Abstract
Many of the major advances in our understanding of how functional brain imaging signals relate to neuronal activity over the previous two decades have arisen from physiological research studies involving experimental animal models. This approach has been successful partly because it provides opportunities to measure both the hemodynamic changes that underpin many human functional brain imaging techniques and the neuronal activity about which we wish to make inferences. Although research into the coupling of neuronal and hemodynamic responses using animal models has provided a general validation of the correspondence of neuroimaging signals to specific types of neuronal activity, it is also highlighting the key complexities and uncertainties in estimating neural signals from hemodynamic markers. This review will detail how research in animal models is contributing to our rapidly evolving understanding of what human neuroimaging techniques tell us about neuronal activity. It will highlight emerging issues in the interpretation of neuroimaging data that arise from in vivo research studies, for example spatial and temporal constraints to neuroimaging signal interpretation, or the effects of disease and modulatory neurotransmitters upon neurovascular coupling. We will also give critical consideration to the limitations and possible complexities of translating data acquired in the typical animals models used in this area to the arena of human fMRI. These include the commonplace use of anesthesia in animal research studies and the fact that many neuropsychological questions that are being actively explored in humans have limited homologs within current animal models for neuroimaging research. Finally we will highlighting approaches, both in experimental animals models (e.g. imaging in conscious, behaving animals) and human studies (e.g. combined fMRI-EEG), that mitigate against these challenges.
Highlights
High field strength functional magnetic resonance imaging (fMRI) in animal models has enabled researchers to study the fine detail of hemodynamic responses, with sub-second temporal precision and in-plane voxel sizes of
It is possible to “stimulate” neurophysiological events, for instance using calcium uncaging by photolysis (e.g. Takano et al, 2006), providing opportunities for very fine levels of control and recording of neurovascular function. This microscopic approach is often combined with highly specific pharmacological or electrophysiological manipulations which may be applied to individual cells. It can be performed in vivo or in vitro, and increasingly research groups will deploy the technique in both modes to address a specific question in order to combine the enhanced control, manipulation and data quality advantages of the in vitro approach with the demonstration of functional relevance that is best achieved in vivo. 2PLSM is becoming established as a “gold standard” method for addressing physiological neurovascular coupling research questions
Much research and discussion has focused upon the relative contributions of these two types of activity to blood oxygen level dependent (BOLD) signals and it is generally recognized that neuroimaging signals correlate best to local field potentials (LFPs) (Logothetis et al, 2001; Viswanathan and Freeman, 2007), spiking activity has been shown to correlate closely in many (Logothetis et al, 2001; Jones et al, 2004), but not all contexts so far investigated (Caesar et al, 2003; Thomsen et al, 2004; Rauch et al, 2008)
Summary
Many of the major advances in our understanding of how functional brain imaging signals relate to neuronal activity over the previous two decades have arisen from physiological research studies involving experimental animal models. This review will detail how research in animal models is contributing to our rapidly evolving understanding of what human neuroimaging techniques tell us about neuronal activity It will highlight emerging issues in the interpretation of neuroimaging data that arise from in vivo research studies, for example spatial and temporal constraints to neuroimaging signal interpretation, or the effects of disease and modulatory neurotransmitters upon neurovascular coupling.
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