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The power of using functional fMRI on small rodents to study brain pharmacology and disease.

Jonckers E, Shah D, Hamaide J, Verhoye M, Van der Linden A - Front Pharmacol (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp Antwerp, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

Example of typical time courses for st-fMRI, rsfMRI, and phMRI.
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Figure 2: Example of typical time courses for st-fMRI, rsfMRI, and phMRI.

Mentions: The aforementioned analyses techniques do not take into account the temporal dynamics of the BOLD-signal after sensory or pharmacological stimulation. Upcoming analysis methods apply spectral analysis to the BOLD time series to obtain information on the temporal behavior of the BOLD response function [for more details see (Muller et al., 2001)]. Figure 2 shows examples of typical time courses for the different techniques and how they are related to the applied stimulus. Both rsfMRI and event related st-fMRI need fast MRI sequences (e.g., TR = 2 s, i.e., one image in 2 s) to be able to acquire BOLD fluctuations and responses to the fast consecutive stimuli, respectively. A typical rsfMRI acquisition lasts 5–12 min. In a block design the length of the different blocks in the paradigm determines the required acquisition speed. Moreover the total scan-length is dependent on the complexity of the paradigm, increasing the number of scans needed when more stimuli are introduced or the differences between stimuli are more subtle. For phMRI the timing is dependent on the pharmacokinetics of the injected compound.


The power of using functional fMRI on small rodents to study brain pharmacology and disease.

Jonckers E, Shah D, Hamaide J, Verhoye M, Van der Linden A - Front Pharmacol (2015)

Example of typical time courses for st-fMRI, rsfMRI, and phMRI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612660&req=5

Figure 2: Example of typical time courses for st-fMRI, rsfMRI, and phMRI.
Mentions: The aforementioned analyses techniques do not take into account the temporal dynamics of the BOLD-signal after sensory or pharmacological stimulation. Upcoming analysis methods apply spectral analysis to the BOLD time series to obtain information on the temporal behavior of the BOLD response function [for more details see (Muller et al., 2001)]. Figure 2 shows examples of typical time courses for the different techniques and how they are related to the applied stimulus. Both rsfMRI and event related st-fMRI need fast MRI sequences (e.g., TR = 2 s, i.e., one image in 2 s) to be able to acquire BOLD fluctuations and responses to the fast consecutive stimuli, respectively. A typical rsfMRI acquisition lasts 5–12 min. In a block design the length of the different blocks in the paradigm determines the required acquisition speed. Moreover the total scan-length is dependent on the complexity of the paradigm, increasing the number of scans needed when more stimuli are introduced or the differences between stimuli are more subtle. For phMRI the timing is dependent on the pharmacokinetics of the injected compound.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp Antwerp, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus