Limits...
Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Ferris CF, Yee JR, Kenkel WM, Dumais KM, Moore K, Veenema AH, Kulkarni P, Perkybile AM, Carter CS - Front Behav Neurosci (2015)

Bottom Line: These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle.The change in BOLD signal to peripheral OT did not show any discernible dose-response.The results from this imaging study do not support a direct central action of peripheral OT on the brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational NeuroImaging, Northeastern University , Boston, MA , USA.

ABSTRACT
A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

No MeSH data available.


Related in: MedlinePlus

Neuroanatomical fidelity. Shown are representative examples of brain images collected during a single imaging session using a multi-slice spin echo, RARE (rapid acquisition with relaxation enhancement) pulse sequence. The column on the right shows axial sections collected during the anatomical scan taken at the beginning of each imaging session using a data matrix of 256 × 256, 22 slices in a field of view of 3.0 cm. The column on the left shows the same images but collected for functional analysis using HASTE, a RARE pulse sequence modified for faster acquisition time. These images were acquired using the same field of view and slice anatomy but a larger data matrix of 96 × 96. The images in the middle column have been smoothed during pre-processing. Note the anatomical fidelity between the functional images and their original anatomical image. The absence of any distortion is necessary when registering the data to atlas to resolve 171 segmented brain areas.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585275&req=5

Figure 1: Neuroanatomical fidelity. Shown are representative examples of brain images collected during a single imaging session using a multi-slice spin echo, RARE (rapid acquisition with relaxation enhancement) pulse sequence. The column on the right shows axial sections collected during the anatomical scan taken at the beginning of each imaging session using a data matrix of 256 × 256, 22 slices in a field of view of 3.0 cm. The column on the left shows the same images but collected for functional analysis using HASTE, a RARE pulse sequence modified for faster acquisition time. These images were acquired using the same field of view and slice anatomy but a larger data matrix of 96 × 96. The images in the middle column have been smoothed during pre-processing. Note the anatomical fidelity between the functional images and their original anatomical image. The absence of any distortion is necessary when registering the data to atlas to resolve 171 segmented brain areas.

Mentions: Animals were scanned at 300 MHz using a quadrature transmit/receive volume coil built into the rat head holder and restraining system for awake animal imaging (Animal Imaging Research, Holden, MA, USA). A video of the rat preparation for imaging is available at www.youtube.com/watch?v=JQX1wgOV3K4. The design of the coil provided complete coverage of the brain from olfactory bulbs to brain stem with excellent B1 field homogeneity. Experiments were conducted using a Bruker Biospec 7.0 T/20-cm USR horizontal magnet (Bruker, Billerica, MA, USA) and a 20-G/cm magnetic field gradient insert (ID = 12 cm) capable of a 120-μs rise time. At the beginning of each imaging session, a high-resolution anatomical data set was collected using the RARE pulse sequence [22 slice; 1.0 mm; field of view (FOV) 3.0 cm; matrix size 256 × 256; repetition time (TR) 2.5 s; echo time (TE) 12 ms; NEX 2; 3 min acquisition time]. Functional images were acquired using a multi-slice half-Fourier acquisition single-shot turbo spin echo (HASTE) pulse sequence. Bruker Paravision automatically finds the basic frequency, shims, power requirements for 90° and 180° pulses and sets the receiver gain. A single scanning session acquired 22 slices, 1.0 mm thick, every 6.0 s (TR), using an effective TE of 48 ms, FOV 3.0 cm, matrix size 96 × 96, NEX 1, and repeated 250 times for a total scanning time of 25 min. The in-plane pixel resolution was 312 μm2. Each scanning session was continuous, starting with 50 baseline image acquisitions, followed by vehicle or OT administration and continuing for another 200 image acquisitions. It should be noted that the ICV experiments did not acquire images from the olfactory bulb as was the case of the IP injections. This difference was due to a slice acquisition of 20 for ICV and 22 for IP. It should also be emphasized that high neuroanatomical fidelity and spatial resolution are critical in identifying distributed neural circuits in any animal imaging study. Many brain areas in a segmented rat atlas have in-plane boundaries of less than 400 μm2 and may extend for over 1000 μm in the rostral/caudal plane. With the development of a segmented, annotated 3D MRI atlas for rats (Ekam Solutions, Boston, MA, USA), it is now possible to localize functional imaging data to precise 3D “volumes of interest” in clearly delineate brain areas. Therefore, it is critical that the functional images are a very accurate reconstruction of the original brain neuroanatomy as shown in Figure 1.


Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Ferris CF, Yee JR, Kenkel WM, Dumais KM, Moore K, Veenema AH, Kulkarni P, Perkybile AM, Carter CS - Front Behav Neurosci (2015)

Neuroanatomical fidelity. Shown are representative examples of brain images collected during a single imaging session using a multi-slice spin echo, RARE (rapid acquisition with relaxation enhancement) pulse sequence. The column on the right shows axial sections collected during the anatomical scan taken at the beginning of each imaging session using a data matrix of 256 × 256, 22 slices in a field of view of 3.0 cm. The column on the left shows the same images but collected for functional analysis using HASTE, a RARE pulse sequence modified for faster acquisition time. These images were acquired using the same field of view and slice anatomy but a larger data matrix of 96 × 96. The images in the middle column have been smoothed during pre-processing. Note the anatomical fidelity between the functional images and their original anatomical image. The absence of any distortion is necessary when registering the data to atlas to resolve 171 segmented brain areas.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585275&req=5

Figure 1: Neuroanatomical fidelity. Shown are representative examples of brain images collected during a single imaging session using a multi-slice spin echo, RARE (rapid acquisition with relaxation enhancement) pulse sequence. The column on the right shows axial sections collected during the anatomical scan taken at the beginning of each imaging session using a data matrix of 256 × 256, 22 slices in a field of view of 3.0 cm. The column on the left shows the same images but collected for functional analysis using HASTE, a RARE pulse sequence modified for faster acquisition time. These images were acquired using the same field of view and slice anatomy but a larger data matrix of 96 × 96. The images in the middle column have been smoothed during pre-processing. Note the anatomical fidelity between the functional images and their original anatomical image. The absence of any distortion is necessary when registering the data to atlas to resolve 171 segmented brain areas.
Mentions: Animals were scanned at 300 MHz using a quadrature transmit/receive volume coil built into the rat head holder and restraining system for awake animal imaging (Animal Imaging Research, Holden, MA, USA). A video of the rat preparation for imaging is available at www.youtube.com/watch?v=JQX1wgOV3K4. The design of the coil provided complete coverage of the brain from olfactory bulbs to brain stem with excellent B1 field homogeneity. Experiments were conducted using a Bruker Biospec 7.0 T/20-cm USR horizontal magnet (Bruker, Billerica, MA, USA) and a 20-G/cm magnetic field gradient insert (ID = 12 cm) capable of a 120-μs rise time. At the beginning of each imaging session, a high-resolution anatomical data set was collected using the RARE pulse sequence [22 slice; 1.0 mm; field of view (FOV) 3.0 cm; matrix size 256 × 256; repetition time (TR) 2.5 s; echo time (TE) 12 ms; NEX 2; 3 min acquisition time]. Functional images were acquired using a multi-slice half-Fourier acquisition single-shot turbo spin echo (HASTE) pulse sequence. Bruker Paravision automatically finds the basic frequency, shims, power requirements for 90° and 180° pulses and sets the receiver gain. A single scanning session acquired 22 slices, 1.0 mm thick, every 6.0 s (TR), using an effective TE of 48 ms, FOV 3.0 cm, matrix size 96 × 96, NEX 1, and repeated 250 times for a total scanning time of 25 min. The in-plane pixel resolution was 312 μm2. Each scanning session was continuous, starting with 50 baseline image acquisitions, followed by vehicle or OT administration and continuing for another 200 image acquisitions. It should be noted that the ICV experiments did not acquire images from the olfactory bulb as was the case of the IP injections. This difference was due to a slice acquisition of 20 for ICV and 22 for IP. It should also be emphasized that high neuroanatomical fidelity and spatial resolution are critical in identifying distributed neural circuits in any animal imaging study. Many brain areas in a segmented rat atlas have in-plane boundaries of less than 400 μm2 and may extend for over 1000 μm in the rostral/caudal plane. With the development of a segmented, annotated 3D MRI atlas for rats (Ekam Solutions, Boston, MA, USA), it is now possible to localize functional imaging data to precise 3D “volumes of interest” in clearly delineate brain areas. Therefore, it is critical that the functional images are a very accurate reconstruction of the original brain neuroanatomy as shown in Figure 1.

Bottom Line: These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle.The change in BOLD signal to peripheral OT did not show any discernible dose-response.The results from this imaging study do not support a direct central action of peripheral OT on the brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational NeuroImaging, Northeastern University , Boston, MA , USA.

ABSTRACT
A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

No MeSH data available.


Related in: MedlinePlus