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'.

Department of Biochemistry and Biophysics University of Pennsylvania Philadelphia PA 19104 USA

Department of Bioengineering UCSD La Jolla CA 92093 USA Department of Opthalmology UCSD La Jolla CA 92093 USA

Department of Mathematical Sciences and Technology Norwegian University of Life Sciences 1432 Ås Norway Department of Physics University of Oslo 0316 Oslo Norway

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

Department of Neurosciences UCSD La Jolla CA 92093 USA

Department of Neurosciences UCSD La Jolla CA 92093 USA Department of Physics John Carroll University University Heights OH 44118 USA

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

Department of Radiology UCSD La Jolla CA 92093 USA

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

Department of Radiology UCSD La Jolla CA 92093 USA Department of Neurosciences UCSD La Jolla CA 92093 USA

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

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

Martinos Center for Biomedical Imaging MGH Harvard Medical School Charlestown MA 02129 USA

Neurosciences Graduate Program 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

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