Discovering optimal features for neuron-type identification from extracellular recordings

Advancements in multichannel recordings of single-unit activity (SUA) in vivo present an opportunity to discover novel features of spatially-varying extracellularly-recorded action potentials (EAPs) that are useful for identifying neuron-types. Traditional approaches to classifying neuron-types often rely on computing EAP waveform features based on conventions of single-channel recordings and thus inherit their limitations. However, spatiotemporal EAP waveforms are the product of signals from underlying current sources being mixed within the extracellular space. We introduce a machine learning approach to demix the underlying sources of spatiotemporal EAP waveforms. Using biophysically realistic computational models, we simulate EAP waveforms and characterize them by the relative prevalence of these sources, which we use as features for identifying the neuron-types corresponding to recorded single units. These EAP sources have distinct spatial and multi-resolution temporal patterns that are robust to various sampling biases. EAP sources also are shared across many neuron-types, are predictive of gross morphological features, and expose underlying morphological domains. We then organize known neuron-types into a hierarchy of latent morpho-electrophysiological types based on differences in the source prevalences, which provides a multi-level classification scheme. We validate the robustness, accuracy, and interpretations of our demixing approach by analyzing simulated EAPs from morphologically detailed models with classification and clustering methods. This simulation-based approach provides a machine learning strategy for neuron-type identification.

Introducing Region Based Pooling for handling a varied number of EEG channels for deep learning models

Introduction

A challenge when applying an artificial intelligence (AI) deep learning (DL) approach to novel electroencephalography (EEG) data, is the DL architecture's lack of adaptability to changing numbers of EEG channels. That is, the number of channels cannot vary neither in the training data, nor upon deployment. Such highly specific hardware constraints put major limitations on the clinical usability and scalability of the DL models.

Methods

In this work, we propose a technique for handling such varied numbers of EEG channels by splitting the EEG montages into distinct regions and merge the channels within the same region to a region representation. The solution is termed Region Based Pooling (RBP). The procedure of splitting the montage into regions is performed repeatedly with different region configurations, to minimize potential loss of information. As RBP maps a varied number of EEG channels to a fixed number of region representations, both current and future DL architectures may apply RBP with ease. To demonstrate and evaluate the adequacy of RBP to handle a varied number of EEG channels, sex classification based solely on EEG was used as a test example. The DL models were trained on 129 channels, and tested on 32, 65, and 129-channels versions of the data using the same channel positions scheme. The baselines for comparison were zero-filling the missing channels and applying spherical spline interpolation. The performances were estimated using 5-fold cross validation.

Results

For the 32-channel system version, the mean AUC values across the folds were: RBP (93.34%), spherical spline interpolation (93.36%), and zero-filling (76.82%). Similarly, on the 65-channel system version, the performances were: RBP (93.66%), spherical spline interpolation (93.50%), and zero-filling (85.58%). Finally, the 129-channel system version produced the following results: RBP (94.68%), spherical spline interpolation (93.86%), and zero-filling (91.92%).

Conclusion

In conclusion, RBP obtained similar results to spherical spline interpolation, and superior results to zero-filling. We encourage further research and development of DL models in the cross-dataset setting, including the use of methods such as RBP and spherical spline interpolation to handle a varied number of EEG channels.

SDA: a data-driven algorithm that detects functional states applied to the EEG of Guhyasamaja meditation

The study presents a novel approach designed to detect time-continuous states in time-series data, called the State-Detecting Algorithm (SDA). The SDA operates on unlabeled data and detects optimal change-points among intrinsic functional states in time-series data based on an ensemble of Ward's hierarchical clustering with time-connectivity constraint. The algorithm chooses the best number of states and optimal state boundaries, maximizing clustering quality metrics. We also introduce a series of methods to estimate the performance and confidence of the SDA when the ground truth annotation is unavailable. These include information value analysis, paired statistical tests, and predictive modeling analysis. The SDA was validated on EEG recordings of Guhyasamaja meditation practice with a strict staged protocol performed by three experienced Buddhist practitioners in an ecological setup. The SDA used neurophysiological descriptors as inputs, including PSD, power indices, coherence, and PLV. Post-hoc analysis of the obtained EEG states revealed significant differences compared to the baseline and neighboring states. The SDA was found to be stable with respect to state order organization and showed poor clustering quality metrics and no statistical significance between states when applied to randomly shuffled epochs (i.e., surrogate subject data used as controls). The SDA can be considered a general data-driven approach that detects hidden functional states associated with the mental processes evolving during meditation or other ongoing mental and cognitive processes.

Transdiagnostic clustering of self-schema from self-referential judgements identifies subtypes of healthy personality and depression

Introduction

The heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders.

Methods

In this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category.

Results

We identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled “Neurotic” (C1), “Extraverted” (C2), “Anxious to please” (C3), “Self-critical” (C4), “Conscientious” (C5). The non-clinical clusters were labeled “Self-confident” (N1), “Low endorsement” (N2), “Non-neurotic” (N3), “Neurotic” (N4), “High endorsement” (N5). The combined clusters were labeled “Self-confident” (NC1), “Externalising” (NC2), “Neurotic” (NC3), “Secure” (NC4), “Low endorsement” (NC5), “High endorsement” (NC6), “Self-critical” (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism.

Discussion

Overall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications.

The past, present and future of neuroscience data sharing: a perspective on the state of practices and infrastructure for FAIR

Neuroscience has made significant strides over the past decade in moving from a largely closed science characterized by anemic data sharing, to a largely open science where the amount of publicly available neuroscience data has increased dramatically. While this increase is driven in significant part by large prospective data sharing studies, we are starting to see increased sharing in the long tail of neuroscience data, driven no doubt by journal requirements and funder mandates. Concomitant with this shift to open is the increasing support of the FAIR data principles by neuroscience practices and infrastructure. FAIR is particularly critical for neuroscience with its multiplicity of data types, scales and model systems and the infrastructure that serves them. As envisioned from the early days of neuroinformatics, neuroscience is currently served by a globally distributed ecosystem of neuroscience-centric data repositories, largely specialized around data types. To make neuroscience data findable, accessible, interoperable, and reusable requires the coordination across different stakeholders, including the researchers who produce the data, data repositories who make it available, the aggregators and indexers who field search engines across the data, and community organizations who help to coordinate efforts and develop the community standards critical to FAIR. The International Neuroinformatics Coordinating Facility has led efforts to move neuroscience toward FAIR, fielding several resources to help researchers and repositories achieve FAIR. In this perspective, I provide an overview of the components and practices required to achieve FAIR in neuroscience and provide thoughts on the past, present and future of FAIR infrastructure for neuroscience, from the laboratory to the search engine.

The hemodynamic response function as a type 2 diabetes biomarker: a data-driven approach

Introduction

There is a need to better understand the neurophysiological changes associated with early brain dysfunction in Type 2 diabetes mellitus (T2DM) before vascular or structural lesions. Our aim was to use a novel unbiased data-driven approach to detect and characterize hemodynamic response function (HRF) alterations in T2DM patients, focusing on their potential as biomarkers.

Methods

We meshed task-based event-related (visual speed discrimination) functional magnetic resonance imaging with DL to show, from an unbiased perspective, that T2DM patients’ blood-oxygen-level dependent response is altered. Relevance analysis determined which brain regions were more important for discrimination. We combined explainability with deconvolution generalized linear model to provide a more accurate picture of the nature of the neural changes.

Results

The proposed approach to discriminate T2DM patients achieved up to 95% accuracy. Higher performance was achieved at higher stimulus (speed) contrast, showing a direct relationship with stimulus properties, and in the hemispherically dominant left visual hemifield, demonstrating biological interpretability. Differences are explained by physiological asymmetries in cortical spatial processing (right hemisphere dominance) and larger neural signal-to-noise ratios related to stimulus contrast. Relevance analysis revealed the most important regions for discrimination, such as extrastriate visual cortex, parietal cortex, and insula. These are disease/task related, providing additional evidence for pathophysiological significance. Our data-driven design allowed us to compute the unbiased HRF without assumptions.

Conclusion

We can accurately differentiate T2DM patients using a data-driven classification of the HRF. HRF differences hold promise as biomarkers and could contribute to a deeper understanding of neurophysiological changes associated with T2DM.

NeuroDecodeR: a package for neural decoding in R

Neural decoding is a powerful method to analyze neural activity. However, the code needed to run a decoding analysis can be complex, which can present a barrier to using the method. In this paper we introduce a package that makes it easy to perform decoding analyses in the R programing language. We describe how the package is designed in a modular fashion which allows researchers to easily implement a range of different analyses. We also discuss how to format data to be able to use the package, and we give two examples of how to use the package to analyze real data. We believe that this package, combined with the rich data analysis ecosystem in R, will make it significantly easier for researchers to create reproducible decoding analyses, which should help increase the pace of neuroscience discoveries.

AngoraPy: A Python toolkit for modeling anthropomorphic goal-driven sensorimotor systems

Goal-driven deep learning increasingly supplements classical modeling approaches in computational neuroscience. The strength of deep neural networks as models of the brain lies in their ability to autonomously learn the connectivity required to solve complex and ecologically valid tasks, obviating the need for hand-engineered or hypothesis-driven connectivity patterns. Consequently, goal-driven models can generate hypotheses about the neurocomputations underlying cortical processing that are grounded in macro- and mesoscopic anatomical properties of the network's biological counterpart. Whereas, goal-driven modeling is already becoming prevalent in the neuroscience of perception, its application to the sensorimotor domain is currently hampered by the complexity of the methods required to train models comprising the closed sensation-action loop. This paper describes AngoraPy, a Python library that mitigates this obstacle by providing researchers with the tools necessary to train complex recurrent convolutional neural networks that model the human sensorimotor system. To make the technical details of this toolkit more approachable, an illustrative example that trains a recurrent toy model on in-hand object manipulation accompanies the theoretical remarks. An extensive benchmark on various classical, 3D robotic, and anthropomorphic control tasks demonstrates AngoraPy's general applicability to a wide range of tasks. Together with its ability to adaptively handle custom architectures, the flexibility of this toolkit demonstrates its power for goal-driven sensorimotor modeling.

An interactive image segmentation method for the anatomical structures of the main olfactory bulb with micro-level resolution

The main olfactory bulb is the key element of the olfactory pathway of rodents. To precisely dissect the neural pathway in the main olfactory bulb (MOB), it is necessary to construct the three-dimensional morphologies of the anatomical structures within it with micro-level resolution. However, the construction remains challenging due to the complicated shape of the anatomical structures in the main olfactory bulb and the high resolution of micro-optical images. To address these issues, we propose an interactive volume image segmentation method with micro-level resolution in the horizontal and axial direction. Firstly, we obtain the initial location of the anatomical structures by manual annotation and design a patch-based neural network to learn the complex texture feature of the anatomical structures. Then we randomly sample some patches to predict by the trained network and perform an annotation reconstruction based on intensity calculation to get the final location results of the anatomical structures. Our experiments were conducted using Nissl-stained brain images acquired by the Micro-optical sectioning tomography (MOST) system. Our method achieved a mean dice similarity coefficient (DSC) of 81.8% and obtain the best segmentation performance. At the same time, the experiment shows the three-dimensional morphology reconstruction results of the anatomical structures in the main olfactory bulb are smooth and consistent with their natural shapes, which addresses the possibility of constructing three-dimensional morphologies of the anatomical structures in the whole brain.

Establishing a nomogram to predict refracture after percutaneous kyphoplasty by logistic regression

Introduction

Several studies have examined the risk factors for post-percutaneous kyphoplasty (PKP) refractures and developed many clinical prognostic models. However, no prior research exists using the Random Forest (RF) model, a favored tool for model development, to predict the occurrence of new vertebral compression fractures (NVCFs). Therefore, this study aimed to investigate the risk factors for the occurrence of post-PKP fractures, compare the predictive performance of logistic regression and RF models in forecasting post-PKP fractures, and visualize the logistic regression model.

Methods

We collected clinical data from 349 patients who underwent PKP treatment at our institution from January 2018 to December 2021. Lasso regression was employed to select risk factors associated with the occurrence of NVCFs. Subsequently, logistic regression and RF models were established, and their predictive capabilities were compared. Finally, a nomogram was created.

Results

The variables selected using Lasso regression, including bone density, cement distribution, vertebral fracture location, preoperative vertebral height, and vertebral height restoration rate, were included in both the logistic regression and RF models. The area under the curves of the logistic regression and RF models were 0.868 and 0.786, respectively, in the training set and 0.786 and 0.599, respectively, in the validation set. Furthermore, the calibration curve of the logistic regression model also outperformed that of the RF model.

Conclusion

The logistic regression model provided better predictive capabilities for identifying patients at risk for post-PKP vertebral fractures than the RF model.