title: A receptor-based model for dopamine-induced fMRI signal.
abstract: This report describes a multi-receptor physiological model of the fMRI temporal response and signal magnitude evoked by drugs that elevate synaptic dopamine in basal ganglia. The model is formulated as a summation of dopamine's effects at D1-like and D2-like receptor families, which produce functional excitation and inhibition, respectively, as measured by molecular indicators like adenylate cyclase or neuroimaging techniques like fMRI. Functional effects within the model are described in terms of relative changes in receptor occupancies scaled by receptor densities and neuro-vascular coupling constants. Using literature parameters, the model reconciles many discrepant observations and interpretations of pre-clinical data. Additionally, we present data showing that amphetamine stimulation produces fMRI inhibition at low doses and a biphasic response at higher doses in the basal ganglia of non-human primates (NHP), in agreement with model predictions based upon the respective levels of evoked dopamine. Because information about dopamine release is required to inform the fMRI model, we simultaneously acquired PET (11)C-raclopride data in several studies to evaluate the relationship between raclopride displacement and assumptions about dopamine release. At high levels of dopamine release, results suggest that refinements of the model will be required to consistently describe the PET and fMRI data. Overall, the remarkable success of the model in describing a wide range of preclinical fMRI data indicate that this approach will be useful for guiding the design and analysis of basic science and clinical investigations and for interpreting the functional consequences of dopaminergic stimulation in normal subjects and in populations with dopaminergic neuroadaptations.
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA. Electronic address: jbm@nmr.mgh.harvard.edu.
authors: Joseph B
authors: JB
authors: Mandeville
authors: Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Christin Y M
authors: CYM
authors: Sander
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors: Bruce G
authors: BG
authors: Jenkins
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors: Jacob M
authors: JM
authors: Hooker
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors: Ciprian
authors: C
authors: Catana
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors: Wim
authors: W
authors: Vanduffel
authors: Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors: Nathaniel M
authors: NM
authors: Alpert
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors: Bruce R
authors: BR
authors: Rosen
authors: Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors: Marc D
authors: MD
authors: Normandin
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004298:Dopamine