Amplifying pathological detection in EEG signaling pathways through cross-dataset transfer learning.

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labeled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labeling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labeled data was available. Our findings demonstrated that a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better in transfer learning when leveraging a larger and more diverse dataset.

Comparison of Radiologists and Deep Learning for US Grading of Hepatic Steatosis.

Background Screening for nonalcoholic fatty liver disease (NAFLD) is suboptimal due to the subjective interpretation of US images. Purpose To evaluate the agreement and diagnostic performance of radiologists and a deep learning model in grading hepatic steatosis in NAFLD at US, with biopsy as the reference standard. Materials and Methods This retrospective study included patients with NAFLD and control patients without hepatic steatosis who underwent abdominal US and contemporaneous liver biopsy from September 2010 to October 2019. Six readers visually graded steatosis on US images twice, 2 weeks apart. Reader agreement was assessed with use of κ statistics. Three deep learning techniques applied to B-mode US images were used to classify dichotomized steatosis grades. Classification performance of human radiologists and the deep learning model for dichotomized steatosis grades (S0, S1, S2, and S3) was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. Results The study included 199 patients (mean age, 53 years ± 13 [SD]; 101 men). On the test set (n = 52), radiologists had fair interreader agreement (0.34 [95% CI: 0.31, 0.37]) for classifying steatosis grades S0 versus S1 or higher, while AUCs were between 0.49 and 0.84 for radiologists and 0.85 (95% CI: 0.83, 0.87) for the deep learning model. For S0 or S1 versus S2 or S3, radiologists had fair interreader agreement (0.30 [95% CI: 0.27, 0.33]), while AUCs were between 0.57 and 0.76 for radiologists and 0.73 (95% CI: 0.71, 0.75) for the deep learning model. For S2 or lower versus S3, radiologists had fair interreader agreement (0.37 [95% CI: 0.33, 0.40]), while AUCs were between 0.52 and 0.81 for radiologists and 0.67 (95% CI: 0.64, 0.69) for the deep learning model. Conclusion Deep learning approaches applied to B-mode US images provided comparable performance with human readers for detection and grading of hepatic steatosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Tuthill in this issue.

Beyond performance: the role of task demand, effort, and individual differences in ab initio pilots.

Aviation safety depends on the skill and expertise of pilots to meet the task demands of flying an aircraft in an effective and efficient manner. During flight training, students may respond differently to imposed task demands based on individual differences in capacity, physiological arousal, and effort. To ensure that pilots achieve a common desired level of expertise, training programs should account for individual differences to optimize pilot performance. This study investigates the relationship between task performance and physiological correlates of effort in ab initio pilots. Twenty-four participants conducted a flight simulator task with three difficulty levels and were asked to rate their perceived demand and effort using the NASA TLX. We recorded heart rate, EEG brain activity, and pupil size to assess changes in the participants' mental and physiological states across different task demands. We found that, despite group-level correlations between performance error and physiological responses, individual differences in physiological responses to task demands reflected different levels of participant effort and task efficiency. These findings suggest that physiological monitoring of student pilots might provide beneficial insights to flight instructors to optimize pilot training at the individual level.

Estimating individual minimum calibration for deep-learning with predictive performance recovery: An example case of gait surface classification from wearable sensor gait data.

Clinical datasets often comprise multiple data points or trials sampled from a single participant. When these datasets are used to train machine learning models, the method used to extract train and test sets must be carefully chosen. Using the standard machine learning approach (random-wise split), different trials from the same participant may appear in both training and test sets. This has led to schemes capable of segregating data points from a same participant into a single set (subject-wise split). Past investigations have demonstrated that models trained in this manner underperform compared to those trained using random-split schemes. Additional training of models via a small subset of trials, known as calibration, bridges the gap in performance across split schemes; however, the amount of calibration trials required to achieve strong model performance is unclear. Thus, this study aims to investigate the relationship between calibration training set size and prediction accuracy on the calibration test set. A database of 30 young, healthy adults performing multiple walking trials across nine different surfaces while fit with inertial measurement unit sensors on the lower limbs was used to develop a deep-learning classifier. For subject-wise trained models, calibration on a single gait cycle per surface yielded a 70% increase in F1-score, the harmonic mean of precision and recall, while 10 gait cycles per surface were sufficient to match the performance of a random-wise trained model. Code to generate calibration curves may be found at (https://github.com/GuillaumeLam/PaCalC).

Generative Models of Brain Dynamics.

This review article gives a high-level overview of the approaches across different scales of organization and levels of abstraction. The studies covered in this paper include fundamental models in computational neuroscience, nonlinear dynamics, data-driven methods, as well as emergent practices. While not all of these models span the intersection of neuroscience, AI, and system dynamics, all of them do or can work in tandem as generative models, which, as we argue, provide superior properties for the analysis of neuroscientific data. We discuss the limitations and unique dynamical traits of brain data and the complementary need for hypothesis- and data-driven modeling. By way of conclusion, we present several hybrid generative models from recent literature in scientific machine learning, which can be efficiently deployed to yield interpretable models of neural dynamics.

Learning Brain Dynamics With Coupled Low-Dimensional Nonlinear Oscillators and Deep Recurrent Networks.

Many natural systems, especially biological ones, exhibit complex multivariate nonlinear dynamical behaviors that can be hard to capture by linear autoregressive models. On the other hand, generic nonlinear models such as deep recurrent neural networks often require large amounts of training data, not always available in domains such as brain imaging; also, they often lack interpretability. Domain knowledge about the types of dynamics typically observed in such systems, such as a certain type of dynamical systems models, could complement purely data-driven techniques by providing a good prior. In this work, we consider a class of ordinary differential equation (ODE) models known as van der Pol (VDP) oscil lators and evaluate their ability to capture a low-dimensional representation of neural activity measured by different brain imaging modalities, such as calcium imaging (CaI) and fMRI, in different living organisms: larval zebrafish, rat, and human. We develop a novel and efficient approach to the nontrivial problem of parameters estimation for a network of coupled dynamical systems from multivariate data and demonstrate that the resulting VDP models are both accurate and interpretable, as VDP's coupling matrix reveals anatomically meaningful excitatory and inhibitory interactions across different brain subsystems. VDP outperforms linear autoregressive models (VAR) in terms of both the data fit accuracy and the quality of insight provided by the coupling matrices and often tends to generalize better to unseen data when predicting future brain activity, being comparable to and sometimes better than the recurrent neural networks (LSTMs). Finally, we demonstrate that our (generative) VDP model can also serve as a data-augmentation tool leading to marked improvements in predictive accuracy of recurrent neural networks. Thus, our work contributes to both basic and applied dimensions of neuroimaging: gaining scientific insights and improving brain-based predictive models, an area of potentially high practical importance in clinical diagnosis and neurotechnology.

Resting-state connectivity stratifies premanifest Huntington's disease by longitudinal cognitive decline rate.

Patient stratification is critical for the sensitivity of clinical trials at early stages of neurodegenerative disorders. In Huntington's disease (HD), genetic tests make cognitive, motor and brain imaging measurements possible before symptom manifestation (pre-HD). We evaluated pre-HD stratification models based on single visit resting-state functional MRI (rs-fMRI) data that assess observed longitudinal motor and cognitive change rates from the multisite Track-On HD cohort (74 pre-HD, 79 control participants). We computed longitudinal performance change on 10 tasks (including visits from the preceding TRACK-HD study when available), as well as functional connectivity density (FCD) maps in single rs-fMRI visits, which showed high test-retest reliability. We assigned pre-HD subjects to subgroups of fast, intermediate, and slow change along single tasks or combinations of them, correcting for expectations based on aging; and trained FCD-based classifiers to distinguish fast- from slow-progressing individuals. For robustness, models were validated across imaging sites. Stratification models distinguished fast- from slow-changing participants and provided continuous assessments of decline applicable to the whole pre-HD population, relying on previously-neglected white matter functional signals. These results suggest novel correlates of early deterioration and a robust stratification strategy where a single MRI measurement provides an estimate of multiple ongoing longitudinal changes.

Baseline multimodal information predicts future motor impairment in premanifest Huntington's disease.

In Huntington's disease (HD), accurate estimates of expected future motor impairments are key for clinical trials. Individual prognosis is only partially explained by genetics. However, studies so far have focused on predicting the time to clinical diagnosis based on fixed impairment levels, as opposed to predicting impairment in time windows comparable to the duration of a clinical trial. Here we evaluate an approach to both detect atrophy patterns associated with early degeneration and provide a prognosis of motor impairment within 3 years, using data from the TRACK-HD study on 80 premanifest HD (pre-HD) individuals and 85 age- and sex-matched healthy controls. We integrate anatomical MRI information from gray matter concentrations (estimated via voxel-based morphometry) together with baseline data from demographic, genetic and motor domains to distinguish individuals at high risk of developing pronounced future motor impairment from those at low risk. We evaluate the ability of models to distinguish between these two groups solely using baseline imaging data, as well as in combination with longitudinal imaging or non-imaging data. Our models show improved performance for motor prognosis through the incorporation of imaging features to non-imaging data, reaching 88% cross-validated accuracy when using baseline non-longitudinal information, and detect informative correlates in the caudate nucleus and the thalamus both for motor prognosis and early atrophy detection. These results show the plausibility of using baseline imaging and basic demographic/genetic measures for early detection of individuals at high risk of severe future motor impairment in relatively short timeframes.

Functional Network Disruptions in Schizophrenia.

It has been long recognized that schizophrenia, unlike certain other mental disorders, appears to be delocalized, i.e., difficult to attribute to a dysfunction of a few specific brain areas, and may be better understood as a disruption of brain's emergent network properties. In this chapter, we focus on topological properties of functional brain networks obtained from fMRI data, and demonstrate that some of those properties can be used as discriminative features of schizophrenia in multivariate predictive setting. While the prior work on schizophrenia networks has been primarily focused on discovering statistically significant differences in network properties, this work extends the prior art by exploring the generalization (prediction) ability of network models for schizophrenia, which is not necessarily captured by such significance tests. Moreover, we show that significant disruption of the topological and spatial structure of functional MRI networks in schizophrenia (a) cannot be explained by a disruption to area-based task-dependent responses, i.e., indeed relates to the emergent properties, (b) is global in nature, affecting most dramatically long-distance correlations, and (c) can be leveraged to achieve high classification accuracy (93%) when discriminating between schizophrenic vs. control subjects based just on a single fMRI experiment using a simple auditory task.

Learning stable and predictive network-based patterns of schizophrenia and its clinical symptoms.

Schizophrenia is often associated with disrupted brain connectivity. However, identifying specific neuroimaging-based patterns pathognomonic for schizophrenia and related symptom severity remains a challenging open problem requiring large-scale data-driven analyses emphasizing not only statistical significance but also stability across multiple datasets, contexts and cohorts. Accurate prediction on previously unseen subjects, or generalization, is also essential for any useful biomarker of schizophrenia. In order to build a predictive model based on functional network feature patterns, we studied whole-brain fMRI functional networks, both at the voxel level and lower-resolution supervoxel level. Targeting Auditory Oddball task data on the FBIRN fMRI dataset (n = 95), we considered node-degree and link-weight network features and evaluated stability and generalization accuracy of statistically significant feature sets in discriminating patients vs. CONTROLS: We also applied sparse multivariate regression (elastic net) to whole-brain functional connectivity features, for the first time, to derive stable predictive features for symptom severity. Whole-brain link-weight features achieved 74% accuracy in identifying patients and were more stable than voxel-wise node-degrees. Link-weight features predicted severity of several negative and positive symptom scales, including inattentiveness and bizarre behavior. The most-significant, stable and discriminative functional connectivity changes involved increased correlations between thalamus and primary motor/primary sensory cortex, and between precuneus (BA7) and thalamus, putamen, and Brodmann areas BA9 and BA44. Precuneus, along with BA6 and primary sensory cortex, was also involved in predicting severity of several symptoms. Overall, the proposed multi-step methodology may help identify more reliable multivariate patterns allowing for accurate prediction of schizophrenia and its symptoms severity.

MINT: Mutual Information Based Transductive Feature Selection for Genetic Trait Prediction.

Whole genome prediction of complex phenotypic traits using high-density genotyping arrays has attracted a lot of attention, as it is relevant to the fields of plant and animal breeding and genetic epidemiology. Since the number of genotypes is generally much bigger than the number of samples, predictive models suffer from the curse of dimensionality. The curse of dimensionality problem not only affects the computational efficiency of a particular genomic selection method, but can also lead to a poor performance, mainly due to possible overfitting, or un-informative features. In this work, we propose a novel transductive feature selection method, called MINT, which is based on the MRMR (Max-Relevance and Min-Redundancy) criterion. We apply MINT on genetic trait prediction problems and show that, in general, MINT is a better feature selection method than the state-of-the-art inductive method MRMR.

Variable-Selection Emerges on Top in Empirical Comparison of Whole-Genome Complex-Trait Prediction Methods.

Accurate prediction of complex traits based on whole-genome data is a computational problem of paramount importance, particularly to plant and animal breeders. However, the number of genetic markers is typically orders of magnitude larger than the number of samples (p >> n), amongst other challenges. We assessed the effectiveness of a diverse set of state-of-the-art methods on publicly accessible real data. The most surprising finding was that approaches with feature selection performed better than others on average, in contrast to the expectation in the community that variable selection is mostly ineffective, i.e. that it does not improve accuracy of prediction, in spite of p >> n. We observed superior performance despite a somewhat simplistic approach to variable selection, possibly suggesting an inherent robustness. This bodes well in general since the variable selection methods usually improve interpretability without loss of prediction power. Apart from identifying a set of benchmark data sets (including one simulated data), we also discuss the performance analysis for each data set in terms of the input characteristics.

Schizophrenia as a network disease: disruption of emergent brain function in patients with auditory hallucinations.

Schizophrenia is a psychiatric disorder that has eluded characterization in terms of local abnormalities of brain activity, and is hypothesized to affect the collective, "emergent" working of the brain. Indeed, several recent publications have demonstrated that functional networks in the schizophrenic brain display disrupted topological properties. However, is it possible to explain such abnormalities just by alteration of local activation patterns? This work suggests a negative answer to this question, demonstrating that significant disruption of the topological and spatial structure of functional MRI networks in schizophrenia (a) cannot be explained by a disruption to area-based task-dependent responses, i.e. indeed relates to the emergent properties, (b) is global in nature, affecting most dramatically long-distance correlations, and (c) can be leveraged to achieve high classification accuracy (93%) when discriminating between schizophrenic vs control subjects based just on a single fMRI experiment using a simple auditory task. While the prior work on schizophrenia networks has been primarily focused on discovering statistically significant differences in network properties, this work extends the prior art by exploring the generalization (prediction) ability of network models for schizophrenia, which is not necessarily captured by such significance tests.

Predictive dynamics of human pain perception.

While the static magnitude of thermal pain perception has been shown to follow a power-law function of the temperature, its dynamical features have been largely overlooked. Due to the slow temporal experience of pain, multiple studies now show that the time evolution of its magnitude can be captured with continuous online ratings. Here we use such ratings to model quantitatively the temporal dynamics of thermal pain perception. We show that a differential equation captures the details of the temporal evolution in pain ratings in individual subjects for different stimulus pattern complexities, and also demonstrates strong predictive power to infer pain ratings, including readouts based only on brain functional images.

Prediction and interpretation of distributed neural activity with sparse models.

We explore to what extent the combination of predictive and interpretable modeling can provide new insights for functional brain imaging. For this, we apply a recently introduced regularized regression technique, the Elastic Net, to the analysis of the PBAIC 2007 competition data. Elastic Net regression controls via one parameter the number of voxels in the resulting model, and via another the degree to which correlated voxels are included. We find that this method produces highly predictive models of fMRI data that provide evidence for the distributed nature of neural function. We also use the flexibility of Elastic Net to demonstrate that model robustness can be improved without compromising predictability, in turn revealing the importance of localized clusters of activity. Our findings highlight the functional significance of patterns of distributed clusters of localized activity, and underscore the importance of models that are both predictive and interpretable.

Adaptive diagnosis in distributed systems.

Real-time problem diagnosis in large distributed computer systems and networks is a challenging task that requires fast and accurate inferences from potentially huge data volumes. In this paper, we propose a cost-efficient, adaptive diagnostic technique called active probing. Probes are end-to-end test transactions that collect information about the performance of a distributed system. Active probing uses probabilistic reasoning techniques combined with information-theoretic approach, and allows a fast online inference about the current system state via active selection of only a small number of most-informative tests. We demonstrate empirically that the active probing scheme greatly reduces both the number of probes (from 60% to 75% in most of our real-life applications), and the time needed for localizing the problem when compared with nonadaptive (preplanned) probing schemes. We also provide some theoretical results on the complexity of probe selection, and the effect of "noisy" probes on the accuracy of diagnosis. Finally, we discuss how to model the system's dynamics using dynamic Bayesian networks (DBNs), and an efficient approximate approach called sequential multifault; empirical results demonstrate clear advantage of such approaches over "static" techniques that do not handle system's changes.