Brain effective connectome based on fMRI and DTI data: Bayesian causal learning and assessment.

Neuroscientific studies aim to find an accurate and reliable brain Effective Connectome (EC). Although current EC discovery methods have contributed to our understanding of brain organization, their performances are severely constrained by the short sample size and poor temporal resolution of fMRI data, and high dimensionality of the brain connectome. By leveraging the DTI data as prior knowledge, we introduce two Bayesian causal discovery frameworks -the Bayesian GOLEM (BGOLEM) and Bayesian FGES (BFGES) methods- that offer significantly more accurate and reliable ECs and address the shortcomings of the existing causal discovery methods in discovering ECs based on only fMRI data. Moreover, to numerically assess the improvement in the accuracy of ECs with our method on empirical data, we introduce the Pseudo False Discovery Rate (PFDR) as a new computational accuracy metric for causal discovery in the brain. Through a series of simulation studies on synthetic and hybrid data (combining DTI from the Human Connectome Project (HCP) subjects and synthetic fMRI), we demonstrate the effectiveness of our proposed methods and the reliability of the introduced metric in discovering ECs. By employing the PFDR metric, we show that our Bayesian methods lead to significantly more accurate results compared to the traditional methods when applied to the Human Connectome Project (HCP) data. Additionally, we measure the reproducibility of discovered ECs using the Rogers-Tanimoto index for test-retest data and show that our Bayesian methods provide significantly more reliable ECs than traditional methods. Overall, our study's numerical and visual results highlight the potential for these frameworks to significantly advance our understanding of brain functionality.

Determining the adjusted initial treatment dose of warfarin anticoagulant medicine using kernel-based support vector regression.

BACKGROUND AND OBJECTIVE: A novel research field in bioinformatics is pharmacogenomics and the corresponding applications of artificial intelligence tools. Pharmacogenomics is the study of the relationship between genotype and responses to medical measures such as drug use. One of the most effective drugs is warfarin anticoagulant, but determining its initial treatment dose is challenging. Mistakes in the determination of the initial treatment dose can result directly in patient death. METHODS: Some of the most successful techniques for estimating the initial treatment dose are kernel-based methods. However, all the available studies use pre-defined and constant kernels that might not necessarily address the problem's intended requirements. The present study seeks to define and present a new computational kernel extracted from a data set. This process aims to utilize all the data-related statistical features to generate a dose determination tool proportional to the data set with minimum error rate. The kernel-based version of the least square support vector regression estimator was defined. Through this method, a more appropriate approach was proposed for predicting the adjusted dose of warfarin. RESULTS AND CONCLUSION: This paper benefits from the International Warfarin Pharmacogenomics Consortium (IWPC) Database. The results obtained in this study demonstrate that the support vector regression with the proposed new kernel can successfully estimate the ideal dosage of warfarin for approximately 68% of patients.

Quantitative determination of concordance in localizing epileptic focus by component-based EEG-fMRI.

BACKGROUND AND OBJECTIVE: Accurate seizure onset zone (SOZ) localization is an essential step in pre-surgical assessment of patients with refractory focal epilepsy. Complex pathophysiology of epileptic cerebral structures, seizure types and frequencies have not been considered as influential features for accurate identification of SOZ using EEG-fMRI. There is a crucial need to quantitatively measure concordance between presumed SOZ and IED-related BOLD response in different brain regions to improve SOZ delineation. METHODS: A novel component-based EEG-fMRI approach is proposed to measure physical distance between BOLD clusters and selected component dipole location using patient-specific high resolution anatomical images. The method is applied on 18 patients with refractory focal epilepsy to localize epileptic focus and determine concordance quantitatively and compare between maximum BOLD cluster with identified component dipole. To measure concordance, distance from a voxel with maximal z-score of maximum BOLD to center of extracted component dipole is measured. RESULTS: BOLD clusters to spikes distances for concordant (<25 mm), partially concordant (25-50 mm), and discordant (>50 mm) groups were significantly different (p < 0.0001). The results showed full concordance in 17 IED types (17.85 ±â€¯4.69 mm), partial concordance in 4 (36.47 ± 8.84 mm), and nodiscordance, which is a significant rise compared to the existing literature. The proposed method is premised on the cross-correlation between the spike template outside the scanner and the highly-ranked extracted components. It successfully surpasses the limitations of conventional EEG-fMRI studies which are largely dependent on inside-scanner spikes. More significantly, the proposed method improves localization accuracy to 97% which marks a dramatic rise compared to conventional works. CONCLUSIONS: This study demonstrated that BOLD changes were related to epileptic spikes in different brain regions in patients with refractory focal epilepsy. In a systematic quantitative approach, concordance levels based on the distance between center of maximum BOLD cluster and dipole were determined by component-based EEG-fMRI method. Therefore, component-based EEG-fMRI can be considered as a reliable predictor of SOZ in patients with focal epilepsy and included as part of clinical evaluation for patients with medically resistant epilepsy.

Context transfer in reinforcement learning using action-value functions.

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents' MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework is Q-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. The Q-values learned during the learning process of the source tasks are mapped to the sets of Q-values for the target task. These transferred Q-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task.

Computational model of excitatory/inhibitory ratio imbalance role in attention deficit disorders.

Impairments in attentional behaviors, including over-selectivity, under-selectivity, distractibility and difficulty in shift of attention, are widely reported in several developmental disorders, including autism. Uncharacteristic inhibitory to excitatory neuronal number ratio (IER) and abnormal synaptic strength levels in the brain are two broadly accepted neurobiological disorders observed in autistic individuals. These neurobiological findings are contrasting and their relation to the atypical attentional behaviors is not clear yet. In this paper, we take a computational approach to investigate the relation of imbalanced IER and abnormal synaptic strength to some well-documented spectrum of attentional impairments. The computational model is based on a modified version of a biologically plausible neural model of two competing minicolumns in IT cortex augmented with a simple model of top-down attention. Top-down attention is assumed to amplify (attenuates) attended (unattended) stimulus. The inhibitory synaptic strength parameter in the model is set such that typical attentional behavior is emerged. Then, according to related findings, the parameter is changed and the model's attentional behavior is considered. The simulation results show that, without any change in top-down attention, the abnormal inhibitory synaptic strength values--and IER imbalance- result in over-selectivity, under-selectivity, distractibility and difficulty in shift of attention in the model. It suggests that the modeled neurobiological abnormalities can be accounted for the attentional deficits. In addition, the atypical attentional behaviors do not necessarily point to impairments in top-down attention. Our simulations suggest that limited changes in the inhibitory synaptic strength and variations in top-down attention signal affect the model's attentional behaviors in the same way. So, limited deficits in the inhibitory strength may be alleviated by appropriate change in top-down attention biasing. Nevertheless, our model proposes that this compensation is not possible for very high and very low values of the inhibitory strength.