohol abuse.

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Brain-state-dependent stimulation during slow-wave sleep is a promising tool for the treatment of psychiatric and neurodegenerative diseases. A widely used slow-wave prediction algorithm required for brain-state-dependent stimulation is based on a specific amplitude threshold in the electroencephalogram. However, due to decreased slow-wave amplitudes in aging and psychiatric conditions, this approach might miss many slow-waves because they do not fulfill the amplitude criterion. Here, we compared slow-wave peaks predicted via an amplitude-based versus a multidimensional approach using a topographical template of slow-wave peaks in 21 young and 21 older healthy adults. We validate predictions against the gold-standard of offline detected peaks. Multidimensionally predicted peaks resemble the gold-standard regarding spatiotemporal dynamics but exhibit lower peak amplitudes. Amplitude-based prediction, by contrast, is less sensitive, less precise and - especially in the older group - predicts peaks that differ from the gold-standard regarding spatiotemporal dynamics. Our results suggest that amplitude-based slow-wave peak prediction might not always be the ideal choice. This is particularly the case in populations with reduced slow-wave amplitudes, like older adults or psychiatric patients. We recommend the use of multidimensional prediction, especially in studies targeted at populations other than young and healthy individuals.

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Describing the location of EEG abnormalities, such as interictal epileptiform discharges, is an important step in the interpretation of EEG recordings and has clinical relevance, as it is expected to point out the region of the brain generating these abnormal signals. Traditionally, the location is reported by specifying the area on the scalp where maximum negativity is located. However, this only reflects the correct localization in the brain when the cortical generator is located on the convexity (radial orientation). When the cortical generator is in the wall of a sulcus (tangential orientation), due to current flow (volume conduction), the maximum negativity is not over the generator, but at a distance from it. Voltage maps are widely available in most EEG reader software programs. Simple rules for reading voltage maps help to estimate the orientation and location of the source in the brain, avoiding false lateralization and false localization. In this seminar in epileptology, using a didactic approach, we explain how to read voltage maps and provide an atlas of voltage maps.

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Perception of quantities, such as numerosity, timing, and size, is essential for behavior and cognition. Accumulating evidence demonstrates neurons processing quantities are tuned, that is, have a preferred quantity amount, not only for numerosity, but also other quantity dimensions and sensory modalities. We argue that quantity-tuned neurons are fundamental to understanding quantity perception. We illustrate how the properties of quantity-tuned neurons can underlie a range of perceptual phenomena. Furthermore, quantity-tuned neurons are organized in distinct but overlapping topographic maps. We suggest that this overlap in tuning provides the neural basis for perceptual interactions between different quantities, without the need for a common neural representational code.

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Topographic maps, a key principle of brain organization, emerge during development. It remains unclear, however, whether topographic maps can represent a new sensory experience learned in adulthood. MaMe, a congenitally blind individual, has been extensively trained in adulthood for perception of a 2D auditory-space (soundscape) where the y- and x-axes are represented by pitch and time, respectively. Using population receptive field mapping we found neural populations tuned topographically to pitch, not only in the auditory cortices but also in the parietal and occipito-temporal cortices. Topographic neural tuning to time was revealed in the parietal and occipito-temporal cortices. Some of these maps were found to represent both axes concurrently, enabling MaMe to represent unique locations in the soundscape space. This case study provides proof of concept for the existence of topographic maps tuned to the newly learned soundscape dimensions. These results suggest that topographic maps can be adapted or recycled in adulthood to represent novel sensory experiences.

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Perceiving numerosity, i.e. the set size of a group of items, is an evolutionarily preserved ability found in humans and animals. A useful method to infer the neural underpinnings of a given perceptual property is sensory adaptation. Like other primary perceptual attributes, numerosity is susceptible to adaptation. Recently, we have shown numerosity-selective neural populations with a topographic organization in the human brain. Here, we investigated whether numerosity adaptation can affect the numerosity selectivity of these populations using ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI). Participants viewed stimuli of changing numerosity (1 to 7 dots), which allowed the mapping of numerosity selectivity. We interleaved a low or high numerosity adapter stimulus with these mapping stimuli, repeatedly presenting 1 or 20 dots respectively to adapt the numerosity-selective neural populations. We analyzed the responses using custom-build population receptive field neural models of numerosity encoding and compared estimated numerosity preferences between adaptation conditions. We replicated our previous studies where we found several topographic maps of numerosity-selective responses. We found that overall, numerosity adaptation altered the preferred numerosities within the numerosity maps, resulting in predominantly attractive biases towards the numerosity of the adapter. The differential biases could be explained by the difference between the unadapted preferred numerosity and the numerosity of the adapter, with attractive biases being observed with higher difference. The results could link perceptual numerosity adaptation effects to changes in neural numerosity selectivity.

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Changes in word production occur across the lifespan. Previous studies have shown electrophysiological, temporal, and functional differences between children and adults accompanying behavioral changes in picture-naming tasks (Laganaro, Tzieropoulos, Fraunfelder, & Zesiger, 2015). Thus, a shift toward adult-like processes in referential word production occurs somewhere between the ages of 13 and 20. Our aim was to investigate when and how children develop adult-like behavior and brain activation in word production. Toward this aim, performance and event-related potentials (ERP) in a referential word production task were recorded and compared for two groups of adolescents (aged 14 to 16 and 17 to 18), children (aged 10 to 13), and young adults (aged 20 to 30). Both groups of adolescents displayed adult-like production latencies, which were longer only for children, while accuracy was lower in the younger adolescents and in children, compared to adults. ERP waveform analysis and topographic pattern analysis revealed significant intergroup differences in key time-windows on stimulus-locked ERPs, both early (150-220 ms)-associated with pre-linguistic processes-and late (280-330 ms)-associated with lexical processes. The results indicate that brain activation underlying referential word production is completely adult-like in 17-year-old adolescents, whereas an intermediate pattern is still observed in adolescents aged 14 to 16 years old, although their production speed, but not their accuracy, is already adult-like.

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While the mechanisms generating the topographic organization of primary sensory areas in the neocortex are well studied, what generates secondary cortical areas is virtually unknown. Using physical parameters representing primary and secondary visual areas as they vary from monkey to mouse, we derived a network growth model to explore if characteristic features of secondary areas could be produced from correlated activity patterns arising from V1 alone. We found that V1 seeded variable numbers of secondary areas based on activity-driven wiring and wiring-density limits within the cortical surface. These secondary areas exhibited the typical mirror-reversal of map topography on cortical area boundaries and progressive reduction of the area and spatial resolution of each new map on the caudorostral axis. Activity-based map formation may be the basic mechanism that establishes the matrix of topographically organized cortical areas available for later computational specialization.

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INTRODUCTION: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté. METHODS: Two participatory workshops with inhabitants of Sibaté were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muña Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality. RESULTS: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muña Reservoir, creating landfilled zones in the urban area of Sibaté. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibaté in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies. DISCUSSION: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibaté during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibaté, which is aggravated by the fact that during those years, more than 50% of the population of Sibaté was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.

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The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon-environment and axon-target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon-axon interactions during the different steps of neural circuit formation.

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Accurately timing sub-second sensory events is crucial when perceiving our dynamic world. This ability allows complex human behaviors that require timing-dependent multisensory integration and action planning. Such behaviors include perception and performance of speech, music, driving, and many sports. How are responses to sensory event timing processed for multisensory integration and action planning? We measured responses to viewing systematically changing visual event timing using ultra-high-field fMRI. We analyzed these responses with neural population response models selective for event duration and frequency, following behavioral, computational, and macaque action planning results and comparisons to alternative models. We found systematic local changes in timing preferences (recently described in supplementary motor area) in an extensive network of topographic timing maps, mirroring sensory cortices and other quantity processing networks. These timing maps were partially left lateralized and widely spread, from occipital visual areas through parietal multisensory areas to frontal action planning areas. Responses to event duration and frequency were closely linked. As in sensory cortical maps, response precision varied systematically with timing preferences, and timing selectivity systematically varied between maps. Progressing from posterior to anterior maps, responses to multiple events were increasingly integrated, response selectivity narrowed, and responses focused increasingly on the middle of the presented timing range. These timing maps largely overlap with numerosity and visual field map networks. In both visual timing map and visual field map networks, selective responses and topographic map organization may facilitate hierarchical transformations by allowing neural populations to interact over minimal distances.

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Functional magnetic resonance imaging (fMRI) was used to estimate neuronal activity in the primary somatosensory cortex of six participants undergoing cutaneous tactile stimulation on skin areas spread across the entire body. Differences between the accepted somatotopic maps derived from Penfield's work and those generated by this fMRI study were sought, including representational transpositions or replications across the cortex. MR-safe pneumatic devices mimicking the action of a Wartenberg wheel supplied touch stimuli in eight areas. Seven were on the left side of the body: foot, lower, and upper leg, trunk beneath ribcage, anterior forearm, middle fingertip, and neck above the collarbone. The eighth area was the glabella. Activation magnitude was estimated as the maximum cross-correlation coefficient at a certain phase shift between ideal time series and measured blood oxygen level dependent (BOLD) time courses on the cortical surface. Maximally correlated clusters associated with each cutaneous area were calculated, and cortical magnification factors were estimated. Activity correlated to lower limb stimulation was observed in the paracentral lobule and superomedial postcentral region. Correlations to upper extremity stimulation were observed in the postcentral area adjacent to the motor hand knob. Activity correlated to trunk, face and neck stimulation was localized in the superomedial one-third of the postcentral region, which differed from Penfield's cortical homunculus.

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Neurobiological systems rely on hierarchical and modular architectures to carry out intricate computations using minimal resources. A prerequisite for such systems to operate adequately is the capability to reliably and efficiently transfer information across multiple modules. Here, we study the features enabling a robust transfer of stimulus representations in modular networks of spiking neurons, tuned to operate in a balanced regime. To capitalize on the complex, transient dynamics that such networks exhibit during active processing, we apply reservoir computing principles and probe the systems' computational efficacy with specific tasks. Focusing on the comparison of random feed-forward connectivity and biologically inspired topographic maps, we find that, in a sequential set-up, structured projections between the modules are strictly necessary for information to propagate accurately to deeper modules. Such mappings not only improve computational performance and efficiency, they also reduce response variability, increase robustness against interference effects, and boost memory capacity. We further investigate how information from two separate input streams is integrated and demonstrate that it is more advantageous to perform non-linear computations on the input locally, within a given module, and subsequently transfer the result downstream, rather than transferring intermediate information and performing the computation downstream. Depending on how information is integrated early on in the system, the networks achieve similar task-performance using different strategies, indicating that the dimensionality of the neural responses does not necessarily correlate with nonlinear integration, as predicted by previous studies. These findings highlight a key role of topographic maps in supporting fast, robust, and accurate neural communication over longer distances. Given the prevalence of such structural feature, particularly in the sensory systems, elucidating their functional purpose remains an important challenge toward which this work provides relevant, new insights. At the same time, these results shed new light on important requirements for designing functional hierarchical spiking networks.

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Eph receptors play pivotal roles in the axon guidance of retinal ganglion cells (RGCs) at the optic chiasm and the establishment of the topographic retinocollicular map. We previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) is specifically involved in the control of retinotectal projections in chicks through the dephosphorylation of EphA and EphB receptors. We subsequently revealed that all the mouse R3 subfamily members (PTPRB, PTPRH, PTPRJ, and PTPRO) of the receptor protein tyrosine phosphatase (RPTP) family inhibited Eph receptors as their substrates in cultured mammalian cells. We herein investigated the functional roles of R3 RPTPs in the projection of mouse retinal axon of both sexes. Ptpro and Ptprj were expressed in mouse RGCs; however, Ptprj expression levels were markedly higher than those of Ptpro Consistent with their expression levels, Eph receptor activity was significantly enhanced in Ptprj-knock-out (Ptprj-KO) retinas. In Ptprj-KO and Ptprj/Ptpro-double-KO (DKO) mice, the number of retinal axons that projected ipsilaterally or to the contralateral eye was significantly increased. Furthermore, retinal axons in Ptprj-KO and DKO mice formed anteriorly shifted ectopic terminal zones in the superior colliculus (SC). We found that c-Abl (Abelson tyrosine kinase) was downstream of ephrin-Eph signaling for the repulsion of retinal axons at the optic chiasm and in the SC. c-Abl was identified as a novel substrate for PTPRJ and PTPRO, and the phosphorylation of c-Abl was upregulated in Ptprj-KO and DKO retinas. Thus, PTPRJ regulates retinocollicular projections in mice by controlling the activity of Eph and c-Abl kinases.SIGNIFICANCE STATEMENT Correct retinocollicular projection is a prerequisite for proper vision. Eph receptors have been implicated in retinal axon guidance at the optic chiasm and the establishment of the topographic retinocollicular map. We herein demonstrated that protein tyrosine phosphatase receptor type J (PTPRJ) regulated retinal axonal projections by controlling Eph activities. The retinas of Ptprj-knock-out (KO) and Ptpro/Ptprj double-KO mice exhibited significantly enhanced Eph activities over those in wild-type mice, and their axons showed defects in pathfinding at the chiasm and retinocollicular topographic map formation. We also revealed that c-Abl (Abelson tyrosine kinase) downstream of Eph receptors was regulated by PTPRJ. These results indicate that the regulation of the ephrin-Eph-c-Abl axis by PTPRJ plays pivotal roles in the proper central projection of retinal axons during development.

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This paper presents the effort of collecting and curating a data set of 15461 molecules tested against the malaria parasite, with robust activity and mode of action annotations. The set is compiled from in-house experimental data and the public ChEMBL database subsets. We illustrate the usefulness of the dataset by building QSAR models for antimalarial activity and QSPR models for modes of actions, as well as by the analysis of the chemical space with the Generative Topographic Mapping method. The GTM models perform well in prediction of both activity and mode of actions, on par with the classical SVM methods. The visualization of obtained maps helps to understand the distribution of molecules corresponding to different modes of action: molecules with similar targets are located close to each other on the map. Therefore, this analysis may suggest new modes of action for non-annotated or even annotated compounds. In perspective, this can be used as a tool for prediction of both antimalarial activity and target for novel, untested compounds.

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Acetylcholine is an important neurotransmitter for the regulation of visual attention, plasticity, and perceptual learning. It is released in the visual cortex predominantly by cholinergic projections from the basal forebrain, where stimulation may produce potentiation of visual processes. However, little is known about the fine organization of these corticopetal projections, such as whether basal forebrain neurons projecting to the primary and secondary visual cortical areas (V1 and V2, respectively) are organized retinotopically. The aim of this study was to map these basal forebrain-V1/V2 projections. Microinjections of the fluorescent retrograde tracer cholera toxin b fragment in different sites within V1 and V2 in Long-Evans rats were performed. Retrogradely labeled cell bodies in the horizontal and vertical limbs of the diagonal band of Broca (HDB and VDB, respectively), nucleus basalis magnocellularis, and substantia innominata (SI), were mapped ex vivo with a computer-assisted microscope stage controlled by stereological software. Choline acetyltranferase immunohistochemistry was used to identify cholinergic cells. Our results showed a predominance of cholinergic projections coming from the HDB. These projections were not retinotopically organized but projections to V1 arised from neurons located in the anterior HDB/SI whereas projections to V2 arised from neurons located throughout the whole extent of HDB/SI. The absence of a clear topography of these projections suggests that BF activation can stimulate visual cortices broadly.

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This work describes a procedure to build generative topographic maps (GTM) as 2D representation of the conformational space (CS) of dipeptides. GTMs with excellent propensities to support highly predictive landscapes of various conformational properties were reported for three dipeptides (AA, KE and KR). CS monitoring via GTMproceeds through the projection of conformer ensembles on the map, producing cumulated responsibility (CR) vectors characteristic of the CS areas covered by the ensemble. Overlap of the CS areas visited by two distinct simulations can be expressed by the Tanimoto coefficient Tc of the associated CRs. This idea was used to monitor the reproducibility of the stochastic evolutionary conformer generation process implemented in S4MPLE. It could be shown that conformers produced by <500 S4MPLE runs reproducibly cover the relevant CS zone at given setup of the driving force field. The propensity of a simulation to visit the native CS zone can thus be quantitatively estimated, as the Tc score with respect to the "native" CR, as defined by the ensemble of dipeptide geometries extracted from PDB proteins. It could be shown that low-energy CS regions were indeed found to fall within the native zone. The Tc overlap score behaved as a smooth function of force field parameters. This opens the perspective of a novel force field parameter tuning procedure, bound to simultaneously optimize the behavior of the in Silico simulations for every possible dipeptide.

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Brain regions are often topographically connected: nearby locations within one brain area connect with nearby locations in another area. Mapping these connection topographies, or 'connectopies' in short, is crucial for understanding how information is processed in the brain. Here, we propose principled, fully data-driven methods for mapping connectopies using functional magnetic resonance imaging (fMRI) data acquired at rest by combining spectral embedding of voxel-wise connectivity 'fingerprints' with a novel approach to spatial statistical inference. We apply the approach in human primary motor and visual cortex, and show that it can trace biologically plausible, overlapping connectopies in individual subjects that follow these regions' somatotopic and retinotopic maps. As a generic mechanism to perform inference over connectopies, the new spatial statistics approach enables rigorous statistical testing of hypotheses regarding the fine-grained spatial profile of functional connectivity and whether that profile is different between subjects or between experimental conditions. The combined framework offers a fundamental alternative to existing approaches to investigating functional connectivity in the brain, from voxel- or seed-pair wise characterizations of functional association, towards a full, multivariate characterization of spatial topography.

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