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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 343 records · Page 19Linked to original sources

Flexible and efficient simulation-based inference for models of decision-making

Inferring parameters of computational models that capture experimental data is a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model--however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed effciently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Here, we provide an effcient SBI method for models of decision-making. Our approach, Mixed Neural Likelihood Estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator, and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model (DDM) and compare its performance to a recently proposed method for SBI on DDMs, called Likelihood Approximation Networks (LANs, Fengler et al. 2021). We show that MNLE is substantially more effcient than LANs: it achieves similar likelihood accuracy with six orders of magnitude fewer training simulations, and is substantially more accurate than LANs when both are trained with the same budget. This enables researchers to train MNLE on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.

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pyNeurode: a real-time neural signal processing framework

Accurate decoding of neural signals often requires assigning extracellular waveforms acquired on the same electrode to their originating neurons, a process known as spike sorting. While many offline sorters are available, accurate online sorting of spikes with many channels is still a challenging problem. Existing online sorters either use simple algorithms with low accuracy, can only process a handful of channels, or depend on a complex runtime environment that is difficult to set up. We have developed a state-of-the-art online spike sorting platform in Python that enables large-scale, fully automatic real-time spike sorting and decoding on hundreds of channels. Our system is cross-platform and works seamlessly with the Open Ephys suite of open-source hardware and software widely used in many neuroscience laboratories worldwide. It also comes with a user-friendly graphical user interface to monitor the cluster quality, spike waveforms and neuronal firing rate. Our platform has comparable accuracy to offline sorters and can achieve an end-to-end sorting latency of around 160 ms for 128-channel signals. It will be useful for research in fundamental neuroscience, closed-loop feedback neuromodulation and brain-computer interfaces.

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Time-resolved parameterization of aperiodic and periodic brain activity

Macroscopic neural dynamics comprise both aperiodic and periodic signal components. Recent advances in parameterizing neural power spectra offer practical tools for evaluating these features separately. Although neural signals vary dynamically and express non-stationarity in relation to ongoing behaviour and perception, current methods yield static spectral decompositions. Here, we introduce Spectral Parameterization Resolved in Time (SPRiNT) as a novel method for decomposing complex neural dynamics into periodic and aperiodic spectral elements in a time- resolved manner. First, we demonstrate with naturalistic synthetic data SPRiNTs capacity to reliably recover time-varying spectral features. We emphasize SPRiNTs specific strengths compared to other time-frequency parameterization approaches based on wavelets. Second, we use SPRiNT to illustrate how aperiodic spectral features fluctuate across time in empirical resting-state electroencephalography data (n = 178), and relate the observed changes in aperiodic parameters over time to participants demographics and behaviour. Lastly, we use SPRiNT to demonstrate how aperiodic dynamics relate to movement behaviour in intracranial recordings in rodents. We foresee SPRiNT responding to growing neuroscientific interests in the parameterization of time-varying neural power spectra and advancing the quantitation of complex neural dynamics at the natural time scales of behaviour. Significance StatementThe new method and reported findings address a growing interest in neuroscience for research tools that can reliably decompose brain activity at the mesoscopic scale into interpretable components. We show that the new approach proposed is capable of tracking transient, dynamic spectral (aperiodic and periodic) components across time, both in synthetic data and in in vivo experimental data. We anticipate that this novel technique, SPRiNT, will enable new neuroscience inquiries that reconcile multifaceted neural dynamics with complex behaviour.

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GLMsingle: a toolbox for improving single-trial fMRI response estimates

Advances in modern artificial intelligence (AI) have inspired a paradigm shift in human neuroscience, yielding large-scale functional magnetic resonance imaging (fMRI) datasets that provide high-resolution brain responses to tens of thousands of naturalistic visual stimuli. Because such experiments necessarily involve brief stimulus durations and few repetitions of each stimulus, achieving sufficient signal-to-noise ratio can be a major challenge. We address this challenge by introducing GLMsingle, a scalable, user-friendly toolbox available in MATLAB and Python that enables accurate estimation of single-trial fMRI responses (glmsingle.org). Requiring only fMRI time-series data and a design matrix as inputs, GLMsingle integrates three techniques for improving the accuracy of trial-wise general linear model (GLM) beta estimates. First, for each voxel, a custom hemodynamic response function (HRF) is identified from a library of candidate functions. Second, cross-validation is used to derive a set of noise regressors from voxels unrelated to the experimental paradigm. Third, to improve the stability of beta estimates for closely spaced trials, betas are regularized on a voxel-wise basis using ridge regression. Applying GLMsingle to the Natural Scenes Dataset and BOLD5000, we find that GLMsingle substantially improves the reliability of beta estimates across visually-responsive cortex in all subjects. Furthermore, these improvements translate into tangible benefits for higher-level analyses relevant to systems and cognitive neuroscience. Specifically, we demonstrate that GLMsingle: (i) improves the decorrelation of response estimates between trials that are nearby in time; (ii) enhances representational similarity between subjects both within and across datasets; and (iii) boosts one-versus-many decoding of visual stimuli. GLMsingle is a publicly available tool that can significantly improve the quality of past, present, and future neuroimaging datasets that sample brain activity across many experimental conditions.

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Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses. HighlightsO_LIAchieved sub-millimeter localization accuracy of subject-wise brain region C_LIO_LIPropose a dedicated non-invasive multi-modal subject-specific registration pipeline C_LIO_LIConstruct brain coordinate system in AC-PC and grayordinate spaces C_LIO_LIEstablish multi-modal MRI and CT brain and cortical templates, MarmosetRIKEN20 C_LIO_LIQuantify intersubject variabilities in marmoset brain C_LIO_LISignificant bias and uncertainty exist in marmoset stereotactic positioning C_LI

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PyZebrascope: an open-source platform for brain-wide neural activity imaging in zebrafish

Understanding how neurons interact across the brain to control animal behaviors is one of the central goals in neuroscience. Recent developments in fluorescent microscopy and genetically-encoded calcium indicators led to the establishment of whole-brain imaging methods in zebrafish, which records neural activity across a brain-wide volume with single-cell resolution. Pioneering studies of whole-brain imaging used custom light-sheet microscopes, and their operation relied on commercially developed and maintained software that is not available globally. Hence it has been challenging to disseminate and develop the technology in the research community. Here, we present PyZebrascope, an open-source Python platform designed for neural activity imaging in zebrafish using light-sheet microscopy. PyZebrascope has intuitive user interfaces and implements essential features for whole-brain imaging, such as two orthogonal excitation beams and eye damage prevention. Its modular architecture allows the inclusion of advanced algorithms for microscope control and image processing. As a proof of concept, we implemented an automatic algorithm for maximizing the image resolution in the brain by precisely aligning the excitation beams to the image focal plane. PyZebrascope enables whole-brain neural activity imaging in fish behaving in a virtual reality environment with a stable high data throughput and low CPU and memory consumption. Thus, PyZebrascope will help disseminate and develop light-sheet microscopy techniques in the neuroscience community and advance our understanding of whole-brain neural dynamics during animal behaviors.

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Distributed network processes account for the majority of variance in localized visual category selectivity

A central goal of neuroscience is to understand how function-relevant brain activations are generated. Here we test the hypothesis that function-relevant brain activations are generated primarily by distributed network flows. We focused on visual processing in human cortex, given the long-standing literature supporting the functional relevance of brain activations in visual cortex regions exhibiting visual category selectivity. We began by using fMRI data from N=352 human participants to identify category-specific responses in visual cortex for images of faces, places, body parts, and tools. We then systematically tested the hypothesis that distributed network flows can generate these localized visual category selective responses. This was accomplished using a recently developed approach for simulating - in a highly empirically constrained manner - the generation of task-evoked brain activations by modeling activity flowing over intrinsic brain connections. We next tested refinements to our hypothesis, focusing on how stimulus-driven network interactions initialized in V1 generate downstream visual category selectivity. We found evidence that network flows directly from V1 were sufficient for generating visual category selectivity, but that additional, globally distributed (whole-cortex) network flows increased category selectivity further. Using null network architectures we also found that each regions unique intrinsic "connectivity fingerprint" was key to the generation of category selectivity. These results generalized across regions associated with all four visual categories tested (bodies, faces, places, and tools), and provide evidence that the human brains intrinsic network organization plays a prominent role in the generation of functionally relevant, localized responses. Author SummaryA fundamental question in neuroscience has persisted for over a century: to what extent do distributed processes drive brain function? The existence of category-selective regions within visual cortex provides long-standing evidence supporting localized computations, wherein specialized functions (e.g., selective responsiveness to face images) are thought to be primarily generated by within-region processes. This account was recently updated to include category selectivity dispersed across visual cortex, in the absence of category-selective regions. Here we provide groundwork evidence demonstrating that locally-exhibited visual-category-selective responses can be accurately generated via distributed activity flowing over globally connected systems. These processes were simulated via empirically-based computational models initialized by stimulus-evoked activity patterns and empirical connectivity matching each category-selective regions unique intrinsic functional connectivity fingerprint. Results demonstrate that activity flowing over the human brains distributed network architecture can account for the generation of category selectivity in visual cortex regions.

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Place cells are non-randomly clustered by field location in CA1 hippocampus

A challenge in both modern and historic neuroscience has been achieving an understanding of neuron circuits, and determining the computational and organizational principles that underlie these circuits. Deeper understanding of the organization of brain circuits and cell types, including in the hippocampus, is required for advances in behavioral and cognitive neuroscience, as well as for understanding principles governing brain development and evolution. In this manuscript, we pioneer a new method to analyze the spatial clustering of active neurons in the hippocampus. We use calcium imaging and a rewarded navigation task to record from 100s of place cells in the CA1 of freely moving rats. We then use statistical techniques developed for and in widespread use in geographic mapping studies, global Morans I and local Morans I to demonstrate that cells that code for similar spatial locations tend to form small spatial clusters. We present evidence that this clustering is not the result of artifacts from calcium imaging, and show that these clusters are primarily formed by cells that have place field around previously rewarded locations. We go on to show that, although cells with similar place fields tend to form clusters, there is no obvious topographic mapping of environmental location onto the hippocampus, such as seen in the visual cortex. Insights into hippocampal organization, as in this study, can elucidate mechanisms underlying motivational behaviors, spatial navigation, and memory formation.

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A Computational Theory of Learning Flexible Reward-Seeking Behavior with Place Cells

An important open question in computational neuroscience is how various spatially tuned neurons, such as place cells, are used to support the learning of reward-seeking behavior of an animal. Existing computational models either lack biological plausibility or fall short of behavioral flexibility when environments change. In this paper, we propose a computational theory that achieves behavioral flexibility with better biological plausibility. We first train a mixture of Gaussian distributions to model the ensemble of firing fields of place cells. Then we propose a Hebbian-like rule to learn the synaptic strength matrix among place cells. This matrix is interpreted as the transition rate matrix of a continuous time Markov chain to generate the sequential replay of place cells. During replay, the synaptic strengths from place cells to medium spiny neurons (MSN) are learned by a temporal-difference like rule to store place-reward associations. After replay, the activation of MSN will ramp up when an animal approaches the rewarding place, so the animal can move along the direction where the MSN activation is increasing to find the rewarding place. We implement our theory into a high-fidelity virtual rat in the MuJoCo physics simulator. In a complex maze, the rat shows significantly better learning efficiency and behavioral flexibility than a rat that implements a neuroscience-inspired reinforcement learning algorithm, deep Q-network.

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Flexing the principal gradient of the cerebral cortex to suit changing semantic task demands

Understanding how thought emerges from the topographical structure of the cerebral cortex is a primary goal of cognitive neuroscience. Recent work has revealed a principal gradient of intrinsic connectivity capturing the separation of sensory-motor cortex from transmodal regions of the default mode network (DMN); this is thought to facilitate memory-guided cognition. However, studies have not explored how this dimension of connectivity changes when conceptual retrieval is controlled to suit the context. We used gradient decomposition of informational connectivity in a semantic association task to establish how the similarity in connectivity across brain regions changes during familiar and more original patterns of retrieval. Multivoxel activation patterns at opposite ends of the principal gradient were more divergent when participants retrieved stronger associations; therefore, when long-term semantic information is sufficient for ongoing cognition, regions supporting heteromodal memory are functionally separated from sensory-motor experience. In contrast, when less related concepts were linked, this dimension of connectivity was reduced in strength as semantic control regions separated from the DMN to generate more flexible and original responses. We also observed fewer dimensions within the neural response towards the apex of the principal gradient when strong associations were retrieved, reflecting less complex or varied neural coding across trials and participants. In this way, the principal gradient explains how semantic cognition is organised in the human cerebral cortex: the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared. Significance statementA central task in neuroscience is to understand how cognition emerges from the topographical structure of cerebral cortex. We used fMRI during a semantic task to assess informational connectivity as participants retrieved stereotypical or more unusual associations. The principal gradient of variation in informational connectivity captured the separation of heteromodal memory regions from unimodal cortex. This separation was reduced when weaker associations were retrieved; these trials also produced higher-dimensional neural responses in heteromodal regions. We conclude that the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared, while more complex and diverse cognition can be generated as this separation in connectivity is reduced.

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Deep Learning-Based Parameter Estimation for Neurophysiological Models of Neuroimaging Data

AO_SCPLOWBSTRACTC_SCPLOWConnectome-based neural mass modelling is the emerging computational neuroscience paradigm for simulating large-scale network dynamics observed in whole-brain activity measurements such as fMRI, M/EEG, and related techniques. Estimating physiological parameters by fitting these models to empirical data is challenging however, due to large network sizes, often physiologically detailed fast-timescale system equations, and the need for long (e.g. tens of minutes) simulation runs. Here we introduce a novel approach to connectome-based neural mass model parameter estimation by employing optimization tools developed for deep learning. We cast the system of differential equations representing both neural and haemodynamic activity dynamics as a deep neural network, implemented within a widely used machine learning programming environment (PyTorch). This allows us to use robust industry-standard optimization algorithms, automatic differentiation for computation of gradients, and other useful functionality. The approach is demonstrated using a connectome-based network with nodal dynamics specified by the two-state RWW mean-field neural mass model equations, which we use here as a model of fMRI-measured activity and correlation fluctuations. Additional optimization constraints are explored and prove fruitful, including restricting the model to domains of parameter space near a bifurcation point that yield metastable dynamics. Using these techniques, we first show robust recovery of physiological model parameters in synthetic data and then, as a proof-of-principle, apply the framework to modelling of empirical resting-state fMRI data from the Human Connectome Project database. For resting state activity, the system can be understood as a deep net that receives uncorrelated noise on its input layer, which is transformed into network-wide modelled functional connectivity on its output layer. This is consistent with the prevailing conception in theoretical neuroscience of resting-state functional connectivity patterns as an emergent phenomenon that is driven by (effectively) random activity fluctuations, which are then in turn spatiotemporally filtered by anatomical connectivity and local neural dynamics.

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Scalable graph analysis tools for the connectomics community

Neuroscientists now have the opportunity to analyze synaptic resolution connectomes that are larger than the memory on single consumer workstations. As dataset size and tissue diversity have grown, there is increasing interest in conducting comparative connectomics research, including rapidly querying and searching for recurring patterns of connectivity across brain regions and species. There is also a demand for algorithm reuse -- applying methods developed for one dataset to another volume. A key technological hurdle is enabling researchers to efficiently and effectively query these diverse datasets, especially as the raw image volumes grow beyond terabyte sizes. Existing community tools can perform such queries and analysis on smaller scale datasets, which can fit locally in memory, but the path to scaling remains unclear. Existing solutions such as neuPrint or FlyBrainLab enable these queries for specific datasets, but there remains a need to generalize algorithms and standards across datasets. To overcome this challenge, we present a software framework for comparative connectomics and graph discovery to make connectomes easy to analyze, even when larger-than-RAM, and even when stored in disparate datastores. This software suite includes visualization tools, a web portal, a connectivity and annotation query engine, and the ability to interface with a variety of data sources and community tools from the neuroscience community. These tools include MossDB (an immutable datastore for metadata and rich annotations); Grand (for prototyping larger-than-RAM graphs); GrandIso-Cloud (for querying existing graphs that exceed the capabilities of a single work-station); and Motif Studio (for enabling the public to query across connectomes). These tools interface with existing frameworks such as neuPrint, graph databases such as Neo4j, and standard data analysis tools such as Pandas or NetworkX. Together, these tools enable tool and algorithm reuse, standardization, and neuroscience discovery.

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CAT - A Computational Anatomy Toolbox for the Analysis of Structural MRI Data

A large range of sophisticated brain image analysis tools have been developed by the neuroscience community, greatly advancing the field of human brain mapping. Here we introduce the Computational Anatomy Toolbox (CAT) - a powerful suite of tools for brain morphometric analyses with an intuitive graphical user interface, but also usable as a shell script. CAT is suitable for beginners, casual users, experts, and developers alike providing a comprehensive set of analysis options, workflows, and integrated pipelines. The available analysis streams - illustrated on an example dataset - allow for voxel-based, surface-based, as well as region-based morphometric analyses. Notably, CAT incorporates multiple quality control options and covers the entire analysis workflow, including the preprocessing of cross-sectional and longitudinal data, statistical analysis, and the visualization of results. The overarching aim of this article is to provide a complete description and evaluation of CAT, while offering a citable standard for the neuroscience community.

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A GPU-based computational framework that bridges Neuron simulation and Artificial Intelligence

Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs at 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience and AI tasks. We investigated how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines; and examined how dendrites protect morphologically detailed neural networks against adversarial attacks in typical image classification tasks.

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Light-sheet microscopy of network activity in 3D neuronal systems

In vitro systems mimicking brain regions, brain organoids, are revolutionizing the neuroscience field. However, characterization of their electrical activity has remained a challenge as this requires readout at millisecond timescale in 3D at single-neuron resolution. While custom-built microscopes used with genetically encoded sensors are now opening this door, a full 3D characterization of organoid neural activity has not been performed yet, limited by the combined complexity of the optical and the biological system. Here, we introduce an accessible minimalistic light-sheet microscope to the neuroscience community. Designed as an add-on to a standard inverted microscope it can be assembled within one day. In contrast to existing simplistic setups, our platform is suited to record volumetric calcium traces. We successfully extracted 4D calcium traces at high temporal resolution by using a lightweight piezo stage to allow for 5Hz volumetric scanning combined with a processing pipeline for true 3D neuronal trace segmentation. As a proof of principle, we created a 3D connectivity map of a stem cell derived neuron spheroid by imaging its activity. Our fast, low complexity setup empowers researchers to study the formation of neuronal networks in vitro for fundamental and neurodegeneration research.

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On the similarities of representations in artificial and brain neural networks for speech recognition

How the human brain supports speech comprehension is an important question in neuroscience. Studying the neurocomputational mechanisms underlying human language is not only critical to understand and develop treatments for many human conditions that impair language and communication but also to inform artificial systems that aim to automatically process and identify natural speech. In recent years, intelligent machines powered by deep learning have achieved near human level of performance in speech recognition. The fields of artificial intelligence and cognitive neuroscience have finally reached a similar phenotypical level despite of their huge differences in implementation, and so deep learning models can--in principle--serve as candidates for mechanistic models of the human auditory system. Utilizing high-performance automatic speech recognition systems, and advanced noninvasive human neuroimaging technology such as magnetoencephalography and multivariate pattern-information analysis, the current study aimed to relate machine-learned representations of speech to recorded human brain representations of the same speech. In one direction, we found a quasi-hierarchical functional organisation in human auditory cortex qualitatively matched with the hidden layers of deep neural networks trained in an automatic speech recognizer. In the reverse direction, we modified the hidden layer organization of the artificial neural network based on neural activation patterns in human brains. The result was a substantial improvement in word recognition accuracy and learned speech representations. We have demonstrated that artificial and brain neural networks can be mutually informative in the domain of speech recognition. Author summaryThe human capacity to recognize individual words from the sound of speech is a cornerstone of our ability to communicate with one another, yet the processes and representations underlying it remain largely unknown. Software systems for automatic speech-to-text provide a plausible model for how speech recognition can be performed. In this study, we used an automatic speech recogniser model to probe recordings from the brains of participants who listened to speech. We found that the parts of the dynamic, evolving representations inside the machine system were a good fit for representations found in the brain recordings, both showing similar hierarchical organisations. Then, we observed where the machines representations diverged from the brains, and made experimental adjustments to the automatic recognizers design so that its representations might better fit the brains. In so doing, we substantially improved the recognizers ability to accurately identify words.

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NRN-EZ: an application to streamline biophysical modeling of synaptic integration using NEURON

One of the fundamental goals in neuroscience is to determine how the brain processes information and ultimately controls the execution of complex behaviors. Over the past four decades, there has been a steady growth in our knowledge of the morphological and functional diversity of neurons, the building blocks of the brain. These cells clearly differ not only for their anatomy and ion channel distribution, but also for the type, strength, location and temporal pattern of activity of the many synaptic inputs they receive. Compartmental modeling programs like NEURON have become widely used in the neuroscience community to address a broad range of research questions, including how neurons integrate synaptic inputs and propagate information through complex neural networks. One of the main strengths of NEURON is its ability to incorporate user-defined information about the realistic morphology and biophysical properties of different cell types. Although the graphical user interface of the program can be used to run initial exploratory simulations, introducing a stochastic representation of synaptic weights, locations and activation times typically requires users to develop their own codes, a task that can be overwhelming for some beginner users. Here we describe NRN-EZ, an interactive application that allows users to specify complex patterns of synaptic input activity that can be integrated as part of NEURON simulations. Through its graphical user interface, NRN-EZ leverages the learning curve to run computational models in NEURON, for users that do not necessarily have a computer science background.

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Evaluating the capabilities and challenges of layer-fMRI VASO at 3T

Sub-millimeter functional imaging has the potential to capture cortical layer-specific functional information flow within and across brain systems. Recent sequence advancements of fMRI signal readout and contrast generations resulted in wide adaptation of layer-fMRI protocols across the global ultra-high-field (UHF) neuroimaging community. However, most layer-fMRI applications are confined to one of {approx}100 privileged UHF imaging centers, and sequence contrasts with unwanted sensitivity to large draining veins. In this work, we propose the application of vein-signal free vascular space occupancy (VASO) layerfMRI sequences at widely accessible 3T scanners. Specifically, we implement, characterize, and apply a cerebral blood volume (CBV)-sensitive VASO fMRI at a 3T scanner setup, as it is typically used in the majority of cognitive neuroscience and clinical neuroscience fMRI studies. We find that the longer [Formula], and stronger relative T1 contrast at 3T can account for some of the lower z-magnetization in the inversion-recovery VASO sequence compared to 7T and 9.4T. In the main series of experiments (N=16), we test the utility of this setup for motor tasks and find that-while being limited by thermal noise-3T layer-fMRI VASO is feasible within conventional scan durations. In a series of auxiliary studies, we furthermore explore the generalizability of the developed layer-fMRI protocols for a larger range of study designs including: visual stimulation, whole brain movie watching paradigms, and cognitive tasks with weaker effect sizes. We hope that the developed imaging protocols will help to increase accessibility of vein-signal free layer-fMRI imaging tools to a wider community of neuroimaging centers. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/501554v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@1b2c6b5org.highwire.dtl.DTLVardef@139b13org.highwire.dtl.DTLVardef@129ff82org.highwire.dtl.DTLVardef@45e9d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

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