Resting state dynamics meets anatomical structure: Temporal multiple kernel learning (tMKL) model

Over the last decade there has been growing interest in understanding the brain activity, in the absence of any task or stimulus, captured by the resting-state functional magnetic resonance imaging (rsfMRI). The resting state patterns have been observed to be exhibiting complex spatio-temporal dynamics and substantial effort has been made to characterize the dynamic functional connectivity (dFC) configurations. However, the dynamics governing the state transitions that the brain undergoes and their relationship to stationary functional connectivity still remains an open problem. One class of approaches attempts to characterize the dynamics in terms of finite number of latent brain states, however, such attempts are yet to amalgamate the underlying anatomical structural connectivity (SC) with the dynamics. Another class of methods links individual dynamic FCs with the underlying SC but does not characterize the temporal evolution of FC. Further, the latent states discovered by previous approaches could not be directly linked to the SC, thereby motivating us to discover the underlying lower-dimensional manifold that represents the temporal structure. In the proposed approach, the discovered manifold is further parameterized as a set of local density distributions, or latent transient states. We propose an innovative method that learns parameters specific to the latent states using a graph-theoretic model (temporal Multiple Kernel Learning, tMKL) that inherently links dynamics to the structure and finally predicts the grand average FC of the test subjects by leveraging a state transition Markov model. The proposed solution does not make strong assumptions about the underlying data and is generally applicable to resting or task data for learning subject-specific state transitions and for successfully characterizing SC-dFC-FC relationship through a unifying framework. Training and testing were done using the rs-fMRI data of 46 healthy participants. tMKL model performs significantly better than the existing models for predicting resting state functional connectivity based on whole-brain dynamic mean-field model (DMF), single diffusion kernel (SDK) model and multiple kernel learning (MKL) model. Further, the learned model was tested on an independent cohort of 100 young, healthy participants from the Human Connectome Project (HCP) and the results establish the generalizability of the proposed solution. More importantly, the model retains sensitivity toward subject-specific anatomy, a unique contribution towards a holistic approach for SC-FC characterization.