title: Studying Brain Circuit Function with Dynamic Causal Modeling for Optogenetic fMRI.
abstract: Defining the large-scale behavior of brain circuits with cell type specificity is a major goal of neuroscience. However, neuronal circuit diagrams typically draw upon anatomical and electrophysiological measurements acquired in isolation. Consequently, a dynamic and cell-type-specific connectivity map has never been constructed from simultaneous measurements across the brain. Here, we introduce dynamic causal modeling (DCM) for optogenetic fMRI experiments-which uniquely allow cell-type-specific, brain-wide functional measurements-to parameterize the causal relationships among regions of a distributed brain network with cell type specificity. Strikingly, when applied to the brain-wide basal ganglia-thalamocortical network, DCM accurately reproduced the empirically observed time series, and the strongest connections were key connections of optogenetically stimulated pathways. We predict that quantitative and cell-type-specific descriptions of dynamic connectivity, as illustrated here, will empower novel systems-level understanding of neuronal circuit dynamics and facilitate the design of more effective neuromodulation therapies.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bernal-Casas
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weitz
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA. Electronic address: ljinhy@stanford.edu.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000502:physiology; D001499:Bayes Theorem; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D015984:Causality; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D005583:Fourier Analysis; D059907:Functional Neuroimaging; D008279:Magnetic Resonance Imaging; D051379:Mice; D008959:Models, Neurological; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D013788:Thalamus / Q000000981:diagnostic imaging / Q000502:physiology
keywords: basal ganglia; direct and indirect pathways; dynamic causal modeling; ofMRI; optogenetic fMRI