title: Dopamine-induced dissociation of BOLD and neural activity in macaque visual cortex.
abstract: Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear, limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA's involvement in diseases such as Parkinson's and schizophrenia, it also plays a role in visual perception. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects.
authors.affiliation: Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany; IMPRS for Cognitive and Systems Neuroscience, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany. Electronic address: daniel.zaldivar@tuebingen.mpg.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zaldivar
authors.affiliation: Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany; University Hospital of Psychiatry, University of Bern, 3000 Bern, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Département de Radiologie Diagnostique 3001, Université de Sherbrooke, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whittingstall
authors.affiliation: Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany; Division of Imaging Science and Biomedical Engineering, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany; Institute of Neuroscience and Psychology, University of Glasgow, 58 Hillhead Street, Glasgow G12 8QB, UK. Electronic address: jozien.goense@glasgow.ac.uk.
authors.forename: Jozien
authors.initials: J
authors.lastname: Goense
mesh_terms: D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D007276:Injections, Intraventricular; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D059629:Signal-To-Noise Ratio; D014793:Visual Cortex / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*
chemical_list: D002230:Carbidopa; D004298:Dopamine