Limits...
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

Activation maps (rats no. 1–7) in response to kainic acid–induced seizures superimposed on the anatomic images. The threshold for statistical significance was set at p < 0.05 (FWE corrected). Rats were sedated with medetomidine (figure reproduced with permission of John Wiley and Sons; Airaksinen et al., 2010).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4612660&req=5

Figure 5: Activation maps (rats no. 1–7) in response to kainic acid–induced seizures superimposed on the anatomic images. The threshold for statistical significance was set at p < 0.05 (FWE corrected). Rats were sedated with medetomidine (figure reproduced with permission of John Wiley and Sons; Airaksinen et al., 2010).

Mentions: The added value of fMRI depends on the pathological phenotype of the disorder and the most prevalent pathologies will be discussed in detail below. The following sections will discuss how different fMRI techniques have led to important insights into several of the most prevalent pathologies. For example, in neurodegenerative disorders changes in brain function potentially precede structural degradation. Both st-fMRI and rsfMRI can be used to study neurological changes on a functional level, which might be of interest in terms of early diagnosis and drug intervention before the occurrence of irreversible damage. During and after therapeutic interventions the same techniques can be used to determine the efficacy of a treatment (both acutely and longitudinally) and assess recovery of functional networks (see Figure 5 for an overview).


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)

Activation maps (rats no. 1–7) in response to kainic acid–induced seizures superimposed on the anatomic images. The threshold for statistical significance was set at p < 0.05 (FWE corrected). Rats were sedated with medetomidine (figure reproduced with permission of John Wiley and Sons; Airaksinen et al., 2010).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Activation maps (rats no. 1–7) in response to kainic acid–induced seizures superimposed on the anatomic images. The threshold for statistical significance was set at p < 0.05 (FWE corrected). Rats were sedated with medetomidine (figure reproduced with permission of John Wiley and Sons; Airaksinen et al., 2010).
Mentions: The added value of fMRI depends on the pathological phenotype of the disorder and the most prevalent pathologies will be discussed in detail below. The following sections will discuss how different fMRI techniques have led to important insights into several of the most prevalent pathologies. For example, in neurodegenerative disorders changes in brain function potentially precede structural degradation. Both st-fMRI and rsfMRI can be used to study neurological changes on a functional level, which might be of interest in terms of early diagnosis and drug intervention before the occurrence of irreversible damage. During and after therapeutic interventions the same techniques can be used to determine the efficacy of a treatment (both acutely and longitudinally) and assess recovery of functional networks (see Figure 5 for an overview).

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