Theta oscillations, ranging from 4-8 Hz, play a significant role in spatial learning and memory functions during navigation tasks. Frontal theta oscillations are thought to play an important role in spatial navigation and memory. Electroencephalography (EEG) datasets are very complex, making any changes in the neural signal related to behaviour difficult to interpret. However, multiple analytical methods are available to examine complex data structures, especially machine learning-based techniques. These methods have shown high classification performance, and their combination with feature engineering enhances their capability. This paper proposes using hidden Markov and linear mixed effects models to extract features from EEG data. Based on the engineered features obtained from frontal theta EEG data during a spatial navigation task in two key trials (first, last) and between two conditions (learner and non-learner), we analysed the performance of six machine learning methods on classifying learner and non-learner participants. We also analysed how different standardisation methods used to pre-process the EEG data contribute to classification performance. We compared the classification performance of each trial with data gathered from the same subjects, including solely coordinate-based features, such as idle time and average speed. We found that more machine learning methods perform better classification using coordinate-based data. However, only deep neural networks achieved an area under the ROC curve higher than 80% using the theta EEG data alone. Our findings suggest that standardising the theta EEG data and using deep neural networks enhances the classification of learner and non-learner subjects in a spatial learning task.

Annotation of multiple regions of interest across the whole mouse brain is an indispensable process for quantitative evaluation of a multitude of study endpoints in neuroscience digital pathology. Prior experience and domain expert knowledge are the key aspects for image annotation quality and consistency. At present, image annotation is often achieved manually by certified pathologists or trained technicians, limiting the total throughput of studies performed at neuroscience digital pathology labs. It may also mean that simpler and quicker methods of examining tissue samples are used by non-pathologists, especially in the early stages of research and preclinical studies. To address these limitations and to meet the growing demand for image analysis in a pharmaceutical setting, we developed AnNoBrainer, an open-source software tool that leverages deep learning, image registration, and standard cortical brain templates to automatically annotate individual brain regions on 2D pathology slides. Application of AnNoBrainer to a published set of pathology slides from transgenic mice models of synucleinopathy revealed comparable accuracy, increased reproducibility, and a significant reduction (~ 50%) in time spent on brain annotation, quality control and labelling compared to trained scientists in pathology. Taken together, AnNoBrainer offers a rapid, accurate, and reproducible automated annotation of mouse brain images that largely meets the experts' histopathological assessment standards (> 85% of cases) and enables high-throughput image analysis workflows in digital pathology labs.

Mouse models are crucial for neuroscience research, yet discrepancies arise between macro- and meso-scales due to sample preparation altering brain morphology. The absence of an accessible toolbox for magnetic resonance imaging (MRI) data processing presents a challenge for assessing morphological changes in the mouse brain. To address this, we developed the MBV-Pipe (Mouse Brain Volumetric Statistics-Pipeline) toolbox, integrating the methods of Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL)-Voxel-based morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) to evaluate brain tissue volume and white matter integrity. To validate the reliability of MBV-Pipe, brain MRI data from seven mice at three time points (in vivo, post-perfusion, and post-fixation) were acquired using a 9.4T ultra-high MRI system. Employing the MBV-Pipe toolbox, we discerned substantial volumetric changes in the mouse brain following perfusion relative to the in vivo condition, with the fixation process inducing only negligible variations. Importantly, the white matter integrity was found to be largely stable throughout the sample preparation procedures. The MBV-Pipe source code is publicly available and includes a user-friendly GUI for facilitating quality control and experimental protocol optimization, which holds promise for advancing mouse brain research in the future.

This study concentrates on the segmentation of intracranial aneurysms, a pivotal aspect of diagnosis and treatment planning. We aim to overcome the inherent instance imbalance and morphological variability by introducing a novel morphology and texture loss reweighting approach. Our innovative method involves the incorporation of tailored weights within the loss function of deep neural networks. Specifically designed to account for aneurysm size, shape, and texture, this approach strategically guides the model to focus on capturing discriminative information from imbalanced features. The study conducted extensive experimentation utilizing ADAM and RENJI TOF-MRA datasets to validate the proposed approach. The results of our experimentation demonstrate the remarkable effectiveness of the introduced methodology in improving aneurysm segmentation accuracy. By dynamically adapting to the variances present in aneurysm features, our model showcases promising outcomes for accurate diagnostic insights. The nuanced consideration of morphological and textural nuances within the loss function proves instrumental in overcoming the challenge posed by instance imbalance. In conclusion, our study presents a nuanced solution to the intricate challenge of intracranial aneurysm segmentation. The proposed morphology and texture loss reweighting approach, with its tailored weights and dynamic adaptability, proves to be instrumental in enhancing segmentation precision. The promising outcomes from our experimentation suggest the potential for accurate diagnostic insights and informed treatment strategies, marking a significant advancement in this critical domain of medical imaging.

Advances in the spatiotemporal resolution and field-of-view of neuroimaging tools are driving mesoscale studies for translational neuroscience. On October 10, 2023, the Center for Mesoscale Mapping (CMM) at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging and the Massachusetts Institute of Technology (MIT) Health Sciences Technology based Neuroimaging Training Program (NTP) hosted a symposium exploring the state-of-the-art in this rapidly growing area of research. "Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging" brought together researchers who use a broad range of imaging techniques to study brain structure and function at the convergence of the microscopic and macroscopic scales. The day-long event centered on areas in which the CMM has established expertise, including the development of emerging technologies and their application to clinical translational needs and basic neuroscience questions. The in-person symposium welcomed more than 150 attendees, including 57 faculty members, 61 postdoctoral fellows, 35 students, and four industry professionals, who represented institutions at the local, regional, and international levels. The symposium also served the training goals of both the CMM and the NTP. The event content, organization, and format were planned collaboratively by the faculty and trainees. Many CMM faculty presented or participated in a panel discussion, thus contributing to the dissemination of both the technologies they have developed under the auspices of the CMM and the findings they have obtained using those technologies. NTP trainees who benefited from the symposium included those who helped to organize the symposium and/or presented posters and gave "flash" oral presentations. In addition to gaining experience from presenting their work, they had opportunities throughout the day to engage in one-on-one discussions with visiting scientists and other faculty, potentially opening the door to future collaborations. The symposium presentations provided a deep exploration of the many technological advances enabling progress in structural and functional mesoscale brain imaging. Finally, students worked closely with the presenting faculty to develop this report summarizing the content of the symposium and putting it in the broader context of the current state of the field to share with the scientific community. We note that the references cited here include conference abstracts corresponding to the symposium poster presentations.

The black box nature of deep neural networks (DNNs) makes researchers and clinicians hesitant to rely on their findings. Saliency maps can enhance DNN explainability by suggesting the anatomic localization of relevant brain features. This study compares seven popular attribution-based saliency approaches to assign neuroanatomic interpretability to DNNs that estimate biological brain age (BA) from magnetic resonance imaging (MRI). Cognitively normal (CN) adults (N = 13,394, 5,900 males; mean age: 65.82 ± 8.89 years) are included for DNN training, testing, validation, and saliency map generation to estimate BA. To study saliency robustness to the presence of anatomic deviations from normality, saliency maps are also generated for adults with mild traumatic brain injury (mTBI, = 214, 135 males; mean age: 55.3 ± 9.9 years). We assess saliency methods' capacities to capture known anatomic features of brain aging and compare them to a surrogate ground truth whose anatomic saliency is known a priori. Anatomic aging features are identified most reliably by the integrated gradients method, which outperforms all others through its ability to localize relevant anatomic features. Gradient Shapley additive explanations, input × gradient, and masked gradient perform less consistently but still highlight ubiquitous neuroanatomic features of aging (ventricle dilation, hippocampal atrophy, sulcal widening). Saliency methods involving gradient saliency, guided backpropagation, and guided gradient-weight class attribution mapping localize saliency outside the brain, which is undesirable. Our research suggests the relative tradeoffs of saliency methods to interpret DNN findings during BA estimation in typical aging and after mTBI.

The brain is an intricate system that controls a variety of functions. It consists of a vast number of cells that exhibit diverse characteristics. To understand brain function in health and disease, it is crucial to classify neurons accurately. Recent advancements in machine learning have provided a way to classify neurons based on their electrophysiological activity. This paper presents a deep-learning framework that classifies neurons solely on this basis. The framework uses data from the Allen Cell Types database, which contains a survey of biological features derived from single-cell recordings from mice and humans. The shared information from both sources is used to classify neurons into their broad types with the help of a joint model. An accurate domain-adaptive model, integrating electrophysiological data from both mice and humans, is implemented. Furthermore, data from mouse neurons, which also includes labels of transgenic mouse lines, is further classified into subtypes using an interpretable neural network model. The framework provides state-of-the-art results in terms of accuracy and precision while also providing explanations for the predictions.

Brain reconstruction, specially of the cerebral cortex, is a challenging task and even more so when it comes to highly gyrified brained animals. Here, we present Stitcher, a novel tool capable of generating such surfaces utilizing MRI data and manual segmentation. Stitcher makes a triangulation between consecutive brain slice segmentations by recursively adding edges that minimize the total length and simultaneously avoid self-intersection. We applied this new method to build the cortical surfaces of two dolphins: Guiana dolphin (Sotalia guianensis), Franciscana dolphin (Pontoporia blainvillei); and one pinniped: Steller sea lion (Eumetopias jubatus). Specifically in the case of P. blainvillei, two reconstructions at two different resolutions were made. Additionally, we also performed reconstructions for sub and non-cortical structures of Guiana dolphin. All our cortical mesh results show remarkable resemblance with the real anatomy of the brains, except P. blainvillei with low-resolution data. Sub and non-cortical meshes were also properly reconstructed and the spatial positioning of structures was preserved with respect to S. guianensis cerebral cortex. In a comparative perspective between methods, Stitcher presents compatible results for volumetric measurements when contrasted with other anatomical standard tools. In this way, Stitcher seems to be a viable pipeline for new neuroanatomical analysis, enhancing visualization and descriptions of non-primates species, and broadening the scope of compared neuroanatomy.

Subdural electrocorticography (ECoG) is a valuable technique for neuroscientific research and for emerging neurotechnological clinical applications. As ECoG grids accommodate increasing numbers of electrodes and higher densities with new manufacturing methods, the question arises at what point the benefit of higher density ECoG is outweighed by spatial oversampling. To clarify the optimal spacing between ECoG electrodes, in the current study we evaluate how ECoG grid density relates to the amount of non-shared neurophysiological information between electrode pairs, focusing on the sensorimotor cortex. We simultaneously recorded high-density (HD, 3 mm pitch) and ultra-high-density (UHD, 0.9 mm pitch) ECoG, obtained intraoperatively from six participants. We developed a new metric, the normalized differential root mean square (ndRMS), to quantify the information that is not shared between electrode pairs. The ndRMS increases with inter-electrode center-to-center distance up to 15 mm, after which it plateaus. We observed differences in ndRMS between frequency bands, which we interpret in terms of oscillations in frequencies below 32 Hz with phase differences between pairs, versus (un)correlated signal fluctuations in the frequency range above 64 Hz. The finding that UHD recordings yield significantly higher ndRMS than HD recordings is attributed to the amount of tissue sampled by each electrode. These results suggest that ECoG densities with submillimeter electrode distances are likely justified.

Neurotechnology and big data are two rapidly advancing fields that have the potential to transform our understanding of the brain and its functions. Advancements in neurotechnology have enabled researchers to investigate the function of the brain at unprecedented levels of granularity at the functional, molecular, and anatomical levels. Thus, resulting in the collection of not only more data, but also larger datasets. To fully harness the potential of big data and advancements in neurotechnology to improve our understanding of the nervous system, there is a need to train a new generation of neuroscientists capable of not only domain expertise, but also the computational and data science skills required to interrogate and integrate big data. Importantly, neuroinformatics is the subdiscipline of neuroscience devoted to the development of neuroscience data and knowledge bases together with computational models and analytical tools for sharing, integration and analysis of experimental data, and advancement of theories about the nervous system function. While there are only a few formal training programs in neuroinformatics, and since neuroinformatics is rarely incorporated into traditional neuroscience training programs, the neuroinformatics community has attempted to bridge the gap between the traditional neuroscience education programs and the needs of the next generation of neuroscience researchers through community initiatives and workshops. Thus, the purpose of this special collection is to highlight several such community efforts which span from in-person workshops to large-scale, global virtual training consortiums and from training students to training-the-trainers.

Characterizing the anatomical structure and connectivity between cortical regions is a critical step towards understanding the information processing properties of the brain and will help provide insight into the nature of neurological disorders. A key feature of the mammalian cerebral cortex is its laminar structure. Identifying these layers in neuroimaging data is important for understanding their global structure and to help understand the connectivity patterns of neurons in the brain. We studied Nissl-stained and myelin-stained slice images of the brain of the common marmoset (Callithrix jacchus), which is a new world monkey that is becoming increasingly popular in the neuroscience community as an object of study. We present a novel computational framework that first acquired the cortical labels using AI-based tools followed by a trained deep learning model to segment cerebral cortical layers. We obtained a Euclidean distance of for the cortical labels acquisition, which was in the acceptable range by computing the half Euclidean distance of the average cortex thickness ( ). We compared our cortical layer segmentation pipeline with the pipeline proposed by Wagstyl et al. (PLoS biology, 18(4), e3000678 2020) adapted to 2D data. We obtained a better mean percentile Hausdorff distance (95HD) of  . Whereas a mean 95HD of  was obtained from Wagstyl et al. We also compared our pipeline's performance against theirs using their dataset (the BigBrain dataset). The results also showed better segmentation quality, Jaccard Index acquired from our pipeline, while was stated in their paper.

Attention Deficit Hyperactivity Disorder (ADHD) is a widespread neurobehavioral disorder affecting children and adolescents, requiring early detection for effective treatment. EEG connectivity measures can reveal the interdependencies between EEG recordings, highlighting brain network patterns and functional behavior that improve diagnostic accuracy. This study introduces a novel ADHD diagnostic method by combining linear and nonlinear brain connectivity maps with an attention-based convolutional neural network (Att-CNN). Pearson Correlation Coefficient (PCC) and Phase-Locking Value (PLV) are used to create fused connectivity maps (FCMs) from various EEG frequency subbands, which are then inputted into the Att-CNN. The attention module is strategically placed after the latest convolutional layer in the CNN. The performance of different optimizers (Adam and SGD) and learning rates are assessed. The suggested model obtained 98.88%, 98.41%, 98.19%, and 98.30% for accuracy, precision, recall, and F1 Score, respectively, using the SGD optimizer in the FCM of the theta band with a learning rate of 1e-1. With the use of FCM, Att-CNN, and advanced optimizers, the proposed technique has the potential to produce trustworthy instruments for the early diagnosis of ADHD, greatly enhancing both patient outcomes and diagnostic accuracy.

Over the past decade, the intricacies of sports-related concussions among female athletes have become readily apparent. Traditional clinical methods for diagnosing concussions suffer limitations when applied to female athletes, often failing to capture subtle changes in brain structure and function. Advanced neuroinformatics techniques and machine learning models have become invaluable assets in this endeavor. While these technologies have been extensively employed in understanding concussion in male athletes, there remains a significant gap in our comprehension of their effectiveness for female athletes. With its remarkable data analysis capacity, machine learning offers a promising avenue to bridge this deficit. By harnessing the power of machine learning, researchers can link observed phenotypic neuroimaging data to sex-specific biological mechanisms, unraveling the mysteries of concussions in female athletes. Furthermore, embedding methods within machine learning enable examining brain architecture and its alterations beyond the conventional anatomical reference frame. In turn, allows researchers to gain deeper insights into the dynamics of concussions, treatment responses, and recovery processes. This paper endeavors to address the crucial issue of sex differences in multimodal neuroimaging experimental design and machine learning approaches within female athlete populations, ultimately ensuring that they receive the tailored care they require when facing the challenges of concussions. Through better data integration, feature identification, knowledge representation, validation, etc., neuroinformaticists, are ideally suited to bring clarity, context, and explainabilty to the study of sports-related head injuries in males and in females, and helping to define recovery.

Leveraging vast neuroimaging and electrophysiological datasets, AI algorithms are uncovering patterns that offer unprecedented insights into brain structure and function. Neuroinformatics, the fusion of neuroscience and AI, is advancing technologies like brain-computer interfaces, AI-driven cognitive enhancement, and personalized neuromodulation for treating neurological disorders. These developments hold potential to improve cognitive functions, restore motor abilities, and create human-machine collaborative systems. Looking ahead, the convergence of neuroscience and AI is set to transform cognitive modeling, decision-making, and mental health interventions. This fusion mirrors the quest for nuclear fusion energy, both driven by the need to unlock profound sources of understanding. As STEM disciplines continue to drive core developments of foundational models of the brain, neuroinformatics promises to lead innovations in augmented intelligence, personalized healthcare, and effective decision-making systems.

Diffusion properties from diffusion tensor imaging (DTI) are exquisitely sensitive to white matter abnormalities incurred during traumatic brain injury (TBI), especially for those patients with chronic post-TBI symptoms such as headaches, dizziness, fatigue, etc. The evaluation of structural and functional connectivity using DTI has become a promising method for identifying subtle alterations in brain connectivity associated with TBI that are otherwise not visible with conventional imaging. This study assessed whether TBI patients with (n = 17) or without (n = 16) chronic symptoms (TBIcs/TBIncs) exhibit any changes in structural connectivity (SC) and mean fractional anisotropy (mFA) of intra- and inter-hemispheric connections when compared to a control group (CG) (n = 13). Reductions in SC and mFA were observed for TBIcs compared to CG, but not for TBIncs. More connections were found to have mFA reductions than SC reductions. On the whole, SC is dominated by ipsilateral connections for all the groups after the comparison of contralateral and ipsilateral connections. More contra-ipsi reductions of mFA were found for TBIcs than TBIncs compared to CG. These findings suggest that TBI patients with chronic symptoms not only demonstrate decreased global and regional mFA but also reduced structural network connectivity.

Schizophrenia is a mental disorder characterized by neurophysiological dysfunctions that result in disturbances in thinking, perception, and behavior. Early identification of schizophrenia can help prevent potential complications and facilitate effective treatment and management of the condition. This paper proposes a computer aided diagnosis system for the early detection of schizophrenia using 19-channel Electroencephalography (EEG) signals from 28 subjects, leveraging statistical moments of Mel-frequency Cepstral Coefficients (MFCC) and ensemble learning. Initially, the EEG signals are passed through a high-pass filter to mitigate noise and remove extraneous data. The feature extraction technique is then employed to extract MFC coefficients from the filtered EEG signals. The dimensionality of these coefficients is reduced by computing their statistical moments, which include the mean, standard deviation, skewness, kurtosis, and energy. Subsequently, the Support Vector Machine based Recursive Feature Elimination (SVM-RFE) is applied to identify pertinent features from the statistical moments of the MFC coefficients. These SVM-RFE-based selected features serve as input for three base classifiers: Support Vector Machine, k-Nearest Neighbors, and Logistic Regression. Additionally, an ensemble learning approach, which combines the predictions of the three classifiers through majority voting, is introduced to enhance schizophrenia detection performance and generalize the results of the proposed approach. The study's findings demonstrate that the ensemble model, combined with SVM-RFE-based selected statistical moments of MFCC, achieves encouraging detection performance, highlighting the potential of machine learning techniques in advancing the diagnostic process of schizophrenia.

Neuroscience education is challenged by rapidly evolving technology and the development of interdisciplinary approaches for brain research. The Human Brain Project (HBP) Education Programme aimed to address the need for interdisciplinary expertise in brain research by equipping a new generation of researchers with skills across neuroscience, medicine, and information technology. Over its ten year duration, the programme engaged over 1,300 experts and attracted more than 5,500 participants from various scientific disciplines in its blended learning curriculum, specialised schools and workshops, and events fostering dialogue among early-career researchers. Key principles of the programme's approach included fostering interdisciplinarity, adaptability to the evolving research landscape and infrastructure, and a collaborative environment with a focus on empowering early-career researchers. Following the programme's conclusion, we provide here an analysis and in-depth view across a diverse range of educational formats and events. Our results show that the Education Programme achieved success in its wide geographic reach, the diversity of participants, and the establishment of transversal collaborations. Building on these experiences and achievements, we describe how leveraging digital tools and platforms provides accessible and highly specialised training, which can enhance existing education programmes for the next generation of brain researchers working in decentralised European collaborative spaces. Finally, we present the lessons learnt so that similar initiatives may improve upon our experience and incorporate our suggestions into their own programme.

CADENCE is an open Python 3-written neuroinformatics tool with Qt6 graphic user interface for supervised calcium events detection. In neuronal ensembles recording during calcium imaging experiments, the output of instruments such as Celena X, Zeiss LSM 5 Live confocal microscope and Miniscope is a movie showing flashing cells somata. There are few pipelines to convert video to relative fluorescence ΔF/F, from simplest ImageJ plugins to sophisticated tools like MiniAn (Dong et al. in Elife 11, https://doi.org/10.7554/eLife.70661 , 2022). Minian, an open-source miniscope analysis pipeline. Elife, 11.). While in some areas of study relative fluorescence ΔF/F may be the desired result in itself, researchers of neuronal ensembles are typically interested in a more detailed analysis of calcium events as indirect proxy of neuronal electrical activity. For such analyses, researchers need a tool to infer calcium events from the continuous ΔF/F curve in order to create a raster representation of calcium events for later use in analysis software, such as Elephant (Denker, M., Yegenoglu, A., & Grün, S. (2018). Collaborative HPC-enabled workflows on the HBP Collaboratory using the Elephant framework. Neuroinformatics, 19.). Here we present such an open tool with supervised calcium events detection.

Neurotransmitter receptor densities are relevant for understanding the molecular architecture of brain regions. Quantitative in vitro receptor autoradiography, has been introduced to map neurotransmitter receptor distributions of brain areas. However, it is very time and cost-intensive, which makes it challenging to obtain whole-brain distributions. At the same time, high-throughput light microscopy and 3D reconstructions have enabled high-resolution brain maps capturing measures of cell density across the whole human brain. Aiming to bridge gaps in receptor measurements for building detailed whole-brain atlases, we study the feasibility of predicting realistic neurotransmitter density distributions from cell-body stainings. Specifically, we utilize conditional Generative Adversarial Networks (cGANs) to predict the density distributions of the M2 receptor of acetylcholine and the kainate receptor for glutamate in the macaque monkey's primary visual (V1) and motor cortex (M1), based on light microscopic scans of cell-body stained sections. Our model is trained on corresponding patches from aligned consecutive sections that display cell-body and receptor distributions, ensuring a mapping between the two modalities. Evaluations of our cGANs, both qualitative and quantitative, show their capability to predict receptor densities from cell-body stained sections while maintaining cortical features such as laminar thickness and curvature. Our work underscores the feasibility of cross-modality image translation problems to address data gaps in multi-modal brain atlases.