Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.

Institute of Computer Science of the Czech Academy of Sciences Pod Vodárenskou věží 271 2 Prague 182 07 Czech Republic

Institute of Computer Science of the Czech Academy of Sciences Pod Vodárenskou věží 271 2 Prague 182 07 Czech Republic; National Institute of Mental Health Topolová 748 Klecany 250 67 Czech Republic

Institute of Computer Science of the Czech Academy of Sciences Pod Vodárenskou věží 271 2 Prague 182 07 Czech Republic; National Institute of Mental Health Topolová 748 Klecany 250 67 Czech Republic; Faculty of Electrical Engineering Czech Technical University Technická 1902 2 Prague 166 27 Czech Republic

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