title: The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements.
abstract: The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed 'bottom-up' forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in the way they drive changes in cerebral blood flow, cerebral metabolic rate of O2 (measurable with quantitative functional Magnetic Resonance Imaging), and electrical currents/potentials (measurable with magneto/electroencephalography). This forward model would then provide the 'ground truth' for the development of new tools for tackling the inverse problem-estimation of neuronal activity from multimodal non-invasive imaging data.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA CEITEC-Central European Institute of Technology and Institute of Physical Engineering, Faculty of Mechanical Engineering, Brno University of Technology, Brno, Czech Republic.
authors: Hana
authors: H
authors: Uhlirova
authors: Department of Neurosciences, UCSD, La Jolla, CA 92093, USA.
authors: Kıvılcım
authors: K
authors: Kılıç
authors: Department of Neurosciences, UCSD, La Jolla, CA 92093, USA Department of Physics, John Carroll University, University Heights, OH 44118, USA.
authors: Peifang
authors: P
authors: Tian
authors: Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Sava
authors: S
authors: Sakadžić
authors: Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Louis
authors: 0000-0001-7202-5176
authors: L
authors: Gagnon
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA.
authors: Martin
authors: M
authors: Thunemann
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA.
authors: Michèle
authors: M
authors: Desjardins
authors: Department of Neurosciences, UCSD, La Jolla, CA 92093, USA.
authors: Payam A
authors: PA
authors: Saisan
authors: Neurosciences Graduate Program, UCSD, La Jolla, CA 92093, USA.
authors: Krystal
authors: K
authors: Nizar
authors: Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Mohammad A
authors: MA
authors: Yaseen
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA.
authors: Donald J
authors: DJ
authors: Hagler
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, 0407 Oslo, Norway.
authors: Matthieu
authors: M
authors: Vandenberghe
authors: Department of Medical Genetics, Oslo University Hospital, 0407 Oslo, Norway NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
authors: Srdjan
authors: S
authors: Djurovic
authors: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, 0407 Oslo, Norway.
authors: Ole A
authors: OA
authors: Andreassen
authors: Department of Bioengineering, UCSD, La Jolla, CA 92093, USA Department of Opthalmology, UCSD, La Jolla, CA 92093, USA.
authors: Gabriel A
authors: GA
authors: Silva
authors: Department of Neurosciences, UCSD, La Jolla, CA 92093, USA.
authors: Eliezer
authors: E
authors: Masliah
authors: Department of Physics, UCSD, La Jolla, CA 92093, USA Department of Electrical and Computer Engineering, UCSD, La Jolla, CA 92093, USA Section of Neurobiology, UCSD, La Jolla, CA 92093, USA.
authors: David
authors: 0000-0001-9797-4722
authors: D
authors: Kleinfeld
authors: Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Sergei
authors: S
authors: Vinogradov
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA.
authors: Richard B
authors: RB
authors: Buxton
authors: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, 1432 Ås, Norway Department of Physics, University of Oslo, 0316 Oslo, Norway.
authors: Gaute T
authors: GT
authors: Einevoll
authors: Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA 02129, USA.
authors: David A
authors: DA
authors: Boas
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA Department of Neurosciences, UCSD, La Jolla, CA 92093, USA.
authors: Anders M
authors: AM
authors: Dale
authors: Department of Radiology, UCSD, La Jolla, CA 92093, USA Department of Neurosciences, UCSD, La Jolla, CA 92093, USA Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA 02129, USA adevor@ucsd.edu.
authors: Anna
authors: A
authors: Devor
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000295:instrumentation / Q000379:methods*; D002560:Cerebrovascular Circulation; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013003:Somatosensory Cortex / Q000502:physiology*
chemical_list: D010100:Oxygen
keywords: BOLD fMRI; CMRO2; cerebral blood flow; magnetoencephalography; neurometabolic; neurovascular