Abstract
Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations.
Highlights
FMRI METHODOLOGYMagnetic resonance imaging tools are widely used to evaluate brain structure and function even in a single experiment
magnetic resonance imaging (MRI) is based on a magnetic field and radiofrequency pulses and most of the MRI applications use the intrinsic tissue contrast relying on different features of 1H protons in tissue water without the need of injecting contrast agents
Brain function can be assessed by measuring cerebral perfusion, blood flow (ASL, dynamic susceptibility contrast (DSC) MRI, and dynamic contrast enhanced (DCE) MRI) and brain activity (Functional MRI, resting state fMRI (rsfMRI), pharmacological modulations on neuronal activity (phMRI); [for review see for example (Denic et al, 2011)]
Summary
Magnetic resonance imaging tools are widely used to evaluate brain structure and function even in a single experiment. Brain function can be assessed by measuring cerebral perfusion, blood flow (ASL, DSC MRI, and DCE MRI) and brain activity (Functional MRI, rsfMRI, phMRI; [for review see for example (Denic et al, 2011)] These different techniques can be applied within a single scanning session. Since its introduction over 20 years ago (Ogawa et al, 1990; Kwong et al, 1992), fMRI has gained immense popularity to study brain activation and brain activity patterns in health (Di Salle et al, 1999; Logothetis, 2008; Bandettini, 2012) and disease (Iannetti and Wise, 2007), both in humans and animal models (Van Der Linden et al, 2007) These methods are especially useful to document the neuro-modulatory actions of pharmacologically active compounds. In this review we try to give an overview of the vast amount of information that can be obtained with small rodent fMRI in pharmacology completed with an overview of specific applications in different animal disease models and their translation to the clinic
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