Diversity of Voltage Activated Calcium Currents in Identified Olfactory Interneurons

In the insect antennal lobe (AL) each olfactory receptor cell projects to one glomerulus and many receptor axons converge in each glomerulus, where they provide synaptic input to local interneurons (LNs) and projection (output) neurons (PNs). The arborizations of LNs are confined to the AL. In contrast, the PNs extend axons to higher order neuropiles of the protocerebrum, including the mushroom bodies and the lateral lobus of the protocerebrum. In particular PNs have been in the focus of intensive studies, because they serve multiple functions and play a key role in the central olfactory pathway. However, the role and functional properties of LNs are less well understood. Towards the goal to better understand the biophysical parameters that mediate olfactory information processing on the cellular level, voltage activated calcium currents (ICa) in olfactory interneurons of the AL from adult cockroach were analyzed: 1) in acutely dissociated cells (in vitro), 2) in an intact brain preparation (in situ), and 3) in unequivocally identified and intact neurons. Using whole cell patch-clamp recordings in current and voltage-clamp mode in combination with single cell staining, uniglomerular PNs (uPNs) and two major types of LNs could be identified by their physiological and morphological properties, which in the following are referred to as type I LNs and type II LNs. In type I LNs odor stimulation and depolarizing current injection elicited overshooting TTX-sensitive action potentials. Voltage-clamp recordings revealed a voltage-activated sodium current, a transient and a sustained potassium current and a calcium current. In contrast, in type II LNs odor stimulation and current injections induced membrane depolarization, but no TTX-sensitive action potentials. In some recordings small (~ 2 mV) 'spikelets' were riding on the odor evoked depolarization. In type II LNs voltage activated sodium currents were not detectable. However, ICa was significantly larger compared to type I LNs and the activation characteristics were significantly different. For type I LNs the voltage for half maximal activation (V0.5(act)) of ICa was -11.1 ± 6.5 mV, which is in the range of V0.5(act) for uPNs (V0.5(act) = -10.6 ± 3.4 mV). In contrast to this, in type II LNs the V0.5(act) of ICa is significantly shifted to more negative potentials (V0.5(act) = -19.4 ± 4.7 mV). These results suggest that the odor-evoked depolarization in type II LNs might be carried largely by ICa and that ICa might play a role in graded synaptic release between type II LNs and other olfactory interneurons

A Solution for Multi-Alignment by Transformation Synchronisation

The alignment of a set of objects by means of transformations plays an important role in computer vision. Whilst the case for only two objects can be solved globally, when multiple objects are considered usually iterative methods are used. In practice the iterative methods perform well if the relative transformations between any pair of objects are free of noise. However, if only noisy relative transformations are available (e.g. due to missing data or wrong correspondences) the iterative methods may fail. Based on the observation that the underlying noise-free transformations can be retrieved from the null space of a matrix that can directly be obtained from pairwise alignments, this paper presents a novel method for the synchronisation of pairwise transformations such that they are transitively consistent. Simulations demonstrate that for noisy transformations, a large proportion of missing data and even for wrong correspondence assignments the method delivers encouraging results.Comment: Accepted for CVPR 2015 (please cite CVPR version

On the Composition and Limitations of Publicly Available COVID-19 X-Ray Imaging Datasets

Machine learning based methods for diagnosis and progression prediction of COVID-19 from imaging data have gained significant attention in the last months, in particular by the use of deep learning models. In this context hundreds of models where proposed with the majority of them trained on public datasets. Data scarcity, mismatch between training and target population, group imbalance, and lack of documentation are important sources of bias, hindering the applicability of these models to real-world clinical practice. Considering that datasets are an essential part of model building and evaluation, a deeper understanding of the current landscape is needed. This paper presents an overview of the currently public available COVID-19 chest X-ray datasets. Each dataset is briefly described and potential strength, limitations and interactions between datasets are identified. In particular, some key properties of current datasets that could be potential sources of bias, impairing models trained on them are pointed out. These descriptions are useful for model building on those datasets, to choose the best dataset according the model goal, to take into account the specific limitations to avoid reporting overconfident benchmark results, and to discuss their impact on the generalisation capabilities in a specific clinical settingComment: 12 pages, 3 figure

Machine learning models for diagnosis and prognosis of Parkinson's disease using brain imaging: general overview, main challenges, and future directions

Parkinson’s disease (PD) is a progressive and complex neurodegenerative disorder associated with age that affects motor and cognitive functions. As there is currently no cure, early diagnosis and accurate prognosis are essential to increase the effectiveness of treatment and control its symptoms. Medical imaging, specifically magnetic resonance imaging (MRI), has emerged as a valuable tool for developing support systems to assist in diagnosis and prognosis. The current literature aims to improve understanding of the disease’s structural and functional manifestations in the brain. By applying artificial intelligence to neuroimaging, such as deep learning (DL) and other machine learning (ML) techniques, previously unknown relationships and patterns can be revealed in this high-dimensional data. However, several issues must be addressed before these solutions can be safely integrated into clinical practice. This review provides a comprehensive overview of recent ML techniques analyzed for the automatic diagnosis and prognosis of PD in brain MRI. The main challenges in applying ML to medical diagnosis and its implications for PD are also addressed, including current limitations for safe translation into hospitals. These challenges are analyzed at three levels: disease-specific, task- specific, and technology-specific. Finally, potential future directions for each challenge and future perspectives are discusse

The effect of dataset confounding on predictions of deep neural networks for medical imaging

The use of Convolutional Neural Networks (CNN) in medical imaging has often outperformed previous solutions and even specialists, becoming a promising technology for Computer-aided-Diagnosis (CAD) systems. However, recent works suggested that CNN may have poor generalisation on new data, for instance, generated in different hospitals. Uncontrolled confounders have been proposed as a common reason. In this paper, we experimentally demonstrate the impact of confounding data in unknown scenarios. We assessed the effect of four confounding configurations: total, strong, light and balanced. We found the confounding effect is especially prominent in total confounder scenarios, while the effect on light and strong confounding scenarios may depend on the dataset robustness. Our findings indicate that the confounding effect is independent of the architecture employed. These findings might explain why models can report good metrics during the development stage but fail to translate to real-world settings. We highlight the need for thorough consideration of these commonly unattended aspects, to develop safer CNN-based CAD systems

Differentiation of primary CNS lymphoma and glioblastoma using Raman spectroscopy and machine learning algorithms

Objective and Methods: Timely discrimination between primary CNS lymphoma (PCNSL) and glioblastoma is crucial for diagnostics and therapy, but most importantly also determines the intraoperative surgical course. Advanced radiological methods allow this to a certain extent but ultimately, biopsy is still necessary for final diagnosis. As an upcoming method that enables tissue analysis by tracking changes in the vibrational state of molecules via inelastic scattered photons, we used Raman Spectroscopy (RS) as a label free method to examine specimens of both tumor entities intraoperatively, as well as postoperatively in formalin fixed paraffin embedded (FFPE) samples. Results: We applied and compared statistical performance of linear and nonlinear machine learning algorithms (Logistic Regression, Random Forest and XGBoost), and found that Random Forest classification distinguished the two tumor entities with a balanced accuracy of 82,4% in intraoperative tissue condition and with 94% using measurements of distinct tumor areas on FFPE tissue. Taking a deeper insight into the spectral properties of the tumor entities, we describe different tumor-specific Raman shifts of interest for classification. Conclusions: Due to our findings, we propose RS as an additional tool for fast and non-destructive, perioperative tumor tissue discrimination, which may augment treatment options at an early stage. RS may further serve as a useful additional tool for neuropathological diagnostics with little requirements for tissue integrity

Lead-DBS v3.0: Mapping Deep Brain Stimulation Effects to Local Anatomy and Global Networks.

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expanding clinical indications for DBS, increasing availability of related research tools, and a growing community of clinician-scientist researchers, however, have led to an ongoing need to maintain, update, and standardize the codebase of Lead-DBS. Major development efforts of the platform in recent years have now yielded an end-to-end solution for DBS-based neuroimaging analysis allowing comprehensive image preprocessing, lead localization, stimulation volume modeling, and statistical analysis within a single tool. The aim of the present manuscript is to introduce fundamental additions to the Lead-DBS pipeline including a deformation warpfield editor and novel algorithms for electrode localization. Furthermore, we introduce a total of three comprehensive tools to map DBS effects to local, tract- and brain network-levels. These updates are demonstrated using a single patient example (for subject-level analysis), as well as a retrospective cohort of 51 Parkinson's disease patients who underwent DBS of the subthalamic nucleus (for group-level analysis). Their applicability is further demonstrated by comparing the various methodological choices and the amount of explained variance in clinical outcomes across analysis streams. Finally, based on an increasing need to standardize folder and file naming specifications across research groups in neuroscience, we introduce the brain imaging data structure (BIDS) derivative standard for Lead-DBS. Thus, this multi-institutional collaborative effort represents an important stage in the evolution of a comprehensive, open-source pipeline for DBS imaging and connectomics

Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging.

Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient's preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field