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Considerations for resting state functional MRI and functional connectivity studies in rodents.

Pan WJ, Billings JC, Grooms JK, Shakil S, Keilholz SD - Front Neurosci (2015)

Bottom Line: However, impediments exist to the optimal application of rs-fMRI in small animals, some similar to those encountered in humans and some quite different.In this review we identify the most prominent of these barriers, discuss differences between rs-fMRI in rodents and in humans, highlight best practices for animal studies, and review selected applications of rs-fMRI in rodents.Our goal is to facilitate the integration of human and animal work to the benefit of both fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Georgia Institute of Technology, Emory University Atlanta, GA, USA.

ABSTRACT
Resting state functional MRI (rs-fMRI) and functional connectivity mapping have become widely used tools in the human neuroimaging community and their use is rapidly spreading into the realm of rodent research as well. One of the many attractive features of rs-fMRI is that it is readily translatable from humans to animals and back again. Changes in functional connectivity observed in human studies can be followed by more invasive animal experiments to determine the neurophysiological basis for the alterations, while exploratory work in animal models can identify possible biomarkers for further investigation in human studies. These types of interwoven human and animal experiments have a potentially large impact on neuroscience and clinical practice. However, impediments exist to the optimal application of rs-fMRI in small animals, some similar to those encountered in humans and some quite different. In this review we identify the most prominent of these barriers, discuss differences between rs-fMRI in rodents and in humans, highlight best practices for animal studies, and review selected applications of rs-fMRI in rodents. Our goal is to facilitate the integration of human and animal work to the benefit of both fields.

No MeSH data available.


Resting state MRI studies in rodents and humans are closely interwoven. Work in rodent models can provide insight into the neurophysiology underlying functional connectivity and the alterations in connectivity observed in different disorders. The application of the technique in animal models can identify potential biomarkers and suggest targets for intervention in humans. Similarly, findings in the human population can suggest targets for multimodal studies that provide new insight into observed alterations. Functional connectivity may be used as a biomarker to evaluate how well an animal model reproduces the deficits observed in humans, or in conjunction with genetic manipulations to understand the origins of network alterations.
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Figure 1: Resting state MRI studies in rodents and humans are closely interwoven. Work in rodent models can provide insight into the neurophysiology underlying functional connectivity and the alterations in connectivity observed in different disorders. The application of the technique in animal models can identify potential biomarkers and suggest targets for intervention in humans. Similarly, findings in the human population can suggest targets for multimodal studies that provide new insight into observed alterations. Functional connectivity may be used as a biomarker to evaluate how well an animal model reproduces the deficits observed in humans, or in conjunction with genetic manipulations to understand the origins of network alterations.

Mentions: Biswal et al. first reported resting state functional connectivity in human subjects in 1995 (Biswal et al., 1995), but the first demonstrations of resting state connectivity in an animal model came a decade later, when the growing application of the technique in humans made the need for a better understanding of its neurophysiological basis apparent (Lu et al., 2006, 2007; Williams et al., 2006, 2010; Pawela et al., 2008; Zhao et al., 2008). Following the success of animal models in characterizing the blood oxygenation level dependent (BOLD) response to stimulation, these studies began to address the similar problem of understanding the sources of the spontaneous BOLD fluctuations used to map functional connectivity (Lu et al., 2007; Shmuel and Leopold, 2008; Magnuson et al., 2010; Schölvinck et al., 2010; Pan et al., 2011, 2013; Liu et al., 2013b). As the application of rs-fMRI in human studies grows, the technique is increasingly being translated to the examination of animal models of neurological and psychiatric disorders. Beginning with a handful of articles describing functional connectivity and its physiological basis in the rat in 2007–2008, the literature has grown to 45 articles involving rs-fMRI in mice and rats in 2014 alone, which examine the effects of depression, drug abuse, plasticity, prenatal stress, and more (Alvarez-Salvado et al., 2014; Goelman et al., 2014; Lu et al., 2014; Williams et al., 2014). Today, research seeking to understand functional connectivity is divided between studies performed on human subjects and studies performed on animal models. While work in humans continues to demonstrate how functional brain networks contribute to physiology and behavior in a way that is immediately relevant to our species, animal research presents an opportunity to examine these relationships at a level that is otherwise impermissible. In this way, the two are intricately interwoven, and it is often the case that recent findings from one species drive current research in the other. The observation of behaviorally and functionally relevant alterations in functional networks in humans motivates animal studies that examine the neurophysiological basis of the alterations, which in turn allows human studies that use the technique to gain insight into pathological and normal brain function. One of the major strengths of functional connectivity mapping is its role as a translational tool that can investigate disease models or scientific hypotheses in a well-controlled environment (Figure 1).


Considerations for resting state functional MRI and functional connectivity studies in rodents.

Pan WJ, Billings JC, Grooms JK, Shakil S, Keilholz SD - Front Neurosci (2015)

Resting state MRI studies in rodents and humans are closely interwoven. Work in rodent models can provide insight into the neurophysiology underlying functional connectivity and the alterations in connectivity observed in different disorders. The application of the technique in animal models can identify potential biomarkers and suggest targets for intervention in humans. Similarly, findings in the human population can suggest targets for multimodal studies that provide new insight into observed alterations. Functional connectivity may be used as a biomarker to evaluate how well an animal model reproduces the deficits observed in humans, or in conjunction with genetic manipulations to understand the origins of network alterations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525377&req=5

Figure 1: Resting state MRI studies in rodents and humans are closely interwoven. Work in rodent models can provide insight into the neurophysiology underlying functional connectivity and the alterations in connectivity observed in different disorders. The application of the technique in animal models can identify potential biomarkers and suggest targets for intervention in humans. Similarly, findings in the human population can suggest targets for multimodal studies that provide new insight into observed alterations. Functional connectivity may be used as a biomarker to evaluate how well an animal model reproduces the deficits observed in humans, or in conjunction with genetic manipulations to understand the origins of network alterations.
Mentions: Biswal et al. first reported resting state functional connectivity in human subjects in 1995 (Biswal et al., 1995), but the first demonstrations of resting state connectivity in an animal model came a decade later, when the growing application of the technique in humans made the need for a better understanding of its neurophysiological basis apparent (Lu et al., 2006, 2007; Williams et al., 2006, 2010; Pawela et al., 2008; Zhao et al., 2008). Following the success of animal models in characterizing the blood oxygenation level dependent (BOLD) response to stimulation, these studies began to address the similar problem of understanding the sources of the spontaneous BOLD fluctuations used to map functional connectivity (Lu et al., 2007; Shmuel and Leopold, 2008; Magnuson et al., 2010; Schölvinck et al., 2010; Pan et al., 2011, 2013; Liu et al., 2013b). As the application of rs-fMRI in human studies grows, the technique is increasingly being translated to the examination of animal models of neurological and psychiatric disorders. Beginning with a handful of articles describing functional connectivity and its physiological basis in the rat in 2007–2008, the literature has grown to 45 articles involving rs-fMRI in mice and rats in 2014 alone, which examine the effects of depression, drug abuse, plasticity, prenatal stress, and more (Alvarez-Salvado et al., 2014; Goelman et al., 2014; Lu et al., 2014; Williams et al., 2014). Today, research seeking to understand functional connectivity is divided between studies performed on human subjects and studies performed on animal models. While work in humans continues to demonstrate how functional brain networks contribute to physiology and behavior in a way that is immediately relevant to our species, animal research presents an opportunity to examine these relationships at a level that is otherwise impermissible. In this way, the two are intricately interwoven, and it is often the case that recent findings from one species drive current research in the other. The observation of behaviorally and functionally relevant alterations in functional networks in humans motivates animal studies that examine the neurophysiological basis of the alterations, which in turn allows human studies that use the technique to gain insight into pathological and normal brain function. One of the major strengths of functional connectivity mapping is its role as a translational tool that can investigate disease models or scientific hypotheses in a well-controlled environment (Figure 1).

Bottom Line: However, impediments exist to the optimal application of rs-fMRI in small animals, some similar to those encountered in humans and some quite different.In this review we identify the most prominent of these barriers, discuss differences between rs-fMRI in rodents and in humans, highlight best practices for animal studies, and review selected applications of rs-fMRI in rodents.Our goal is to facilitate the integration of human and animal work to the benefit of both fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Georgia Institute of Technology, Emory University Atlanta, GA, USA.

ABSTRACT
Resting state functional MRI (rs-fMRI) and functional connectivity mapping have become widely used tools in the human neuroimaging community and their use is rapidly spreading into the realm of rodent research as well. One of the many attractive features of rs-fMRI is that it is readily translatable from humans to animals and back again. Changes in functional connectivity observed in human studies can be followed by more invasive animal experiments to determine the neurophysiological basis for the alterations, while exploratory work in animal models can identify possible biomarkers for further investigation in human studies. These types of interwoven human and animal experiments have a potentially large impact on neuroscience and clinical practice. However, impediments exist to the optimal application of rs-fMRI in small animals, some similar to those encountered in humans and some quite different. In this review we identify the most prominent of these barriers, discuss differences between rs-fMRI in rodents and in humans, highlight best practices for animal studies, and review selected applications of rs-fMRI in rodents. Our goal is to facilitate the integration of human and animal work to the benefit of both fields.

No MeSH data available.