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A Systematic Nomenclature for the Drosophila Ventral Nervous System

The fruit fly, Drosophila melanogaster, is an established and powerful model system for neuroscience research with wide relevance in biology and medicine. Until recently, research on the Drosophila brain was hindered by the lack of a complete and uniform nomenclature. Recognising this problem, the Insect Brain Name Working Group produced an authoritative hierarchical nomenclature system for the adult insect brain, using Drosophila melanogaster as the reference framework, with other taxa considered to ensure greater consistency and expandability (Ito et al., 2014). Here, we extend this nomenclature system to the sub-gnathal regions of the adult Drosophila nervous system, thus providing a systematic anatomical description of the ventral nervous system (VNS). This portion of the nervous system includes the thoracic and abdominal neuromeres that were not included in the original work and contains the motor circuits that play essential roles in most fly behaviours.

neuroscience

Modelling Theta-Band Connectivity Between Occipital And Frontal Lobes: A Methodological MEG Study

Measuring functional connectivity between cortical regions of the human brain has become an important area of research. Modern theory suggests that brain networks exhibit non-stationarity, constantly forming and reforming depending on task demands. A robust means of determining effective connectivity in the short-lived neural responses that occur in event related paradigms would allow the investigation of event related cortico-cortical dynamics. We present such a mathematical model of wave propagation, motivated by current neuroscience literature, and demonstrate the utility of the method in a clinical sample of schizophrenia patients. MEG data were acquired in 10 patients with schizophrenia and 12 healthy controls during a relevance modulation task. Data were filtered into the theta band (4-8Hz) and source localised using a beamformer. The model was implemented using Fourier analysis methods which uncovered an event related travelling wave moving from the visual to frontal cortices. The model was validated using Monte Carlo phase randomisation and compared with another plausible model of wave propagation in the cortex. Results from the clinical sample revealed that wave speed was modulated by task condition and patients were found to have less difference between conditions (ANOVA revealing a significant interaction between group and condition, p<0.05). In conclusion, our method provides a simple and robust means to investigate event related cortico-cortical brain dynamics in individuals and groups in the task positive state.

neuroscience

When Group Means Fail: Can One Size Fit All?

The present study examined whether a cognitive process model that is inferred based on group data holds, and is meaningful, at the level of the individual person. Investigation of this issue is tantamount to questioning that the same set and configuration of cognitive processes is present within all individuals, a usually untested assumption in standard group-based experiments. Search from memory as assessed with the Sternberg memory scanning paradigm is among the most widely studied phenomena in cognitive psychology. According to the original memory scanning model, search is serial and exhaustive. Here we critically examined the validity of this model across individuals and practice. 32 younger adults completed 1488 trials of the Sternberg task distributed over eight sessions. In the first session, group data followed the pattern predicted by the original model, replicating earlier findings. However, data from the first session were not sufficiently reliable for identifying whether each individual complied with the serial exhaustive search model. In sessions six to eight, when participants performed near asymptotic levels of performance, between-person differences were reliable, group data deviated substantially from the original memory search model, and the model fit only 13 of the 32 participants data. Our findings challenge the proposition that one general memory search process exists within a group of healthy younger adults, and questions the testability of this proposition at the individual level in single-session experiments. Implications for cognitive psychology and cognitive neuroscience are discussed with reference to earlier work emphasizing the explicit consideration of potentially existent individual differences.

neuroscience

Just above chance: is it harder to decode information from human prefrontal cortex BOLD signals?

Understanding the nature and form of prefrontal cortex representations that support flexible behavior is an important open problem in cognitive neuroscience. In humans, multi-voxel pattern analysis (MVPA) of fMRI BOLD measurements has emerged as an important approach for studying neural representations. An implicit, untested assumption underlying many PFC MVPA studies is that the base rate of decoding information from PFC BOLD activity patterns is similar to that of other brain regions. Here we estimate these base rates from a meta-analysis of published MVPA studies and show that the PFC has a significantly lower base rate for decoding than visual sensory cortex. Our results have implications for the design and interpretation of MVPA studies of prefrontal cortex, and raise important questions about its functional organization.

neuroscience

Identification Of Animal Behavioral Strategy By Inverse Reinforcement Learning ~ Its Application To Thermotaxis In C. elegans ~

Animals are able to reach a desired state in an environment by controlling various behavioral patterns. Identification of the behavioral strategy used for this control is important for understanding animals decision-making and is fundamental to dissect information processing done by the nervous system. However, methods for quantifying such behavioral strategies have not been fully established. In this study, we developed an inverse reinforcement-learning (IRL) framework to identify an animals behavioral strategy from behavioral time-series data. As a particular target, we applied this framework to C. elegans thermotactic behavior; after cultivation at a constant temperature with or without food, the fed and starved worms prefer and avoid from the cultivation temperature on a thermal gradient, respectively. Our IRL approach revealed that the fed worms used both absolute and temporal derivative of temperature and that their strategy comprised mixture of two strategies: directed migration (DM) and isothermal migration (IM). The DM is a strategy that the worms efficiently reach to specific temperature, which explained thermotactic behaviors of the fed worms. The IM is a strategy that the worms track along a constant temperature, which reflects isothermal tracking well observed in previous studies. We also showed the neural basis underlying the strategies, by applying our method to thermosensory neuron-deficient worms. In contrast to fed animals, the strategy of starved animals indicated that they escaped the cultivation temperature using only absolute, but not temporal derivative of temperature. Thus, our IRL-based approach is capable of identifying animal strategies from behavioral time-series data and will be applicable to wide range of behavioral studies, including decision-making of other organisms.\n\nAuthor SummaryUnderstanding animal decision-making has been a fundamental problem in neuroscience and behavioral ecology. Many studies analyze actions that represent decision-making in behavioral tasks, in which rewards are artificially designed with specific objectives. However, it is impossible to extend this artificially designed experiment to a natural environment, because in a natural environment, the rewards for freely-behaving animals cannot be clearly defined. To this end, we must reverse the current paradigm so that rewards are identified from behavioral data. Here, we propose a new reverse-engineering approach (inverse reinforcement learning) that can estimate a behavioral strategy from time-series data of freely-behaving animals. By applying this technique with thermotaxis in C. elegans, we successfully identified the reward-based behavioral strategy.

neuroscience

EyeBallGUI: A Tool For Visual Inspection And Binary Marking of Multi-Channel Bio-Signals

A wide range of studies in human neuroscience rely on the analysis of electrophysiological bio-signals such as electroencephalogram (EEG) where customized data analysis may require supervised artefact rejection, binary marking through visual inspection, selection of noise and artefact samples for pre-processing algorithms, and selection of clinically-relevant signal segments in neurological conditions. Nevertheless, the existing preprocessing tools do not provide the needed flexibility to handle such tasks efficiently. We therefore developed a free open-source Graphical User Interface (GUI), EyeBallGUI, that allows visualization and flexible, manual marking (binary classification) of multi-channel bio-signal data. EyeBallGUI, developed for MATLAB(R), allows the user to interactively and accurately inspect and mark multi-channel digitized data with no restriction on marking periods of data in subsets of channels (a restriction in place in existing tools). The new tool facilitates precise, manual marking of bio-signals by allowing any desired segment of data to be marked in any subset of channels. It is therefore of utility in circumstances where such flexibility is essential. The developed GUI is an auxiliary analysis tool that shall facilitate neural signal (pre-)processing applications where it is desirable to perform accurate supervised artefact rejection, flexible data marking for increased data retention yield, extraction of specific signal segments by expert users from sample data, or labeling of data for clinical and scientific research purposes.

neuroscience

Salience network dynamics underlying successful resistance of temptation

Self-control and the ability to resist temptation are critical for successful completion of long-term goals. Contemporary models in cognitive neuroscience emphasize the primary role of prefrontal cognitive control networks in aligning behavior with such goals. Here we use gaze pattern analysis and dynamic functional connectivity fMRI data to explore how individual differences in the ability to resist temptation are related to intrinsic brain dynamics of the cognitive control and salience networks. Behaviorally, individuals exhibit greater gaze distance from target location (e.g. higher distractibility) during presentation of tempting erotic images compared with neutral images. Individuals whose intrinsic dynamic functional connectivity patterns gravitate towards configurations in which salience detection systems are less strongly coupled with visual systems resist tempting distractors more effectively. The ability to resist tempting distractors was not significantly related to intrinsic dynamics of the cognitive control network. These results suggest that susceptibility to temptation is governed in part by individual differences in salience network dynamics, and provide novel evidence for involvement of brain systems outside canonical cognitive control networks in contributing to individual differences in self-control.

neuroscience

Mass univariate testing biases the detection of interaction effects in whole-brain analysis of variance.

Whole-brain analysis of variance (ANOVA) is a common analytic approach in cognitive neuroscience. Researchers are often interested in exploring whether brain activity reflects to the interaction of two factors. Disordinal interactions -- where there is a reversal of the effect of one independent variable at a level of a second independent variable -- are common in the literature. It is well established in power-analyses of factorial ANOVAs that certain patterns of interactions, such as disordinal (e.g., cross-over interactions) require less power than others to detect. This fact, combined with the perils of mass univariate testing suggests that testing for interactions in whole-brain ANOVAs, may be biased towards the detection of disordinal interactions. Here, we report on a series of simulated analysis --including whole-brain fMRI data using realistic multi-source noise parameters-- that demonstrate a bias towards the detection of disordinal interactions in mass-univariate contexts. Moreover, results of these simulations indicated that spurious disordinal interactions are found at common thresholds and cluster sizes at the group level. Moreover, simulations based on implanting true ordinal interaction effects can nevertheless appear like crossover effects at realistic levels of signal-to-noise ratio (SNR) when performing mass univariate testing at the whole-brain level, potentially leading to erroneous conclusions when interpreted as is. Simulations of varying sample sizes and SNR levels show that this bias is driven primarily by SNR and larger sample sizes do little to ameliorate this issue. Together, the results of these simulations argue for caution when searching for ordinal interactions in whole-brain ANOVA.

neuroscience

Attention is required for knowledge-based sequential grouping of syllables into words

How the brain sequentially groups sensory events into temporal chunks and how this process is modulated by attention are fundamental questions in cognitive neuroscience. Sequential grouping includes bottom-up primitive grouping and top-down knowledge-based grouping. In speech perception, grouping acoustic features into syllables can rely on bottom-up acoustic continuity cues but grouping syllables into words critically relies on the listeners lexical knowledge. This study investigates whether top-down attention is required to apply lexical knowledge to group syllables into words, by concurrently monitoring neural entrainment to syllables and words using electroencephalography (EEG). When attention is directed to a competing speech stream or cross-modally to a silent movie, neural entrainment to syllables is weakened but neural entrainment to words largely diminishes. These results strongly suggest that knowledge-based grouping of syllables into words requires top-down attention and is a bottleneck for the neural processing of unattended speech.

neuroscience

Local-Global Parcellation of the Human Cerebral Cortex From Intrinsic Functional Connectivity MRI

A central goal in systems neuroscience is the parcellation of the cerebral cortex into discrete neurobiological \"atoms\". Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility of in-vivo human cortical parcellation. Almost all previous parcellations relied on one of two approaches. The local gradient approach detects abrupt transitions in functional connectivity patterns. These transitions potentially reflect cortical areal boundaries defined by histology or visuotopic fMRI. By contrast, the global similarity approach clusters similar functional connectivity patterns regardless of spatial proximity, resulting in parcels with homogeneous (similar) rs-fMRI signals. Here we propose a gradient-weighted Markov Random Field (gwMRF) model integrating local gradient and global similarity approaches. Using task-fMRI and rs-fMRI across diverse acquisition protocols, we found gwMRF parcellations to be more homogeneous than four previously published parcellations. Furthermore, gwMRF parcellations agreed with the boundaries of certain cortical areas defined using histology and visuotopic fMRI. Some parcels captured sub-areal (somatotopic and visuotopic) features that likely reflect distinct computational units within known cortical areas. These results suggest that gwMRF parcellations reveal neurobiologically meaningful features of brain organization and are potentially useful for future applications requiring dimensionality reduction of voxel-wise fMRI data. Multi-resolution parcellations generated from 1489 participants are available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Schaefer2018_LocalGlobal)

neuroscience

Revisiting Chemoaffinity Theory: Chemotactic Implementation Of Topographic Axonal Projection

Neural circuits are wired by chemotactic migration of growth cones guided by extracellular guidance cue gradients. How growth cone chemotaxis builds the macroscopic structure of the neural circuit is a fundamental question in neuroscience. I addressed this issue in the case of the ordered axonal projections called topographic maps in the retinotectal system. In the retina and tectum, the erythropoietin-producing hepatocellular (Eph) receptors and their ligands, the ephrins, are expressed in gradients. According to Sperrys chemoaffinity theory, gradients in both the source and target areas enable projecting axons to recognize their proper terminals, but how axons chemotactically decode their destinations is largely unknown. To identify the chemotactic mechanism of topographic mapping, I developed a mathematical model of intracellular signaling in the growth cone that focuses on the growth cones unique chemotactic property of being attracted or repelled by the same guidance cues in different biological situations. The model presented mechanism by which the retinal growth cone reaches the correct terminal zone in the tectum through alternating chemotactic response between attraction and repulsion around a preferred concentration. The model also provided a unified understanding of the contrasting relationships between receptor expression levels and preferred ligand concentrations in EphA/ephrinA- and EphB/ephrinB-encoded topographic mappings. Thus, this study redefines the chemoaffinity theory in chemotactic terms.\n\nAuthor SummaryThis study revisited the chemoaffinity theory for topographic mapping in terms of chemotaxis. According to this theory, the axonal growth cone projects to specific targets based on positional information encoded by chemical gradients in both source and target areas. However, the mechanism by which the chemotactic growth cone recognizes its proper terminal site remains elusive. To unravel this mystery, I mathematically modeled a growth cone exhibiting concentration-dependent attraction and repulsion to chemotactic cues. The model identified a novel growth cone guidance mechanism in topographic mapping, highlighting the importance of the growth cones unique ability to alternate between attraction and repulsion. Furthermore, an extension of the model provided possible molecular mechanisms for contrasting two types of topographic mappings observed in the retinotectal system.

neuroscience

Gravitational Signals Underlie Tonic Muscle Activity During Goal-Directed Reaching

Human reaching movements require complex muscle activations to produce the forces necessary to move the limb in a controlled manner. How gravity and the complex kinetic properties of the limb contribute to the generation of the muscle activation pattern by the central nervous system (CNS) is a long-standing question in neuroscience. To address this question, muscle activity is often subdivided into static and phasic components. The former is thought to be related to posture maintenance and transitions between postures. The latter represents the remainder of muscle activity and is thought to be related to active movement production and the compensation for the kinetic properties of the limb. In the present study, we directly addressed how this subdivision of muscle activity into static and phasic components is related to the corresponding components of active muscle torques. Eight healthy subjects pointed in virtual reality to visual targets arranged to create a standard center-out reaching task in three dimensions. Muscle activity and motion capture data were synchronously collected during the movements. The motion capture data were used to calculate gravitational and dynamic components of active muscle torques using a dynamic model of the arm with 5 degrees of freedom. Principal Component Analysis (PCA) was then applied to muscle activity and the torque components, separately, to reduce the dimensionality of the data. Muscle activity was also reconstructed from gravitational and dynamic torque components. Results show that the gravitational and dynamic components of muscle torque represent a significant amount of variance in muscle activity. This method could be used to identify static and phasic components of muscle activity using muscle torques. The contribution of both components to the overall muscle activity was largely equal, unlike their relative contribution to active muscle torques, which may reflect a neural control strategy.

neuroscience

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

neuroscience

Removal Of Inhibition Uncovers Latent Movement Preparation Dynamics

The motor system prepares for movements well in advance of their execution. In the gaze control system, premotor neurons that produce a burst of activity for the movement are also active leading up to the saccade. The dynamics of preparatory neural activity have been well described by stochastic accumulator models, and variability in the accumulation dynamics has been shown to be correlated with reaction times of the eventual saccade, but it is unclear whether this activity is purely preparatory in nature or has features indicative of a hidden movement command. We explicitly tested whether preparatory neural activity in premotor neurons of the primate superior colliculus has \"motor potential\". We removed inhibition on the saccadic system using reflex blinks, which turn off downstream gating, and found that saccades can be initiated before underlying activity reaches levels seen under normal conditions. Accumulating low-frequency activity was predictive of eye movement dynamics tens of milliseconds in advance of the actual saccade, indicating the presence of a latent movement command. We also show that reaching threshold is not a necessary condition for movement initiation, contrary to the postulates of accumulation-to-threshold models. The results bring into question extant models of saccade generation and support the possibility of a concurrent representation for movement preparation and generation.\n\nSignificance StatementHow the brain plans for upcoming actions before deciding to initiate them is a central question in neuroscience. Popular theories suggest that movement planning and execution occur in serial stages, separated by a decision boundary in neural activity space (e.g., \"threshold\"), which needs to be crossed before the movement is executed. By removing inhibitory gating on the motor system, we show here that the activity required to initiate a saccade can be flexibly modulated. We also show that evolving activity during movement planning is a hidden motor command. The results have important implications for our understanding of how movements are generated, in addition to providing useful information for decoding movement intention based on planning-related activity.\n\nImpact StatementNon-invasive disinhibition of the oculomotor system shows that ongoing preparatory activity in the superior colliculus has movement-generating potential and need not rise to threshold in order to produce a saccade.

neuroscience

A Complete Electron Microscopy Volume Of The Brain Of Adult Drosophila melanogaster

Drosophila melanogaster has a rich repertoire of innate and learned behaviors. Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping. Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM. We developed a custom high-throughput EM platform and imaged the entire brain of an adult female fly. We validated the dataset by tracing brain-spanning circuitry involving the mushroom body (MB), intensively studied for its role in learning. Here we describe the complete set of olfactory inputs to the MB; find a new cell type providing driving input to Kenyon cells (the intrinsic MB neurons); identify neurons postsynaptic to Kenyon cell dendrites; and find that axonal arbors providing input to the MB calyx are more tightly clustered than previously indicated by light-level data. This freely available EM dataset will significantly accelerate Drosophila neuroscience.\n\nHIGHLIGHTS- A complete adult fruit fly brain was imaged, using electron microscopy (EM)\n- The EM volume enables brain-spanning mapping of neuronal circuits at the synaptic level\n- Olfactory projection neurons cluster more tightly in mushroom body calyx than expected from light-level data\n- The primary postsynaptic targets of Kenyon cells (KCs) in the MB are other KCs, as well as the anterior paired lateral (APL) neuron\n- A newly discovered cell type, MB-CP2, integrates input from several sensory modalities and provides microglomerular input to KCs in MB calyx\n- A software pipeline was created in which EM-traced skeletons can be searched for within existing large-scale light microscopy (LM) databases of neuronal morphology, facilitating cell type identification and discovery of relevant genetic driver lines

neuroscience

Inferential Pitfalls In Decoding Neural Representations

A key challenge for cognitive neuroscience is to decipher the representational schemes of the brain. A recent class of decoding algorithms for fMRI data, stimulus-feature-based encoding models, is becoming increasingly popular for inferring the dimensions of neural representational spaces from stimulus-feature spaces. We argue that such inferences are not always valid, because decoding can occur even if the neural representational space and the stimulus-feature space use different representational schemes. This can happen when there is a systematic mapping between them, as shown by two simulations. In one simulation, we successfully decoded the binary representation of numbers from their decimal features. Since binary and decimal number systems use different representations, we cannot conclude that the binary representation encodes decimal features. In the second simulation, we successfully decoded the HSV color representation from the RGB representation of colors, even though these color spaces have different geometries and their dimensions have different interpretations. Detailed analysis of the predicted colors showed systematic deviations from the ground truth despite the high decoding accuracy, indicating that decoding accuracy on its own is not sufficient for making representational inferences. The same argument applies to the decoding of neural patterns from stimulus-feature spaces and we urge caution in inferring the nature of the neural code from such methods. We discuss ways to overcome these inferential limitations.

neuroscience

The Brain As An Efficient And Robust Adaptive Learner

Understanding how the brain learns to compute functions reliably, efficiently and robustly with noisy spiking activity is a fundamental challenge in neuroscience. Most sensory and motor tasks can be described as dynamical systems and could presumably be learned by adjusting connection weights in a recurrent biological neural network. However, this is greatly complicated by the credit assignment problem for learning in recurrent networks, e.g. the contribution of each connection to the global output error cannot be determined based only on locally accessible quantities to the synapse. Combining tools from adaptive control theory and efficient coding theories, we propose that neural circuits can indeed learn complex dynamic tasks with local synaptic plasticity rules as long as they associate two experimentally established neural mechanisms. First, they should receive top-down feedbacks driving both their activity and their synaptic plasticity. Second, inhibitory interneurons should maintain a tight balance between excitation and inhibition in the circuit. The resulting networks could learn arbitrary dynamical systems and produce irregular spike trains as variable as those observed experimentally. Yet, this variability in single neurons may hide an extremely efficient and robust computation at the population level.

neuroscience

Different Brain Networks Underlying Intelligence In Autism Spectrum Disorders And Typically Developing Children

BackgroundThere has been sustained clinical and cognitive neuroscience research interest in how network correlates of brain-behaviour relationships might be altered in Autism Spectrum Disorders (ASD) and other neurodevelopmental disorders. As previous work has mostly focused on adults, the nature of whole-brain connectivity networks underlying intelligence in pediatric cohorts with abnormal neurodevelopment requires further investigation.\n\nMethodsWe used network-based statistics (NBS) to examine the association between resting-state functional Magnetic Resonance Imaging (fMRI) connectivity and fluid intelligence ability in male children (n=50) with Autism Spectrum Disorders (ASD; M=10.45, SD=1.58 years and in controls (M=10.38, SD=0.96 years) matched on fluid intelligence performance, age and sex. Repeat analyses were performed in independent sites for validation and replication.\n\nResultsDespite being equivalent on fluid intelligence ability to strictly matched neurotypical controls, boys with ASD displayed a subnetwork of significantly increased associations between functional connectivity and fluid intelligence. Between-group differences remained significant at higher edge thresholding, and results were validated in independent-site replication analyses in an equivalent age and sex-matched cohort with ASD. Regions consistently implicated in atypical connectivity correlates of fluid intelligence in ASD were the angular gyrus, posterior middle temporal gyrus, occipital and temporo-occipital regions.\n\nConclusionDevelopment of fluid intelligence neural correlates in young ASD males is aberrant, with an increased strength in intrinsic connectivity association during childhood. Alterations in whole-brain network correlates of fluid intelligence in ASD may be a compensatory mechanism that allows equal task performance to neurotypical peers.

neuroscience