Sergey Plis

Spontaneous fluctuations are a hallmark of recordings of neural signals, emergent over time scales spanning milliseconds and tens of minutes. However, investigations of intrinsic brain organization based on resting-state functional magnetic resonance imaging have largely not taken into account the presence and potential of temporal variability, as most current approaches to examine functional connectivity (FC) implicitly assume that relationships are constant throughout the length of the recording. In this work, we describe an approach to assess whole-brain FC dynamics based on spatial independent component analysis, sliding time window correlation, and k-means clustering of windowed correlation matrices. The method is applied to resting-state data from a large sample (n = 405) of young adults. Our analysis of FC variability highlights particularly flexible connections between regions in lateral parietal and cingulate cortex, and argues against a labeling scheme where such regions are treated as separate and antagonistic entities. Additionally, clustering analysis reveals unanticipated FC states that in part diverge strongly from stationary connectivity patterns and challenge current descriptions of interactions between large-scale networks. Temporal trends in the occurrence of different FC states motivate theories regarding their functional roles and relationships with vigilance/arousal. Overall, we suggest that the study of time-varying aspects of FC can unveil flexibility in the functional coordination between different neural systems, and that the exploitation of these dynamics in further investigations may improve our understanding of behavioral shifts and adaptive processes.

Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager's toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building block the restricted Boltzmann machine. We also describe a novel constraint-based approach to visualizing high dimensional data. We use it to analyze the effect of parameter choices on data transformations. Our results show that deep learning methods are able to learn physiologically important representations and detect latent relations in neuroimaging data.

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

Abstract Recent critical commentaries unfavorably compare deep learning (DL) with standard machine learning (SML) approaches for brain imaging data analysis. However, their conclusions are often based on pre-engineered features depriving DL of its main advantage — representation learning. We conduct a large-scale systematic comparison profiled in multiple classification and regression tasks on structural MRI images and show the importance of representation learning for DL. Results show that if trained following prevalent DL practices, DL methods have the potential to scale particularly well and substantially improve compared to SML methods, while also presenting a lower asymptotic complexity in relative computational time, despite being more complex. We also demonstrate that DL embeddings span comprehensible task-specific projection spectra and that DL consistently localizes task-discriminative brain biomarkers. Our findings highlight the presence of nonlinearities in neuroimaging data that DL can exploit to generate superior task-discriminative representations for characterizing the human brain.