Brain Network Evaluation by Functional-Guided Effective Connectivity Reinforcement Learning Method Indicates Therapeutic Effect for Tinnitus.

Using functional connectivity (FC) or effective connectivity (EC) alone cannot effectively delineate brain networks based on functional magnetic resonance imaging (fMRI) data, limiting the understanding of the mechanism of tinnitus and its treatment. Investigating brain FC is a foundational step in exploring EC. This study proposed a functionally guided EC (FGEC) method based on reinforcement learning (FGECRL) to enhance the precision of identifying EC between distinct brain regions. An actor-critic framework with an encoder-decoder model was adopted as the actor network. The encoder utilizes a transformer model; the decoder employs a bidirectional long short-term memory network with attention. An FGEC network was constructed for the enrolled participants per fMRI scan, including 65 patients with tinnitus and 28 control participants healthy at the enrollment time. After 6 months of sound therapy for tinnitus and prospective follow-up, fMRI data were acquired again and retrospectively categorized into an effective group (EG) and an ineffective group (IG) according to the treatment effect. Compared with FC and EC, the FGECRL method demonstrated better accuracy in discriminating between different groups, highlighting the advantage of FGECRL in identifying brain network features. For the FGEC network of the EG and IG per state (before and after treatment) and healthy controls, effective therapy is characterized by a similar pattern of FGEC network between patients with tinnitus after treatment and healthy controls. Deactivated information output in the motor network, somatosensory network, and medioventral occipital cortex may biologically indicate effective treatment. The maintenance of decreased EC in the primary auditory cortex may represent a failure of sound therapy, further supporting the Bayesian inference theory for tinnitus perception. The FGEC network can provide direct evidence for the mechanism of sound therapy in patients with tinnitus with distinct outcomes.

MetaCAE: Causal autoencoder with meta-knowledge transfer for brain effective connectivity estimation.

Using machine learning methods to estimate brain effective connectivity networks from functional magnetic resonance imaging (fMRI) data has gradually become one of the hot subjects in the fields of neuroscience. In particular, the encoder-decoder based methods can effectively extract the connections in fMRI time series, which have achieved promising performance. However, these methods generally use Granger causality model, which may identify false directions due to the non-stationary characteristic of fMRI data. Additionally, fMRI datasets have limited sample sizes, which significantly constrains the development of these methods. In this paper, we propose a novel brain effective connectivity estimation method based on causal autoencoder with meta-knowledge transfer, called MetaCAE. The proposed approach employs a causal autoencoder (CAE) to extract causal dependencies from non-stationary fMRI time series, and leverages meta-knowledge transfer to improve the estimation accuracy on small-sample data. More specifically, MetaCAE first employs a temporal convolutional encoder to extract non-stationary temporal information from fMRI time series. Then it uses a structural equation model-based decoder to decode causal relationships between brain regions. Finally, it utilizes a model-agnostic meta-learning method to learn the meta-knowledge of the shared brain effective connectivity among different subjects, and transfers the meta-knowledge to the CAE to enhance its estimation ability on small-sample fMRI data. Comprehensive experiments on both simulated and real-world data demonstrate the efficacy of MetaCAE in estimating brain effective connectivity.

Amortization Transformer for Brain Effective Connectivity Estimation from fMRI Data.

Using machine learning methods to estimate brain effective connectivity networks from functional magnetic resonance imaging (fMRI) data has garnered significant attention in the fields of neuroinformatics and bioinformatics. However, existing methods usually require retraining the model for each subject, which ignores the knowledge shared across subjects. In this paper, we propose a novel framework for estimating effective connectivity based on an amortization transformer, named AT-EC. In detail, AT-EC first employs an amortization transformer to model the dynamics of fMRI time series and infer brain effective connectivity across different subjects, which can train an amortized model that leverages the shared knowledge from different subjects. Then, an assisted learning mechanism based on functional connectivity is designed to assist the estimation of the brain effective connectivity network. Experimental results on both simulated and real-world data demonstrate the efficacy of our method.

Brain effective connectivity analysis facilitates the treatment outcome expectation of sound therapy in patients with tinnitus.

Tinnitus is associated with abnormal functional connectivity of multiple regions of the brain. However, previous analytic methods have disregarded information on the direction of functional connectivity, leading to only a moderate efficacy of pretreatment planning. We hypothesized that the pattern of directional functional connectivity can provide key information on treatment outcomes. Sixty-four participants were enrolled in this study: eighteen patients with tinnitus were categorized into the effective group, twenty-two patients into the ineffective group, and twenty-four healthy participants into the healthy control group. We acquired resting-state functional magnetic resonance images prior to sound therapy and constructed an effective connectivity network of the three groups using an artificial bee colony algorithm and transfer entropy. The key feature of patients with tinnitus was the significantly increased signal output of the sensory network, including the auditory, visual, and somatosensory networks, and parts of the motor network. This provided critical insights into the gain theory of tinnitus development. The altered pattern of functional information orchestration, represented by a higher degree of hypervigilance-driven attention and enhanced multisensory integration, may explain poor clinical outcomes. The activated gating function of the thalamus is one of the key factors for a good prognosis in tinnitus treatment. We developed a novel method for analyzing effective connectivity, facilitating an understanding of the tinnitus mechanism and treatment outcome expectation based on the direction of information flow.