Deep Learning Analyses of Brain MRI to Identify Sustained Attention Deficit in Treated Obstructive Sleep Apnea: A Pilot Study.

Purpose: Persistent sustained attention deficit (SAD) after continuous positive airway pressure (CPAP) treatment is a source of quality of life and occupational impairment in obstructive sleep apnea (OSA). However, persistent SAD is difficult to predict in patients initiated on CPAP treatment. We performed secondary analyses of brain magnetic resonance (MR) images in treated OSA participants, using deep learning, to predict SAD. Methods: 26 middle-aged men with CPAP use of more than 6 hours daily and MR imaging were included. SAD was defined by psychomotor vigilance task lapses of more than 2. 17 participants had SAD and 9 were without SAD. A Convolutional Neural Network (CNN) model was used for classifying the MR images into +SAD and -SAD categories. Results: The CNN model achieved an accuracy of 97.02±0.80% in classifying MR images into +SAD and -SAD categories. Assuming a threshold of 90% probability for the MR image being correctly classified, the model provided a participant-level accuracy of 99.11±0.55% and a stable image level accuracy of 97.45±0.63%. Conclusion: Deep learning methods, such as the proposed CNN model, can accurately predict persistent SAD based on MR images. Further replication of these findings will allow early initiation of adjunctive pharmacologic treatment in high-risk patients, along with CPAP, to improve quality of life and occupational fitness. Future augmentation of this approach with explainable artificial intelligence methods may elucidate the neuroanatomical areas underlying persistent SAD to provide mechanistic insights and novel therapeutic targets.

Inferring excitation-inhibition dynamics using a maximum entropy model unifying brain structure and function.

Neural activity coordinated across different scales from neuronal circuits to large-scale brain networks gives rise to complex cognitive functions. Bridging the gap between micro- and macroscale processes, we present a novel framework based on the maximum entropy model to infer a hybrid resting-state structural connectome, representing functional interactions constrained by structural connectivity. We demonstrate that the structurally informed network outperforms the unconstrained model in simulating brain dynamics, wherein by constraining the inference model with the network structure we may improve the estimation of pairwise BOLD signal interactions. Further, we simulate brain network dynamics using Monte Carlo simulations with the new hybrid connectome to probe connectome-level differences in excitation-inhibition balance between apolipoprotein E (APOE)-ε4 carriers and noncarriers. Our results reveal sex differences among APOE-ε4 carriers in functional dynamics at criticality; specifically, female carriers appear to exhibit a lower tolerance to network disruptions resulting from increased excitatory interactions. In sum, the new multimodal network explored here enables analysis of brain dynamics through the integration of structure and function, providing insight into the complex interactions underlying neural activity such as the balance of excitation and inhibition.

Autocatalytic-protection for an unknown locus CRISPR-Cas countermeasure for undesired mutagenic chain reactions.

The mutagenic chain reaction (MCR) is a genetic tool to use a CRISPR-Cas construct to introduce a homing endonuclease, allowing gene drive to influence whole populations in a minimal number of generations (Esvelt et al., 2014; Gantz and Bier, 2015; Gantz and Bier, 2016). The question arises: if an active genetic terror event is released into a population, could we prevent the total spread of the undesired allele (Gantz, et al., 2015; Webber et al., 2015)? Thus far, effective protection methods require knowledge of the terror locus (Grunwald et al., 2019). Here we introduce a novel approach, an autocatalytic-Protection for an Unknown Locus (a-PUL), whose aim is to spread through a population and arrest and decrease an active terror event's spread without any prior knowledge of the terror-modified locus, thus allowing later natural selection and ERACR drives to restore the normal locus (Hammond et al., 2017). a-PUL, using a mutagenic chain reaction, includes (i) a segment encoding a non-Cas9 endonuclease capable of homology-directed repair suggested as Type II endonuclease Cpf1 (Cas12a), (ii) a ubiquitously-expressed gene encoding a gRNA (gRNA1) with a U4AU4 3'-overhang specific to Cpf1 and with crRNA specific to some desired genomic sequence of non-coding DNA, (iii) a ubiquitously-expressed gene encoding two gRNAs (gRNA2/gRNA3) both with tracrRNA specific to Cas9 and crRNA specific to two distinct sites of the Cas9 locus, and (iv) homology arms flanking the Cpf1/gRNA1/gRNA2/gRNA3 cassette that are identical to the region surrounding the target cut directed by gRNA1 (Khan, 2016; Zetsche et al., 2015). We demonstrate the proof-of-concept and efficacy of our protection construct through a Graphical Markov model and computer simulation.

Connectome Signatures of Hyperexcitation in Cognitively Intact Middle-Aged Female APOE-ε4 Carriers.

Synaptic dysfunction is hypothesized to be one of the earliest brain changes in Alzheimer's disease, leading to "hyperexcitability" in neuronal circuits. In this study, we evaluated a novel hyperexcitation indicator (HI) for each brain region using a hybrid resting-state structural connectome to probe connectome-level excitation-inhibition balance in cognitively intact middle-aged apolipoprotein E (APOE) ε4 carriers with noncarriers (16 male/22 female in each group). Regression with three-way interactions (sex, age, and APOE-ε4 carrier status) to assess the effect of APOE-ε4 on excitation-inhibition balance within each sex and across an age range of 40-60 years yielded a significant shift toward higher HI in female carriers compared with noncarriers (beginning at 50 years). Hyperexcitation was insignificant in the male group. Further, in female carriers the degree of hyperexcitation exhibited significant positive correlation with working memory performance (evaluated via a virtual Morris Water task) in three regions: the left pars triangularis, left hippocampus, and left isthmus of cingulate gyrus. Increased excitation of memory-related circuits may be evidence of compensatory recruitment of neuronal resources for memory-focused activities. In sum, our results are consistent with known Alzheimer's disease sex differences; in that female APOE-ε4 carriers have globally disrupted excitation-inhibition balance that may confer greater vulnerability to disease neuropathology.

Deep learning applied to polysomnography to predict blood pressure in obstructive sleep apnea and obesity hypoventilation: a proof-of-concept study.

STUDY OBJECTIVES: Nocturnal blood pressure (BP) profile shows characteristic abnormalities in OSA, namely acute postapnea BP surges and nondipping BP. These abnormal BP profiles provide prognostic clues indicating increased cardiovascular disease risk. We developed a deep neural network model to perform computerized analysis of polysomnography data and predict nocturnal BP profile. METHODS: We analyzed concurrently performed polysomnography and noninvasive beat-to-beat BP measurement with a deep neural network model to predict nocturnal BP profiles from polysomnography data in 13 patients with severe OSA. RESULTS: A good correlation was noted between measured and predicted postapnea systolic and diastolic BP (Pearson r ≥ .75). Moreover, Bland-Altman analyses showed good agreement between the 2 values. Continuous systolic and diastolic BP prediction by the deep neural network model was also well correlated with measured BP values (Pearson r ≥ .83). CONCLUSIONS: We developed a deep neural network model to predict nocturnal BP profile from clinical polysomnography signals and provide a potential prognostic tool in OSA. Validation of the model in larger samples and examination of its utility in predicting CVD risk in future studies is warranted.

Compressive sensing of sparse tensors.

Compressive sensing (CS) has triggered an enormous research activity since its first appearance. CS exploits the signal's sparsity or compressibility in a particular domain and integrates data compression and acquisition, thus allowing exact reconstruction through relatively few nonadaptive linear measurements. While conventional CS theory relies on data representation in the form of vectors, many data types in various applications, such as color imaging, video sequences, and multisensor networks, are intrinsically represented by higher order tensors. Application of CS to higher order data representation is typically performed by conversion of the data to very long vectors that must be measured using very large sampling matrices, thus imposing a huge computational and memory burden. In this paper, we propose generalized tensor compressive sensing (GTCS)-a unified framework for CS of higher order tensors, which preserves the intrinsic structure of tensor data with reduced computational complexity at reconstruction. GTCS offers an efficient means for representation of multidimensional data by providing simultaneous acquisition and compression from all tensor modes. In addition, we propound two reconstruction procedures, a serial method and a parallelizable method. We then compare the performance of the proposed method with Kronecker compressive sensing (KCS) and multiway compressive sensing (MWCS). We demonstrate experimentally that GTCS outperforms KCS and MWCS in terms of both reconstruction accuracy (within a range of compression ratios) and processing speed. The major disadvantage of our methods (and of MWCS as well) is that the compression ratios may be worse than that offered by KCS.

Multilinear Discriminant Analysis for Higher-Order Tensor Data Classification.

In the past decade, great efforts have been made to extend linear discriminant analysis for higher-order data classification, generally referred to as multilinear discriminant analysis (MDA). Existing examples include general tensor discriminant analysis (GTDA) and discriminant analysis with tensor representation (DATER). Both the two methods attempt to resolve the problem of tensor mode dependency by iterative approximation. GTDA is known to be the first MDA method that converges over iterations. However, its performance relies highly on the tuning of the parameter in the scatter difference criterion. Although DATER usually results in better classification performance, it does not converge, yet the number of iterations executed has a direct impact on DATER's performance. In this paper, we propose a closed-form solution to the scatter difference objective in GTDA, namely, direct GTDA (DGTDA) which also gets rid of parameter tuning. We demonstrate that DGTDA outperforms GTDA in terms of both efficiency and accuracy. In addition, we propose constrained multilinear discriminant analysis (CMDA) that learns the optimal tensor subspace by iteratively maximizing the scatter ratio criterion. We prove both theoretically and experimentally that the value of the scatter ratio criterion in CMDA approaches its extreme value, if it exists, with bounded error, leading to superior and more stable performance in comparison to DATER.

Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation.

In this article, we present path length associated community estimation (PLACE), a comprehensive framework for studying node-level community structure. Instead of the well-known Q modularity metric, PLACE utilizes a novel metric, Ψ(PL), which measures the difference between intercommunity versus intracommunity path lengths. We compared community structures in human healthy brain networks generated using these two metrics and argued that Ψ(PL) may have theoretical advantages. PLACE consists of the following: (1) extracting community structure using top-down hierarchical binary trees, where a branch at each bifurcation denotes a collection of nodes that form a community at that level, (2) constructing and assessing mean group community structure, and (3) detecting node-level changes in community between groups. We applied PLACE and investigated the structural brain networks obtained from a sample of 25 euthymic bipolar I subjects versus 25 gender- and age-matched healthy controls. Results showed community structural differences in posterior default mode network regions, with the bipolar group exhibiting left-right decoupling.

Optimal Perturbation Control of General Topology Molecular Networks.

In this paper, we develop a comprehensive framework for optimal perturbation control of dynamic networks. The aim of the perturbation is to drive the network away from an undesirable steady-state distribution and to force it to converge towards a desired steady-state distribution. The proposed framework does not make any assumptions about the topology of the initial network, and is thus applicable to general-topology networks. We define the optimal perturbation control as the minimum-energy perturbation measured in terms of the Frobenius-norm between the initial and perturbed probability transition matrices of the dynamic network. We subsequently demonstrate that there exists at most one optimal perturbation that forces the network into the desirable steady-state distribution. In the event where the optimal perturbation does not exist, we construct a family of suboptimal perturbations, and show that the suboptimal perturbation can be used to approximate the optimal limiting distribution arbitrarily closely. Moreover, we investigate the robustness of the optimal perturbation control to errors in the probability transition matrix, and demonstrate that the proposed optimal perturbation control is robust to data and inference errors in the probability transition matrix of the initial network. Finally, we apply the proposed optimal perturbation control method to the Human melanoma gene regulatory network in order to force the network from an initial steady-state distribution associated with melanoma and into a desirable steady-state distribution corresponding to a benign cell.

A framework for quantifying node-level community structure group differences in brain connectivity networks.

We propose a framework for quantifying node-level community structures between groups using anatomical brain networks derived from DTI-tractography. To construct communities, we computed hierarchical binary trees by maximizing two metrics: the well-known modularity metric (Q), and a novel metric that measures the difference between inter-community and intra-community path lengths. Changes in community structures on the nodal level were assessed between generated trees and a statistical framework was developed to detect local differences between two groups of community structures. We applied this framework to a sample of 42 subjects with major depression and 47 healthy controls. Results showed that several nodes (including the bilateral precuneus, which have been linked to self-awareness) within the default mode network exhibited significant differences between groups. These findings are consistent with those reported in previous literature, suggesting a higher degree of ruminative self-reflections in depression.

M-idempotent and self-dual morphological filters.

In this paper, we present a comprehensive analysis of self-dual and m-idempotent operators. We refer to an operator as m-idempotent if it converges after m iterations. We focus on an important special case of the general theory of lattice morphology: spatially variant morphology, which captures the geometrical interpretation of spatially variant structuring elements. We demonstrate that every increasing self-dual morphological operator can be viewed as a morphological center. Necessary and sufficient conditions for the idempotence of morphological operators are characterized in terms of their kernel representation. We further extend our results to the representation of the kernel of m-idempotent morphological operators. We then rely on the conditions on the kernel representation derived and establish methods for the construction of m-idempotent and self-dual morphological operators. Finally, we illustrate the importance of the self-duality and m-idempotence properties by an application to speckle noise removal in radar images.

Information-theoretic model of evolution over protein communication channel.

In this paper, we propose a communication model of evolution and investigate its information-theoretic bounds. The process of evolution is modeled as the retransmission of information over a protein communication channel, where the transmitted message is the organism's proteome encoded in the DNA. We compute the capacity and the rate distortion functions of the protein communication system for the three domains of life: Archaea, Bacteria, and Eukaryotes. The tradeoff between the transmission rate and the distortion in noisy protein communication channels is analyzed. As expected, comparison between the optimal transmission rate and the channel capacity indicates that the biological fidelity does not reach the Shannon optimal distortion. However, the relationship between the channel capacity and rate distortion achieved for different biological domains provides tremendous insight into the dynamics of the evolutionary processes of the three domains of life. We rely on these results to provide a model of genome sequence evolution based on the two major evolutionary driving forces: mutations and unequal crossovers.

Inverse perturbation for optimal intervention in gene regulatory networks.

MOTIVATION: Analysis and intervention in the dynamics of gene regulatory networks is at the heart of emerging efforts in the development of modern treatment of numerous ailments including cancer. The ultimate goal is to develop methods to intervene in the function of living organisms in order to drive cells away from a malignant state into a benign form. A serious limitation of much of the previous work in cancer network analysis is the use of external control, which requires intervention at each time step, for an indefinite time interval. This is in sharp contrast to the proposed approach, which relies on the solution of an inverse perturbation problem to introduce a one-time intervention in the structure of regulatory networks. This isolated intervention transforms the steady-state distribution of the dynamic system to the desired steady-state distribution. RESULTS: We formulate the optimal intervention problem in gene regulatory networks as a minimal perturbation of the network in order to force it to converge to a desired steady-state distribution of gene regulation. We cast optimal intervention in gene regulation as a convex optimization problem, thus providing a globally optimal solution which can be efficiently computed using standard toolboxes for convex optimization. The criteria adopted for optimality is chosen to minimize potential adverse effects as a consequence of the intervention strategy. We consider a perturbation that minimizes (i) the overall energy of change between the original and controlled networks and (ii) the time needed to reach the desired steady-state distribution of gene regulation. Furthermore, we show that there is an inherent trade-off between minimizing the energy of the perturbation and the convergence rate to the desired distribution. We apply the proposed control to the human melanoma gene regulatory network. AVAILABILITY: The MATLAB code for optimal intervention in gene regulatory networks can be found online: http://syen.ualr.edu/nxbouaynaya/Bioinformatics2010.html.

Video tracking based on sequential particle filtering on graphs.

In this paper, we develop a novel solution for particle filtering on general graphs. We provide an exact solution for particle filtering on directed cycle-free graphs. The proposed approach relies on a partial-order relation in an antichain decomposition that forms a high-order Markov chain over the partitioned graph. We subsequently derive a closed-form sequential updating scheme for conditional density propagation using particle filtering on directed cycle-free graphs. We also provide an approximate solution for particle filtering on general graphs by splitting graphs with cycles into multiple directed cycle-free subgraphs. We then use the sequential updating scheme by alternating among the directed cycle-free subgraphs to obtain an estimate of the density propagation. We rely on the proposed method for particle filtering on general graphs for two video tracking applications: 1) object tracking using high-order Markov chains; and 2) distributed multiple object tracking based on multi-object graphical interaction models. Experimental results demonstrate the improved performance of the proposed approach to particle filtering on graphs compared with existing methods for video tracking.

Robustness of inverse perturbation for discrete event control.

We study the robustness of the inverse perturbation solution in discrete-time systems modeled by homogeneous Markov chains. We cast the optimal inverse perturbation control as a strictly convex optimization problem, which admits a unique global solution. We show that the optimal inverse perturbation control is robust to estimation errors in the original network. The derived results are applied to the Human melanoma gene regulatory network, where the aim is to force the network to converge to a desired steady-state distribution of gene regulation.

A particle filtering framework for joint video tracking and pose estimation.

A method is introduced to track the object's motion and estimate its pose directly from 2-D image sequences. Scale-invariant feature transform (SIFT) is used to extract corresponding feature points from image sequences. We demonstrate that pose estimation from the corresponding feature points can be formed as a solution to Sylvester's equation. We show that the proposed approach to the solution of Sylvester's equation is equivalent to the classical SVD method for 3D-3D pose estimation. However, whereas classical SVD cannot be used for pose estimation directly from 2-D image sequences, our method based on Sylvester's equation provides a new approach to pose estimation. Smooth video tracking and pose estimation is finally obtained by using the solution to Sylvester's equation within the importance sampling density of the particle filtering framework. Finally, computer simulation experiments conducted over synthetic data and real-world videos demonstrate the effectiveness of our method in both robustness and speed compared with other similar object tracking and pose estimation methods.

Virtual focus and depth estimation from defocused video sequences.

In this paper, we present a novel method for virtual focus and object depth estimation from defocused video captured by a moving camera. We use the term virtual focus to refer to a new approach for producing in-focus image sequences by processing blurred videos captured by out-of-focus cameras. Our method relies on the concept of Depth-from-Defocus (DFD) for virtual focus estimation. However, the proposed approach overcomes limitations of DFD by reformulating the problem in a moving-camera scenario. We introduce the interframe image motion model, from which the relationship between the camera motion and blur characteristics can be formed. This relationship subsequently leads to a new method for blur estimation. We finally rely on the blur estimation to develop the proposed technique for object depth estimation and focused video reconstruction. The proposed approach can be utilized to correct out-of-focus video sequences and can potentially replace the expensive apparatus required for auto-focus adjustments currently employed in many camera devices. The performance of the proposed algorithm is demonstrated through error analysis and computer simulated experiments.

Attraction-repulsion expectation-maximization algorithm for image reconstruction and sensor field estimation.

In this paper, we propose an attraction-repulsion expectation-maximization (AREM) algorithm for image reconstruction and sensor field estimation. We rely on a new method for density estimation to address the problems of image reconstruction from limited samples and sensor field estimation from randomly scattered sensors. Density estimation methods often suffer from undesirable phenomena such as over-fitting and over-smoothing. Specifically, various density estimation techniques based on a Gaussian mixture model (GMM) tend to cluster the Gaussian functions together, thus resulting in over-fitting. On the other hand, other approaches repel the Gaussian functions and yield over-smooth density estimates. We propose a method that seeks an equilibrium between over-fitting and over-smoothing in density estimation by incorporating attraction and repulsion forces among the Gaussian functions and determining the optimal balance between the competing forces experimentally. We model the attractive and repulsive forces by introducing the Gibbs and inverse Gibbs distributions, respectively. The maximization of the likelihood function augmented by the Gibbs density mixture is solved under the expectation-maximization (EM) method. Computer simulation results are provided to demonstrate the effectiveness of the proposed AREM algorithm in image reconstruction and sensor field estimation.