A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism

Agnès Aubert, Luc Pellerin, Pierre Magistretti, Robert Costalat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Functional neuroimaging has undergone spectacular developments in recent years. Paradoxically, its neurobiological bases have remained elusive, resulting in an intense debate around the cellular mechanisms taking place upon activation that could contribute to the signals measured. Taking advantage of a modeling approach, we propose here a coherent neurobiological framework that not only explains several in vitro and in vivo observations but also provides a physiological basis to interpret imaging signals. First, based on a model of compartmentalized energy metabolism, we show that complex kinetics of NADH changes observed in vitro can be accounted for by distinct metabolic responses in two cell populations reminiscent of neurons and astrocytes. Second, extended application of the model to an in vivo situation allowed us to reproduce the evolution of intraparenchymal oxygen levels upon activation as measured experimentally without substantially altering the initial parameter values. Finally, applying the same model to functional neuroimaging in humans, we were able to determine that the early negative component of the blood oxygenation level-dependent response recorded with functional MRI, known as the initial dip, critically depends on the oxidative response of neurons, whereas the late aspects of the signal correspond to a combination of responses from cell types with two distinct metabolic profiles that could be neurons and astrocytes. In summary, our results, obtained with such a modeling approach, support the concept that both neuronal and glial metabolic responses form essential components of neuroimaging signals.

Original languageEnglish (US)
Pages (from-to)4188-4193
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number10
DOIs
StatePublished - Mar 6 2007

Keywords

  • Astrocyte-neuron interactions
  • Blood oxygenation level-dependent signal
  • Lactate
  • Mathematical model
  • NADH

ASJC Scopus subject areas

  • General

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