Integrative bioinformatics and artificial intelligence analyses of transcriptomics data identified genes associated with major depressive disorders including NRG1.

Major depressive disorder (MDD) is a common mental disorder and is amongst the most prevalent psychiatric disorders. MDD remains challenging to diagnose and predict its onset due to its heterogeneous phenotype and complex etiology. Hence, early detection using diagnostic biomarkers is critical for rapid intervention. In this study, a mixture of AI and bioinformatics were used to mine transcriptomic data from publicly available datasets including 170 MDD patients and 121 healthy controls. Bioinformatics analysis using gene set enrichment analysis (GSEA) and machine learning (ML) algorithms were applied. The GSEA revealed that differentially expressed genes in MDD patients are mainly enriched in pathways related to immune response, inflammatory response, neurodegeneration pathways and cerebellar atrophy pathways. Feature selection methods and ML provided predicted models based on MDD-altered genes with ≥75% of accuracy. The integrative analysis between the bioinformatics and ML approaches identified ten key MDD-related biomarkers including NRG1, CEACAM8, CLEC12B, DEFA4, HP, LCN2, OLFM4, SERPING1, TCN1 and THBS1. Among them, NRG1, active in synaptic plasticity and neurotransmission, was the most robust and reliable to distinguish between MDD patients and healthy controls amongst independent external datasets consisting of a mixture of populations. Further evaluation using saliva samples from an independent cohort of MDD and healthy individuals confirmed the upregulation of NRG1 in patients with MDD compared to healthy controls. Functional mapping to the human brain regions showed NRG1 to have high expression in the main subcortical limbic brain regions implicated in depression. In conclusion, integrative bioinformatics and ML approaches identified putative non-invasive diagnostic MDD-related biomarkers panel for the onset of depression.

Effects of age, gender, and hemisphere on cerebrovascular hemodynamics in children and young adults: Developmental scores and machine learning classifiers.

A constant blood supply to the brain is required for mental function. Research with Doppler ultrasonography has important clinical value and burgeoning potential with machine learning applications in studies predicting gestational age and vascular aging. Critically, studies on ultrasound metrics in school-age children are sparse and no machine learning study to date has used color duplex ultrasonography to predict age and classify age-group. The purpose of our study is two-fold: first to document cerebrovascular hemodynamics considering age, gender, and hemisphere in three arteries; and second to construct machine learning models that can predict and classify the age and age-group of a participant using ultrasonography metrics. We record peak systolic, end-diastolic, and time-averaged maximum velocities bilaterally in internal carotid, vertebral, and middle cerebral arteries from 821 participants. Results confirm that ultrasonography values decrease with age and reveal that gender and hemispheres show more similarities than differences, which depend on age, artery, and metric. Machine learning algorithms predict age and classifier models distinguish cerebrovascular hemodynamics between children and adults. Blood velocities, rather than blood vessel diameters, are more important for classifier models, and common and distinct variables contribute to age classification models for males and females.

A Toolbox and Crowdsourcing Platform for Automatic Labeling of Independent Components in Electroencephalography.

Independent Component Analysis (ICA) is a conventional approach to exclude non-brain signals such as eye movements and muscle artifacts from electroencephalography (EEG). A rejection of independent components (ICs) is usually performed in semiautomatic mode and requires experts' involvement. As also revealed by our study, experts' opinions about the nature of a component often disagree, highlighting the need to develop a robust and sustainable automatic system for EEG ICs classification. The current article presents a toolbox and crowdsourcing platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE) available via link http://alice.adase.org/. The ALICE toolbox aims to build a sustainable algorithm to remove artifacts and find specific patterns in EEG signals using ICA decomposition based on accumulated experts' knowledge. The difference from previous toolboxes is that the ALICE project will accumulate different benchmarks based on crowdsourced visual labeling of ICs collected from publicly available and in-house EEG recordings. The choice of labeling is based on the estimation of IC time-series, IC amplitude topography, and spectral power distribution. The platform allows supervised machine learning (ML) model training and re-training on available data subsamples for better performance in specific tasks (i.e., movement artifact detection in healthy or autistic children). Also, current research implements the novel strategy for consentient labeling of ICs by several experts. The provided baseline model could detect noisy IC and components related to the functional brain oscillations such as alpha and mu rhythm. The ALICE project implies the creation and constant replenishment of the IC database, which will improve ML algorithms for automatic labeling and extraction of non-brain signals from EEG. The toolbox and current dataset are open-source and freely available to the researcher community.

Consciousness in a multilevel architecture: What causes the lateralization of effective connectivity under resting state?

Here we present our answers to a critical commentary by Elkhonon Goldberg on our recent publication (Velichkovsky et al., 2018). To avoid discussions about novelty effects in the human brain activity and memory processes, we narrowed down this response to a reanalysis of our data along the lines proposed in the commentary, namely to comparing the effective links between symmetrical brain structures during the first and the last parts of a prolonged resting-state fMRI experiment. We also tested for sex differences in our results and checked for a stability of top-down interactions during the course of experiment because learning is often expressed in the weakening of upper level control over low-level mechanisms. Our attempts to test the predictions based on the novelty hypothesis has led to mixed results suggesting that the discovered right-to-left dominance of causal connections at rest may have a deeper origin than supposed in the Goldberg's commentary.

Consciousness in a multilevel architecture: Evidence from the right side of the brain.

By taking into account Bruce Bridgeman's interest in an evolutionary framing of human cognition, we examine effective (cause-and-effect) connectivity among cortical structures related to different parts of the triune phylogenetic stratification: archicortex, paleocortex and neocortex. Using resting-state functional magnetic resonance imaging data from 25 healthy subjects and spectral Dynamic Causal Modeling, we report interactions among 10 symmetrical left and right brain areas. Our results testify to general rightward and top-down biases in excitatory interactions of these structures during resting state, when self-related contemplation prevails over more objectified conceptual thinking. The right hippocampus is the only structure that shows bottom-up excitatory influences extending to the frontopolar cortex. The right ventrolateral cortex also plays a prominent role as it interacts with the majority of nodes within and between evolutionary distinct brain subdivisions. These results suggest the existence of several levels of cognitive-affective organization in the human brain and their profound lateralization.