Neural manifolds in V1 change with top-down signals from V4 targeting the foveal region.

High-dimensional brain activity is often organized into lower-dimensional neural manifolds. However, the neural manifolds of the visual cortex remain understudied. Here, we study large-scale multi-electrode electrophysiological recordings of macaque (Macaca mulatta) areas V1, V4, and DP with a high spatiotemporal resolution. We find that the population activity of V1 contains two separate neural manifolds, which correlate strongly with eye closure (eyes open/closed) and have distinct dimensionalities. Moreover, we find strong top-down signals from V4 to V1, particularly to the foveal region of V1, which are significantly stronger during the eyes-open periods. Finally, in silico simulations of a balanced spiking neuron network qualitatively reproduce the experimental findings. Taken together, our analyses and simulations suggest that top-down signals modulate the population activity of V1. We postulate that the top-down modulation during the eyes-open periods prepares V1 for fast and efficient visual responses, resulting in a type of visual stand-by state.

Facilitating the Sharing of Electrophysiology Data Analysis Results Through In-Depth Provenance Capture.

Scientific research demands reproducibility and transparency, particularly in data-intensive fields like electrophysiology. Electrophysiology data are typically analyzed using scripts that generate output files, including figures. Handling these results poses several challenges due to the complexity and iterative nature of the analysis process. These stem from the difficulty to discern the analysis steps, parameters, and data flow from the results, making knowledge transfer and findability challenging in collaborative settings. Provenance information tracks data lineage and processes applied to it, and provenance capture during the execution of an analysis script can address those challenges. We present Alpaca (Automated Lightweight Provenance Capture), a tool that captures fine-grained provenance information with minimal user intervention when running data analysis pipelines implemented in Python scripts. Alpaca records inputs, outputs, and function parameters and structures information according to the W3C PROV standard. We demonstrate the tool using a realistic use case involving multichannel local field potential recordings of a neurophysiological experiment, highlighting how the tool makes result details known in a standardized manner in order to address the challenges of the analysis process. Ultimately, using Alpaca will help to represent results according to the FAIR principles, which will improve research reproducibility and facilitate sharing the results of data analyses.

A modular and adaptable analysis pipeline to compare slow cerebral rhythms across heterogeneous datasets.

Neuroscience is moving toward a more integrative discipline where understanding brain function requires consolidating the accumulated evidence seen across experiments, species, and measurement techniques. A remaining challenge on that path is integrating such heterogeneous data into analysis workflows such that consistent and comparable conclusions can be distilled as an experimental basis for models and theories. Here, we propose a solution in the context of slow-wave activity (<1 Hz), which occurs during unconscious brain states like sleep and general anesthesia and is observed across diverse experimental approaches. We address the issue of integrating and comparing heterogeneous data by conceptualizing a general pipeline design that is adaptable to a variety of inputs and applications. Furthermore, we present the Collaborative Brain Wave Analysis Pipeline (Cobrawap) as a concrete, reusable software implementation to perform broad, detailed, and rigorous comparisons of slow-wave characteristics across multiple, openly available electrocorticography (ECoG) and calcium imaging datasets.

Neuronal Population Activity in Macaque Visual Cortices Dynamically Changes through Repeated Fixations in Active Free Viewing.

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys (Macaca fuscata): the primary and secondary visual cortices (V1, V2) and the inferotemporal cortex (IT). We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a smaller number of spikes, thereby allowing for discrimination between individual objects with smaller energy.

Research Data Management and Data Sharing for Reproducible Research-Results of a Community Survey of the German National Research Data Infrastructure Initiative Neuroscience.

Science is changing: the volume and complexity of data are increasing, the number of studies is growing and the goal of achieving reproducible results requires new solutions for scientific data management. In the field of neuroscience, the German National Research Data Infrastructure (NFDI-Neuro) initiative aims to develop sustainable solutions for research data management (RDM). To obtain an understanding of the present RDM situation in the neuroscience community, NFDI-Neuro conducted a comprehensive survey among the neuroscience community. Here, we report and analyze the results of the survey. We focused the survey and our analysis on current needs, challenges, and opinions about RDM. The German neuroscience community perceives barriers with respect to RDM and data sharing mainly linked to (1) lack of data and metadata standards, (2) lack of community adopted provenance tracking methods, (3) lack of secure and privacy preserving research infrastructure for sensitive data, (4) lack of RDM literacy, and (5) lack of resources (time, personnel, money) for proper RDM. However, an overwhelming majority of community members (91%) indicated that they would be willing to share their data with other researchers and are interested to increase their RDM skills. Taking advantage of this willingness and overcoming the existing barriers requires the systematic development of standards, tools, and infrastructure, the provision of training, education, and support, as well as additional resources for RDM to the research community and a constant dialogue with relevant stakeholders including policy makers to leverage of a culture change through adapted incentivization and regulation.

Evaluating the statistical similarity of neural network activity and connectivity via eigenvector angles.

Neural systems are networks, and strategic comparisons between multiple networks are a prevalent task in many research scenarios. In this study, we construct a statistical test for the comparison of matrices representing pairwise aspects of neural networks, in particular, the correlation between spiking activity and connectivity. The "eigenangle test" quantifies the similarity of two matrices by the angles between their ranked eigenvectors. We calibrate the behavior of the test for use with correlation matrices using stochastic models of correlated spiking activity and demonstrate how it compares to classical two-sample tests, such as the Kolmogorov-Smirnov distance, in the sense that it is able to evaluate also structural aspects of pairwise measures. Furthermore, the principle of the eigenangle test can be applied to compare the similarity of adjacency matrices of certain types of networks. Thus, the approach can be used to quantitatively explore the relationship between connectivity and activity with the same metric. By applying the eigenangle test to the comparison of connectivity matrices and correlation matrices of a random balanced network model before and after a specific synaptic rewiring intervention, we gauge the influence of connectivity features on the correlated activity. Potential applications of the eigenangle test include simulation experiments, model validation, and data analysis.

Emerging principles of spacetime in brains: Meeting report on spatial neurodynamics.

How do neurons and networks of neurons interact spatially? Here, we overview recent discoveries revealing how spatial dynamics of spiking and postsynaptic activity efficiently expose and explain fundamental brain and brainstem mechanisms behind detection, perception, learning, and behavior.

Comparing Surrogates to Evaluate Precisely Timed Higher-Order Spike Correlations.

The generation of surrogate data, i.e., the modification of data to destroy a certain feature, can be considered as the implementation of a null-hypothesis whenever an analytical approach is not feasible. Thus, surrogate data generation has been extensively used to assess the significance of spike correlations in parallel spike trains. In this context, one of the main challenges is to properly construct the desired null-hypothesis distribution and to avoid altering the single spike train statistics. A classical surrogate technique is uniform dithering (UD), which displaces spikes locally and uniformly distributed, to destroy temporal properties on a fine timescale while keeping them on a coarser one. Here, we compare UD against five similar surrogate techniques in the context of the detection of significant spatiotemporal spike patterns. We evaluate the surrogates for their performance, first on spike trains based on point process models with constant firing rate, and second on modeled nonstationary artificial data to assess the potential detection of false positive (FP) patterns in a more complex and realistic setting. We determine which statistical features of the spike trains are modified and to which extent. Moreover, we find that UD fails as an appropriate surrogate because it leads to a loss of spikes in the context of binning and clipping, and thus to a large number of FP patterns. The other surrogates achieve a better performance in detecting precisely timed higher-order correlations. Based on these insights, we analyze experimental data from the pre-/motor cortex of macaque monkeys during a reaching-and-grasping task.

Latency shortening with enhanced sparseness and responsiveness in V1 during active visual sensing.

In natural vision, neuronal responses to visual stimuli occur due to self-initiated eye movements. Here, we compare single-unit activity in the primary visual cortex (V1) of non-human primates to flashed natural scenes (passive vision condition) to when they freely explore the images by self-initiated eye movements (active vision condition). Active vision enhances the number of neurons responding, and the response latencies become shorter and less variable across neurons. The increased responsiveness and shortened latency during active vision were not explained by increased visual contrast. While the neuronal activities in all layers of V1 show enhanced responsiveness and shortened latency, a significant increase in lifetime sparseness during active vision is observed only in the supragranular layer. These findings demonstrate that the neuronal responses become more distinct in active vision than passive vision, interpreted as consequences of top-down predictive mechanisms.

1024-channel electrophysiological recordings in macaque V1 and V4 during resting state.

Co-variations in resting state activity are thought to arise from a variety of correlated inputs to neurons, such as bottom-up activity from lower areas, feedback from higher areas, recurrent processing in local circuits, and fluctuations in neuromodulatory systems. Most studies have examined resting state activity throughout the brain using MRI scans, or observed local co-variations in activity by recording from a small number of electrodes. We carried out electrophysiological recordings from over a thousand chronically implanted electrodes in the visual cortex of non-human primates, yielding a resting state dataset with unprecedentedly high channel counts and spatiotemporal resolution. Such signals could be used to observe brain waves across larger regions of cortex, offering a temporally detailed picture of brain activity. In this paper, we provide the dataset, describe the raw and processed data formats and data acquisition methods, and indicate how the data can be used to yield new insights into the 'background' activity that influences the processing of visual information in our brain.

Revealing Whole-Brain Causality Networks During Guided Visual Searching.

In our daily lives, we use eye movements to actively sample visual information from our environment ("active vision"). However, little is known about how the underlying mechanisms are affected by goal-directed behavior. In a study of 31 participants, magnetoencephalography was combined with eye-tracking technology to investigate how interregional interactions in the brain change when engaged in two distinct forms of active vision: freely viewing natural images or performing a guided visual search. Regions of interest with significant fixation-related evoked activity (FRA) were identified with spatiotemporal cluster permutation testing. Using generalized partial directed coherence, we show that, in response to fixation onset, a bilateral cluster consisting of four regions (posterior insula, transverse temporal gyri, superior temporal gyrus, and supramarginal gyrus) formed a highly connected network during free viewing. A comparable network also emerged in the right hemisphere during the search task, with the right supramarginal gyrus acting as a central node for information exchange. The results suggest that all four regions are vital to visual processing and guiding attention. Furthermore, the right supramarginal gyrus was the only region where activity during fixations on the search target was significantly negatively correlated with search response times. Based on our findings, we hypothesize that, following a fixation, the right supramarginal gyrus supplies the right supplementary eye field (SEF) with new information to update the priority map guiding the eye movements during the search task.

Global organization of neuronal activity only requires unstructured local connectivity.

Modern electrophysiological recordings simultaneously capture single-unit spiking activities of hundreds of neurons spread across large cortical distances. Yet, this parallel activity is often confined to relatively low-dimensional manifolds. This implies strong coordination also among neurons that are most likely not even connected. Here, we combine in vivo recordings with network models and theory to characterize the nature of mesoscopic coordination patterns in macaque motor cortex and to expose their origin: We find that heterogeneity in local connectivity supports network states with complex long-range cooperation between neurons that arises from multi-synaptic, short-range connections. Our theory explains the experimentally observed spatial organization of covariances in resting state recordings as well as the behaviorally related modulation of covariance patterns during a reach-to-grasp task. The ubiquity of heterogeneity in local cortical circuits suggests that the brain uses the described mechanism to flexibly adapt neuronal coordination to momentary demands.

On the Complexity of Resting State Spiking Activity in Monkey Motor Cortex.

Resting state has been established as a classical paradigm of brain activity studies, mostly based on large-scale measurements such as functional magnetic resonance imaging or magneto- and electroencephalography. This term typically refers to a behavioral state characterized by the absence of any task or stimuli. The corresponding neuronal activity is often called idle or ongoing. Numerous modeling studies on spiking neural networks claim to mimic such idle states, but compare their results with task- or stimulus-driven experiments, or to results from experiments with anesthetized subjects. Both approaches might lead to misleading conclusions. To provide a proper basis for comparing physiological and simulated network dynamics, we characterize simultaneously recorded single neurons' spiking activity in monkey motor cortex at rest and show the differences from spontaneous and task- or stimulus-induced movement conditions. We also distinguish between rest with open eyes and sleepy rest with eyes closed. The resting state with open eyes shows a significantly higher dimensionality, reduced firing rates, and less balance between population level excitation and inhibition than behavior-related states.

Detection and evaluation of bursts in terms of novelty and surprise.

The detection of bursts and also of response onsets is often of relevance in understanding neurophysiological data, but the detection of these events is not a trivial task. We build on a method that was originally designed for burst detection using the so-called burst surprise as a measure. We extend this method and provide a proper significance measure. Our method consists of two stages. In the first stage we model the neuron's interspike interval (ISI) distribution and make an i.i.d. assumption to formulate our null hypothesis. In addition we define a set of 'surprising' events that signify deviations from the null hypothesis in the direction of 'burstiness'. Here the so-called (strict) burst novelty is used to measure the size of this deviation. In the second stage we determine the significance of this deviation. The (strict) burst surprise is used to measure the significance, since it is the negative logarithm of the significance probability. After showing the consequences of a non-proper null hypothesis on burst detection performance, we apply the method to experimental data. For this application the data are divided into a period for parameter estimation to express a proper null hypothesis (model of the ISI distribution), and the rest of the data is analyzed by using that null hypothesis. We find that assuming a Poisson process for experimental spike data from motor cortex is rarely a proper null hypothesis, because these data tend to fire more regularly and thus a gamma process is more appropriate. We show that our burst detection method can be used for rate change onset detection, because a deviation from the null hypothesis detected by (strict) burst novelty also covers an increase of firing rate.

odMLtables: A User-Friendly Approach for Managing Metadata of Neurophysiological Experiments.

An essential aspect of scientific reproducibility is a coherent and complete acquisition of metadata along with the actual data of an experiment. The high degree of complexity and heterogeneity of neuroscience experiments requires a rigorous management of the associated metadata. The odML framework represents a solution to organize and store complex metadata digitally in a hierarchical format that is both human and machine readable. However, this hierarchical representation of metadata is difficult to handle when metadata entries need to be collected and edited manually during the daily routines of a laboratory. With odMLtables, we present an open-source software solution that enables users to collect, manipulate, visualize, and store metadata in tabular representations (in xls or csv format) by providing functionality to convert these tabular collections to the hierarchically structured metadata format odML, and to either extract or merge subsets of a complex metadata collection. With this, odMLtables bridges the gap between handling metadata in an intuitive way that integrates well with daily lab routines and commonly used software products on the one hand, and the implementation of a complete, well-defined metadata collection for the experiment in a standardized format on the other hand. We demonstrate usage scenarios of the odMLtables tools in common lab routines in the context of metadata acquisition and management, and show how the tool can assist in exploring published datasets that provide metadata in the odML format.

3d-SPADE: Significance evaluation of spatio-temporal patterns of various temporal extents.

The Spike Pattern Detection and Evaluation (SPADE) analysis is a method to find reoccurring spike patterns in parallel spike train data, and to determine their statistical significance. Here we introduce an extension of the original statistical testing procedure which explicitly accounts for the temporal duration of the patterns. The extension improves the performance in the presence of patterns with different durations, as here demonstrated by application to various synthetic data. We further introduce an implementation of SPADE in form of a sub-module of the Python library Elephant (ELEctroPHysiological ANalysis Toolkit). The code is made publicly available on GitHub, together with detailed documentation, tutorials, and the results presented here.

Evaluation of Spike Sorting Algorithms: Application to Human Subthalamic Nucleus Recordings and Simulations.

An important prerequisite for the analysis of spike synchrony in extracellular recordings is the extraction of single-unit activity from the multi-unit signal. To identify single units, potential spikes are separated with respect to their potential neuronal origins ('spike sorting'). However, different sorting algorithms yield inconsistent unit assignments, which seriously influences subsequent spike train analyses. We aim to identify the best sorting algorithm for subthalamic nucleus recordings of patients with Parkinson's disease (experimental data ED). Therefore, we apply various prevalent algorithms offered by the 'Plexon Offline Sorter' and evaluate the sorting results. Since this evaluation leaves us unsure about the best algorithm, we apply all methods again to artificial data (AD) with known ground truth. AD consists of pairs of single units with different shape similarity embedded in the background noise of the ED. The sorting evaluation depicts a significant influence of the respective methods on the single unit assignments. We find a high variability in the sortings obtained by different algorithms that increases with single units shape similarity. We also find significant differences in the resulting firing characteristics. We conclude that Valley-Seeking algorithms produce the most accurate result if the exclusion of artifacts as unsorted events is important. If the latter is less important ('clean' data) the K-Means algorithm is a better option. Our results strongly argue for the need of standardized validation procedures based on ground truth data. The recipe suggested here is simple enough to become a standard procedure.

Second type of criticality in the brain uncovers rich multiple-neuron dynamics.

Cortical networks that have been found to operate close to a critical point exhibit joint activations of large numbers of neurons. However, in motor cortex of the awake macaque monkey, we observe very different dynamics: massively parallel recordings of 155 single-neuron spiking activities show weak fluctuations on the population level. This a priori suggests that motor cortex operates in a noncritical regime, which in models, has been found to be suboptimal for computational performance. However, here, we show the opposite: The large dispersion of correlations across neurons is the signature of a second critical regime. This regime exhibits a rich dynamical repertoire hidden from macroscopic brain signals but essential for high performance in such concepts as reservoir computing. An analytical link between the eigenvalue spectrum of the dynamics, the heterogeneity of connectivity, and the dispersion of correlations allows us to assess the closeness to the critical point.

Task-dependent functional organizations of the visual ventral stream.

The visual hierarchy of the ventral stream has been widely studied. However, it remains unclear how the hierarchical system organizes its functional coupling during top-down cognitive process. The present fMRI study investigated task-dependent functional connectivity along the ventral stream, while twenty-eight participants performed object recognition tasks that required different types of visual processing: i) searching or ii) memorizing visual objects embedded in natural scene images or iii) free viewing of the same images. Utilizing a seed-based approach that explicitly compared task-specific BOLD time-series, we identified task-dependent functional connectivity of the visual ventral stream, demonstrating different correlation structures. Searching for a target object manifested both correlated and anti-correlated structures, separating the visual areas V1 and V4 from the posterior part of the inferior temporal cortex (PIT). In contrast, the ventral stream structure remained correlated during memorizing objects, but increased the correlation between the right V4 and PIT. On the other hand, V1 and V4 showed task-dependent activation, whereas PIT was deactivated. These results highlight the context-dependent nature of the visual ventral stream and shed light on how the visual hierarchy is selectively organized to bias object recognition toward features of interest.