Disentangling causal webs in the brain using functional Magnetic Resonance Imaging: A review of current approaches

In the past two decades, functional Magnetic Resonance Imaging has been used to relate neuronal network activity to cognitive processing and behaviour. Recently this approach has been augmented by algorithms that allow us to infer causal links between component populations of neuronal networks. Multiple inference procedures have been proposed to approach this research question but so far, each method has limitations when it comes to establishing whole-brain connectivity patterns. In this work, we discuss eight ways to infer causality in fMRI research: Bayesian Nets, Dynamical Causal Modelling, Granger Causality, Likelihood Ratios, LiNGAM, Patel's Tau, Structural Equation Modelling, and Transfer Entropy. We finish with formulating some recommendations for the future directions in this area

Effective Self-Management for Early Career Researchers in the Natural and Life Sciences

Early career researchers (ECRs) are faced with a range of competing pressures in academia, making self-management key to building a successful career. The Organization for Human Brain Mapping undertook a group effort to gather helpful advice for ECRs in self-management. Keywords: ECRs; career development; early career researchers; mentoring; networking; self-managemen

Neuronal Causes and Behavioural Effects: a Review on Logical, Methodological, and Technical Issues With Respect to Causal Explanations of Behaviour in Neuroscience

Elucidating causal, neurobiological underpinnings of behaviour is an ultimate goal of every neuroscientific study. However, due to the complexity of the brain as well as the complexity of the human environment, finding a~causal architecture that underlies behaviour remains a~formidable challenge. In this manuscript, we review the logical and conceptual issues with respect to causal research in neuroscience.First, we review the state of the art interventional and computational approaches to infer causal brain-behaviour relationships. We provide an~overview of potential issues, flaws, and confounds in these studies. We conclude that studies on the causal structure underlying behaviour should be performed by accumulating evidence coming from several lines of experimental and modelling studies. Lastly, we also propose computational models including artificial neuronal networks and simulated animats as a~potential breakthrough to causal brain-behaviour investigations

Circuit to construct mapping: a mathematical tool for assisting the diagnosis and treatment in Major Depressive Disorder

Major Depressive Disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand, and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH RDoC Initiative, in which a concept of ‘constructs’ as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning - cognition, genetics, brain anatomy and neurophysiology.In this review, we propose a new approach which we called Circuit to Construct Mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD.The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime towards personalized medicine, assisting the diagnosis and treatment of MDD

Questions and controversies in the study of time-varying functional connectivity in resting fMRI

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain's functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as "dynamic" or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience