Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Evaluation of the Effect of a Continuous Treatment: A Machine Learning Approach with an Application to Treatment for Traumatic Brain Injury.

For a continuous treatment, the generalised propensity score (GPS) is defined as the conditional density of the treatment, given covariates. GPS adjustment may be implemented by including it as a covariate in an outcome regression. Here, the unbiased estimation of the dose-response function assumes correct specification of both the GPS and the outcome-treatment relationship. This paper introduces a machine learning method, the 'Super Learner', to address model selection in this context. In the two-stage estimation approach proposed, the Super Learner selects a GPS and then a dose-response function conditional on the GPS, as the convex combination of candidate prediction algorithms. We compare this approach with parametric implementations of the GPS and to regression methods. We contrast the methods in the Risk Adjustment in Neurocritical care cohort study, in which we estimate the marginal effects of increasing transfer time from emergency departments to specialised neuroscience centres, for patients with acute traumatic brain injury. With parametric models for the outcome, we find that dose-response curves differ according to choice of specification. With the Super Learner approach to both regression and the GPS, we find that transfer time does not have a statistically significant marginal effect on the outcomes

The neurobiology of functional neurological disorders characterised by impaired awareness

We review the neurobiology of Functional Neurological Disorders (FND), i.e., neurological disorders not explained by currently identifiable histopathological processes, in order to focus on those characterised by impaired awareness (functionally impaired awareness disorders, FIAD), and especially, on the paradigmatic case of Resignation Syndrome (RS). We thus provide an improved more integrated theory of FIAD, able to guide both research priorities and the diagnostic formulation of FIAD. We systematically address the diverse spectrum of clinical presentations of FND with impaired awareness, and offer a new framework for understanding FIAD. We find that unraveling the historical development of neurobiological theory of FIAD is of paramount importance for its current understanding. Then, we integrate contemporary clinical material in order to contextualise the neurobiology of FIAD within social, cultural, and psychological perspectives. We thus review neuro-computational insights in FND in general, to arrive at a more coherent account of FIAD. FIAD may be based on maladaptive predictive coding, shaped by stress, attention, uncertainty, and, ultimately, neurally encoded beliefs and their updates. We also critically appraise arguments in support of and against such Bayesian models. Finally, we discuss implications of our theoretical account and provide pointers towards an improved clinical diagnostic formulation of FIAD. We suggest directions for future research towards a more unified theory on which future interventions and management strategies could be based, as effective treatments and clinical trial evidence remain limited