title: A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series.
abstract: Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in multivariate patterns of voxel activity.
authors.affiliation: Department of Theoretical Neuroscience, Bernstein Center for Computational Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Demanuele
authors.affiliation: Department of Theoretical Neuroscience, Bernstein Center for Computational Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bähner
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Plichta
authors.affiliation: Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Department of Theoretical Neuroscience, Bernstein Center for Computational Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Department of Theoretical Neuroscience, Bernstein Center for Computational Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Durstewitz
keywords: Hidden Markov Models; classifiers; decision making; discriminant analysis; machine learning; multivariate pattern analysis; prefrontal cortex; working memory